Mendelian Inheritance and Pedigree Analysis Flashcards
Mendelian patterns of inheritance
Autosomal dominant
Autosomal recessive
X-linked
Non-mendelian patterns of inheritance
Mitochondrial
Mosaic
Imprinted
Uniparental disomy
Autosomal trait
On one of the 22 pairs of non-sex chromosome
X-linked trait
on the x chromosome
Holandric trait
on the y chromosome
Sex-limited trait
only manifests in 1 sex
Penetrance
proportion of people with a particular allele (genotype) who manifest the trait (phenotype)
Expressivity
Severity-how present is the trait?
Locus
the site on a chromosome where a gene is located
Alleles
alternate forms of a gene at a particular locus; most genes have two alleles, one on each chromosome (except genes on sex chromosomes)
Homozygous
both alleles the same
Heterozygous
two alleles different
Mendel’s first law
Independent segregation: transmission of each allele to offspring with equal frequency
Mendel’s second law
Independent assortment: transmission of an allele at one locus is independent of transmission of alleles at other loci
Why is assortment independent?
Meiotic recombination
Pedigree symbols
- F = circle
- M = square
Autosomal recessive traits
- Expressed only when both alleles are for trait (homozygous)
- “horizontal transmission” = many cases in one generation while family history negative
- M and F affected equally
- 25% risk in child from heterozygous parents
How are carriers of autosomal recessive alleles identified?
Level of gene product (gene dosage) is half normal
Describe the relationship between gene dosage and phenotype in autosomal recessive disorders.
- Heterozygotes have no clinical phenotype; level of gene product is not highly critical
- Homozygotes have complete enzyme deficiency and thus phenotype
Examples of autosomal recessive disorders
- Hemoglobinopathies
- Tay-sachs
- CF
- Gaucher
- PKU
- Galactosemia
- Oculocutaneous albinism
- Infantile polycystic kidney disease
- Hurler
Autosomal dominant traits
- Expressed when only 1 allele is for a trait (heterozygotes have phenotype)
- “vertical” transmission: anyone with the trait has a parent with the trait
- M and F equally affected
- 50% risk in child with affected parent
- if neither parent affected, child can have trait due to new mutation
Examples of autosomal dominant disorders
- Marfan
- Neurofibromatosis
- Adult-type polycystic kidney disease
- Apert syndrome
- Osteogenesis imperfecta
- Achondroplasia
- Huntington
Codominant traits
- Traits determined by both alleles expressed (neither dominant)
- Ex: ABO blood types
X-linked recessive traits
- Usually in M (recessive, and F have two X’s)
- If mother carrier: 50% daughters carriers and 50% sons affected
- If father carrier: daughters all carriers and no sons affected
X-linked recessive disorders
- Red-green colorblindness
- G6PD deficiency
- Hemophilia
- Fragile-X
- Duchenne muscular dystrophy
X-linked dominant traits
- Expressed in M and F
- No father -> son transmission
- Mother with trait: 50% of sons and daughters with trait
- Father with trait: all daughters affected, no sons affected
Gene dosage and autosomal recessive disorders
- If one allele is defective (heterozygosity), half normal amount of gene product made
- For most enzymes half is enough => homozygosity leads to disease
Hemizygosity
- Males have only one X chromosome and thus only 1 allele
- Defect in this one allele can produce disease
Lyonization
- Inactivation of one X chromosome in each cell early in development
Allelic mosaicism
- Different cells express different X alleles in females as a result of lyonization
- Females may be heterozygous overall but allelic expression is mosaic by cell or tissue
Gene codominance
- Two alleles (WT and mutant) often expressed equally.
- Genes are not dominant or recessive! Phenotypes are
Genetic fitness
- Capacity to procreate and pass on genes
- Requires survival to reproductive age
Reconcile fitness and the presence of childhood lethal genetic disorders over generations.
- Recessive: asymptomatic carriers “fit”
- Dominant: occur due to new mutations
Autosomal dominant disorders and genes prone to recurrent mutations
- Type 1 Collagen => osteogenesis imperfecta
- Neurofibromin => neurofibromatosis
- FGFR3 => achondroplasia (mutation risk increases with increased paternal age)
Haldane rule
- Gene frequency for lethal x-linked disorders is stable because of new mutations which account for 1/3 of all new cases
- Otherwise, we’d expect frequency to decrease over generations as affected males “aren’t fit”
Linkage analysis
Used to trace inheritance of a trait or disease by presence of a linked trait
