Download 5. Gene350 Animal Genetics 3 August 2009

Gene350 Animal Genetics
Lecture 5
3 August 2009
Last Time
• Study chromosomes
– The normal karyotypes of animals
– Chromosomal abnormalities
– Chromosomal abnormalities of animals
Today
• Pedigree analysis
 How to read pedigrees
 Basic patterns of inheritance
• autosomal, recessive
• autosomal, dominant
• X-linked, recessive
• X-linked, dominant (very rare)
 Applying pedigree analysis - practice
 Extensions of Mendelian inheritance
Goal: understand the diversity of
genotype =>phenotype relationships

Pedigree analysis
Goal: recognize and predict pedigrees for four common patterns of trait
inheritance
Pedigree analysis
 In humans and many animals, pedigree
analysis is an important tool for studying
inherited diseases and other traits
 Pedigree analysis uses family trees and
information about affected individuals to:
 figure out the genetic basis of a disease or trait from its
inheritance pattern
 predict the risk of disease in future offspring in a family
(genetic counseling)
Most common
signs and
symbols used in
pedigree
analysis
Categories of inheritance
• Autosomal recessive
– e.g., PKU, Tay-Sachs, albinism
• Autosomal dominant
– e.g., Huntington’s Disease
• X-linked recessive
– e.g., color-blindness, hemophilia
• X-linked dominant
– e.g., hypophosphatemia
• Y-linked
• Organelle
Autosomal recessive inheritance in
pedigrees
An autosomal recessive disorder is
revealed by the appearance of the
phenotype in both male and female
progeny of unaffected individuals, who
may be inferred to be heterozygous
carriers
Autosomal recessive traits
• Trait is rare in pedigree
• Trait often skips
generations (hidden in
heterozygous carriers)
• Trait affects males and
females equally
Sample pedigree - cystic fibrosis
male
female
affected individuals
Autosomal dominant disorders
Autosomal dominant (AD) disorders are those in which both heterozygotes
and homozygous dominant individuals show the abnormal phenotype.
One copy of the mutant gene is sufficient for expression of the abnormal
phenotype = haplo-insufficiency
(Note: In fact, in some AD diseases the homozygous genotype is
incompatible with life)
Autosomal dominant pedigrees
• Trait is common in the pedigree
• Trait is found in every generation
• Affected individuals transmit the trait to ~1/2 of
their progen (regardless of sex)
Characteristics of pedigrees for AD disorders:
- Every individual developing the disease must have an affected parent
(except in cases of de novo mutations)
- Males and females are equally likely to inherit the allele and be affected
(autosomal disorder)
- Recurrence risk (the probability that a genetic disorder that is present in
a patient will recur in another member of the family) for each child of an
affected parent is 1⁄2. If one parent is a heterozygote for a particular
gene, their offspring will either inherit the gene or they will not, with each
outcome equally likely.
- Normal siblings of affected individuals cannot pass the trait on to their
offspring. If an affected individual’s siblings are not affected, they do not
carry the mutation and cannot pass it on to their own offspring (thus a
dominant mutant allele should be lost rapidly from the population if it
affects greatly the fitness of the carrier).
Autosomal recessive diseases in humans
& animals
• For each of these, overdominance
(heterozygote superiority) has been suggested
as a factor in maintaining the disease alleles at
high frequency in some populations
X-linked recessive disorders
are characterized by the following pedigree pattern:
(1) Many more males than females develop the disease (ie. show
the phenotype)
(2) None of the offspring of an affected male are affected, but all of
its daughters must be heterozygous carriers (half the sons born to
these carrier daughters are affected)
X-linked recessive pedigrees
• Trait is rare in pedigree
• Trait skips generations
• Affected fathers DO NOT
pass to their sons
• Males are more often
affected than females
X-linked recessive traits
ex. Hemophilia in European royalty
X-linked dominant disorders
are characterized by the following pedigree pattern:
(1) Affected males pass the condition on to all their
daughters but none of their sons (unlike dominant autosomal
disorders where daugthers and sons have an equal
probability to inherit the disease)
(2) Affected females are mostly heterozygotes. When mated to
unaffected males, they pass the condition on to 1/2 of their
sons and 1/2 of their daughters (same pattern than for
autosomal dominant disorder)
Note: X-linked dominant disorder are rare traits in human
and animals (ex: hypophosphatemia: low levels of inorganic
phosphate in the blood.) Diagnose is complicated by the process
of X inactivation in females.
X-linked dominant diseases
• X-linked dominant diseases are extremely unusual
• Often, they are lethal (before birth) in males and
only seen in females
ex. incontinentia pigmenti (skin lesions)
ex. X-linked rickets (bone lesions)
X-linked dominant pedigrees
• Trait is common in pedigree
• Affected fathers pass to ALL of their daughters
• Males and females are equally likely to be affected
Organelle inheritance
• Mitochondria and chloroplasts
– small number of genes on circular chromosome
– mostly inherited through maternal lineage via
egg cytoplasm
• Examples
– white green variegation in plants
– poky mutant in Neurospora
– Maternal inheritance also shown to primarily
occur in humans and animals but some
controversy on possible paternal contributions as
well (and possible recombination between
maternal and paternal mitochondrial genomes)
Pedigree Analysis in real life
Remember:
• dominant traits may be rare in populations
• recessive traits may be common in populations
• alleles may come into the pedigree from 2 sources
• mutation and migration
• often traits are more complex
• affected by environment & other genes
Strategy for
interpreting
pedigrees:
systematically
rule out each of
the options
Based on this pedigree, how is cystic fibrosis
inherited?
(a) Autosomal dominant
(b) Autosomal recessive
(c) X-linked dominant
(d) X-linked recessive
Based on this pedigree, how is cystic fibrosis
inherited?
(a) Autosomal dominant
(b) Autosomal recessive
(c) X-linked dominant
(d) X-linked recessive
Based on this pedigree, how is this trait inherited?
(a) Autosomal dominant
(b) Autosomal recessive
(c) X-linked dominant
(d) X-linked recessive
(e) Can’t tell with info provided.
Based on this pedigree, how is this trait inherited?
(a) Autosomal dominant
(b) Autosomal recessive
(c) X-linked dominant
(d) X-linked recessive
(e) Can’t tell with info provided.
Based on this pedigree, how is this trait inherited?
(a) Autosomal dominant
(b) Autosomal recessive
(c) X-linked dominant
(d) X-linked recessive
(e) Can’t tell with information provided.
Based on this pedigree, how is this trait inherited?
(a) Autosomal dominant
(b) Autosomal recessive
(c) X-linked dominant
(d) X-linked recessive
(e) Can’t tell with information provided.
Based on this pedigree, how is this trait inherited?
(a) Autosomal dominant
(b) Autosomal recessive
(c) X-linked dominant
(d) X-linked recessive
(e) Can’t tell with information provided.
Based on this pedigree, how is this trait inherited?
(a) Autosomal dominant
(b) Autosomal recessive
(c) X-linked dominant
(d) X-linked recessive
(e) Can’t tell with information provided.
Pedigree Analysis in real life: complications
Sex-limited expression
=> trait only found in males OR females