Reading Notes

Chapter 6- Pedigree Analysis, Applications, and Genetic Testing

Three important techniques used by geneticists to investigate human genetic characteristics:

1. Pedigrees
2. Twin studies
3. Adoption studies

Analysis of Pedigrees

A pedigree is a pictorial representation of a family history, essentially a family tree that outlines
the inheritance of one or more characteristics

When a particular characteristic or disease is observed in a person, a geneticist often studies

the family of that affected person by drawing a pedigree
Autosomal Recessive Traits

Normally appear with equal frequency in both sexes and appear only when a person inherits
two alleles for that trait, one from each parent

If the trait is uncommon, most parents of affected offspring are heterozygous an unaffected;
consequently, the trait skips generations

When an affected person mates with someone outside the family (aa x AA), usually none of the
children display the trait, although all will be carriers (heterozygous)

A recessive trait is more likely to appear in a pedigree when two people within the same family
mate because there is a greater chance of both parents carrying the same recessive allele

Consanguinity- mating between closely related people

A number of human metabolic diseases are inherited as autosomal recessive traits

Autosomal Dominant Traits

Appear in both sexes with equal frequency, and both sexes are capable of transmitting these
traits to their offspring

Every person with a dominant trait must have inherited the allele from at least one parent;
therefore, it does not skip generations

If an autosomal dominant allele is rare, most people displaying the trait are heterozygous.
When one parent is affected and heterozygous and the other parent is unaffected,
approximately half of the offspring will be affected

If both parents have the trait and are heterozygous, approximately ¾ will be affected.
Unaffected people do not transmit the trait to their descendants, provided that the trait is fully
penetrant

One condition that is usually considered to be autosomal dominant is familial

hypercholesterolemia
X-Linked Recessive Traits

They have a distinctive pattern of inheritance. First, these traits appear more frequently in
males than in females because males need to inherit only a single copy of the allele to display
the trait, whereas females must inherit two copies of the allele

Cannot be passed from father to son

Because a male inherits his X chromosome from his mother, affected males are usually born to
unaffected mothers who carry an allele for the trait. It is passed from unaffected female to
affected male to unaffected female (it skips generations)

Individuals whose heterozygous genotype can be definitively determined from the pedigree are
called obligate carriers

When a woman displays an X-linked recessive trait, she must be homozygous for the trait, and
all of her sons will also display the trait

X-Linked Dominant Traits

They appear in both males and females, although they often appear more frequently in females

Each person with an X-linked dominant trait must have an affected parent. It does not skip
generations

Affected men pass the trait to all their daughters and none of their sons (because sons get their
X from their mother)

Affected women pass the trait to about half of their sons and half of their daughters

Y-Linked Traits

Exhibit a specific, easily recognized pattern of inheritance. Only males are affected, and the trait
is passed from father to son

If a man is affected, all his male offspring should also be affected. It does not skip generations.
However, little genetic information is found on the human Y chromosome

There is only one copy of the Y chromosome: therefore, Y-linked traits are neither dominant
nor recessive
Summary
Genetic Mosaicism

Condition in which regions of tissue within a single individual have different chromosome
constitutions

Often, somatic mutations or errors in the separation of chromosomes during early

development lead to genetically distinct groups of cells within the body. There can also be
exchanges of cells and DNA between twins or between mother and child during pregnancy

Studying Twins and Adoptions

Provide natural experiments for separating the effects of genes and environmental factors on
differences in trait

Types of Twins
o Dizygotic: non-identical twins arise when two separate eggs are fertilized by two
different sperm, producing genetically distinct zygotes. Share about 50% of their genes,
which is the same percentage that any pair of siblings share
o Monozygotic- identical twins result when a single egg, fertilized by a single sperm, splits
in development in two separate embryos. They are genetically identical and share 100%
of their genes

Concordance in Twins
If both members of a twin pair have a trait, the twins are said to be concordant; if only one
member of the pair has the trait, the twins are said to be discordant

Concordance: the percentage of twin pairs that are concordant for a trait. Because identical
twins share 100% of their genes and dizygotic twins share only 50%, genetically influenced
traits should exhibit higher concordance in monozygotic twins

Example: when one member of a monozygotic twin pair has epilepsy, the other twin of the pair
has epilepsy about 59% of the time; thus, monozygotic concordance for epilepsy is 59%

When a dizygotic twin has epilepsy, however, the other twin has epilepsy only 19% of the time
(19% dizygotic concordance)

The higher concordance in monozygotic twins suggests that genes influence epilepsy

Any discordance between monozygotic twins is usually due to environmental factors because
monozygotic twins are genetically identical
Adoption Studies

If adoptees and their adoptive parents show similarities in a characteristic, these similarities can
be attributed to environmental factors. If, on the other hand, adoptees and their biological
parents show similarities, these are due to genetic factors

Genetic Counseling and Genetic Testing

Genetic counseling provides information to patients with genetic disorders and other who are
concerned about hereditary conditions. It is an educational process that helps patients and
family members deal with many aspects of having a genetic condition

Genetic testing recognizes the potential for a genetic condition at an early age. It allows people
to make informed choices about reproduction. In other cases, genetic testing allows early
intervention that may lessen or even prevent the development of a condition

Prenatal Genetic Testing: include procedures for diagnosing several hundred genetic diseases
and disorders. The major purpose of prenatal tests is to provide families with the information
that they need to make choices during pregnancies and prepare for the birth of a child with a
genetic condition
o Ultrasonography (ultrasound)
o Amniocentesis- procedure for obtaining a sample of amniotic fluid from the uterus.
Amniotic fluid is a substance that fills the amniotic sac and surrounds the developing
fetus- contains fetal cells that can be cultured and used for genetic testing
o Chorionic Villus Sampling (CVS)- can be performed earlier (10th to 12th week) and
collects a larger amount of fetal tissue, which eliminates the need for culturing the cells
o Maternal Blood Screening Tests- these tests do not determine the presence of a genetic
problem; rather, they simply indicate that the fetus is at increased risk of a problem
o Preimplantation Genetic Diagnosis (PGD)- implantation of an embryo without a genetic
disorder into the mother’s uterus

Newborn Screening- all states in the US and many other countries require by law that newborn
infants be tested for some genetic diseases and conditions. These genetic conditions were
chosen because early identification can be to effective treatment. For example,
phenylketonuria is an autosomal recessive disease that, if not treated at an early age, can result
in intellectual disability. But early intervention, through a modified diet prevents this outcome

Heterozygote Screening- members of a population are tested to identify heterozygous carriers

of a disease-causing allele who are healthy but have the potential to produce children who
have the disease
Interpreting Genetic Tests

Some genetic diseases can be caused by any different mutations. For example, more than a
thousand different mutations at a single locus can cause cystic fibrosis.

Genetic tests typically screen for only the most common mutations; uncommon and rare
mutations are not detected. Therefore, a negative result does not mean that a genetic defect is
absent

For many genetic diseases for which penetrance is incomplete only elevates a person’s risk of
acquiring the disease. In this case, it provides little useful information to a specific person