CYTOGENETICS

2nd Year – BS Medical Technology | 2nd Sem – 1st Block

BSMT 2A
PPT AND DISCUSSION

Module 1 - ORIGIN AND IMPORTANCE OF GENETICS not understood, greatly facilitates classification and recognition
TOPIC 1: THE HISTORICAL CONTEXT OF GENETICS of structural aberations.
Since the dawn of civilization, humankind has recognized the • 1963 – chromosome 5 short arm partial deletion in Cri du Chat
influence of heredity and applied its principles to improvement of cultivated syndrome, D-chromosome deletion in patient with bilateral
crops and domestic animals. Most of the mechanisms of heredity, however, retinoblastoma.
remained a mystery until the 19th century, when genetics as a systematic • In the late 80’s introduction of FISH (Fluorescence In-Situ
science began. Genetics arose out of the identification of genes, the Hybridization)
fundamental units responsible for heredity, as a scientific discipline MODERN GENETICS
stemmed from the work of Gregor Mendel in the middle of the 19th century. 3 Main Branches
All present research inn genetics can be traced back to Mendel’s discovery • Transmission Genetics – the study of the passing of traits from
of the laws governing the inheritance of traits. one generation to the next.
The word genetics was introduced in 1905 by English biologist • Molecular Genetics – the study of the chemical structure of
William Bateson, who was one of the discoveries of Mendel’s work and who genes and how they operate at the molecular level.
become champion of Mendel’s principles of inheritance. • Population Genetics – the study of the variation of genes
• Hippocrates (c.460 -375 BCE), known as the father of medicine, between and within population
believed in the inheritance of acquired, and to account to this, he TOPIC 2: APPLICATION OF GEENTICS
devised the hypothesis known as pangenesis. In recent advances in molecular biology allow us to develop and
• Aristotle (384-322 BCE) emphasized the importance of blood in apply the tools and concepts of molecular genetics to the conservation of
heredity. He thought that the blood supplied generative material biological resources. Working with the design and implement studies that
for building all parts of the adult body and he reasoned that blood provide genetic and genomic information for a broad range of applications.
was the basis for passing on this generative power to the next
generation. (blood lines, blood ties). Applications of Genetics to Agriculture
• 17th and 18th centuries the idea of preformation using the newly • This involves breeding animals and plants by selectively choosing
developed microscopes. those with desirable qualities.
• Jean-Baptiste Lamarck a French biologist invoked the idea of “the Application of Genetics in Medicine
influence of acquired characters” not as an explanation for • Medical genetics is any application of genetic principles
heredity but as a model for evolution. to medical practice. This includes studies of inheritance, mapping
• Alfred Russel Wallace a British naturalist originally postulated the disease genes, diagnosis and treatment, and genetic counseling.
theory of evolution by natural selection. Applications of Genetics in Blood Typing
• 1900 – marked the “rediscovery of Mendel’s by Hugo de Vries, • ABO blood group system, the classification of human blood based
Carl Correns and Erich Tschermark. on the inherited properties of red blood cells (erythrocytes) as
• 1915 – The basic principles of Mendelian Genetics had been determined by the presence or absence of the antigens A and B,
applied to a wide variety of organism. (Fruit fly) which are carried on the surface of the red cells. Persons may thus
• 1925 – Mendelian Model was widely studied. have type A, type B, type O, or type AB blood.
• Comes from the Latin GENESIS which means birth or more Applications of Genetics Biology
broadly, it is the study of heredity. • Genetics is a branch of biology concerned with the study
GENETICS of genes, genetic variation, and heredity in organisms.
• Is the study of genes, genetic variation, and heredity in living Applications of Genetics in Human Life.
organism • Genetics can help us to understand why people look the way they
• It is generally considered a field of biology, but it interacts do and why some people are more prone to certain diseases than
frequently with many of the life sciences. others. Genetics can help health-care professionals to identify
• It is a strongly linked with the study of information systems certain conditions in babies before they are born using techniques
• The study of heredity in general and of genes in particular. such as prenatal testing.
• Genetics forma one of the central pillars of biology and overlap Module 2 – THE CELL
CYTOLOGY Cytogenetics is the branch of genetics that correlates the
• The branch of biology concerned with the structure and function structure, number, and behavior of chromosomes with heredity and
of plant and animal cells diseases.
CYTOGENETICS
• The study of inheritance in relation to the structure and function
of chromosomes
Conventional Cytogenetics
• A branch of genetics that is concerned with the study of the
structure and function of the cell, especially the chromosomes.
• Is an exciting, dynamic field of study which analyzes the number Molecular Cytogenetics
and structure of human and animal chromosomes
• Changes that affect the number and / or structure of the
chromosomes with growth, development, and how the body Molecular Biology
functions.
• The study of chromosomes and genomic structure, function, and
variation and their role in human disease and heredity.
100 trillion cells
a. Chromosomes analysis/karyotyping
b. Fluorescence in situ hybridization
c. Genomic microarray analysis
THE BIRTH OF HUMAN CYTOGENETICS
• 1956: Joe Hin Tjio and Albert Levan count the full complement of THE CELL
46 human Chromosomes • Basic unit of the living organism
• Thomas Painter – 30 years after, the count of 48 chromosomes • Because of this, it creates different organization of the body.
were studied. • The average human being is composed around 100 trillion cells
• 1968 Caspersson et. al – differential staining of chromosomes • It would take as many as 50 cells to cover the area of a dot on the
produces a recognizable banding pattern (chromosomal letter “I”
barcode) along the length of the chromosomes. Chromosomes History of Cells and The Cell Theory
are related to differences in base pair composition, gene density, • Cytology – the study of cells
repetitive elements, chromatin packaging but molecular basis is

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 • English Scientist Robert Hooke (1665)- make used of an • Cell membrane is fluid. Molecules in cell membranes are constantly
improvised microscope to examine a cork (plant). Hooked called moving and changing
what he saw “Cells”
• Anton van Leeuwenhoek (1673)- a Dutch microscope maker, was A. Cell Membrane Proteins
first to view organism (living things), he used a simple, handheld a. Proteins help move large molecules or aid in cell recognition
microscope to view pond water and scrapings from his teeth. b. Peripheral proteins are attached on the surface (inner or
• Robert Brown (1833)- discovered the nucleus outer)
• Matthias Schleiden (1838) – German Botanist discovered the cells c. Integral proteins are embedded completely through the
in plants. All plants “are composed of cells” membrane
• Theodor Schwann (1838) – discovered that animals were made B. Cell membrane in plants
of cells a. Lies immediately against the cell wall in plant cells
• Rudolf Virchow (1855) – a German medical doctor observed that b. Pushes out against the cell wall to maintain cell shape
cells divide, he reasoned that all cells come from other pre- C. Phospholipids
existing cells by cell division. Debunked Theory of Spontaneous a. Heads – contain glycerol & phosphate and are hydrophilic
Generation (attract water)
b. Tails – made of fatty acids and are hydrophobic (repel water)
Cell Theory c. Make up a bilayer where tails point inward toward each other
• The combined work of Schleiden, Schwann, and Virchow make up d. Can move laterally to allow small molecules (O2, Co2, H2O to
the modern “Cell Theory” enter)
• The Cell Theory States that: 2. CYTOPLASM
a. All things are made of cells • The content found between the nucleus and the cell membrane
b. Cells are the basic unit of structure and function in an • Cytosol is the fluid medium where the cytoplasmic structures
organism (basic unit of life) are embedded
c. Cells come from the reproduction of existing cells (cell • Bulk protoplasm, contain the network of the fine tubes and
division) filaments known as cytoskeleton – that provide internal
Cell Diversity support for the cell.
• Cells within the same organism show enormous Diversity in • Gives the cell a definite shape and allow it to move
a. Size 3. NUCLEUS
b. Shape • control organelle
c. Internal organization • controls the normal activities of the cell
Cell Size • contains the DNA in chromosomes
• Female egg – largest cell in human body; seen without the aid of • bounded by a nuclear envelope (membrane) with pores
a microscope. • usually the largest organelle
• Most cells are visible only with a microscope • brain of nucleus
• Two reasons why cell is considered small • bordered by a porous membrane – nuclear envelope.
a. Reason 1 – limited in size by the ratio between their outer • Contains thin fibers of DNA and protein called chromatin
surface area and their volume. A small cell has more surface • Rod shaped chromosomes
area than a large cell for a given volume of cytoplasm. • Contain a small round nucleolus
b. Reason 2 – the cell’s nucleus (the brain) can only control a • Produces ribosomal RNA which makes ribosomes
certain amount of living, active cytoplasm. • Usually spherical organelles
Cell shape • Found in the center of the cell
• Diversity of form reflects a diversity of function. The shape of a • Made up of carbohydrates, lipids, protein and nucleice acid –
cell depends on its function DNA nad RNA
A. Functions
Simple or Complex Cells a. Responsible for the genetic and metabolic control
• Prokaryotes b. Directs the production of proteins in the cell
• Very common in bacteria c. Governs all major activities and functions in the cell
• Nucleoid region (center) contains the DNA B. Nuclear Envelope
• Surrounded by cell membrane and cell wall a. Double membrane surrounding nucleus
(peptidoglycan) b. Also called nuclear membrane
• Contains ribosomes (no membrane) in their cytoplasm c. Containe nuclear pores for materials to enter and
to make proteins leave the nucleus
• Cells that lack a nucleus or membrane bound organelles 4. NUCLEOLUS
• Include bacteria • Inside nucleus
• Simple type of cell, single, circular chromosomes • Disappears when cell divides
• Eukaryotes • Makes ribosomes that make proteins
• Cells that have a nucleus and membrane-bound
organelles 5. RIBOSOMES (MICROSOMES)
• Include protists, fungi, plants, and animals • Small non-membrane bound organelles
• More complex type of cells • Contain two sub units
• Contains 3 basic cell structures (Cell membrane, • Site of protein synthesis.
Cytoplasm with organelles, nucleus) • Protein factory of the cell
• Plant and animal cell • Either free floating or attached to the endoplasmic reticulum
• Compare and contrast • Made of proteins and rRNA
• Prokaryotes – cell membrane, contain dna, ribosomes, cytoplasm. • Protein factories for cell
• Eukaryotes – nucleus, endoplasmic reticulum, golgi apparatus, • Join amino acids to make proteins through protein synthesis
lysosomes, vacuoles, mitochondria, cytoskeleton. 6. ENDOPLASMIC RETICULUM
• Network of hollow membrane tubules
ORGANELLES • Connect to nuclear envelope and cell membrane
• Very small (microscopic), perform various functions for a cell,
• Functions in synthesis of cell products and transport
found in the cytoplasm, may or may not be membrane-bound
• Complex network of transport channel
a. Smooth or agranular
1. PLASMA MEMBRANE
o Ribosome free and functions in poison detoxification.
• The boundary of the cell. Composed of three distinct layers. Two o A network of channels, but looks ribosomes. It is made up
layers of fat and one layer of protein. (Hydrophobic and hydrophilic
of lipids and protein and it involved in the synthesis of
regions) surrounds outside of all cells. Controls what enters or lipids and detoxification of drugs.
leaves the cell. Living layer.
o Site for steroid synthesis (hormones of the adrenal glands)
CYTOGENETICS | 2
 o Lipids or fat synthesis arrange to form a hallow cylinder. Tubulin is the protein that
o Synthesis of enzymes of carbohydrates metabolism makes the microtubules
concerned with the rapid transport system conveying • Centrioles participate in the cell reproduction and in producing
proteins through canals either to the exterior of the cell or basal bodies of cilia and flagella)
to the gold complex where they are pack and released 12. CYTOSKELETON
from the cell • Helps cell maintain cell shape
b. Rough • Also help move organelles around
o Contains ribosomes and releases newly made protein • Made of proteins
from the cell • Microfilaments are threadlike and made of actin
o Has ribosomes on its surface • Microtubules are tubelike and made of tubulin
o Makes membrane proteins and proteins for export out of • Framework of the cell
cell • Contains small microfilaments and larger microtubules
o Proteins are made by ribosomes on ER surface. They are • They support the cell, giving it its shape and help with the
then threaded into the interior of the rough ER to be movement of its organelles
modified and transported protein synthesis 13. MITOCHONDRIA (chondriosomes)
7. ENDOMEMBRANE SYSTEM
• Double membranous
• Includes nuclear membrane connected to ER connected to cell
• It’s the size of a bacterium
membrane (transport)
• Contains its own DNA; mDNA
8. GOLGI APPARATUS
• Produces high energy compound ATP
• A series of flattened sacs that modifies, packages, stores, and
• Powerhouse of the cell
transports materials out of the cell.
• Generate cellular energy (ATP)
• Works with the ribosomes and ER
• More active cells like muscle cells have more mitochondria
• Stacks of flattened sacs
• Both plants and animals have mitochondria
• Have a shipping side (cis face) and receiving side (trans face)
• Site of cellular respiration (burning glucose)
• Receive proteins made by ER
• Spherical, rod-shaped, cigar or sausage shape somewhat
• Transport vesicles with modified proteins pinch off the ends.
hollow structure
• Consist of several flattened tubular membranes stacked upon
• Formation of energy rich compounds especially ATP
each other termed CISTERNAE and dilated terminal areas as
either end of the cisternae called VACUOLES. • Their inner membrane makes in-folding called cristae, where
special chemical reactions take place
• Its chemical composition is mostly lipids and proteins
• Chemically, the mitochondria is made up of carbohydrates,
• It is a center of processing, packaging and storing complex
lipids, proteins, and nucleic acid.
proteins and procedures of lysosomes.
• Its function is cellular respiration of the aerobic types (the one
• Packaging of protein secretory materials formed in the ER and
that requires oxygen)
where carbohydrates synthesis with in the golgi complex are
• Cellular respiration is a chemical process that breaks down
added to the protein as GLYCOPROTEIN.
simple food molecules to produce energy. This energy is then
a. Golgi bodies
stored in ATP molecules and its made accessible to cell
o looks like a stack of pancakes
o Modify, sort, and package molecules from ER for storage activities
or transport out of cell • Mitochondria come from cytoplasm in the egg cell during
o Materials are transported from rough ER to golgi to the fertilization, therefore, we inherit our mitochondria from our
cell membrane by VESICLES mother.
9. LYSOSOMES 14. PLASTIDS
• Recycling center, recycle cellular debris • Round or oval bodies containing pigments commonly found in
• Membrane bound organelle containing a variety of enzymes plants.
• Internal pH is 5 a. Chloroplast
• Help digest food particles inside or outside the cell o Green pigment
• Contain digestive enzymes. Breaks down food, bacteria, and o Green colored bodies containing chlorophyll
worn-out cell parts for cells o Green pigment visible in the cytoplasm of green plants
• Programmed for cell death (apoptosis) o site of photosynthesis, powerhouse unit of plants cell
• Lyse and release enzymes to break down and recycle cell parts. b. Leucoplastids or leucoplast
• Known as suicidal bags o Colorless plastids present in non-photosynthesizing plant
• Pre-formed membrane, bound, dense appearing structure or tissue
packages of HYDROLYTIC ENZYME collectively known as Acid o Serve as storage depots for starch, synthesis starch from
Hydrolases/ sugar
c. Chromoplast or chromoplastids
• Enzymes within the lysosomes can be digest and therefore
o Variously colored plastids
destroy all components of the cell, hence are called suicide
o Colored bodies plant cells containing various pigments
bags
o Gives brown, red, blue, orange, yellow color. Responsible
• Lysosomes are spherical, single-membrane bags made of lipids
for varied colors of petal, fruits and vegetables.
and proteins that hold digestive enzymes inside
15. CHOLORPLAST
• The cellular digestion, the breakdown of large molecules into
• Double membrane
small ones.
• Center section contains grana
• Relate to aging and degenerative processes
• Thylakoid(coins) make up the grana
a. Lysosome Digestion
o Cells take in food by phagocytosis • Stroma, gel-like material surrounding grana
o Lysosomes digest the food and get rid of wastes • Found int plants and algae
10. CILIA AND FLAGELLA • Found only in producers
• Function in moving cells, in moving fluids, or in small particles • Use energy from sunlight to make own food(glucose)
across the cell surface • Energy from sun stored in the chemical bonds of sugars
• Cilia are shorter more numerous on cells 16. VACUOLE
• Flagella are longer and fewer (usually1-3) on cells • Sacs that help in food digestion or helping the cell maintain its
11. CENTRIOLES water balance.
• Granular structure located just outside the nucleus and found • Found mostly in plants and protist
in all animal cells and primitive plants of self-duplicating • Fluid filled sacks for storage
organelles • Small or absent in animal cells
• With in centrosomes is a pair of small rod-like called centrioles • Plants cells have a large central vacuole
• They are two cylindrical bodies in animal cells perpendicular to • In plants, they store cell sap. Includes storage of sugars, proteins,
each other. Each centrioles contains 9 triplets of microtubules minerals, lipids, wastes, salts, water, and enzymes

CYTOGENETICS | 3
17. PEROXISOMES (microbodies) • When a cell is going to divide, it grows large, the number of
• Similar to lysosomes in that they are membrane bounds sacs organelles doubles, the amount of DNA doubles as DNA
which contain enzymes. replication occurs.
• Involved either in the production of hydrogen peroxide or the • Cell cycle – regular sequence of growth and division that
destruction of hydrogen peroxide to water. eukaryotic cells undergo.
18. MICROTUBULES and MICROFILAMENTS • Divided into three main stages:
• Are long, thin cylinders dispersed in the cell a. Interphase
• Microtubules are made of the protein tubulin and structure the b. Mitosis
cytoskeleton of the cell together with the microfilaments c. Cytokinesis
• Microfilaments are made of the protein action
• Responsible for the movement of structures and substances
inside the cell
MOLECULE MOVEMENT & CELLS
• Passive Transport
• Active Transport
• Endocytosis
• Exocytosis
MITOSIS AND MEIOSIS
The process of cell division is highly regulated. Life begins in a
single cell yet in a short period of time the process of cell division produces
trillions of cells, each specialized for special functions. Over 200 different
types of cells are found in the body, and although each is specialized, they ● Cell cycle happens on both the Interphase and Mitosis, although
work together in harmony. Occurs during your entire life. Even now, your in mitosis considering interphase as not a part of it because this is
body is producing thousands of new blood cells, skin cells and cells that line just the resting phase.
your respiratory and digestive tracts. ● Interphase is where different cell cycles take place, especially the
replication.
Cellular Reproduction ● In mitosis, this is already the divided cell passes. Under it are the
• Is one of the basic characteristics of life: the process of Mitosis Karyokinesis and Cytokinesis.
and Meiosis allow organisms to produce, grow and repair ● Karyokinesis, this is the division of the nucleus.
damaged tissues. ● Cytokinesis, this is the division of the cytoplasm.
• The understanding of cellular reproduction has led to the study of
stem cells, which have the potential to offer treatments for many FACTORS OF CELL DIVISION:
human diseases. a. Cell Size
Why do cells divide? b. Karyoplasmic Ratio
• For growth, repair and reproduction c. Mitogens
d. Cytokinin
When do cells divide?
• Most limiting factor in size is the size of the cell membrane. Again, cell cycles have two major phases; Interphase and mitotic phase.
• Cells must obtain nutrients During interphase the cell grows and the DNA is being replicated. During the
• As volume increases , cell surface area does not increase as mitotic phase, the replicated DNA and the cytoplasmic contents are being
greatly. separated forming two daughter cells.
• Larger cells require a larger surface area for survival
4-STAGE PROCESS:
SIGNIFICANCE OF CELL DIVISION 1. Cell increases in size.
a. Cell multiplication - formation of new cells from pre-existing cells. 2. Copies its DNA
b. Continuity - through cell division it maintains the continuity of a 3. Prepares to divide
living matter from generations after generations 4. Divides
c. Asexual Reproduction - absence of the gametes, present on the
plants. Control of the Cell
d. Multicellular Organisms - its body is formed by innumerable cells. • The cell cycle is controlled at three
They’re formed by repeated editions of a single cell/zygote. 1. During G1 prior to the S stage
e. Growth - the growth of organisms involves the growth and 2. During G2 prior to the M stage
division of its cells. 3. During the M stage prior to the end of mitosis, DNA damage
f. Cell Size - through cell division it helps in the maintenance of a can also stop the cell cycle at the G1 checkpoint.
particular cell size which is very essential for efficiency and the
control of the cells activities. INTERPHASE
g. Genetic Similarity - despite being different in structure and
• Interphase is made up of 3 separate parts (G1,S, G2)
function. It’s helpful in the proper coordination.
• Interphase is the stage that the cell is in for most of its life.
h. Regeneration - cell division occurs in regeneration of parts or the
G1 – Growth Phase
whole organisms.
• Cell doubles in size
i. Repair - heal injured areas of our body. Worn out cells are
• Cell produces all the structure it needs to carry out its functions
replaced by new ones.
• Think of this phase as the cell just living its normal life.
j. Sexual Reproduction - requires special type of cell division
(Meiosis). S-DNA copying
k. Reshuffling of Genetic Traits - because of Meiosis it introduces • Cell makes a copy of its DNA (replication)
variability. • This happens because the new cell needs all of the direction for
l. Mutations - during cell division there is a process called its function and survival
replications on the genetic materials so any changes on this • Think of this phase as placing the DNA on a copy machine
activity would result in formations that could lead to a change in G2-Preparation
our body. • Cells prepares to divide
• Cell produces structures needed for cell division
• Think of this phase as the cell double checking everything it needs
The Cell Cycle
to divide
• The cell cycle is an orderly set of stages that place between the
Growth factors signal the cell cycle control system
time a eukaryotic cell divides and the time resulting daughter cells
• There are three major checkpoints in the cell cycle
also divide.
▪ G1 – commitment to divide, growth factors present, size of
cell.

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 ▪ G2- check the proper DNA replication
▪ M- all chromosomes attached to spindle
• The cell cycle control system is a cycling set of molecules in the
cell that triggers and coordinates key events in the cell cycle.
• Checkpoints in the cell cycle can stop an event or signal an event
to proceed.

The Cell Cycle Multiplies Cells

● The cell cycle is an ordered sequence of events that extends:
➔ From the time a cell is first formed from a dividing
parent cell
➔ Until its own division.
G1 is the primary stage of Interphase. Takes 5-6 hours. Here, the
characteristics of the chromosome fibers are less coiled, slender, extended
fully, and ready for transcription. It is lengthier than other phases and they
vary from cell to cell.
S (DNA synthesis) is responsible for the synthesis or replication of
DNA. In this way, the genetic material of a cell is doubled before it enters
mitosis or meiosis, allowing there to be enough DNA to be split into
daughter cells.
G2 phase, this is succeeded by the S phase. Extra protein is often
synthesized, and the organelles multiply until there are enough for two
cells. Other cell materials such as lipids for the membrane may also be
produced. Additional growth of cells may be observed before the cell enters Growth Factors Signal The Cell Cycle Control System
the phase of mitosis. The cell cycle control system is a cycling set of molecules in the
cell that:
● Triggers and
● Coordinates key events in the cell cycle.
Checkpoints in the cell cycle can
● Stop an event or
● Signal an event to proceed.

G1 – Commitment to divide, growth factors present, size of cell,

G2 - Check for proper DNA replication
M - All chromosomes attached to spindle fibers

Cell Cycle progresses by action of Cdks

● Cyclins
- proteins produced by the cell during cell division
(internal signaling protein)
G0 (resting phase), a period in the cycle in which the cell exits in ● Cyclin-dependent kinases (Cdk)
a quiescence state, in which cells reside until they receive appropriate - cyclin is required to activate these enzymes
signals. - activates cell proteins by phosphorylating them
(proteins needed for S phase) needed to go through G1
checkpoint
● MPF - Maturation-promoting factor (mitosis promoting factor)
- aka Mitosis- promoting factor is a cyclin -Cdk complex
- phosphorylates proteins needed for mitosis
- needed to go through G2 checkpoint

MITOSIS
• Organisms grow by the addition of cell
• In multicellular organism some of these cells perform functions
M phase involves two distinct divisions which are mitosis and different from the cells.
meiosis. • The process of a cell becoming different is differentiation
• The word mitosis comes from the Greek word for "thread or fibril"
The regulation of this cycle is controlled by checkpoints that
• Organisms grow by the addition of cells.
detect if the cell contains a damaged DNA and to ensure that the cells do
• In multicellular organisms some of these cells perform functions
not replicate. If damaged DNA is detected in any checkpoint, activation of a
different from other cells.
checkpoint is increased with the presence of protein P53. P53 is a tumor
• The process of a cell becoming different is differentiation.
suppressor gene that stops the progression of cell cycle. It is also the one
responsible for repairing the damaged cell. • Under normal conditions once an animal cell becomes specialized
it can no longer form an entire organism, however, plant cells are
totipotent (capable of developing into a complete organism) and
any cell can form an entire plant.
• Mitosis is also known as somatic cell division.
CYTOGENETICS | 5
 • Meristem, region of cells capable of division and growth in plants. a. During prophase I “Crossing Over” occurs, is one of the
• The four stages of Mitosis (PMAT) two major occurrences of meiosis (The other is non-
a. Prophase disjunction).
b. Metaphase b. During crossing over segments on nonsister Chromatids
c. Anaphase break and reattach to the other chromatid. The
d. Telophase Chiasmata (chiasma) are the sites of crossing over.
Interphase • Tetrad is tow chromosomes or four chromatids. (sister and
• The chromosomes are in an extended form and seen as chromatin nonsister chromatids)
in the electron microscope Metaphase I
• The nucleus is visible • Shortest phase, tetrads align on the metaphase plate
Prophase • Independent Assortment Occurs:
a. Orientation of homologous pair to poles is random
• The chromosomes are seen to consist of two chromatids joined
b. Variation
by a centromere
c. Formula: 2n
• The centrioles move apart toward opposite poles in the cell
Anaphase I
• Spindle fibers are produced and extended from each centromere
• Homologous chromosomes separate and move towards the poles
• The nuclear membrane starts to disappear.
• Sister chromatids remains attached at their centromeres.
• The nucleus is no longer visible
Telophase I
Metaphase
• Each pole now has haploid sets of chromosomes
• The chromosomes are lined up at the equator of the cell.
• Cytokinesis occurs and two haploid daughter cells are formed.
• The spindle fibers from each centriole are attached to the
centromeres of the chromosomes. Meiosis II
• The nuclear membrane has disappeared. • No interphase II (or very short -no more DNA replication)
Anaphase • Meiosis II is similar to Meiosis I
• The centromeres split and the sister chromatids separate as each • Prophase II, Metaphase II, Anaphase II and Telophase same with
is pulled to an opposite pole mitosis
Telophase • Prophase II - Same as prophase in mitosis
• The chromosomes become longer, thinner and less distance • Metaphase II - Same as metaphase in mitosis
• Nuclear membrane form • Anaphase II - Same as anaphase in mitosis. Sister chromatids
• The nucleolus appears separate
• Cell division is nearly complete • Telophase II - Same as telophase in mitosis. Nuclei form.
Cytokinesis occurs. 4 haploid daughter cells produced.

MEIOSIS
• Is the process by which gametes (sex cells), with half the number
of chromosomes are produced
• During meiosis diploid cells are reduced to haploid cells
• Diploid (2n) to haploid (1n)
• If meiosis did not occur the chromosomes number in each new
generation would double. The offspring would die.
• Meiosis is two cell division (called meiosis I and meiosis II), with
only one duplication of chromosomes
• 4 daughter cells (haploid)
Module 3 – MENDELIAN INHERITANCE
• Meiosis leads to genetic diversity
Genetics is the branch of Biology that deals with heredity and
o 3 ways genetic diversity is increased by meiosis:
variation. Evolution in the 21st century that expanded and diversified. No
▪ 2 parents contribute ½ of the genetic material to
longer adequate to just study genetics, to properly identify the area of
offspring
study, requires the use of modifiers. (ex. Molecular, medical, behavioral
▪ Crossing-over in prophase I
Genetics)
▪ Chromosome alignment in Metaphase I
Mendellian genetics – transmission of traits from one generation
o Meiosis produces cells that are not identical (unique
to next. Genetics involve modifiers now. Genetics is centered on the study
gametes)
of Genes. Centered element are genes.
• SPERMATOGENESIS – meiosis in male
• OOGENESIS – meiosis in females
Basic concept of heredity is at least old as civilization itself; it was
Meiosis I not coincident that animals, plants produce offspring similar to parents.
• Cell division that reduces the chromosomes number by one half. Reproduction usually restricted to the same general group.
• Four phases PROPHASE I, METAPHASE I, ANAPHASE I, TELOPHASE
I It was observed before, exact copies were never made, there are
slight variations seen. Farmers are aware that desirable traits could be
Interphase I manipulated by carefully selecting specific animals or plants were allowed
• Similar to mitosis interphase, chromosomes replicate (5 phases) to produce, but no records left by the ancient Egyptian at that time. But
• Chromosome replicate (S phase) they practice cross pollinations of plants as a means o improving plants. No
• Each duplicates chromosome consists of two identical sister records prior to those of Greeks, no work of Gregor Mendel.
chromatids at their centromeres.
• Centriole pairs also duplicated. Methods of Genetic Study
Prophase I 1. Pedigree Analysis
• Longest and most complex phase 2. Karyotyping
• 90% of the meiotic process is sent in prophase 3. Planned Experimental Breeding
• Chromosomes are condensed 4. Twin Study
• Synapsis occurs: homologous chromosomes come together to 5. Statistical Analysis
form a tetrad.

CYTOGENETICS | 6
 In the ten years G. Mendel worked on his plants in the garden of Incomplete Dominance
the monastery, he made the greatest discovery in biology that has been • Situation in which one allele is not completely dominant over
made in the last five hundred years. (Thomas Hunt Morgan- American another. Example. Red and white flowers are crossed and pink
geneticist). flowers are produced.

Gene
Gene is classically defined as a unit of heredity. At the molecular
level, a gene is a segment of DNA that has the information to produce a
functional project. Unit of heredity.

The Relationship of Gene and Traits

• Traits are any characteristics that an organism displays
• Three categories Codominance
a. Morphological Traits • Situation in which both alleles of a gene contribute to the
b. Physiological Traits phenotype of the organism.
c. Behavioral Traits

Four levels of Biological Organization +

a. Molecular Level
b. Cellular level
c. Organism level Multiple Alleles
d. Population level • Three or more alleles of the same gene. Even though three or
more alleles exist for a particular trait, an individual can only have
TERMINOLOGIES two alleles- one form the mother and one form the father.
Traits
• A trait is a specific characteristic that varies from one individual to
another, any characteristics that can be passed from parent to
offspring. Our traits are being manifested, expressed, showed.
Examples: Brown hair, blue eyes, tall, curly
Heredity
• Passing of traits from parent to offspring
Allele
• Alleles are the different possibilities for a given trait. Every trait Polygenic traits
has at least two alleles (one from the mother and one from the • Trait controlled by two or more genes; polygenic traits often show
father). Two forms of a gene (dominant & recessive). Represent a wide range of phenotypes.
what kind of traits inherited.
• A particular form a gene, presumably reflecting a certain DNA Genome — the entire set of genes in chromosomes
sequence, such as A1 or A2. Example: eye color – brown, blue, Locus — a fixed location on a strand of DNA where a gene or one of its
green alleles is located.
Genotype Inheritance — is the process by which the characteristics of individual are
• The allelic constitution of a given individual. Example. AA, BB passed to their offspring.
• Gene combination for a trait (RR, Rr, rr ) Sex Determination — the sex of an organism is determined by a special sex
• Genotype of Alleles: chromosome. Female (x), Male (y)
R = red flower r = blue flower
• Genotypes Different forms of a trait that
a. HOMOZYGOUS genotype – gene combination involving Alleles R, r, T, t
a gene may have
2 dominant or 2 recessive genes (RR, rr); also called
PURE An organism with two alleles
Homozygous RR, rr, TT, tt
b. HETEROZYGOUS genotype – gene combination of one that are the same
dominant & one recessive allele (Rr) also called HYBRID. An organism with two
Phenotype Heterozygous Rr, Tt
different alleles for a trait
• The morphological, biochemical, behavior, or other properties of
an organism, observe the transmission of traits to the next The physical appearance of
Tall, short, curly,
generation. Example: Brown eyes, long hair. Phenotype an organism (what we look
straight
Dominant gene like)
• Is a segment of DNA information that is used to make Genotype The genes of an organism RR, TT, Rr, Tt, rr, tt
chromosomes. When an allele is dominant it is expressed in the A trait that dominates or Represented by an
phenotype is what chromosomes is present in the organism. Dominant covers up the other form of uppercase letter R or
• Stronger of two genes expressed in the hybrid, represented by a the trait T
capital letter (R) Represented by a
Recessive gene A trait that is covered up by a
Recessive lowercase letter
• Is a gene that can be masked by a dominant gene. dominant trait
r or t
• Gene that shows up less often in a cross; represented by a
lowercase letter (r) Gregor Mendel (1822-1884)
Dominant • Responsible for the Laws governing Inheritance of Traits
• Traits refers to a genetic feature that “hides” the recessive trait in • Austrian monk
the phenotype of an individual. • Studied the inheritance of traits in pea plants
• Developed the laws of inheritance
• Dominant trait refers to a genetic feature that "hides" the recessive trait • Mendel’s work was not recognized until the turn of the 20th
in the phenotype of an individual. century
• The term "recessive" describes a trait that is covered over or dominated) • Between 1856 and 1863, Mendel cultivated and tested some
by another form of that trait and seems to disappear. 28,00 pea plants, he found that the plants offspring retained traits
• Homozygous –two alleles that are the same for a trait (Pure) of the parents
• Heterozygous – two different alleles for a trait (Hybrid) • Mendel stated that physical traits are inherited as “particles” he
did not know that the “particles” were actually chromosomes &
DNA

CYTOGENETICS | 7
 MENDEL’S PEA PLANT EXPERIMENTS Mendel chose the garden PEA, (Pisum sativum), the term gamete is used to
Why peas, Pisum sativum? describe haploid reproductive cells that can unite to form a zygote. In
• Can be grown in a small area, produce lots of offspring, produce plants, male gametes (sperm) are produced within pollen grains formed in
pure planta when allowed to self-pollinate several generations the anthers. The female gametes(eggs) are contained within ovules that
and can be artificially cross form in the ovaries.
• Reproduction in flowering plants
a. Pollen contains sperm produced by the stamen; ovary The fertilization to occur, a pollen grains lands on the stigma, which
contains eggs found inside the flower stimulates the growth of the pollen tube.
b. Pollen carries sperm to the eggs for fertilization. This enables sperm cell to enter the stigma and migrate toward an ovule.
c. Self-fertilization can occur in the same flower. Fertilization occurs when a sperm enters the microphyle, an opening in the
d. Cross -fertilization can occurs between flowers ovule wall, and fuses with an egg cell.
How Mendel Began?
• Mendel hand-pollinated flowers using a paintbrush, he could snip Mendel's data laid the groundwork for genetics
the stamens to prevent self-pollination covered each flower with • Gregor Mendel showed that traits are inherited as discrete units. (without
a cloth bag, He traced traits through the several generations knowing about DNA)
• Mendel produced pure strains by allowing the plants to self- Mendel made three key decisions in his experiments.
pollinate for several generations used purebred plants
• Mendel used pollen to fertilize selected pea plants controlled breeding
• P generation was crossed to produce F1 generation (interrupted observed seven "either-or" traits
the self-pollination process by removing male flowers parts so he Mendel used pollen to fertilize selected pea plants
could control the traits through pollination to create purebred P generation was crossed to produce Fl generation
plants. interrupted the self-pollination process by removing male flower
• 1856, Mendel began his historic studies on pea plants for 8 years, parts so he could control the traits through pollination to create
he grew and crossed thousands of pea plants on a small 23-by purebred plants.
115-foot plot.
• He published his work, entitled “Experiment on Plant Hybrids”, in Mendel observed patterns in the first and second generations of his crosses.
1866 FIGURE 6.10
MONOHYBRID CROSS RESULTS
Eight Pea Plant Traits MENDEL'S
Seed Shape Round (R) or Wrinkled (r) F2 TRAITS DOMINANT RECESSIVE RATIO
Seed color Yellow (Y) or Green (y)
Pea shape 5474 round 1850 wrinkled 2.96:1
Pod shape Smooth (S) or Wrinkled (s)
Pod color Green (G) or Yellow (g) Pea color 6022 yellow 2001 green 3.01:1
Seed coat color Gray (G) or White (g) Flower color 705 purple 224 white 3.15:1
Flower position Axial (A) or Terminal (a)
Plant height Tall (T) or Short (t) Pod shape 882 smooth 299 constricted 2.95:1
Flower color Purple (P) or White (p) Pod color 428 green 152 yellow 2.82:1
Flower position 651 axial 207 terminal 3.14:1
Plant height 787 tall 277 short 2.84:1

TYPES OF GENETIC CROSSES

• Monohybrid cross – cross involving a single trait ex. Flower color
• Dihybrid cross – cross involving two traits. Ex. Flower color and
plant height
Did the observed ration match the theoretical ratio?
• The theoretical or expected ration of plans producing round or Monohybrid Crosses
wrinkled seeds is 3 rounds: 1 wrinkled. Mendel’s observed ratio a. P1 Monohybrid Cross
was 2. 96: 1 • Homozygous dominant x Homozygous recessive
• The discrepancy is due to statistical error • Offspring all Heterozygous (hybrids)
• The larger the sample the more nearly the results approximately • Offspring called F1 generation
to the theoretical ration. • Genotypic and Phenotypic ration is All an alike
• Generation “Gap” Ex: P1 Monohybrid Cross
a. P1 (Parental Generation) – the parental generation in a Traits: Seed Shape
breeding experiment. Alleles: R – Round r- Wrinkled
b. F1 (First Generation) – the 1st filial generation or first- Cross: Round seeds x Wrinkled seeds
generation offspring in a breeding experiment, from RR x rr
breeding individuals from the P1 generation. r r
c. F2 (Second Generation) – the second-generation offspring R Rr Rr
in a breeding experiment. (2nd filial generation) R Rr Rr

Genotype: Rr (R is dominant with r as recessive)

Phenotype: Round
Genotype Ratio: All alike
Phenotype Ratio: All alike

b. F1 Monohybrid Cross
Cross 2 pure Plants Results in all Hybrids Cross 2 hybrids • Heterozygous x heterozygous
• Offspring:
Continued the work of Mendel Experiment 25% homozygous dominant RR
CARL CORRENS of Germany 50% heterozygous Rr
HUGO de VRIES of The Netherlands 25% homozygous recessive rr
ERICH von TSCHERMAK of Austria • Offspring called F2 generation
• Genotypic ratio: 1:2:1
Mendel's study of genetics grew out of his interest in ornamental flowers.
• Phenotypic ratio: 3:1
When two distinct individual with different characteristics are bred or
Ex: F1 Monohybrid Cross
crossed it is called HYBRIDIZATION experiment. Their offspring is called
Traits: Seed Shape
HYBRIDS.
CYTOGENETICS | 8
 Alleles: R – Round r- Wrinkled b. Law of Independent Assortment
Cross: Round seeds x Wrinkled seeds • Genes for different traits can segregate independently during
Rr x Rr formation of gametes. Two different genes randomly assort the
R r alleles during formation of haploid cells.
R RR Rr • Alleles for different traits are distributed to sex cells (& offspring)
r Rr rr independently of one another. This law can be illustrated using
dihybrid crosses.
Genotype: RR, Rr, rr c. Law of Dominance
Phenotype: Round and wrinkled • Some alleles are dominant while others are recessive; an
Genotype Ratio: 1:2:1 organism with at least one dominant allele will display the effect
Phenotype Ratio: 3:1 of the dominant allele.
RR (round) • Organisms inherit two copies of each gene, one from each
Rr (round) parent.
Rr (round) • In many cases, one allele is dominant (or expressed) while the
rr (wrinkled) other is recessive (o masked)
• In a cross of parents that are pure for contrasting traits, only one
c. F2 Monohybrid Cross (1st) form of the trait will appear in the next generation.
• Homozygous x heterozygous • All the offspring will be heterozygous and express only the
• Offspring: dominant trait.
50% Homozygous RR or rr E.g. RR x rr yields all Rr (round seeds)
50% Heterozygous Rr
• Phenotypic Ratio is: 1:1 DIHYBRID CROSSES
• Called test Cross because the offspring have SAME genotype, A breeding experiment that tracks the inheritance of two traits
two possible crosses Homozygous dominant and hybrid Mendel’s Law of Independent Assortment”
Ex: F2 Monohybrid Cross a. Each pair of alleles segregates independently during gamete
Traits: Seed Shape formation
Alleles: R – Round r- Wrinkled b. Formula: 2n (n= # of heterozygous)
Cross: Round seeds x Wrinkled seeds
RR x Rr
R r
R RR Rr
R RR Rr

Genotype: RR, Rr
Phenotype: Round
Genotype Ratio: 1:1
Phenotype Ratio: All alike
RR (round) PUNNETT SQUARE, MULTIPLICATION METHOD AND FORKED-LINE METHOD
Rr (round) Punnett Square
• It is a method originally proposed by British geneticist Reginald C.
Punnett. Who employed it for determining the genetic outcome of
Ex: F2 Monohybrid Cross (2nd) crosses.
Traits: Seed Shape • How to make a Punnett Square
Alleles: R – Round r- Wrinkled a. Make the grid
Cross: Wrinkled seeds x round seeds ▪ Place the alleles of the gametes of one parent along
rr x Rr the top of a grid and those of the other parent along
R r the left-hand side.
r RR rr
r RR rr

Genotype: RR, rr
Phenotype: Round and Wrinkled
Genotype Ratio: 1:1
b. Fill the grid
Phenotype Ratio: 1:1
▪ Combine the parent alleles inside the boxes. The letter
RR (round)
shows the genotypes of the offspring.
rr (wrinkled)

MENDEL’S LAW OF INHERITANCE

a. Law of Segregation
• The two copies of a gene separated (or separate) from each
other during transmission from parent to offspring.
• Therefore, only one copy of each gene is found is a gamete. At
fertilization, two gametes combined randomly, potentially
producing different allelic combinations.
• P Generation or parental generation- the true-breeding parents
were crossed to each other.
• F I generation - producing offspring for the first filial generation.
• F2 generation - producing offspring for the second filial
generation.
• During the formation of gametes (eggs or sperm), the two alleles c. Fill in the offspring
responsible for a trait separate from each other ▪ Use the law of dominance to determine the phenotypes
• Alleles for a trait are then "recombined" at fertilization, and phenotypes ration of the offspring.
producing the genotype for the traits of the offspring

CYTOGENETICS | 9
Multiplication Method
• The multiplication of product rule is a simple way to determine the
likelihood of getting a particular result from any cross, regardless of
the number of traits involved
Ex.
P – (3 tall + 1 dwarf) ( 3 round + 1 wrinkled) (3 Yellow + 1 green)

First Multiply:
(3 tall +1 dwarf) (3 round + 1 wrinkled)
= (9 tell, round +3 tall, wrinkled + 3 dwarf, round + 1 dwarf, wrinkled) Chromosome size
• Measured at mitotic metaphase generally measured in length in
Next , Multiple this product by diameter.
(3 yellow + 1 green) (9 tell, round +3 tall, wrinkled + 3 dwarf, • Plants usually have longer chromosomes than animals
round + 1 dwarf, wrinkled) • Plant chromosomes are generally 0.8-7um in length where as
= 27 tall, round, yellow + 9 tall, wrinkled, yellow + 9 dwarf, round, yellow + animal chromosome are 0.5-4um in length
3 dwarf, wrinkled, yellow + 9 tall, round, green + 3 tall, wrinkled, green +3
• Varies from species to species
dwarf, round, green + 1 dwarf, wrinkled, green.
Chromosome structure
Forked-Line Method
a. Centromere
• is based on the assumption of independent assortment of all the genes b. Chromatid
involved. c. Secondary constriction and satellite
d. Telomere
e. Chromomere
f. Chromonema
g. Matrix

Human Pedigrees
Chromosomes are classified as
• A pedigree is a diagram that depicts the biological relationships
a. Metacentric
between an organism and its ancestors.
b. Submetacentric
• It comes from the French “pied de grue” (“crane’s foot”) because the
c. Acrocentric
branches and lines of a pedigree resemble a thin crane’s leg with its
d. Telocentric
branching toes.

• Chromosomes are bundles of tightly coiled DNA located within the

Example: nucleus of almost every cell in our body. Humans have 23 pairs of
chromosome, one set comes from your mother and one set comes
from your father. Any deviation from the normal karyotype is known
as chromosome abnormality.

• Nucleosomes, a single length of DNA is wrapped many times around

lots of proteins called HISTONES, to form structure called
nucleosomes.

• If these 22 pairs are autosomes (non-sex chromosomes) and look the

same for both males and females. One pair sex chromosome so differ
CHROMOSOMES depending on whether you are male or female
• Rod shaped structure formed during cell division, they are known as
the bearers of heredity characteristics, which are transmitted to the Types of chromosomes
offspring during the fertilization process. a. Sex chromosomes, determine the sex of an organism
• Characteristics: darkly-staining definite bodies within the nucleus of a Female – XX
eukaryotic cell. Male – XY
b. Autosomes, all other chromosomes (44 autosomal chromosomal)
• Composition: consist of DNA, RNA and protein
• Are structures within the living cells that contain the genetic material
Homologous chromosomes
• In eukaryotic cells, this complex between DNA and protein is chromatin
• Two copies of each autosome (maternal and paternal), they are
same in size, they are same in size, shape, and carry genes for the
same trait
Diploid (2n)
• Cells have two sets – 46 chromosomes
Haploid (n)
• Cells have one set of chromosomes – 23 chromosomes (gametes)

CYTOGENETICS | 10
Karyotype Types of deletion
• The homologous pair are then placed in order of descending size. a. Interstitial deletion/ intercalary
The sex chromosomes are places at the end. b. Terminal deletion
• A picture of chromosomes arranged in this way is known as a
karyotype.

Human chromosomes
a. Group A (1-3) c. Inversions
Large chromosomes with approximately median A portion of the chromosome has broken off, turned upside
centromeres down and reattached, therefore the genetic material is inverted and
b. Group B (4-5) sequence is distributed
Large chromosomes with submedian centromeres,
chromosome 4 is slightly longer. Kinds of inversion
c. Group C (6-12 and the X chromosomes) a. Paracentric inversion
Medium size chromosome with submedian b. Pericentric inversion
centromeres, the X chromosomes resembles the longer
chromosomes in these group, especially chromosome 6
d. Group D (13-15)
Medium-sized chromosome with nearly terminal
centromeres (acrocentric). Satellites have been detected in all the
three chromosome pairs

Types of chromosome changes

a. Changes in structure
b. Duplications
c. Deletion (defeciencies)
d. Inversions
e. Translocations
f. Insertions d. Translocation
A portion of one chromosome is transferred to another
Changes in number chromosomes
a. Euploidy level (autopolyploids, allopolypoids) • Interstitial translocation/ Robertsonian translocation
b. Aneuploidy (monosomies, trisomies)
• Reciprocal translocation
Changes in chromosomal structure
a. Duplication
A portion of the chromosome is duplicated, resulting in extra
genetic material.

Categories of duplications
• Tandem duplication
• Reverse duplication
e. Insertion
• Displaced duplication
A portion of one chromosome has been deleted from its
normal place and inserted into another chromosome

Changes in chromosomal number

a. Aneuploidy
An abnormal number of chromosomes, and occurs when an individual
is missing either a chromosome from a pair or has more than town
chromosome of a pair.

b. Deletions b. Monosomy
A portion of the chromosome is missing or deleted. The loss of a single chromosome, individual is called monosomic and
their chromosomal composition is 2N-1

c. Nullisomy
The loss of both homologous chromosome, individual is called
nullisomic and their chromosomal composition is 2N-2

d. Trisomy
The gain of an extra copy of a chromosome, individual is called trisomic
and their chromosomal composition is 2N+1
CYTOGENETICS | 11
e. Tetrasomic
The gain of an extra pair of homologous chromosome, individual is
called tetrasomic and their chromosomal composition is 2N+2

Inborn errors of metabolism

1. Hereditary disorders of carbohydrate metabolism
2. Fructosemia
3. Galactosemia
4. Von gierke’s disease (glucose-6-phosphate deficiency)
5. Forbes (amylo 1-1-6 glucosidase deficiency)
6. Pompe’s (alpha 1-4-glucosidase deficiency)
7. Phosphoglucomutase deficiency

Errors of amino acid metabolism

1. Phenylketonuria (PKU)
2. Tyrosinemia
3. Alcaaptonuria
4. Albinism
5. Maple syrup urine disease

Disorders of lipid metabolism

1. Gaucher’s disease
2. Krabbe’s disease
3. Niemann pick disease
4. Fabry’s
5. Tay sachs

SEX DETERMINATION
• The sex of an individual is determined by the sex chromosomes
contributed to the zygote by the sperm and the egg
• An egg can donate an X A sperm can donate an X or Y Therefore
the sperm determines the sex of a child
• Punnett squares are used to predict the outcome of sex-linked
inheritance.
• Most disorders are recessive, some are dominant,
• A "carrier" is a female who is heterozygous for the trait

Patterns of Inheritance Pedigrees

• A pedigree is a genetic family tree that shows how prevalent a
trait is in a family unit from generation to generation.
• They are often used to track the expression of genetic conditions
and disorders.
• Squares represent males and circles females.
• A coloured in shape means that person has the trait in estion.
• A half coloured in shape means that they are carrying an allele for
a recessive trait.

Human Pedigree
• A pedigree is a diagram that depicts the biological relationship
between an organism and its ancestors.
• It comes from the French "pied de grue" (`crane's foot) because
the branches and lines of a pedigree resemble a thin crane's leg
with its branching toes.

Inheritance Pattern
Autosomal Inheritance
a. Autosomal Dominant Inheritance
b. Autosomal Recessive Inheritance
',Sex-linked Inheritance
a. X-Linked Recessive
b. X-Linked Dominant
c. Y-Linked Inheritance

Autosomal Dominant Inheritance

Autosomal means not on the sex chromosomes.
Refers to those situations in which a single copy of an allele is sufficient to
cause expression of a trait.

CYTOGENETICS | 12
Autosomal Dominant Inheritance 2. All the daughters of an affected male will be affected but none of the
1. Every affected person should have at least one affected parent. sons.
2. Males and females should be equally often affected.
3. An affected person has at least a 50% chance of transmitting the Vitamin D resistant rickets which can lead to bone deformities, particularly
dominant allele to each offspring. in the lower limbs (bowed legs).

Autosomal Dominant Inheritance Ex.

• Progeria (caused by a mutation) in which the person ages very
rapidly. They die before they can reproduce. DNA REPLICATION and PROTEIN SYNTHESIS
• Huntington's Disease in which the central nervous system starts WHAT IS THE PURPOSE OF REPLICATION?
to break down around the age of 30 The purpose of replication is to produce two identical copies of a DNA
molecule. This is essential for cell division during growth or repair of
Autosomal Recessive Inheritance damaged tissues. DNA replication ensures that each new cell receives its
• Refers to those situations where two recessive alleles result in a own copy of the DNA.
trait being expressed. WHEN and WHERE?
1. An affected person may not have affected parents. Parents would be Replication happens in the nucleus of the cell during the process of
carriers.
Interphase before the cell division.
2. Affects both sexes equally. Can appear to skip generations.
DNA REPLICATION FACTS
3. Two affected parents will have affected children 100% of the time.
• In human cells, 50 nucleotides are added every second to a new strand
Autosomal Recessive Examples of DNA
• Albinism is a genetic condition which is the loss of pigment in hair, • Replication takes 8 hours in the human body/cells.
skin and eyes. • DNA polymerase has a built in “proof-reading” functions to correct
• Tay Sachs is a genetic disorder which is a build up of fatty deposits errors.
in the brain, eventually proving to be fatal. • Errors are limited to 1 error/billion nucleotide.
• DNA has to be copied before a cell divides.
Codominant Inheritance • DNA is copied during the S or synthesis phase of Interphase.
• Sickle cell Anemia is a codominant condition/disorder in which
• New cells will need identical DNA strands.
there is a defect in hemoglobin, an important protein in red blood
cells. • Accuracy and Repair – DNA copied with a high degree of accuracy.
• An individual homozygous for sickle cells suffers from blood clots • Mutation – change in the nucleotide sequence of DNA: it can have
to important organs, anemia and usually dies rematurely. serious effect on an organism, can be harmful or beneficial.
• An individual heterozygous for normal and sickle cells does not KEY PLAYERS (Enzymes)
suffer the full disorder, but some red blood cells still have • HELICASE – unzipping enzymes/unzipping the two strands of DNA helix
defective hemoglobin.In certain areas of the world this is an • DNA POLYMERASE – builders/replicates the DNA molecules to build
advantage. Malaria is caused by a protist that prefers normal new strands
blood cells. If some of your blood cells are damaged, you are less • PRIMASE – primer/figuring out the work/guide, made up of RNA
likely to become a host! (Heterozygous Advantage) • LIGASE – gluer/glues/seals the fragments
OKAZAKI FRAGMENTS
Sex-linked Inheritance
Reiji Okazaki (1930-1975) was a Japanese Molecule Biologist
• Some traits are located on the sex chromosomes, so the
DNA REPLICATION IS “SEMI-CONSERVATIVE”
inheritance of these traits depends on the sex of the parent
carrying the trait. • One strand of the DNA is old and one strand is new – product for
• Most known sex-linked traits are- linked (carried on the X replication
chromosome). This is probably because the X chromosome is • Each 2-stranded daughter molecule is only half new
much larger than the V chromosome • One original strand was used to make the new strand
• More than one dozen enzymes and other proteins participate in DNA
Sex-linked Disorders replication
• Some sex-linked traits are associated with disorders. • The replication of a DNA molecule begins at special sites called origin
• Most are found on the X chromosome, Y-linked disorders are rare. of replication, where the two strands are separated.
• Males are at a much greater risk for inheriting sex-disorders • A eukaryotic chromosome may have hundreds or even thousands of
because they only inherit one X, so if the X has the allele for the
replication origins.
disorder, they will suffer from the disorder.
• Replication is fast and accurate
• Recessive lethal X-linked traits result in death.
ENZYMES IN DNA REPLICATION
• Ex. Hemophilia is a recessive X-linked trait.
• 1st step of replication is to unzip the double helix of DNA molecule,
X — linked Recessive Inheritance carried out by the enzyme helicase which breaks the hydrogen bonds
• Refers to those situations where a recessive allele on the X holding the complementary bases of a DNA together, A with T and C
chromosome can lead to a trait/condition or disorder with G.
• Males are affected more often than females. Ratio of 8:1. • The separation of two single strands of DNA causes Y shape that is
• Affected males will transmit the allele to all daughters, but not to called the replication fork. The two separated strands will act as
sons. template for making a new DNA.
• Homozygous recessive females can arise only from matings in • One strand is oriented in the 3 prime to 5’ prime direction that is
which the father is affected and the mother is affected or a towards the replication fork called the leading strand. The other strand
carrier. oriented in the 5 prime to 3 prime direction that is away from the
replication fork called the lagging strand.
X — linked Recessive Disorders
• As a result of their different orientation the two strands replicated
1. Hemophilia which is the inability of the blood to clot properly.
differently.
2. Duchenne Muscular Dystrophy which causes progressive and
degenerative muscle weakness. • The direction of replication is from 5 prime to 3 prime.
• Aside from helicase, Gyrase (also referred to as topoisomerase) which
X — linked Dominant Inheritance reduces the supercoiling and builds up during the DNA unwinding, also
• Refers to situations where a single dominant allele on the X have the presence of SSB (binding protein) that usually holds the
chromosome can lead to a trait/condition. strands.
• Very uncommon • In the process of replication, in leading strand, a short piece of RNA
1. Twice as many females are affected as males. Usually, half the children called the primer produced by the enzyme primase it comes along and
of an affected female will be affected, regardless of sex. bind to the end of the leading strand. The primer acts as the starting

CYTOGENETICS | 13
 point for DNA synthesis. The DNA polymerase would bind to the • Transfer RNA – transports and positions amino acids, an RNA that
leading strand and then walks along it adding new complementary delivers amino acids to the site forprotein synthesis, smallest of the
nucleotide bases to the strand of the DNA in a 5 prime to 3 prime RNAs, possessing only about 75-90 nucleotides
direction. This site of replication is called continuous. Transcription – the process by which DNA directs the synthesis to hnrna to
• For the lagging strand, numerous RNA primers are made by a primase mrna molecules that carry the coded information needed for protein
enzyme and binding it to a various point along the lagging strand, so synthesis.
the chance of a DNA which we call Okazaki fragment are added to the • hnRNA – called free mRNA, (undergoes process to be mRNA)
lagging strand also in a 5’ to 3’ direction this site or replication is a • 3 main types of RNA that can be seen in transcription – mRNA, tRNA,
called a discontinuous as the Okazaki fragments will need to be joined rRNA
up later. THREE MAIN TYPES OF RNA ARE PREDOMINANTLY SYNTHESIZED
• Once all the bases are match up, an enzyme called exonuclease will • mRNA – transcript copy of a gene used to encode polypeptide
strip away the primers, the gaps where the primer where are then • tRNA – clover leaf shaped sequence that carries an amino acid
filled by a yet more complementary nucleotide, the new strand is prof • rRNA – a primary component of ribosomes
read to make that there is no mistakes in the DNA sequence and finally
the enzyme called ligase will seal up the sequence of the DNA into two • Transcription – first part of the central dogma of molecular biology,
continuous double strand. The result of DNA replication is two DNA transfer of genetic, a strand of RNA is made to complement a strand of
molecules consisting of 1 new and 1 old chain of nucleotides. DNA
• This is why DNA replication is semi-conservative, half of the chain is GENE EXPRESSION
part of the original DNA molecule and half is a brand new. The new • Transcription – in the nucleus
DNA automatically winds up into a double helix. Dna sequence is transcribed into RNA sequence
DIFFERENT ENZYMES RESPONSIBLE Initiated when RNA polymerase binds to a promoter binding site
• DNA polymerase III extends the strand in the 5’ to 3’ direction – moves along the DNA strand and adds corresponding RNA
• DNA polymerase I degrades the RNA primer and replaces it with DNA nucleotide disengages at a stop signal
• DNA ligase joins the DNA fragments into a continuous daughter strand • RNA polymerase binda to a site on the DNA at the start of a gene
synthesis continues in a 5’ to 3’ direction. Lagging strand – (sewuence of DNA that is transcribed into RNA is called a gene)
discontinuous • RNA polymerase separates the DNA strands and synthesizes a
TRANSCRIPTION AND TRANSLATION complementary RNA copy from the antisense DNA strand
• In eukaryotic cells transcription takes place in the nucleus, during • It does this by covalently binding ribonucleotide triphosphates that
transcription DNA is used as template to make a molecule of mRNA, aligh opposite their exposed complementary partner
molecules of mRNA leaves the nucleus and goes to the ribosomes in RNA POLYMERASE
the cytoplasm where the translation occurs. • Only one of two DNA strands (template) is transcribed
• During translation the genetic code in the mRNA is read and used to • Non-transcribed strand is termed coding strand – same as RNA (except
make a protein T’s are U’s)
• The two processes are sum up in the Central Dogma of biology • Both in bacteria and eukaryotes, the polymerase adds ribonucleotides
PROCESSES OF PROTEIN SYNTHESIS to the growing 3’ end of an RNA chain
• Transcription – genetic template for a protein is copied and carried out • Synthesis proceeds in 5’ to 3’ direction
to the cytoplasm. • Once the RNA sequence has been synthesized:
• Translation – template serves as a series of codes for the amino acid o RNA polymerase will detach from the DNA molecule
sequence of the protein o RNA detaches from the DNA
• Gene Expression – (summary of the process) collective of transcription o The double helix reforms
and translation • Sense strand is coding strand of the double stranded DNA which runs
DNA RNA from 5’ to 3’ direction based on the template strand which runs from
Sugar – deoxyribonucleic acid Ribose 3’ to 5’ direction Considered as positive sense, contains the
Bases – A, C, G, T ACGU complementary nucleotide sequence to its antisense strand of double
Double stranded Single stranded stranded DNA
Stay in nucleus Leaves nucleus • Antisense strand - Called the template.
• RNA molecules are much smaller than the DNA molecules they just • Sense strand has the information than would be readable on the RNA,
only range from 75 nucleotides and a few thousands of the nucleotides called the coding strand.
• Single stranded nature of RNA does not prevent the portions an RNA • Antisense is the non-coding strand, but ironically, when you’re making
molecule from folding back itself and forming a double helical region RBNA, the proteins that are involved in making RNA read the antisense
• If the bases’ sequence along the two portions of an RNA strand are strand in order to create a sense strand for the mRNA.
complementary, the structure would result to a hairpin look, and the • Antisense RNAs plays a crucial role in regulating gene expression at
amount of a double helical structure present in an RNA varies with an multiple levels, such as at replication, transcription, and translation. In
RNA type, but a value of a 50% is not atypical addition, artificial antisense RNAs can effectively regulate the
• RNA molecules found in the human cells are categorized into 5 major expression of related genes in host cells.
distinguished in functions. • Template strand is the strand which serves as the template for the
RIBONUCLEIC ACIDS mRNA synthesis during transcription.
• Heterogenous nuclear RNA (hnRNA) – formed directly by the DNA • Usually, RNA polymerase, which in the enzyme involved in the
transcription, the post transcription processing converts the hnRNA transcription of genes goes into mRNAs, adds nucleotides in the 5’ to
into mRNA. (primary transcript) 3’ direction to the growing strand of mRNA.
• Messenger RNA – directs which amino acids are assembled into • Therefore, the template strand should be directed from 3’ to 5’
polypeptides, carries instructions for protein synthesis or genetic direction in order to add complementary nucleotides in the growing
information for the site of protein synsthesis, molecular mass varies of mRNA strand in the 5’ to 3’ direction.
the protein whose synthesis it will direct. • Hence the DNA strand which consists of 3’ to 5’ directionally the
• Small nuclear Snrna – facilitates the conversions of the hnRNA to a double stranded DNA may serve as the template strand in
mRNA, contains about 100-200 nucleotides transcription.
• Ribosomal RNA – site of polypeptide chain assembly, combines with • That means that is the DNA strand in the double-stranded DNA witch
specific protein to form ribosomes, the physical site for protein possible for the amino acid sequence of the polynucleotide chain.
synthesis. Ribosomes have molecular masses on the order of 3 million • DNA strand. In the double stranded DNA is called non template. The
atomic mass unit, presence of ribosome has no informational functions template strand is also called the anti-sense strand

CYTOGENETICS | 14
• Non-coding strand is called the informational strand. Informational • In eukaryotic, the new mRNA is not yet ready for translation, so it is
strand not involved in RNA synthesis, gives the sequence present in the called pre-mRNA, must go through more processing before its leaves
hnRNA strand being synthesized. the nucleus as mature mRNA. Processes include splicing, editing, and
• Difference of template and coding strand. Template is antisense strand polyadenylations.
while coding is sense strand. Antisense strand takes part in • SPLICING – removes introns from the mRNA, introns are regions that
transcription, while coding strand has no role in transcription. do not code for protein, the mRNA consists only of regions called exons
• Template, in the DNA strand which acts as the template for the that codes for protein. Ribonucleoproteins are small in the nucleus that
synthesis of RNAs, polarity from 3’ to 5’, and is complementary to the contains the RNA and these are needed for the splicing process.
RNA strand. • Once pre-mRNA is formed it undergoes splicing and at the end of the
• Coding strand which is used to determine the sequence of RNA coding, strand there is CAP and POLY-A-TAIL.
polarity of from 5’ to 3’, and is complementary to the DNA strand
except for thymine. MODIFICATION of mRNA
• RNA polymerase – binds different nucleotides. • On its way out of eukaryotic cell nucleus
• Template strand – contains anti-codons, Coding strand- contains the • Each end of a “pre-mRNA” molecule is odified in a particular way
codons. o The 5’ end receives a modified nucleotide CAP
• Hydrogen bonding o The 3’ end gets a POLY-A-TAIL
o Template strand: hydrogen bonds between the template • CAP – 5’ prme cap is a specifically attached nucleotide on the 5’ end of
strand synthesizing mRNA. Temporary During transcription. a primary transcript such as precursor.
o Coding strand: No hydrogen bonds are formed between the • POLY-A-TAIL – polyadenylation, protects the mRNA molecule from
coding strand and nd synthesizing mRNA during enzymatic degradation in the mRNA. Stability of the molecule.
transcription o RNA polymerase I – forms the pre-mRNA
• Transfer RNA o RNA polymerase III – forms the tRNA
o Template strand contains the same nucleotide sequence as THESE MODIFICATIONS SHOWS SEVERAL FUNCTIONS
the tRNA. • They seem to facilitate the exports of mRNA
o Coding Strand contains the complementary nucleotide as the • They protect mRNA from hydrolytic enzymes
tRNA • They help ribosomes attach to the 5’ end
TRANSCRIPTION RNA processing
• Promoter – transcription starts at RNA polymerase binding sites called • Proteins often have a modular architecture consisting of discrete
promoters on DNA template strand. structural and functional region called domains.
• Initiation – other eukaryotic factors bind, assembling a transcription • In many cases different exons code for the different domains in a
complex. protein.
o RNA polymerase begins to unwind DNA helix POST TERMINATION RNA PROCESSING
• Elongation - transcription bubble moves down DNA at constant rate • Most eukaryotic mRNAs aren’t ready to be translated into protein
leaving growing RNA strands from the bubble. directly after being transcribed from DNA. mRNA requires processing.
• Termination – stop sequence at the end of the gene causes • Transcription of RNA processing occur in the nuclei. After this, the
phosphodiester bond to cease, and RNA polymerase to release DNA. mRNA moves to the cytoplasm for translation.
• Eukaryotic transcription differs from prokaryotic transcription • The cell adds a protective cap to one end, and a tail of A’s to the other
o Three RNA polymerase enzymes end. These both function to protect the RNA from enzymes that would
o Initiation complex forms at promoter degrade.
o RNAs are modified after transcription TRANSLATION
SPLICED GENE TRANSCRIPTS • second part of the central dogma of molecular biology, process in
• DNA sequence specifying a protein is broken into segments (exons) which genetic code in the mRNA is ready to make a protein. After
scattered among longer noncoding segments (introns). mRNA leaves the nucleus, it moves to the ribosomes which consists of
• Initially, primary RNA transcript is produced for the entire gene. the rRNA and the proteins.
o snRNA associate with proteins to form spliceosomes. • Each tRNA molecule has an anticodon for amino acids. Anticodon is
Spliceosomes – splices parts of strand gene that are not complementary to codon for an amino acid.
needed for translation. • Translation is the process of protein synthesis in which the genetic
GENES and RNA SPLICING information encoded in mRNA is translated into a sequence of amino
• Most human genes and their RNA transcript have long noncoding acids in a polypeptide chain.
stretches of nucleotides that lie between coding regions. KEY COMPONENTS
• These noncoding regions are called intervening sequences, or • that enables genetic code to synthesize polypeptides
INTRONS. o tRNA molecules have an anticodons of three bases that
• The other regions are called EXONS because they are eventually binds to a complementary codon on mRNA.
expressed, usually translated into amino acid sequences. o tRNA molecules carry the amino acid corresponding to three
RNA SPLICING codon mRNA has a sequence of codon that specifis the
• During RNA processing, intron sequences are cut out of primary amino acid sequence of the polypeptide.
transcript before it is used in polypeptide synthesis. o Ribosomes:
• Remaining exon sequences are spliced together to form final ▪ Act as the binding site for mRNA and tRNA
processed mRNA. ▪ Catalyze the peptide bonds of the polypeptide
• RNA splicing removes introns and joins exons, creating a mRNA o The number of ribosomes present in a cell for a higher
molecule with acontinuous coding sequence. organism varies from a hundreds pr thousands, even a few
• In eukaryotes, RNA splicing is carried out by SPLICEOSOMES. millions in an organism.
• EXONS – gene segments that codes for genetic information, helps • A cell translates a mRNA message in protein with the help of tRNA.
express the egentic message. INTRONS – gene segment does not for • Molecules of tRNA are not identical
genetic information, interrupts the genetic message. EXONS and o Each has anticodon on the end, the anticodon base-pairs
INTRONS are transcribed during the production of hnRNA. To remove with a complementary codon on mRNA
the introns, the remaining exons are joined together to form a o Each carries a specific amino acids on one end
shortened RNA strand that carries the genetic information. • A tRNA molecule consists of a single RNA strand that is only about 80
• Alternative splicing – process by which several different proteins that nucletides long. Flattened into one place to reveal its base pairing. A
are a various of a basic structure can be produced from a single gene. tRNA molecule ooks like a cloveleaf.
• Accurate translation requires two steps:

CYTOGENETICS | 15
 o 1st a correct match between a tRNA and an amino acid done • Reading frame (triplet)
by the enzymes o Each code for one amino acid
o AMINOACYL tRNA SYNTHETASE – binds amino acid in the • Genetic code is a set of rules by which information encoded in mRNA
tRNA sequence is converted into protein (amino acid sequence) by living
o 2nd a correct match between the tRNA anticodon and a cells.
mRNA codon. • Codons are a triplet of bases which encodes a particular amino acid
o Flexible pairing at the third base of a codon is called Wobble • As there are four bases, there are 64 different codons. Combinations
and allows some tRNAs to bind to more than one codon. (4x4x4=64)
• A ribosome is composed of two halves. A large subunit and a small • The codons can translate for 20 amino acids.
subunit. During translation, ribosomal subunits assemble together like • Different codons can translate for the amino acid therefore the genetic
a sandwich on the strand of mRNA. code is said to be degenerate.
o Each subunit is composed of RNA molecules and proteins • The order of codons determines the amino acid sequence for a protein
o Small subunit binds to the mRNA • The coding region always starts with a START codon (AUG) therefore
o Large subunit has binding sites for tRNAs and also catalyze the first amino acid is all polypeptides in methionine.
the peptide bonds between amino acids. • The coding region of mRNA terminates with a STOP codon – the STOP
• Ribosomes facilitates specific coupling of tRNA anticodons with mRNA codon does not add an amino acid – instead it causes the release of
codons in protein synthesis. the polypeptide.
• The two ribosomal subunits (large and small) are made of protein and • How are the instructions for assembling amino acids into proteins
ribosomal RNA. They move through the nuclear pores on their way out encoded into DNA?
of the nucleus, they will either go to the free (floating into cytoplasm) o There are 20 amino acids, but there are only 4 nucleotide
or bounded ribosomes. bases in DNA
THREE BINDING SITES OF RIBOSOMES • How many bases correspond to an amino acid?
• P site – holds the tRNA that carries the growing polypeptide. (peptidyl o If a single nucleotide coded for an amino acid, there could
site) only be 4 amino acids
• A site – holds the tRNA that carries the next amino acids to be added o If two nucleotides coded for amino acids, the maximum
to the chain. (Aminoacyl site) number of combinations would give 4x4 or 16 amino acids,
• E site – exit site, where discharge tRNAs leaves the ribosomes. not enough
o E-P-A arrange in ribosomes o However, if three nucleotides code for amino acids, there
TRANSLATION could be 4x4x4 or 64 combinations for amino acids, more
• Begins when initial portion of mRNA molecule binds to rRNA in a than enough for the 20 amino acids.
ribosome • Codons: 3 base codes for the production of a specific amino acid,
• tRNA molecule with complementary anticodon binds to exposed sequence of three of the four different nucleotides. Since there are 4
codon on mRNA bases and 3 positions in each codon, there are 4x4x4 = 64 possible
• some tRNA molecules recognize more than one codon codons.
BUILDING A POLYPEPTIDE • 64 codons but only 20 amino acids, therefore must have more than 1
• Three stages – Initiation, Elongation, Termination codon.
• The AUG start codon is recognized by methionyl tRNA on Met. Once • 3 of the 64 codons are as STOP signals, they are found at the end of
the start codon has been identified, the ribosome incorporates amino every gene and mark the end of the protein.
acids into a polypeptide chain. • Once codon is used as a START, it is at the start of every protein.
• RNA is decoded by tRNA molecules, which each transport specific • Universal: in all living organism.
amino acids to the growing chain • Amino acids are carried by tRNA.
• Translation ends when a stop code (UAA, UAG, UGA) is reached o The anticodon on tRNA is complementary to the codons on
INITIATION mRNA
• Brings together mRNA, tRNA with the first amino acids and two o To protect against harmful effects of mutation.
ribosomal subunits. o Degeneracy/Redundancy – this can protect against
• A small ribosome subunit binds with mRNA and a special initiator tRNA, mutation.
the small subunits locate the starting codon AUG. • Translation – proteins being synthesized
• Large subunit then attaches to the small subunits with the mRNA • One amino acid can code for two or more codons.
“sandwich” in between. The tRNA moves into P site. A site – open. • One codon has three bases, same as anticodon.
ELONGATION SUMMARY
Amino acids are added one by one to the proceeding amino acids. • TRANSCRIPTION - Copy information from DNA, after copying will
Each addition involves protein called elongation factors, and occurs in three undergo process of splicing introns are removed, and exons will attach,
steps. at the end of the strand sealed there is CAP and POLY-A-TAIL, once
o Codon recognition – 2 codons meet, codon of mRNA and ready is now called mRNA
tRNA, bringing a aspecific amino acid. From p site to a site. • Once pre-mRNA undergoes splicing, no more introns, it is called now
o Peptide bond formation mRNA and will be released in the cytoplasm going to the ribosomes.
o Translocation – part of translation, in which ribosomes moves • Ribosomes, this is where it is translated what was transcribed in DNA
RNA molecules three base position so that a new codon can for protein synthesis
occupy the ribosomal a site. • APE site. tRNA has anticodon complementary to codon of mRNA.
TERMINATION • The amino acid attached to tRNA is called AMINOACYL tRNA
• This reaction releases the polypeptide and the translation assembly SYNTHETASE. After A site going to P site then amino acids combine to
then comes apart. form polypeptide. Then going to exit ready for next amino acids until
• A number of ribosomes can translate a single mRNA simultaneously reach codon STOP, once stop is reached, release factor will release
forming a polyribosomes. polypeptide chain.
• The final step in translation is termination. When the ribosomes
reacges STOP sodon, there is no corresponding transfer RNA. Instead, THE MOLECULAR BASIS OF INHERITANECE
a small protein called “release factor” attaches to the stop codon. The • There are three molecules at the heart of genetics; DNA, RNA, and
release factor causes the whole complex to fall apart: mRNA, two Proteins. DNA and RNA are two types of Nucleic Acids. Protein is
ribosome subunits, the new polypeptide. The messenger RNA can be considered as a very important biomolecule in our body because it
translated many times, to produce many protein copies. really helps in the development of our body.
GENETIC CODE
• Consists of series of information blocks called codons.
CYTOGENETICS | 16
• The most remarkable property of living cells is their ability to produce CHARGAFF’S RULE
or come up with the exact replicas of themselves. • Adenine must pair with Thymine
• In the Gene, we could see the basic substances responsible for the • Guanin must pair with Cytosine
different activities for the different information that are passed on • The bases form weak hydrogen bond
from generations to generations. • Nucleotides in each strand are linked by 5’ - 3' phosphodiester bonds
• According to studies, in the next 60 seconds your body will produce • Bases on opposite strands are linked by hydrogen bonding: A with T
enough new DNA that if it was linked together, it would stretch 100,000 and G with C
km. • Pyrimidine - a monocyclic base with a six -membered ring (thymine,
1962: NOBEL RPIZE IN PHYSIOLOGY AND MEDICINE cytosine and uracil).
• Watsons, J.D and F. H. Crick, “Molecular Structure of Nucleic Acids: • Purine - bicyclic base with fused five and six-membered ring (adenine
A structure for Deoxynucleic Acids”. Nature 171 (1953), p. 738. and guanine).
• The three scientists behind this study were James D. Watson, OTHER INFO
Francis H. Crick and Maurice H. F. Wilkins. • Rosalind Franklin took diffraction x-ray photographs of DNA crystals.
• Discovered Nucleic Acid was Friedrich Miescher around 1869 • In the 1950’s, Watson & Crick built the first model of DNA using
while studying the nuclei of the RBC. Franklin's x-rays.
CENTRAL DOGMA OF BIOLOGY DOUBLE HELIX
• Most DNA has a right -hand twist with 10 base pairs in a complete turn.
• Left twisted DNA is called Z-DNA or southpaw DNA
• Hot spots occur where right and left twisted DNA meet producing
mutations.
• Stands for Deoxyribonucleic acid made up of subunits called
nucleotides.
• Nucleotide made of:
1. Phosphate group
2. 5-carbon sugar
Refers to the different processes specially in the process of protein
3. Nitrogenous base
synthesis. We have the Replication, Transcription, Translation.

ANTIPARALLEL STRANDS
The Importance of Central Dogma to modern biology is that without this • One strand of DNA goes from 5’ to 3’ (sugars)
process, reproduction of species would not occur as genetic information • The other strand is opposite in direction going 3’ to 5’ (sugars)
would not be able to stored and produce proteins which are essential in
biochemical processes.
DNA (DEOXYRIBONUCLEIC ACID)
• DNA directs the machinery of a cell to make specific proteins, and,
therefore, DNA indirectly controls all of the functioning of all living
things.
• DNA stores the hereditary information of an individual.
• DNA has the ability to mutate (change). It allows a new characteristics
and abilities to appear that helps survive and produce a living organism
(evolution). Remember that DNA is a nucleotide polymer in which each
of the monomers contains deoxyribose, a phosphate and one other
heterocyclic bases (Adenine, Cytosine, Guanine and the Thymine).
• This allows for new characteristics and abilities to appear which may
help an individual to survive and reproduce (EVOLUTION).
• Self-replication: DNA has the ability to make copies of itself. This
undergoes before the cell divide.
DNA STRUCTURE
• DNA is composed of four nucleotides, each containing: adenine,
cytosine, thymine, or guanine.
• The amounts of A = T, G = C and purines = pyrimidines (Chargaff's Rule)
• DNA is a double - stranded helix with antiparallel strands (Watson and
Crick).
• Uracil present in the RNA but not in the DNA. Uracil usually replaces the
Thymine in the RNA structure.
• Erwin Chargaff showed the amounts of the four bases on DNA (A, T, C, • The 5’ and 3’ mean "five prime and three prime" which indicate the
G) carbon numbers in the DNA's sugar backbone.
• In a body or somatic cell: • The 5’ carbon has a PHOSPHATE group attached to it and the 3’ prime
o A = 30.3% carbon a HYDROXYL (-OH) group. This asymmetry gives a DNA strand
o T = 30.3% a direction.
o G = 19.9%
o C = 19.9%

CYTOGENETICS | 17
 • replication fork: The Y-shaped structure formed during the initiation of
replication.
• semiconservative replication: the method used to replicate DNA in which
the double -stranded molecule is separated and each strand acts as a
template for a new strand to be synthesized, so the resulting DNA
molecules are composed of one new strand of nucleotides and one old
strand of nucleotides.
• telomerase: an enzyme that contains a catalytic part and an inbuilt RNA
THE BASIC PRINCIPLE: BASE PAIRING TO A TEMPLATE STRAND template; it functions to maintain telomeres at chromosome ends.
• The relationship between structure and function is manifest in the • telomere: the DNA at the end of linear chromosomes.
double helix. REPLICATION COPIES THE GENETIC INFORMATION
• Since the two strands of DNA are complementary each strand acts as a • A single strand of DNA serves as a template for a new strand.
template for building a new strand in replication. • The rules of base pairing direct replication.
• DNA is replicated during the S (synthesis) stage of the cell cycle.
Q1: If there is 30% Adenine, how much Cytosine is present? • Each body cell gets a complete set of identical DNA.
A: There would be 20% Cytosine
Adenine (30%) = Thymine (30%)
Guanine (20%) = Cytosine (20%)
Therefore, 60% A-T and 40% C-G
Q2: If a piece of double stranded DNA has a guanine content of 26%, what
proportion of thymine do you expect?
A: T = 24%
DNA REPLICATION AND PROTEIN SYNTHESIS
What is the purpose of replication?
• The purpose of DNA replication is to produce two identical copies of a
DNA molecule. This is essential for cell division during growth or repair of
damaged tissues. DNA replication ensures that each new cell receives its
own copy of the DNA.
• Replication happens on the Interphase.
• The process by which new DNA molecules are generated is what we call
as DNA replication.
• It is a biochemical process by which DNA molecules produces exact
duplicates/copies of themselves.
DNA REPLICATION FACTS
• In human cells, 50 nucleotides are added every second to a new strand
of DNA. KEY PLAYERS
• The Replication process takes about 8 hours in human cells. Enzymes:
• DNA polymerase has a built in "proof-reading” functions to correct a. HELICASE – unzipping enzymes / unzipping the two strands of
errors. DNA helix.
• Errors are limited to error / billion nucleotide. b. DNA POLYMERASE – builders / replicates the DNA molecules to
• DNA has to be copied before a cell divides. build new strands.
• DNA is copied during the S or synthesis phase of Interphase. c. Primase – Primer / figuring out the work / guide. It’s made up of
• New cells will need identical DNA strands. RNA.
• Accuracy and Repair – DNA copied with a high degree of accuracy. d. Ligase – gluer / glues the fragments / seals the fragments.
• Mutation – change in the nucleotide sequence of DNA; it can have a Proteins carry out the process of replication.
serious effect on organism, can be harmful or beneficial. • DNA serves only as a template.
• Environmental factors can damage the DNA. Ex. Ultraviolet radiation of • DNA just stores the information.
the SUN. • Enzymes and other proteins do the actual work of replication.
TERMINOLOGIES o Enzymes unzip the double helix
• DNA ligase: the enzyme that catalyzes the joining of DNA fragments o Free-floating nucleotides form hydrogen bonds
together. Point of Origin (DNA sequence)
• DNA polymerase: an enzyme that synthesizes a new strand of DNA I – Helicase unwinds DNA
complementary to a template strand. II – SSB (single stranded binding) proteins binds to DNA strands.
• helicase: an enzyme that helps to open up the DNA helix during DNA III – Primase creates primer
replication by breaking the hydrogen bonds. IV – DNA Polymerase begins to build (important enzymes that added
• lagging strand: during replication of the 3’ to 5’ strand, the strand that is base.)
replicated in short fragments and away from the replication fork. MUTATIONS
Changes in DNA that affect genetic information
• leading strand: the strand that is synthesized continuously in the to
WHAT are mutations?
3direction that is synthesized in the direction of the replication fork.
• Changes in the nucleotide sequence of DNA
• mismatch repair: a form of DNA repair in which non complementary • May occur in somatic cells (aren’t passed to offspring)
nucleotides are recognized, excised, and replaced with correct nucleotide. • May occur in gametes (eggs and sperm) ad be passed to offspring
• mutation: a permanent variation in the nucleotide sequence of a genome. • Due to intrinsic and extrinsic factors. (errors)
• nucleotide excision repair: a form of DNA repair in which the DNA MUTATIONS
molecule is unwound and separated in the region of the nucleotide • The word mutation was similar to the French word “mutacioun” which
damage, the damaged nucleotides are removed and replaced with new literally means “process of changing”
nucleotides using the complementary strand and the DNA strand is • Originally, mutation derived from the latin word “mutare” the meaning
resealed and allowed to rejoin its complement. of this is to change
• Okazaki fragments: the DNA fragments that are synthesized in short HISTORY
stretches on the lagging strand. • The term “mutation” was coined by Hugo De Vries in 1890
• primer: a short stretch of RNA nucleotides that is required to initiate • Seth Wrigth an English Farmer noticed the first mutation. 1971 (male
replication and allow DNA polymerase to bind and begin replication. lambs)

CYTOGENETICS | 18
• In 1927, H.J. Miller performed experiments of artificial mutagenesis (used (carcinogens), obesity, hormones, chronic inflammation) – (other
xrays and introduced mutation, noble prize award in 1946) environmental agent that causes gene mutations)
TERMINOLOGY ARE MUTATIONS HELPFUL OR HARMFUL?
• Muton – smallest unit of gene capable of undergoing mutations, • Mutations happen regularly
represented by nucletides • Mutations are helpful
• Mutator gene – gene causes another gene to undergo spontaneous • Mutations are harmful
mutation • Almost all mutations are neutral
• Mutable gene – gene that shows very high rates of mutations as • Many mutations are repaired by enzymes
compared to other genes • Some type of skin cancers and leukemia result from somatic mutations
• Mutant – organism, self-knowing mutant phenotype due to a mutable • Some mutations may improve an organism’s survival (beneficial_
in gene HELPFUL MUTATIONS
• Mutagen – physical or chemical agent • Some mutations have a positive effect on the organism. They are called
• Gene mutations – also called point mutations, changes which alters the beneficial mutations.
chemical structures of a gene at a molecular level • Mutations can be positive (helpful)
CHARACTERISTIC FEATURE OF MUTATIONS • Some mutations can provide an advantage which helps the organism
• Mutations are mostly recessive and very rarely dominant survive
• Most mutations have harmful effects and very few are beneficial HARMFUL MUTATIONS
• They may be due to a change in a gene, group of genes or in an entire • Mutations can be negative (harmful)
chromosome • Some mutations are harmful and hurt the organism’s chances for
• If gene mutations are not lethal, the mutant individuals may survive survival
CLASSIFICATION OF MUTATIONS • They reduce the organism’s chance for survival and reproduction
a. Based on direct mutations • Any mutation leading to a disease: (ex. Cystic fibrosis, sickle-cell
• Forward mutation – any change from a wild type(normal phenotype, anemia, hemophilia)
nonmutated) allele to a mutant allele • Such mutations are likely to be harmful:
• Backward mutation – reverse mutation, a change from mutant allele o A genetic disorder
to a wild type allele o Cancer
b. Based on source/cause of mutation o Chromosomal disorders
• Spontaneous mutation – occur naturally o Diagnostic genetic disorder
• Induced mutation – originates in response to mutagenic fragments Neutral mutations
c. Based on tissue origin • Mutation can be neutral (not harmful, not helpful)
• Somatic mutation – mutation in somatic tissue • Some mutations do not affect the organism’s survival
• Germinal mutation – mutation in reproductive tissue Forward and Backward mutations
d. Based on effect on survival • Forward – wild type to mutant
• Lethal mutation – kills the individual that carries the mutation, zero • Backward (reverse) – mutant to wild type
survival Macro and Micro mutations
• Sub-lethal mutation – mortality is more than 50% of the individual • Macro – change/differences is obviously observed
that carries the mutation • Micro – change/differences not obviously identified
• Sub-vital mutation – mortality is less than 50% INDUCED AND SPONTANEOUS MUTATION
• Vital mutation – all the mutant individuals will survive a. Induced
e. Based on trait or character affected • caused by the changes in DNA brought about by some
• Morphological mutation – alters in the morphological features of environmental factors called mutagens (example, UV light, xrays,
individual gamma rays) (individual exposed to mutagenic agents)
• Biochemical mutation – alters the biochemical functions of an b. Spontaneous
individual • They are mainly caused during DNA replication or incorporation of
f. Based on visibility/morphological mutation incorrect nucleotide in the growing DNA chain
• Macro-mutations – produces distinct morphological change on • They occur naturally by changes in DNA sequence during replication
individual’s phenotype (detected easily w/out confusion) (do not show symptoms, in contrast induced mutation shows
• Micro-mutations – invisible, a small phenotypic effect that cannot immediate effect on an organism)
be recognized on an individual (easily confused with effects that is c. Induced vs Spontaneous Mutation
produced on or due to environment) • Once an individual is affected, there is error in DNA repair,
g. Based on the site of mutation or cytological basis transcription, polymesiration, replication
• Chromosomal mutation – associated with detectable changes in WHAT ARE MUTAGENS?
chromosome number/structure • Mutagens are caused by environmental factors known as mutagens
• Gene or point mutations – produced by alteration in the base • Mutagens are chemical or physical agents that interact with DN to cause
sequence mutations
• Cytoplasmic mutations – changes in different parts of the cell such • Mutagens something that causes the DNA code to change (mutate)
as chloroplast and mitochondria • Type of mutagens: Radiation, Chemicals, and Infectious Agents
MUTATION MAY LEAD TO GENETIC DISORDER CHROMOSOME MUTATIONS
A sudden heritable change in the genetic material of an organism, as a May involve:
result progeny may exhibit an altered form, size and composition • Changing the structure of a chromosomes (even numbers)
THERE ARE TWO WAYS IN WHICH MUTATION CAN OCCUR • Loss or gain of part of a chromosome
a. Mutations can be inherited • Five types:
• This means that if a parent has a mutation in his/her DNA then o Deletion
the mutation is passed on to his/her children o Inversion
b. Mutations can be acquired o Translocation
• This happens when environmental agents damage DNA or when o Nondisjunction
mistakes occur when a cell copies its DNA prior to cell division o Duplication
WHAT DO GENE MUTATIONS DO? GENE MUTATIONS
A gene mutation can instruct a healthy cell to: • Changes in the nucleotide sequence of a gene
▪ Allow rapid growth • May involve a single nucleotide
▪ Fail to stop on uncontrolled cell growth • May b due to copying errors, chemicals, viruses
▪ Make mistakes when repairing DNA errors • Normal gene (normal protein) to mutated gene (abnormal or no
WHAT CAUSES GENE MUTATIONS? protein)
• Gene mutation you’re born with TYPES OF GENE MUTATIONS
• Gene mutations that occur after birth (a number of forces can cause gene a. Point mutations – one base in a DNA is replaced with another base
mutations, such as smoking, radiation, viruses, cancer-causing chemicals • Substitutions

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 • Insertions MUTAGENIC AGENTS – INCREASES MUTATION RATE
• Deletions – base or some bases deleted from the gene • These include:
sequence o A variety of chemicals act as mutagens
• Inversions – genes inverted and inserted back into the original a. Bromouracil, structurally similar to DNA bases, and are
sequence inserted in place of normal bases
b. Frameshift – inserts or deletes a base in a molecule b. Ethidium bromide has a structure that allows it to wedge
POINT MUTATION within the DNA double helix
• Change of a single nucleotide • Exposure to high energy radiation (bombardment by alpha, beta, or
• Includes the deletion, insertion, or substitution, inversion of one gamma particles) or ultraviolet light can have a similar effect.
nucleotide in a gene EXAMPLE OF CHEMICAL MUTATIONS
o Silent mutations – non-expressive, a new codon codes for the • The Chernobyl babies – radiation causes defects
same amino acids as the wide-type one • Gigantism
o Missense mutations – substitution one amino acid for another GENETIC ENGINEERING
o Nonsense mutations – convert an amino acid into a stop codon. • Is the modification of an organism’s genetic code through artificial
The effect is to shorten the resulting protein. means. Often involves transferring a specific trait (gene) from one
o Sense mutation – opposite of nonsense mutation. Stop codon is organism in a plant or animal of an entirely different species. (first
converted into an amino acid codon. organism to genetically engineer were bacteria, 1973, and mice in 1974.
SUBSTITUTIONS Insulin producing bacteria commercialized in 1982, and genetically food
• Only affect a single codon have been available since 1994, GMO)
• Effect may not be serious unless they affect an amino acid that is • Ways:
essential for the structure and function of the finished protein molecule o Selective breeding
a. No change o GMO’s – organism w/ altered DNA
o Glu – Glu o Cloning
b. Disaster o Gene therapy – introduction of genes into existing cells to
o Amino acid – STOP prevent/cure wide range disease, correcting defective genes
POINT MUTATION (1960s – first concept of gene therapy was introduced, 2007 – trial
• Sickle cell disease is the result of one nucleotide substitution for inherited retinal diseases, 2006 – successful treatment two
• Occurs in the hemoglobin gene patients with Chronic granulomatous disease)
FRAMESHIFT MUTATION TYPES OF GENE THERAPY
• Original – the fat cat ate the wee rat • Somatic gene therapy – transferred to somatic cells (bone marrow cells)
• (“a” is added) – the fat caa tat eth ewe era t • Germ Line therapy – transferred to egg and sperm cells, can be inherited
a. Additions – a frameshift mutation VECTORS IN GENE THERAPY
b. Deletions– a frameshift mutation a. Viral vectors – viruses introduce their genetic material into the host
BACKGROUND TO PHENYLKETONURIA cell as part of their replication cycle
• Phenylalanine and tyrosine are two amino acids that humans obtain from ▪ Retrovirus
protein in their diet. During normal metabolism, excess phenylalanine is ▪ Adenovirus
acted upon by an enzyme phenylalanine hydroxide. ▪ Adeno-associated virus
• Phenylalanine aka PKU ▪ Herpes simplex virus
• PKU is a hereditary disorder caused by a genetic defect which disrupts b. Non-viral Vectors
this metabolic pathway o Pure DNA construct – direct introduction of DNA to target
• An affected person lacks the normal allele of the gene required to make tissues, large quantities of DNA is injected periodically
the enzyme phenylalanine hydroxide o DNA molecular conjugates – avoid lysosomal breakdown of DNA
• Owing this inborn error in metabolism, phenylalanine is no longer ▪ Lipoplexes
converted to tyrosine o Human artificial chromosomes – advantages is that gene therapy
• Instead it undergoes alternative pathways which produces toxins which has the ability to imitate and even prevent hereditary diseases,
affect the metabolism of brain cells and severely limit mental a chance to survive, eradicate diseases to future generations
development disadvantage is long lasting therapy, due to a rapid dividing cells
DNA RECOMBINANT
• New born babies are screened for PKU, and sufferers are put on a diet
(contains genetic material from two different organisms)
containing minimum phenylalanine
• Issues involved in the application of genetic technology
• As a result the worst effects of PKU can be kept to a minimum
• Gene technologies:
• Albanism
o Polymerase chain reaction (PCR) – (device in 1983, detecting covid,
• Results from a mutation which prevents the formation of enzyme 3
used in forensic investigations)
(melanocyte tyrosinase)
o Cutting out DNA fragments using restriction enzymes – (plased into
• As a result albinos fail to synthesize melanin
a well and covered in buffer’s solution, conducts electricity)
• Due to total lack of pigment Albino’s have characteristic
▪ Electrophoresis
o Very pale skin which fails to tan
STEPS IN RDNA
o White hair
▪ Cell membrane dissolution
o The color of the iris is usually blue/gray or light brown with some
▪ Isolation of plasmids fraction
people having a reddish or violet hue reflected through iris
▪ Cleavage of plasmid DNA
o In some cases, vision problems
▪ Gene removal from another organism
• They must avoid ultraviolet radiation and may require to ware tinted ▪ Gene-plasmid splicing
glasses to assist with photophobia ▪ Uptake of recombinant DNA
CYSTIC FIBROSIS
• Mucus is a slimy substance secreted by the inner lining of the wind pipe
and intestine.
• Mucus is made of a glycoprotein which makes it thick, slimy, and perfect
for protection and lubrication
• The genetic information for coding this glycoprotein is chromosome 7
• If the info on the gene for the glycoprotein is altered, two outcomes:
o Homozygous for the mutant allele: make abnormally thick and
sticky mucuos leading to lung congestion and blockage of the
pancreatic duct – CYSTIC FIBROSIS
o Heterozygous for the mutant allele: they carry the mutant allele
masked in their genotype

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