Linkage, Association & Mapping Of Disease Genes Flashcards
How was sickle cell anaemia discovered
Funcional cloning
Define bivalent
Homologous chromosomes held together in early prophase I- bound tightly together and in perfect alignment by a protein lattice called a synaptonemal complex
What affects the chance that two loci will be inherited together
-distance between the two loci
-recombination frequency
Outline the measure of linkage
-Unit of measurement is the centimorgan (cM)
-1cM equates to approx 1000kb of genome
What is a haplotype
A series of genetic variants that tend to be inherited together
Outline limitations of linkage analysis
-used in family studies, where only 1/2 recombinations occur per meiosis per chromosome
-recombination breaks down the link between alleles at different loci in populations over many generations
Outline association tests
-based on linkage disequilibrium
-dense markers required
-markers need to be very close to causative variant
-higher resolution
-identifies genetic variants associated with disease
Define linkage disequilibrium
Measures whether alleles occur together more frequently than expected in a population
Outline association testing for dichotomous traits
Compare frequency of alleles in cases vs controls
Outline association testing for quantitative traits
Compare the mean trait value for each genotype
Outline TAG SNPs
One SNP that is genotyped to capture information about a whole haplotype block, capture variation across the whole genome
Outline genome-wide association testing
-gene chips are used, able to genotype 0.5 mil SNPs from an induvidual at once
-Tag SNPs are selected to tag haplotype, after genotyping allele frequencies are compared at each SNP
How is the genome-wide association study displayed
Manhattan plot
Outline linkage analysis
-based on recombination
-family data
-few markers required
-can find disease loci located ‘far’ from marker
-low resolution
-identify mutations that cause the disease
How do association tests work
Disease causing mutations can be mapped by finding marker polymorphisms that are associated with the disease trait more often than you would expect in the general population
