Genetic Analysis in Humans Flashcards
Problems of genetic analysis in humans
- Can’t do controlled mating
- Few progeny
- Long generation time
- Few useful single gene variants
- Analysis based on pedigrees (family trees)
Symbols used in pedigree
Squares - Male
Circle - Female
Shaded- Affected
Not shaded - Not affected
Diamond - Sex unknown
Line between shapes - Marriage
Two lines between shapes - Consanguineous marriage
Lines through shape - Dead
Vertical line - Offspring
Consanguineous relationships
Same allele inherited from same ancestor which can result in increased frequency of genetic disorders
Don’t assume single gene disorder
Chromosomal defect (rearrangement or aneuploidy – later lecture)
Not inherited (not all congenital disorders are genetic disorders)
Multifactorial (several genes involved – later lecture)
Mitochondrial
Mitochondrial inheritance
Material inheritance - all children of affected mothers are affected e.g. some forms of Leigh’s disease - movement disorder
Often severe
Males typically more often affected, but not always
Penetrance
The proportion of people with the relevant genotype who show the character
Expressivity
Degree to which an individual with the relevant genotype displays the characteristics of a condition
Variable expressivity in neurofibromatosis (NF1, or von Recklinghausen)
Mild - cafe au lait patches
Moderate - Small neurofibromas
Severe - Large neurofibromas
Identifying disease genes by mapping
- Pedigree analysis to identify mode of inheritance
- Recombination mapping using molecular markers (VNTRs/STRs)
Haplotype analysis
Identify small set of candidate genes
Identify mutation(s) by sequencing of exons
LOD scores
-Measure of probability of linkage between disease gene and marker in a given pedigree - affected by allele frequency
Logarithm of odds ratio (concordance:non-concordance of phenotype with marker allele)
Z>3: likely to be linked (1/1000 likelihood that data is due to chance, not linkage)
Z< -2: unlikely to be linked
Used in GWAS
