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Week 1 genetics-upload

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This document outlines key concepts in transmission genetics and Mendelian inheritance. It defines important genetic terms like genes, alleles, homozygous, heterozygous, dominant, and recessive. It reviews Gregor Mendel's experiments with pea plants in the 1860s, which disproved earlier hypotheses about inheritance and established the discrete units of inheritance that are passed from parents to offspring. The document also explains the concept of a monohybrid cross using a simple example and how it can be used to predict offspring genotypes and phenotypes based on Mendel's theory of segregation.

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Genetics/lab BIOL 3600 DA7 De Santis 3046 Fall 2014 Lecture: M,W,F 4:15 - 5:05 pm Lab: Parker 219 Monday 6-8:45 pm Wednesday 6-8:45 pm

2

Review of the syllabus Instructor Dr. Paula Faria Waziry Office: UPP North 3450 suite 103 Phone: 2-2872 (don’t leave message!) Skype: paula.waziry Office hours: by appointment E-mail – waziry@nova.edu Lab assistant Nishant Talati Text Pierce, Benjamin A 2014. Genetics: A Conceptual Approach, 5th Edition, W.H. Freeman, New York, NY (ISBN number 2013951443) Website All course materials will be posted on Blackboard prior to the class period - PowerPoint presentations - Lab information - http://www.slideshare.net/paulawaziry1 (when BB is down...)

3

Review of the syllabus Class assignments Unit exams (40% of final grade) - 2 will be given (20% each) - Each will consist of three sections – multiple choice, short answer, essay - Responsible for all material covered in the Powerpoint presentations. - ~90 minutes to complete - Make-ups – must have an approved excuse in writing (as per the NSU catalog) - Must contact me ASAP (before the exam, if possible) - If don’t have excuse in writing, points will be deducted for make-up Final exam (20% of final grade) – cumulative Quizzes – lab and lecture (15% of final grade) - Approx. 10 minutes each - Only covers material since the last quiz - You can drop 2 lowest quizzes grades. - No make-ups unless you have an excuse in writing.

4

Review of the syllabus Lab assignments Lab final (10% of final grade) - Cumulative – all labs and techniques - See lab syllabus for more information Lab reports, lab attendance and participation (15% of final grade) - You must keep a written account of all experiments during the semester - Include purpose, methods, results, and discussion/conclusion for ALL EXPERIMENTS DONE - Unexcused absences will result in major point deductions

5

Review of the syllabus Grades The final average will be calculated as follows: two unit tests @ 20% each ```40% Final exam 20% Quizzes 15% Lab final 10% Lab activities 15% 100% The grading scale: 93% = A, 90-92%=A-, 87-89%=B+, 83-86%=B, 80-82%=B-, 77-79%=C+, 73-76%=C, 70-72%=C-, 60-69%=D, <60%=F

6

Tips for success 1. Attendance is required at all lectures, labs, and exams - You are responsible for getting any missed info 2. Ask questions in class and participate in discussions 3. Don’t just read and highlight the handouts. Understand and practice questions. 4. You will be responsible for the conceptual material covered in class/ Powerpoints. 5. Be considerate: no cell phones, texting, Internet surfing, facebooking, dozing off, sleeping, snoring…

7

Chapter 1 Introduction to Genetics  People have understood the hereditary nature of traits and have practiced genetics for thousands of years  The rise in agriculture began when people started to apply genetic principles to the domestication of plants and animals

8

 Pharmaceutical industry:  Numerous drugs are synthesized by fungi and bacteria.  Ex: growth hormone, insulin  In medicine:  Many diseases and disorders have a hereditary component.  Ex: hemophilia, sickle-cell anemia, diabetes, muscular dystrophy, EMD1: Emerin; Xq28; Recessive EMD2: Lamin A/C; 1q21.2; Dominant EMD3: SYNE1; 6q25; Dominant EMD4: SYNE2; 14q23; Dominant Other: Sporadic & Dominant from A Kornberg MD

9

2 years-old Kristian Hutchinson-Gilford Progeria 12 years-old Ashley and 2-weeks old brother Evan

10

Defect in Lamina A processing Hutchinson-Gilford Progeria Lamin A/C (a) Lamin A (c) DAPI Control Patient

11

Samuel Dales mRNA Ribosomal subunits tRNA snRNPs Proteins with NES hnRNPs Ribosomal proteins Proteins with NLS snRNPs

12

TPR (translocated promoter region) The Nuclear Pore Complex Nup98 Nup98 Nup98

13

Nucleoporin Translocations in Acute Leukemia Fusion Transcript • Nup98-HOXA9 • Nup98-HOXD13 • Nup98-PMX1 • Nup98-DDX10 • Nup98-RAP1GDS1 • Nup98-TOP1 • DEK-Nup214 • SET-Nup214 Translocation t(7; 11)(p15; p15) t(2; 11)(q31; p15) t(1; 11)(q23; p15) inv(11)(p15; q22) t(4; 11)(q21; p15) t(11; 20)(p15; q11) t(6; 9)(p23; q34) inv(9)

14

Genetic Diversity and evolution  Living organisms have an important feature in common: all use similar genetic systems  A complete set of genetic instructions for any organism is its genome  All genomes are encoded in nucleic acid: either DNA or RNA • Suggestive of a common ancestor

15

 Since all organisms have similar genetic systems, the study of one organism’s genes reveals principles that apply to other organisms STAT 1 P P SGTAAT S1 motif Accessory TF motifs TATA Accessory TF factors

16

Nucleoporins and Nuclear Traffic Proteins are involved with Mitotic Spindle Checkpoints and Ageing Baker DJ, Jeganathan KB, Malureanu L, Perez-Terzic C, Terzic A, van Deursen JM. J Cell Biol. 2006 Feb 13;172(4):529-40.  Enabling us to use animal models to study diseases or natural processes

17

Influenza A pandemic - Influenza virus killed as many as 50 million people in a single year (1918-1919) - Extremely virulent - Fast, nasty, killed all ages - Up until 2006, had no idea why it was so virulent - Had no way to tell if a similar strain was forming - In October 2005, scientists recreated the 1918 strain using various genetic techniques - Obtained samples of the virus from preserved wax specimen and from a Eskimo woman who had died from it - Able to characterize it and maybe predict / prevent future outbreaks

18

Microarray study reveals changes in regulation of genes Upon influenza viral infection Replication-dependent genes Geiss G, J.Virol, May 2001,p4321-4331

19

Cells expressing low levels of Rae1 are susceptible to influenza infection

20

Influenza virus targets the mRNA export machinery and the nuclear pore complex. Satterly, Tsai, van Deursen, Nussenzveig, Wang, Faria, Levay, Levy, Fontoura. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1853-8.

21

Genetics What is it? http://www.youtube.com/watch?v=0Onw OKiMVb8&feature=channel_video_title

22

• Genetics = Study of HEREDITY and VARIATION - Heredity = Passing down of traits from one generation to another - Variation = Differences in inherited characteristics among members of a population

23

Genetics What is it? • Genetics has many subfields 1. Transmission genetics – Study of heredity - How traits are passed down between generations - Example: My mom has disease, spouse's uncle has same disease  Will our kids have it? - Is allele dom/rec, is it on X chr or autosome? 2. Molecular genetics – Structure and function of individual genes - Includes study of cancer (cancer genetics), genetic engineering (manipulation of genes), study of chromosome structure (cytogenetics) 3. Population/Evolutionary genetics – Study genetic variation in populations - Includes conservation genetics

24

Week 1 genetics-upload

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History of genetics • Early genetics was more philosophy than science - No experimentation - Many concepts were incorrect - Pangenesis – traits collected from all over body and put into sperm/eggs - Pre-formationism – little person inside of gametes (homunculus) - Blending inheritance – actual mixing of genetic information

26

“Blending”

27

History of genetics • Technological and scientific developments changed genetics in 1800s - Microscopes invented – direct observation of gametes - Darwin and Mendel revolutionize genetics - Evolutionary and transmission genetics begin - Chromosomes observed and discovered to carry genetic information (early 1900s)

28

Chapter 2 Chromosomes and Cellular Reproduction

29

1. Nucleus vs nucleoid - Nucleus – Membrane-enclosed organelle inside of eukaryotic cells that holds the chromosomes - Nucleoid – Region of a prokaryotic cell cytoplasm in which the chromosome resides 2. Chromosome - Single piece of DNA + proteins - Can be linear (eukaryotes) or circular (prokaryotes) - Eukaryotes have many, prokaryotes have one - Divided into many genes

30

The Nucleus in Context (the central dogma)

31

• Origin of the Nucleus: Most likely, from invagination of cell membrane of an ancient bacterium. The interior of the nucleus is topologically equivalent of the cytoplasm. • The ER is continuous with the nuclear membrane. The intermembrane space is topologically equivalent to the extracellular space. Evolution of the Eukaryotic Nucleus

32

Week 1 genetics-upload

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Week 1 genetics-upload

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Chromosome Territories Chromosome distribution is not random

35

Chromosome Territories  Chromosomes maintain their individuality  they have fixed homes spatially limited volume  Each chromosome of a specific cell type can be assigned a preferential position relative to the center of the nucleus  territories have highly branched and interconnected channels Good Review: Meaburn and Misteli, Nature, Jan 25, 2007, vol445, pp379 - 381

36

Chromosome Structure • Centromere: attachment point for spindle microtubules • Telomeres: tips of a linear chromosome • Origins of replication: where the DNA synthesis begins

37

At times a chromosome Consists of one single chromatid At other times it consists of 2 (sister) chromatids The telomeres are the stable ends of chromosomes The centromere is a constricted region of the chromosome where The kinetochores form and the Spindle microtubules attach

38

Centromeres can be located at different sites on a chromosome

39

3. Gene - Defined segment of a chromosome that provides the instructions to make a single product (a protein) - One chromosome may be subdivided into 1,000 different genes 1 chromosome insulin ATP synthase actin hemoglobin  Chromosomes are divided into genes, which are composed of DNA 4. Diploid vs. haploid - Most eukaryotic organisms have 2 copies of each chromosome in each of their somatic cells - 2 copies = 2n = DIPLOID - Gamete cells (e.g. sperm and eggs) contain only 1 copy - 1 copy = 1n = HAPLOID

40

• Some more genetic terms (and how they relate to one another): 5. Alleles - Alternate forms of the same gene caused by minor differences in the DNA sequnce 6. Genotype vs phenotype - Genotype – The genetic makeup of an organism (what the genes look like) - Phenotype – The actual observable characteristics that we see - Influenced by the genotype and the environment eye color blue eyes brown eyes

41

Quick review of Mitosis http://www.youtube.com/watch?v=AhgRhXl7w_g&feature=fvst

42

Week 1 genetics-upload

43

Genetic consequences of the cell cycle • Producing two cells that are genetically identical to each other and with the cell that gave rise to them. • Newly formed cells contain a full complement of chromosomes. • Each newly formed cell contains approximately half (but not necessarily identical) the cytoplasm and organelle content of the original parental cell.

44

Quick review of Meiosis http://www.youtube.com/watch?v=iCL6 d0OwKt8&feature=channel_video_title

45

Room for genetic variation

46

Week 1 genetics-upload

47

Room for genetic vatiation

48

Week 1 genetics-upload

49

Genetic Variation is Produced through the random distribution of chromosomes in meiosis Genetic Variation is Produced through crossing over • Try Animation 2.3 file:///E:/media/ch02/Animations/0203_genetic_va r_meiosis.html

50

Consequences of Meiosis and Genetic Variation • Four cells are produced from each original cell. • Chromosome number in each new cell is reduced by half. The new cells are haploid. • Newly formed cells from meiosis are genetically different from one another and from the parental cell.

51

Concept Check Which of the following events takes place in meiosis II, but not in meiosis I? a. crossing over b. contraction of chromosomes c. separation of homologous chromosomes d. separation of chromatids

52

Transmission genetics Mendel and beyond

53

Chapter 3 Basic Principles of Heredity

54

Transmission genetics Overview • Transmission genetics  Study of how genes/traits are passed down through generations - Wrong hypotheses in history: - Pangenesis: Traits absorbed from all over body  sperm/eggs - Lemarckism: Kids inherit their parents acquired characteristics - Preformationism: Little people inside of gametes (homunculus) - Blending inheritance: Traits of parents blend  passed on • Gregor Mendel – 1850-60s - Experiments with peas disproved all above - Found discrete units of inheritance passed down - Provide instructions for brand new organism - No blending - Unique combination of genes provides unique traits in offspring

55

Transmission genetics Review of terminology • Genes = Short segments of chromosomes/DNA that provide instructions to make a polypeptide • Alleles – Different forms (variations) of the same gene that result from minor differences in the DNA sequence - Example: Gene controlling melanin • Homozygous vs. heterozygous Homozygous – Organism has 2 copies of the same allele for a given gene Heterozygous – Organism has 2 different alleles for a given gene • Dominant vs. recessive - In a heterozygous individual, both alleles are expressed (assuming no imprinting) - However, one allele often has a greater impact on the final observable trait - Those alleles that mask the effects of other alleles  DOMINANT Those alleles that get masked  RECESSIVE

56

Simple Mendelian inheritance Monohybrid cross • Simple Mendelian inheritance - Each trait is controlled by one gene, each gene controls one trait - Alleles have a clear dominant-recessive relationship - Individuals have expected phenotype - If examining more than 1 gene  they are on separate chromosomes • Monohybrid cross (1 gene) - Example: Human earlobe shape - Dominant allele  Unattached (E) Recessive allele  Attached (e) - Example mating: Two heterozygotes (Ee x Ee) - Need to predict offspring genotypes/phenotypes - Theory of segregation – Two copies of the gene are segregated and packaged into separate gametes - 1 gets the "E" and the other the "e"  Predict a 3:1 ratio of dom:rec phenotypes - Only a probability – may not see exact ratio E e EE Ee Ee ee E e

57

Transmission genetics Review of terminology • Genetic shorthand - Dominant allele  Capital letter Recessive allele  Lowercase letter Choose letter wisely! A = normal melanin production AA (homozygous dominant) a = no melanin aa (homozygous recessive) Aa (heterozygous) • Genotype vs. phenotype Genotype – Genetic background of a trait (AA, aa, Aa) Phenotype – Actual observable trait that we see (skin color) - Multiple genotypes can give rise to the same phenotype (e.g. AA and Aa) - Not all individuals with a given genotype will have the expected phenotype • Generation shorthand - P = Parental generation - F1 = First filial generation (produced from mating two parents) - F2 = Second generation (produced from mating 2 F1 offspring)

58

• Why was Mendel so successful? 1) His choice of experimental subject, the pea plant (Pisum sativum) is easy to cultivate and grow relatively rapidly ( by 17th century standards); 2) Peas produce many offspring (seeds); 3) Large variety of traits and traits were genetically pure; 4) He focused on characteristics that have 2 forms; 5) He adopted an experimental approach and used math! 6) He kept careful records of his experiments and was very patient…

59

Simple Mendelian inheritance Monohybrid and dihybrid crosses • Simple Mendelian inheritance - Each trait is controlled by one gene, each gene controls one trait - Alleles have a clear dominant-recessive relationship - Individuals have expected phenotype - If examining more than 1 gene  they are on separate chromosomes • Monohybrid cross (1 gene) - Example: Human earlobe shape - Dominant allele  Unattached (E) Recessive allele  Attached (e) - Example mating: Two heterozygotes (Ee x Ee) - Need to predict offspring genotypes/phenotypes - Theory of segregation – Two copies of the gene are segregated and packaged into separate gametes - 1 gets the "E" and the other the "e"  Predict a 3:1 ratio of dom:rec phenotypes - Only a probability – may not see exact ratio E e EE Ee Ee ee E e

60

• Dihybrid cross (2 genes) - Mendel's original experiments: - Done to determine if inheritance of one gene affects inheritance of another - Found that when genes are on different (nonhomologous) chromosomes, they move independently during meiosis and don't affect one another  Principle of independent assortment - Example (assuming independent assortment): - Earlobe shape (gene E) and hairline shape (F – widow's peak, f – straight) - If mate EeFf x EeFf, what phenotypic ratios in offspring? FIRST SEPARATE THE GENES… E e EE Ee Ee ee E e F f FF Ff Ff ff F f Then do separate Punett squares…

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E e EE Ee Ee ee E e F f FF Ff Ff ff F f INDEPENDENT TERMS E_F_ = double dom. = 3/4 x 3/4 = 9/16 eeF_ = 1 rec, 1 dom = 1/4 x 3/4 = 3/16 E_ff = 1 dom, 1 rec = 3/4 x 1/4 = 3/16 eeff = double rec. = 1/4 x 1/4 = 1/16 9:3:3:1 9+3+3+1=16 Remember that UPPER CASE TRAIT IS DOMINANT FOR PHENOTYPE!!! NOW COUNT THE PHENOTYPES!!!

62

Simple Mendelian inheritance Monohybrid and dihybrid crosses • Dihybrid cross (2 genes) - Example problem: - Imagine you mate a person who has attached earlobes and a smooth hairline with a person who is heterozygous for both genes. What is the probability of them having a child with unattached earlobes and a widow's peak hairline? - Step 1: Convert to letters - Parent 1 = attached, smooth  eeff - Parent 2 = EeFf - ? offspring = E_F_ (2nd letter for each doesn't matter) e e Ee Ee ee ee E e f f Ff Ff ff ff F f - Step 2: Do two Punett squares - Split up the E's from the F's - Step 3: Do the math - Multiply the individual probabilities - E_F_ = 1/2 x 1/2 = 1/4

More Related Content

Week 1 genetics-upload

  • 1. Genetics/lab BIOL 3600 DA7 De Santis 3046 Fall 2014 Lecture: M,W,F 4:15 - 5:05 pm Lab: Parker 219 Monday 6-8:45 pm Wednesday 6-8:45 pm
  • 2. Review of the syllabus Instructor Dr. Paula Faria Waziry Office: UPP North 3450 suite 103 Phone: 2-2872 (don’t leave message!) Skype: paula.waziry Office hours: by appointment E-mail – waziry@nova.edu Lab assistant Nishant Talati Text Pierce, Benjamin A 2014. Genetics: A Conceptual Approach, 5th Edition, W.H. Freeman, New York, NY (ISBN number 2013951443) Website All course materials will be posted on Blackboard prior to the class period - PowerPoint presentations - Lab information - http://www.slideshare.net/paulawaziry1 (when BB is down...)
  • 3. Review of the syllabus Class assignments Unit exams (40% of final grade) - 2 will be given (20% each) - Each will consist of three sections – multiple choice, short answer, essay - Responsible for all material covered in the Powerpoint presentations. - ~90 minutes to complete - Make-ups – must have an approved excuse in writing (as per the NSU catalog) - Must contact me ASAP (before the exam, if possible) - If don’t have excuse in writing, points will be deducted for make-up Final exam (20% of final grade) – cumulative Quizzes – lab and lecture (15% of final grade) - Approx. 10 minutes each - Only covers material since the last quiz - You can drop 2 lowest quizzes grades. - No make-ups unless you have an excuse in writing.
  • 4. Review of the syllabus Lab assignments Lab final (10% of final grade) - Cumulative – all labs and techniques - See lab syllabus for more information Lab reports, lab attendance and participation (15% of final grade) - You must keep a written account of all experiments during the semester - Include purpose, methods, results, and discussion/conclusion for ALL EXPERIMENTS DONE - Unexcused absences will result in major point deductions
  • 5. Review of the syllabus Grades The final average will be calculated as follows: two unit tests @ 20% each ```40% Final exam 20% Quizzes 15% Lab final 10% Lab activities 15% 100% The grading scale: 93% = A, 90-92%=A-, 87-89%=B+, 83-86%=B, 80-82%=B-, 77-79%=C+, 73-76%=C, 70-72%=C-, 60-69%=D, <60%=F
  • 6. Tips for success 1. Attendance is required at all lectures, labs, and exams - You are responsible for getting any missed info 2. Ask questions in class and participate in discussions 3. Don’t just read and highlight the handouts. Understand and practice questions. 4. You will be responsible for the conceptual material covered in class/ Powerpoints. 5. Be considerate: no cell phones, texting, Internet surfing, facebooking, dozing off, sleeping, snoring…
  • 7. Chapter 1 Introduction to Genetics  People have understood the hereditary nature of traits and have practiced genetics for thousands of years  The rise in agriculture began when people started to apply genetic principles to the domestication of plants and animals
  • 8.  Pharmaceutical industry:  Numerous drugs are synthesized by fungi and bacteria.  Ex: growth hormone, insulin  In medicine:  Many diseases and disorders have a hereditary component.  Ex: hemophilia, sickle-cell anemia, diabetes, muscular dystrophy, EMD1: Emerin; Xq28; Recessive EMD2: Lamin A/C; 1q21.2; Dominant EMD3: SYNE1; 6q25; Dominant EMD4: SYNE2; 14q23; Dominant Other: Sporadic & Dominant from A Kornberg MD
  • 9. 2 years-old Kristian Hutchinson-Gilford Progeria 12 years-old Ashley and 2-weeks old brother Evan
  • 10. Defect in Lamina A processing Hutchinson-Gilford Progeria Lamin A/C (a) Lamin A (c) DAPI Control Patient
  • 11. Samuel Dales mRNA Ribosomal subunits tRNA snRNPs Proteins with NES hnRNPs Ribosomal proteins Proteins with NLS snRNPs
  • 12. TPR (translocated promoter region) The Nuclear Pore Complex Nup98 Nup98 Nup98
  • 13. Nucleoporin Translocations in Acute Leukemia Fusion Transcript • Nup98-HOXA9 • Nup98-HOXD13 • Nup98-PMX1 • Nup98-DDX10 • Nup98-RAP1GDS1 • Nup98-TOP1 • DEK-Nup214 • SET-Nup214 Translocation t(7; 11)(p15; p15) t(2; 11)(q31; p15) t(1; 11)(q23; p15) inv(11)(p15; q22) t(4; 11)(q21; p15) t(11; 20)(p15; q11) t(6; 9)(p23; q34) inv(9)
  • 14. Genetic Diversity and evolution  Living organisms have an important feature in common: all use similar genetic systems  A complete set of genetic instructions for any organism is its genome  All genomes are encoded in nucleic acid: either DNA or RNA • Suggestive of a common ancestor
  • 15.  Since all organisms have similar genetic systems, the study of one organism’s genes reveals principles that apply to other organisms STAT 1 P P SGTAAT S1 motif Accessory TF motifs TATA Accessory TF factors
  • 16. Nucleoporins and Nuclear Traffic Proteins are involved with Mitotic Spindle Checkpoints and Ageing Baker DJ, Jeganathan KB, Malureanu L, Perez-Terzic C, Terzic A, van Deursen JM. J Cell Biol. 2006 Feb 13;172(4):529-40.  Enabling us to use animal models to study diseases or natural processes
  • 17. Influenza A pandemic - Influenza virus killed as many as 50 million people in a single year (1918-1919) - Extremely virulent - Fast, nasty, killed all ages - Up until 2006, had no idea why it was so virulent - Had no way to tell if a similar strain was forming - In October 2005, scientists recreated the 1918 strain using various genetic techniques - Obtained samples of the virus from preserved wax specimen and from a Eskimo woman who had died from it - Able to characterize it and maybe predict / prevent future outbreaks
  • 18. Microarray study reveals changes in regulation of genes Upon influenza viral infection Replication-dependent genes Geiss G, J.Virol, May 2001,p4321-4331
  • 19. Cells expressing low levels of Rae1 are susceptible to influenza infection
  • 20. Influenza virus targets the mRNA export machinery and the nuclear pore complex. Satterly, Tsai, van Deursen, Nussenzveig, Wang, Faria, Levay, Levy, Fontoura. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1853-8.
  • 21. Genetics What is it? http://www.youtube.com/watch?v=0Onw OKiMVb8&feature=channel_video_title
  • 22. • Genetics = Study of HEREDITY and VARIATION - Heredity = Passing down of traits from one generation to another - Variation = Differences in inherited characteristics among members of a population
  • 23. Genetics What is it? • Genetics has many subfields 1. Transmission genetics – Study of heredity - How traits are passed down between generations - Example: My mom has disease, spouse's uncle has same disease  Will our kids have it? - Is allele dom/rec, is it on X chr or autosome? 2. Molecular genetics – Structure and function of individual genes - Includes study of cancer (cancer genetics), genetic engineering (manipulation of genes), study of chromosome structure (cytogenetics) 3. Population/Evolutionary genetics – Study genetic variation in populations - Includes conservation genetics
  • 25. History of genetics • Early genetics was more philosophy than science - No experimentation - Many concepts were incorrect - Pangenesis – traits collected from all over body and put into sperm/eggs - Pre-formationism – little person inside of gametes (homunculus) - Blending inheritance – actual mixing of genetic information
  • 27. History of genetics • Technological and scientific developments changed genetics in 1800s - Microscopes invented – direct observation of gametes - Darwin and Mendel revolutionize genetics - Evolutionary and transmission genetics begin - Chromosomes observed and discovered to carry genetic information (early 1900s)
  • 28. Chapter 2 Chromosomes and Cellular Reproduction
  • 29. 1. Nucleus vs nucleoid - Nucleus – Membrane-enclosed organelle inside of eukaryotic cells that holds the chromosomes - Nucleoid – Region of a prokaryotic cell cytoplasm in which the chromosome resides 2. Chromosome - Single piece of DNA + proteins - Can be linear (eukaryotes) or circular (prokaryotes) - Eukaryotes have many, prokaryotes have one - Divided into many genes
  • 30. The Nucleus in Context (the central dogma)
  • 31. • Origin of the Nucleus: Most likely, from invagination of cell membrane of an ancient bacterium. The interior of the nucleus is topologically equivalent of the cytoplasm. • The ER is continuous with the nuclear membrane. The intermembrane space is topologically equivalent to the extracellular space. Evolution of the Eukaryotic Nucleus
  • 34. Chromosome Territories Chromosome distribution is not random
  • 35. Chromosome Territories  Chromosomes maintain their individuality  they have fixed homes spatially limited volume  Each chromosome of a specific cell type can be assigned a preferential position relative to the center of the nucleus  territories have highly branched and interconnected channels Good Review: Meaburn and Misteli, Nature, Jan 25, 2007, vol445, pp379 - 381
  • 36. Chromosome Structure • Centromere: attachment point for spindle microtubules • Telomeres: tips of a linear chromosome • Origins of replication: where the DNA synthesis begins
  • 37. At times a chromosome Consists of one single chromatid At other times it consists of 2 (sister) chromatids The telomeres are the stable ends of chromosomes The centromere is a constricted region of the chromosome where The kinetochores form and the Spindle microtubules attach
  • 38. Centromeres can be located at different sites on a chromosome
  • 39. 3. Gene - Defined segment of a chromosome that provides the instructions to make a single product (a protein) - One chromosome may be subdivided into 1,000 different genes 1 chromosome insulin ATP synthase actin hemoglobin  Chromosomes are divided into genes, which are composed of DNA 4. Diploid vs. haploid - Most eukaryotic organisms have 2 copies of each chromosome in each of their somatic cells - 2 copies = 2n = DIPLOID - Gamete cells (e.g. sperm and eggs) contain only 1 copy - 1 copy = 1n = HAPLOID
  • 40. • Some more genetic terms (and how they relate to one another): 5. Alleles - Alternate forms of the same gene caused by minor differences in the DNA sequnce 6. Genotype vs phenotype - Genotype – The genetic makeup of an organism (what the genes look like) - Phenotype – The actual observable characteristics that we see - Influenced by the genotype and the environment eye color blue eyes brown eyes
  • 41. Quick review of Mitosis http://www.youtube.com/watch?v=AhgRhXl7w_g&feature=fvst
  • 43. Genetic consequences of the cell cycle • Producing two cells that are genetically identical to each other and with the cell that gave rise to them. • Newly formed cells contain a full complement of chromosomes. • Each newly formed cell contains approximately half (but not necessarily identical) the cytoplasm and organelle content of the original parental cell.
  • 44. Quick review of Meiosis http://www.youtube.com/watch?v=iCL6 d0OwKt8&feature=channel_video_title
  • 45. Room for genetic variation
  • 47. Room for genetic vatiation
  • 49. Genetic Variation is Produced through the random distribution of chromosomes in meiosis Genetic Variation is Produced through crossing over • Try Animation 2.3 file:///E:/media/ch02/Animations/0203_genetic_va r_meiosis.html
  • 50. Consequences of Meiosis and Genetic Variation • Four cells are produced from each original cell. • Chromosome number in each new cell is reduced by half. The new cells are haploid. • Newly formed cells from meiosis are genetically different from one another and from the parental cell.
  • 51. Concept Check Which of the following events takes place in meiosis II, but not in meiosis I? a. crossing over b. contraction of chromosomes c. separation of homologous chromosomes d. separation of chromatids
  • 53. Chapter 3 Basic Principles of Heredity
  • 54. Transmission genetics Overview • Transmission genetics  Study of how genes/traits are passed down through generations - Wrong hypotheses in history: - Pangenesis: Traits absorbed from all over body  sperm/eggs - Lemarckism: Kids inherit their parents acquired characteristics - Preformationism: Little people inside of gametes (homunculus) - Blending inheritance: Traits of parents blend  passed on • Gregor Mendel – 1850-60s - Experiments with peas disproved all above - Found discrete units of inheritance passed down - Provide instructions for brand new organism - No blending - Unique combination of genes provides unique traits in offspring
  • 55. Transmission genetics Review of terminology • Genes = Short segments of chromosomes/DNA that provide instructions to make a polypeptide • Alleles – Different forms (variations) of the same gene that result from minor differences in the DNA sequence - Example: Gene controlling melanin • Homozygous vs. heterozygous Homozygous – Organism has 2 copies of the same allele for a given gene Heterozygous – Organism has 2 different alleles for a given gene • Dominant vs. recessive - In a heterozygous individual, both alleles are expressed (assuming no imprinting) - However, one allele often has a greater impact on the final observable trait - Those alleles that mask the effects of other alleles  DOMINANT Those alleles that get masked  RECESSIVE
  • 56. Simple Mendelian inheritance Monohybrid cross • Simple Mendelian inheritance - Each trait is controlled by one gene, each gene controls one trait - Alleles have a clear dominant-recessive relationship - Individuals have expected phenotype - If examining more than 1 gene  they are on separate chromosomes • Monohybrid cross (1 gene) - Example: Human earlobe shape - Dominant allele  Unattached (E) Recessive allele  Attached (e) - Example mating: Two heterozygotes (Ee x Ee) - Need to predict offspring genotypes/phenotypes - Theory of segregation – Two copies of the gene are segregated and packaged into separate gametes - 1 gets the "E" and the other the "e"  Predict a 3:1 ratio of dom:rec phenotypes - Only a probability – may not see exact ratio E e EE Ee Ee ee E e
  • 57. Transmission genetics Review of terminology • Genetic shorthand - Dominant allele  Capital letter Recessive allele  Lowercase letter Choose letter wisely! A = normal melanin production AA (homozygous dominant) a = no melanin aa (homozygous recessive) Aa (heterozygous) • Genotype vs. phenotype Genotype – Genetic background of a trait (AA, aa, Aa) Phenotype – Actual observable trait that we see (skin color) - Multiple genotypes can give rise to the same phenotype (e.g. AA and Aa) - Not all individuals with a given genotype will have the expected phenotype • Generation shorthand - P = Parental generation - F1 = First filial generation (produced from mating two parents) - F2 = Second generation (produced from mating 2 F1 offspring)
  • 58. • Why was Mendel so successful? 1) His choice of experimental subject, the pea plant (Pisum sativum) is easy to cultivate and grow relatively rapidly ( by 17th century standards); 2) Peas produce many offspring (seeds); 3) Large variety of traits and traits were genetically pure; 4) He focused on characteristics that have 2 forms; 5) He adopted an experimental approach and used math! 6) He kept careful records of his experiments and was very patient…
  • 59. Simple Mendelian inheritance Monohybrid and dihybrid crosses • Simple Mendelian inheritance - Each trait is controlled by one gene, each gene controls one trait - Alleles have a clear dominant-recessive relationship - Individuals have expected phenotype - If examining more than 1 gene  they are on separate chromosomes • Monohybrid cross (1 gene) - Example: Human earlobe shape - Dominant allele  Unattached (E) Recessive allele  Attached (e) - Example mating: Two heterozygotes (Ee x Ee) - Need to predict offspring genotypes/phenotypes - Theory of segregation – Two copies of the gene are segregated and packaged into separate gametes - 1 gets the "E" and the other the "e"  Predict a 3:1 ratio of dom:rec phenotypes - Only a probability – may not see exact ratio E e EE Ee Ee ee E e
  • 60. • Dihybrid cross (2 genes) - Mendel's original experiments: - Done to determine if inheritance of one gene affects inheritance of another - Found that when genes are on different (nonhomologous) chromosomes, they move independently during meiosis and don't affect one another  Principle of independent assortment - Example (assuming independent assortment): - Earlobe shape (gene E) and hairline shape (F – widow's peak, f – straight) - If mate EeFf x EeFf, what phenotypic ratios in offspring? FIRST SEPARATE THE GENES… E e EE Ee Ee ee E e F f FF Ff Ff ff F f Then do separate Punett squares…
  • 61. E e EE Ee Ee ee E e F f FF Ff Ff ff F f INDEPENDENT TERMS E_F_ = double dom. = 3/4 x 3/4 = 9/16 eeF_ = 1 rec, 1 dom = 1/4 x 3/4 = 3/16 E_ff = 1 dom, 1 rec = 3/4 x 1/4 = 3/16 eeff = double rec. = 1/4 x 1/4 = 1/16 9:3:3:1 9+3+3+1=16 Remember that UPPER CASE TRAIT IS DOMINANT FOR PHENOTYPE!!! NOW COUNT THE PHENOTYPES!!!
  • 62. Simple Mendelian inheritance Monohybrid and dihybrid crosses • Dihybrid cross (2 genes) - Example problem: - Imagine you mate a person who has attached earlobes and a smooth hairline with a person who is heterozygous for both genes. What is the probability of them having a child with unattached earlobes and a widow's peak hairline? - Step 1: Convert to letters - Parent 1 = attached, smooth  eeff - Parent 2 = EeFf - ? offspring = E_F_ (2nd letter for each doesn't matter) e e Ee Ee ee ee E e f f Ff Ff ff ff F f - Step 2: Do two Punett squares - Split up the E's from the F's - Step 3: Do the math - Multiply the individual probabilities - E_F_ = 1/2 x 1/2 = 1/4