Efficient genome-wide sequencing and low-coverage pedigree analysis from noninvasively collected samples

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

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Research 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.

Original languageEnglish (US)
Pages (from-to)699-714
Number of pages16
JournalGenetics
Volume203
Issue number2
DOIs
StatePublished - Jun 2016
Externally publishedYes

Keywords

  • Baboons
  • Capture-based enrichment
  • Genome resequencing
  • Noninvasive samples
  • Paternity analysis
  • Pedigree

ASJC Scopus subject areas

  • General Medicine

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