We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Comprehensive variation discovery in single human genomes.
- Authors
Weisenfeld, Neil I; Yin, Shuangye; Sharpe, Ted; Lau, Bayo; Hegarty, Ryan; Holmes, Laurie; Sogoloff, Brian; Tabbaa, Diana; Williams, Louise; Russ, Carsten; Nusbaum, Chad; Lander, Eric S; MacCallum, Iain; Jaffe, David B
- Abstract
Complete knowledge of the genetic variation in individual human genomes is a crucial foundation for understanding the etiology of disease. Genetic variation is typically characterized by sequencing individual genomes and comparing reads to a reference. Existing methods do an excellent job of detecting variants in approximately 90% of the human genome; however, calling variants in the remaining 10% of the genome (largely low-complexity sequence and segmental duplications) is challenging. To improve variant calling, we developed a new algorithm, DISCOVAR, and examined its performance on improved, low-cost sequence data. Using a newly created reference set of variants from the finished sequence of 103 randomly chosen fosmids, we find that some standard variant call sets miss up to 25% of variants. We show that the combination of new methods and improved data increases sensitivity by several fold, with the greatest impact in challenging regions of the human genome.
- Subjects
HUMAN genetic variation; GENOMICS; ETIOLOGY of diseases; GENETIC polymorphisms; SHOTGUN sequencing
- Publication
Nature Genetics, 2014, Vol 46, Issue 12, p1350
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.3121