Efficient Genome-Wide Sequencing and Low-Coverage Pedigree Analysis from Noninvasively Collected Samples

• DOI: 10.1534/genetics.116.187492
• Publication Date: 2016-04-21T05:50:32Z
• Authors: Noah Snyder-Mackler; William H Majoros; Michael L Yuan; Amanda O Shaver; Jacob B Gordon; Gisela H Kopp; Stephen A Schlebusch; Jeffrey D Wall; Susan C Alberts; Sayan Mukherjee; Xiang Zhou; Jenny Tung
• Keywords: Genotyping Techniques; Investigations; Feces; 03 medical and health sciences; 0302 clinical medicine; capture-based enrichment; Genetics; Animals; genome resequencing; 0303 health sciences; paternity analysis; Genome; Human Genome; pedigree; DNA; Sequence Analysis, DNA; Biological Sciences; baboons; Pedigree; noninvasive samples; Biochemistry and cell biology; Sequence Analysis; Software; Developmental Biology; Papio

AbstractResearch on the genetics of natural populations was revolutionized in the 1990s by methods for genotyping noninvasively collected samples. However, these methods have remained largely unchanged for the past 20 years and lag far behind the genomics era. To close this gap, here we report an optimized laboratory protocol for genome-wide capture of endogenous DNA from noninvasively collected samples, coupled with a novel computational approach to reconstruct pedigree links from the resulting low-coverage data. We validated both methods using fecal samples from 62 wild baboons, including 48 from an independently constructed extended pedigree. We enriched fecal-derived DNA samples up to 40-fold for endogenous baboon DNA and reconstructed near-perfect pedigree relationships even with extremely low-coverage sequencing. We anticipate that these methods will be broadly applicable to the many research systems for which only noninvasive samples are available. The lab protocol and software (“WHODAD”) are freely available at www.tung-lab.org/protocols-and-software.html and www.xzlab.org/software.html, respectively.