23: Genetic Inheritance Flashcards
Proband
First person diagnosed in a pedigree (propositus)
Recurrence risk of an autosomal dominant trait
50%
Offspring percentages when two carriers of an autosomal recessive trait mate
25% unaffected
50% carrier
25% affected
Diseased allele on X in males is called what?
Hemiazygos
Two ways females can have an X-liked recessive trait
- Homozygous for the trait (XX)
2. Lyonization occurs
Five examples of X-linked dominant traits
- Vitamin D resistant rickets
- Alport syndrome
- Incontinentia pigmenti
- Fragile X Syndrome
- Rett Syndrome
Structure of mito DNA
Double stranded, circular
Where does mito DNA transcription occur?
In mito, independent of nucleus
Introns in mito DNA
There are none
Mutations in mito DNA
10x higher rate than nDNA, with no DNA damage repair mechanisms
Mutational load (in terms of mito diseases)
The threshold of diseased mito needed to cause symptoms
Euploidy
Cells with normal number of chromosomes
Polyploidy
Cells contain a complete set of extra chromosomes in a cell (not compatible with human life)
Aneuploidy
Cells contain missing or additional individual chromosomes (monosomy, trisomy)
Nondisjunction
Abnormal separation of 1+ pairs of homologous chromosomes or sister chromatids
Nondisjunction in germline mutation vs somatic fetal mutation
Germline: during meiosis: transmissible to next generation
Somatic mutation during fetal mitosis: individual will exhibit mosaicism
Uniparental disomy (UPD)
Individual receives two copies of a chromosome (or part of chromosome) from one parent, and no copies from the other parent
Effect of UPD
Usually no effect since most genes are not imprinted, but may result in a lack of active copies for imprinted genes
Genomic imprinting
Some genes have one allele transcriptionally inactivated/methylated
About how many human genes are known to be imprinted?
About 100 (mostly found in clusters)
Do epigenetic imprints get passed on?
No, they only last the lifetime of that somatic cell
Reciprocal vs Robertsonian translocations
Reciprocal: exchange of material between non-homologous chromosomes
Robertsonian: long arm of two acrocentric chromosomes combine, short arm is lost
Two things gene frequencies specify
- Proportion of each allele in a population
2. Proportion of each genotype in a population
How to measure gene frequency under simple conditions and assumptions
Direct counting
Hardy-Weinberg Equation
P^2 + 2pq +q^2 = 1
What is Hardy Weinberg used for?
Estimating gene frequency using disease prevalence data
Polygenic trait
Traits in which variations are thought to be caused by combined effects of multiple genes
Multifactorial traits
Environmental factors cause variation in traits
Distribution of multifactorial traits in society
Follow a bell shaped curve
Liability distribution
For multifactorial diseases that are either present or absent, a threshold of liability must be crossed for the disease to be expressed
Three ways recurrence risks for multifactorial diseases increase
- More than 1 family member affected
- Proband has a severe version of the disease
- Proband is of the less commonly affected sex
