Genomics (Essential Methods) || Identification of Polymorphic Markers for Genetic Mapping

✍ Scribed by Starkey, Mike; Elaswarapu, Ramnath

• Publisher: John Wiley & Sons, Ltd
• Year: 2010
• Weight: 589 KB
• Category: Article
• ISBN: 0470711574
• DOI: 10.1002/9780470711675.ch2

✦ Synopsis

Single nucleotide polymorphisms (SNPs) are the most prevalent form of DNA sequence variation in humans. At the end of 2008, public databases contained more than 12 million entries of genetic variants in humans, the vast majority of which are SNPs [1]. While the incidence of SNPs in the human genome is roughly 1 per 1000 bp on average, SNPs tend to cluster locally [2], creating regions of high SNP density with long stretches of 'SNP deserts' in between [3]. While an SNP could conceivably have four alleles (A, C, G, T), most are biallelic, with A/G the most common allele combination. Since DNA is a double helix, the opposite strand has alleles T and C. Consequently, an A/G SNP can also be described as a T/C SNP, depending upon orientation. An estimated 63% of known SNPs are A/G, 17% are A/C, 8% are C/G, 4% are A/T and the remaining 8% are single base insertions or deletions [3].

Owing to their widespread distribution across the genome, and facilitated by development of high-throughput genotyping technologies, SNPs have become important tools for genetic association studies. In an effort to understand the underlying structure of genetic variation in humans, the International HapMap Consortium [4, 5] characterized nearly 4 million SNPs in four geographically diverse human populations: the Yoruba in Ibadan, Nigeria (YRI); the CEPH population with European ancestry in Utah, USA (CEU); Han Chinese in Beijing, China (CHB); and Japanese in Tokyo, Japan. These data enabled the construction of a high-resolution haplotype map describing the block-like structure of linkage disequilibrium (LD) in the human genome. Large-scale, genome-wide association studies made possible