Alternative variant of a gene
segment of DNA occupying a particular position or location on a chromosome
common or prevailing allele; present in the majority of individuals
Define variant or mutant allele
allele that differs from the wild-type
permanent change in the DNA sequence
a set of alleles at a locus or
a cluster of loci on a chromosome
When two or more alleles are relatively common
the set of alleles that make up a person’s genetic constitution
the observable expression of a genotype as a morphological, clinical, cellular or biochemical trait
A single abnormal gene or gene pair that produces multiple diverse phenotypic effects
e.g. which organ systems are involved, signs / symptoms of a disease, when signs / symptoms occur
Define Single Gene Disorder
disorder determined primarily by the alleles at a single locus
- compound heterozygote
- pair of identical alleles at a locus
- different alleles at a locus
- two different mutant alleles at a locus
- only one copy of a gene (e.g. an abnormal gene on X in an XY male)
What’s up with mitrochondrial DNA?
mitochondrial DNA (and the genes they encode for) are present in tens to thousands of copies per cell.
What is a proband?
individual of interest in a pedigree
also: propositus or index case
Define fitness in regards to a pedigree
measure of the impact of a condition on reproduction
the number of offspring an affected individual can have who survive to reproductive age
Hemophilia A and B are _______ disorders caused by mutations in which genes?
F8 and F9 respectively
Racial predilection of hemophilia?
Which is more rare, Hemophilia A or B?
B, 1 in 100,000
A, 1 in 10,000
What is the most common mutation in clotting factor VIII ?
intrachromosomal recombination between sequences in intron 22 of F8 and homologous sequences telomeric to F8
results in an inversion deleting the carboxyl terminus of VIII (the clotting protein)
Diagram how factors 8, 9 and 10 interact in the clotting cascade.
F8 & F9 complex
Active F10 activates more F8 & F9
Factor IX functions as a _________ and factor VIII functions as a _________.
What is the common mutation in Factor 9?
Many different mutations identified, but no most common mutation has been identified.
bleeding into joint spaces
Though rare, what is the genetic mechanism that could cause females to have hemophilia?
skewed X chromosome inactivation
What is the only current curative treatment for hemophilia A or B?
How are hemophilia A and B diagnosed and distinguished?
measurement of activity levels of factor VIII and IX
What is the (non-curative) standard of care for hemophilia and the current life expectancy?
Intravenous replacement of the deficient factor
65 years of age
When do most point mutations and the common F8 inversion mutation occur?
During male meiosis
When do deletion mutations for hemophilia usually occur?
During female meiosis
- Mendel’s Law of Segregation?
2. Mendel’s Law of Independent Assortment?
- Alleles segregate at meiosis into gametes.
2. The segregation of each pair of alleles is independent.