Thursday, 24 January 2013

Pubmed Highlight: direct haplotyping of a human genome

In this recent article, authors from Craig Venter Institute explore a new method to reconstruct chromosome length haplotypes using genotyping and NGS data. Following this procedure one can leverage on short-read sequencing of sperm-cell haploid genome to reconstruct chromosome length haplotypes for any individual for which the diploid genome is known. Moreover they also demonstrate the ability to detect recombination events with a median resolution of less than 100kb.
InSequence has also a post covering this innovative paper!

Genome Res. 2013 Jan 2

Kirkness EF, Grindberg RV, Yee-Greenbaum J, Marshall CR, Scherer SW, Lasken RS, Venter JC. 
The J Craig Venter Institute

There is increasing evidence that the phenotypic effects of genomic sequence variants are best understood in terms of variant haplotypes rather than as isolated polymorphisms. Haplotype analysis is also critically important for uncovering population histories, and for the study of evolutionary genetics. Although the sequencing of individual human genomes to reveal personal collections of sequence variants is now well established, there has been slower progress in the phasing of these variants into pairs of haplotypes along each pair of chromosomes. Here, we have developed a distinct approach to haplotyping that can yield chromosome-length haplotypes, including the vast majority of heterozygous SNPs in an individual human genome. This approach exploits the haploid nature of sperm cells, and employs a combination of genotyping and low-coverage sequencing on a short-read platform. In addition to generating chromosome-length haplotypes, the approach can directly identify recombination events (averaging 1.1 per chromosome) with a median resolution of less than 100 kb.

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