Linkage Flashcards
What is linkage?
The tendency of genes on the same chromosome to segregate/be inherited together.
True or false: in order to use linked markers to assess the risk of affected/carrier child, you must first clone the gene.
False: The CF gene was not yet identified when the linkage diagnostic tests were developed.
True or false: Theta represents the recombination frequency as a proportion, not a percentage, and Theta=0.5 means there was independent assortment of the genes (i.e. they are not linked).
True
What do cis and trans phases refer to?
Cis (coupling) is if alleles are on the same chromosome. Trans (repulsion) is if they are on different chromosomes.
What is LOD?
Log of the Odds. It provides an estimate of recombination frequency between two markers and an assessment of how strong the evidence for linkage is. LOD>0 at a given theta suggests linkage; LOD3 is strong evidence for linkage.
What is linkage equilibrium?
Occurrence of specific combinations of alleles in cis at two or more loci at a frequency equal to the frequency of the respective allele in the population.
True or false: With time, the region of linkage disequilibrium around a new mutation increases as subsequent meioses recombine the DNA.
False: as subsequent meioses recombine the DNA, the region of linkage disequilibrium around (what was once) a new mutation decreases (i.e. recombination between the mutated segment and its neighboring loci gets closer and closer to the mutated segment).
What determines the rate at which loci reach linkage equilibrium?
Recombination frequency… if Rf is low, then the two loci will remain linked (in cis) at a frequency unequal to the frequency of each allele in the population.
What two criteria must be met in order for individuals affected by linkage disequilibrium to have the same marker allele?
The mutation origin was in a founding individual and the mutation is recent in origin.
What is a haplotype map?
Linkage disequilibrium map of millions of single nucleotide polymorphisms (SNPs) across four distinct populations: European, W. African, Han Chinese, Japanese.
What percent of SNPs on a haplotype map are in rough linkage equilibrium?
90%
What are clusters of SNPs in linkage disequilibrium on a haplotype map called?
LD blocks
True or false: Haplotype mapping helped us to determine that rates or recombination are NOT as uniform as was once thought (vary from 0.01 cM/Mb to 60 cM/Mb).
True
What is haplotype?
A group of alleles in cis at closely linked loci; inherited as a unit. (i.e. a group of linked genes).
How can you use a HapMap and linkage disequilibrium to determine where a disease gene is?
Scan the HapMap for SNPs that are associated with families having a disease. Finding an LD block associated with these affected individuals suggests the gene is somewhere in that LD block region of the chromosome. The SNPs within an LD block that are in the most linkage disequilibrium are likely closest to the disease-causing gene.
