Download Pedigree Analysis in Human Genetics

Patterns of Inheritance
Pedigree Analysis in
Human Genetics
Chapter 4
OMIM
!  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
Pedigrees
I
1
2
II
2
1
P
3
Pedigrees, cont.
Pedigrees, cont.
Male
or
or
Affected individual
or
Proband; first case in
family that was identified
Mating
I
II
1
2
3
Parents and children.
Roman numerals
symbolize generations.
Arabic numbers
symbolize birth order
within generation (boy,
girl, boy)
?
Dizygotic twins
Female
Mating between
relatives
(consanguineous)
?
Unaffected individual
P
P
or
Offspring of unknown sex
or
Questionable
whether individual
has trait
Asymptomatic/
presymptomatic
Aborted or stillborn offspring
Known heterozygotes
Carrier of X-linked
recessive trait
Deceased offspring
Infertility
Indicates date of death
Monozygotic twins
d. 1910 d. 1932
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%
Some Autosomal Recessive Traits
Pedigree: An Autosomal Recessive Trait
Example: Cystic Fibrosis
!  Cystic fibrosis
•  A fatal recessive genetic disorder associated with
abnormal secretions of the exocrine glands
The CF Gene and Organ Systems
Affected by Cystic Fibrosis
Cystic Fibrosis Gene Product
!  CFTR protein controls the movement of chloride
ions across the plasma membrane
Example: Sickle Cell Anemia
Autosomal Dominant Traits
!  Sickle cell anemia
•  An autosomal recessive disorder
•  Produces abnormal hemoglobin (blood transport
protein)
Some Autosomal Dominant Traits
!  Characteristics of autosomal dominant traits
•  Every affected individual has at least one affected
parent (except in traits with high mutation rates)
•  If an affected individual is heterozygous and has
an unaffected mate, each child has a 50% chance
of being affected
•  Two affected individuals can have an unaffected
child
Pedigree: An Autosomal Dominant Trait
Example: Marfan Syndrome
Aorta
!  Marfan syndrome
•  An autosomal dominant genetic
disorder that affects the skeletal
system, cardiovascular system,
and eyes
Vena
cava
Pulmonary
artery
Right
auricle
Area of
aorta
effected in
Marfan
syndrome
Right
auricle
Left
ventricle
Right
ventricle
Left
ventricle
Right
ventricle
Normal Heart
Marfan Syndrome
Flo Hyman
Sex Linked Traits
!  X-linked
•  Pattern of inheritance that results from genes
located on the X chromosome
!  Y-linked
•  Pattern of inheritance that results from genes
located only on the Y chromosome
Distribution of Sex Chromosomes
X and Y: Human Sex Chromosomes
Males Have Hemizygous Genes
!  Hemizygous
•  A gene present on the X chromosome that is
expressed in males in both the recessive and
dominant condition
X-Linked Dominant Traits
!  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
!  On average, twice as many daughters as sons
are affected
Pedigree: Hypophosphatemia
X-Linked Recessive Traits
!  X-linked recessive traits affect males more than
females because males are hemizygous for
genes on the X chromosome
Pedigree:
X-Linked Recessive Inheritance
X-Linked Recessive Inheritance
!  Affected males receive the mutant allele from
their mother and transmit it to all of their
daughters, but not to their sons
•  Daughters of affected males are usually
heterozygous
•  Sons of heterozygous females have a 50%
chance of being affected
Example: Color Blindness
!  Color blindness
•  Defective color vision caused by reduction or
absence of visual pigments
•  Three forms: red, green, and blue blindness
Testing For Color Blindness
Color Blindness: The Eye
!  Defects in cone
proteins cause color
blindness
Genetics in Society:
Duchenne Muscular Dystrophy
!  Dystrophin proteins that
normally stabilize the
muscle cells during
contraction are defective
•  Plasma membranes are
torn apart by muscle
contraction, causing
death of muscle tissue
Hemophilia and History
Paternal Inheritance: Y Chromosome
Some Genes on the 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
Pedigree: Y-Linked Traits
Some Mitochondrial Disorders
Mitochondrial Inheritance
Pedigree: 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
Age-Related Phenotypic Expression
!  Huntington disease
•  An autosomal dominant disorder associated with
progressive neural degeneration and dementia
•  Adult onset is followed by death in 10 to 15 years
!  Porphyria
•  An autosomal dominant disorder that leads to
intermittent attacks of pain and dementia
•  Symptoms first appear in adulthood
Porphyria variegata -Pleiotropy
King George III
Symptoms:
Red urine,
Abdominal pain,
Constipation,
Rapid pulse,
Stupor,
Delirium,
Convulsions,
Madness
Two Aspects of Phenotypic Variation
!  Penetrance
•  The probability that a disease phenotype will appear
when a disease-related genotype is present (e.g.
Polydactyly or Camptodactyly).
•  25% penetrance means that only 1/4 of the population
with the disease-related genotype show the phenotype.
!  Expressivity
Incomplete Penetrance
!  Camptodactyly
•  A dominant trait (immobile, bent little fingers) with
variable expression
one hand affected
no penetrance
•  The range of phenotypic variation associated with a
given phenotype (e.g. Camptodactyly: one hand or both
hands affected)
both hands affected