Michael R. Cummings
Chapter 4
Pedigree Analysis in
Human Genetics
David Reisman • University of South Carolina
Aborted or stillborn
offspring
Male
Female
Deceased offspring
Mating
Mating between relatives
(consanguineous)
I
II
1
2
3
Parents and children.
Roman numerals symbolize
generations. Arabic
numbers symbolize birth
order within generation
(boy, girl, boy)
P
Monozygotic twins
or
Unaffected individual
or
Affected individual
or
Proband; first case in
family that was identified
P
or
Known heterozygotes
Dizygotic twins
Carrier of X-linked
recessive trait
Offspring of unknown sex
Infertility
Fig. 3-16, p. 60
Human Pedigrees
Ancestry.com—beware this can be addictive!
Patterns of Inheritance
 Patterns in the pedigree are used to determine how
a trait is inherited
•
•
•
•
•
•
Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive
Y-linked
Mitochondrial inheritance
4.2 Autosomal Recessive Traits
 Characteristics of autosomal recessive traits
• For rare traits, most affected individuals have
unaffected parents
• All children of affected parents are affected
• The risk of an affected child with heterozygous
parents is 25%
• The trait is expressed in both males and females
4.2 Autosomal Recessive Pedigree
Example of an Autosomal Recessive Trait :
Cystic Fibrosis
 Cystic fibrosis: A fatal recessive genetic disorder
associated with abnormal secretions of the exocrine
glands
 1 in 25 Americans of European descent
 1 in 46 Americans of Hispanic descent
 1 in 65 African Americans
 1 in 250 Asian Americans
Cystic Fibrosis Gene Product (CTRF)
 The CFTR gene was identified in 1989
 CFTR protein controls the movement of chloride ions
across the plasma membrane
 Water moves from the outside of the cell to the
inside
 In lung cells, this makes the mucus very thick
Exploring Genetics::
 Noah’s “flesh was white as snow”
• From the Book of Enoch the Prophet
 Phenotype: Lack of pigmentation
 Albinism is inherited as an autosomal recessive trait
 From chapter 1—old paintings and historical texts
described birth defects that were inherited
4.3 Autosomal Dominant Traits
 Characteristics of autosomal dominant traits
• Heterozygotes exhibit the phenotype
• Every affected individual has at least one affected
parent (except in traits with high mutation rates)
• Two affected individuals can have an unaffected child
• Usually an affected family member in each generation
4.3 Autosomal Dominant Pedigree
Example of an Autosomal Dominant Trait:
Marfan Syndrome
 Marfan syndrome
• An autosomal dominant genetic disorder that
affects the skeletal system, cardiovascular
system, and eyes
• Individuals are tall, thin, long arms and legs. Thin
fingers
• Heart defects
• Abraham Lincoln?????
4.4 Sex Linked Inheritance
 Genes on sex chromosomes have a distinct pattern
of inheritance
 X-linked
• When a gene for a particular trait is located on the X
chromosome
 Y-linked
• Pattern of inheritance that results from genes located
only on the Y chromosome
For sex-linked traits males are Hemizygous
 Hemizygous
• Refers to males when the gene for a trait is on the Xor Y- chromosome.
• Since males have just one X-chromosome, and one
Y-chromosome, they will express whatever allele is
present—the recessive or dominant
Fig. 4-10, p. 79
X-Linked Dominant Traits
 Quite rare inheritance pattern (only 3 known)
 Affected males produce all affected daughters and
no affected sons
 A heterozygous affected female will transmit the trait
to half of her children
• Sons and daughters are equally affected
(e.g., vitamin D resistant rickets)
X-Linked Recessive Traits
 X-linked recessive traits affect males more than
females because males are hemizygous for genes
on the X chromosome
 Color blindness
• Defective color vision caused by reduction or absence
of visual pigments
• Three forms: red, green, and blue blindness
• About 8% of the male population in the US affected
Testing For Color Blindness
 People with normal color vision see the number 29
in the chart; those who are color-blind cannot see
the number
Fig. 4-14, p. 81
X-linked recessive trait Punnett square
Pause the presentation and try to answer these
questions.
A woman who is heterozygous for color-blindness is
expecting a child. The father had normal vision.
What is the probability that, if female, the child will
be color-blind? What about the probability for a
male child?
X-linked recessive trait Punnett square
XC
Y
XC
XCXC
XCY
Xc
XCXc
XcY
Zero probability the baby, if female will be color-blind, but there
is a 50% chance she will be a carrier. And there is a 50%
chance that, if male, he will be color-blind.
Example of an X-linked Recessive Trait:
Muscular Dystrophy
 Muscular dystrophy
• A group of genetic diseases associated with
progressive degeneration of muscle tissue
• Duchenne and Becker muscular dystrophy are
inherited as X-linked recessive traits
• Duchenne muscular dystrophy (DMD) affects 1 in
3,500 males in the US
4.5 Paternal Inheritance: Y Chromosome
 Only males have Y chromosomes
• Genes on the Y chromosome are passed directly from
father to son
 All Y-linked genes are expressed
• Males are hemizygous for genes on the Y
chromosome
 To date only 36 Y-linked traits have been identified
4.6 Non-Mendelian Maternal Inheritance:
Mitochondrial Genes
 Mitochondria
• Cytoplasmic organelles that convert energy from food
into ATP (ATP powers cellular functions)
• Have their own DNA that codes 37 mitochondrial
genes
 Genetic disorders in mitochondrial DNA are
associated with defects in energy conversion
Mitochondrial Inheritance
 Mitochondria (and genetic disorders caused by
mutations in mitochondrial genes) are maternally
inherited
 Mitochondria are transmitted from mothers to all
their offspring through the cytoplasm of the egg
4.7 An Online Catalog of Human Genetic
Traits
 OMIM
• Genetic traits are described, cataloged, and
numbered in a database called Online Mendelian
Inheritance in Man
• OMIM is updated daily and contains information about
all known human genetic traits
• Each trait is assigned an OMIM number
• There are more that 10,000 entries
• **Chapter 4 Web Assignment on OMIM (See the
course site for week 2 assignments.)
Fig. 4-20, p. 86
4.8 Many Factors can Affect the Pattern of
Inheritance
 Variations in gene expression affect pedigree
analysis and assignment of genotypes to members
of the pedigree
 Several factors can affect gene expression
• Interactions with other genes
• Interactions between genes and the environment
4.8 Many Factors can Affect the Pattern of
Inheritance
 Phenotypes are often age related (onset of
symptoms occurs in adulthood)
• Example: Huntington disease
 Penetrance and expressivity cause variations in
phenotype
• Penetrance: the probability the the phenotype will
appear
• Expressivity: The range of phenotypes from a given
genotype
Penetrance and Expressivity
Baby Born In Bay Area With 12 Functioning Fingers, 12 Toes
Posted: 6:07 pm PST January 30, 2009Updated: 2:25 pm PST November
13, 2009
DALY CITY, Calif. -- A Daly City couple is beaming after becoming the proud
parents of a healthy but incredibly rare baby boy this month.
Baby Kamani Hubbard has six-fully formed and functional fingers and toes
on his hands and feet. It's called "polydactyly" -- extra digits -- not an
uncommon genetic trait, but Bay Area doctors say they've never seen a
case so remarkable.
Born at San Francisco's Saint Luke's Hospital three weeks ago, Hubbarb
seemed so perfect at birth no one noticed.
(Polydactyly is an autosomal dominant trait that was in the father’s family.)