Linkage Analysis and the International HapMap Project Flashcards
When the causative gene of a genetic disease has not been identified, the next investigative step is to map the gene locus to a chromosomal region. For single - gene disorders w/ unknown pathophysiology, this mapping is usually accomplished by ____ to detect cosegregation of a trait w/ genomic markers of known location. This is often followed by ____ of candidate genes that are known from current human genome databases to be located within the defined linked chromosomal region.
family linkage studies; mutation screening
In practice, it is difficult to detect linkages using marker loci more than about 25 Mb apart & thus a linkage search of the genome (3280 Mb) requires at least ____ well - spaced polymorphic markers.
131
What are the genetic markers often used in linkage studies?
polymorphic microsatellite
single nucleotide polymorphism
T/F. Microsatellite are more useful for genome - wide disease association studies than SNP markers because of their high abundance, low mutation rate & the ease of high - throughput SNP genotyping.
False. SNPs>Microsatellites
In addition, if loci are very close together, then recombination between them is highly unlikely & alleles at such loci will pass together through the family. Such a tract of closely linked alleles is known as a ____.
haplotype
On account of ____, haplotype analysis can be clinically useful in an affected family in w/c a causative mutation has not yet been identified by predicting the presence or absence of an alteration in a closely associated disease gene.
linkage disequilibrium
_____ reflects the background pattern of adjacent DNA markers at the time the original mutation occurred: due to their proximity to the gene and hence lack of intervening recombination, adjacent markers will tend to remain in association as a ____.
Linkage disequilibrium; mutation - specific haplotype
As a result of the recombination sites having been at specific regions, rather than evenly distributed throughout the genome, sequence variation within the modern human genome tends to be present in discrete _____ within w/c there is high linkage disequilibrium.
haplotype blocks
The ____ was initiated in October 2002 in order to compare the DNA sequences of different individuals & thus identify regions of similarity in w/c the genetic variants are shared between individuals.
International HapMap Project
An important aspect of the HapMap Project has been the detection of haplotypes not only by extensive analysis of SNPs, but also by the identification of so - called ____ that can be used to uniquely represent each of the haplotype blocks thus detected.
‘tag’ SNPs
Individual alleles can influence one’s susceptibility to two or more conditions. For instance, a ____ gene variant that is associated w/ a reduced susceptibility to type 2 diabetes also confers an increased risk of prostate cancer, perhaps on account of an altered potential for cell degeneration or proliferation.
TCF2
