Display options
Cite
Ryu S, Han J, Norden-Krichmar TM, et al. Effective discovery of rare variants by pooled target capture sequencing: A comparative analysis with individually indexed target capture sequencing. Mutat Res. 2018;809:24-31doi: 10.1016/j.mrfmmm.2018.03.007.
Ryu, S., Han, J., Norden-Krichmar, T. M., Schork, N. J., & Suh, Y. (2018). Effective discovery of rare variants by pooled target capture sequencing: A comparative analysis with individually indexed target capture sequencing. Mutation research, 80924-31. https://doi.org/10.1016/j.mrfmmm.2018.03.007
Ryu, Seungjin, et al. "Effective discovery of rare variants by pooled target capture sequencing: A comparative analysis with individually indexed target capture sequencing." Mutation research vol. 809 (2018): 24-31. doi: https://doi.org/10.1016/j.mrfmmm.2018.03.007
Ryu S, Han J, Norden-Krichmar TM, Schork NJ, Suh Y. Effective discovery of rare variants by pooled target capture sequencing: A comparative analysis with individually indexed target capture sequencing. Mutat Res. 2018 May;809:24-31. doi: 10.1016/j.mrfmmm.2018.03.007. Epub 2018 Mar 30. PMID: 29677560; PMCID: PMC5962423.
Copy Download .nbib Format: NLM
Share it on

Mutat Res. 2018 May;809:24-31. doi: 10.1016/j.mrfmmm.2018.03.007. Epub 2018 Mar 30.

Effective discovery of rare variants by pooled target capture sequencing: A comparative analysis with individually indexed target capture sequencing.

Mutation research

Seungjin Ryu, Jeehae Han, Trina M Norden-Krichmar, Nicholas J Schork, Yousin Suh

Affiliations

  1. Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  2. The Scripps Research Institute, La Jolla, CA 92037, USA.
  3. The Scripps Research Institute, La Jolla, CA 92037, USA; J. Craig Venter Institute, La Jolla, CA, 92037, USA.
  4. Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA; Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. Electronic address: [email protected].

PMID: 29677560 PMCID: PMC5962423 DOI: 10.1016/j.mrfmmm.2018.03.007

Abstract

Identification of all genetic variants associated with complex traits is one of the most important goals in modern human genetics. Genome-wide association studies (GWAS) have been successfully applied to identify common variants, which thus far explain only small portion of heritability. Interests in rare variants have been increasingly growing as an answer for this missing heritability. While next-generation sequencing allows detection of rare variants, its cost is still prohibitively high to sequence a large number of human DNA samples required for rare variant association studies. In this study, we evaluated the sensitivity and specificity of sequencing for pooled DNA samples of multiple individuals (Pool-seq) as a cost-effective and robust approach for rare variant discovery. We comparatively analyzed Pool-seq vs. individual-seq of indexed target capture of up to 960 genes in ∼1000 individuals, followed by independent genotyping validation studies. We found that Pool-seq was as effective and accurate as individual-seq in detecting rare variants and accurately estimating their minor allele frequencies (MAFs). Our results suggest that Pool-seq can be used as an efficient and cost-effective method for discovery of rare variants for population-based sequencing studies in individual laboratories.

Copyright © 2018 Elsevier B.V. All rights reserved.

Keywords: Genetic variant; Individually indexed target capture sequencing; Pooled target capture sequencing; Rare variant

References

  1. PLoS One. 2013 Nov 07;8(11):e80422 - PubMed
  2. Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1193-8 - PubMed
  3. Nature. 2012 Nov 1;491(7422):56-65 - PubMed
  4. BMC Genomics. 2012 Nov 14;13:618 - PubMed
  5. Bioinformatics. 2010 Jun 15;26(12):i318-24 - PubMed
  6. Bioinformatics. 2009 Sep 1;25(17):2283-5 - PubMed
  7. Nat Genet. 2010 Oct;42(10):851-8 - PubMed
  8. Nucleic Acids Res. 2001 Jan 1;29(1):308-11 - PubMed
  9. Genome Res. 2010 Sep;20(9):1297-303 - PubMed
  10. Cell. 2010 Apr 16;141(2):210-7 - PubMed
  11. Genetics. 2010 Sep;186(1):207-18 - PubMed
  12. Nature. 2012 Sep 6;489(7414):57-74 - PubMed
  13. Bioinformatics. 2009 Aug 15;25(16):2078-9 - PubMed
  14. Genome Biol. 2011 Sep 28;12(9):R93 - PubMed
  15. Nat Methods. 2009 Apr;6(4):263-5 - PubMed
  16. PLoS One. 2011;6(11):e26279 - PubMed
  17. Nature. 2010 Sep 2;467(7311):52-8 - PubMed
  18. Nat Genet. 2011 May;43(5):491-8 - PubMed
  19. Nucleic Acids Res. 2013 Jan;41(Database issue):D64-9 - PubMed
  20. Front Genet. 2013 Aug 26;4:160 - PubMed
  21. Nature. 2009 Oct 8;461(7265):747-53 - PubMed
  22. Am J Hum Genet. 2011 Jul 15;89(1):82-93 - PubMed
  23. Am J Hum Genet. 2013 Jan 10;92(1):15-27 - PubMed
  24. Nature. 2010 Oct 28;467(7319):1061-73 - PubMed
  25. Bioinformatics. 2009 Jul 15;25(14):1754-60 - PubMed
  26. PLoS Genet. 2011 Feb 03;7(2):e1001289 - PubMed
  27. PLoS One. 2011 Mar 30;6(3):e18353 - PubMed
  28. JAMA. 2003 Oct 15;290(15):2030-40 - PubMed
  29. Am J Hum Genet. 2008 Sep;83(3):311-21 - PubMed
  30. Nucleic Acids Res. 2010 Sep;38(16):e164 - PubMed
  31. Nature. 2001 Feb 15;409(6822):860-921 - PubMed
  32. Nature. 2014 Jan 23;505(7484):550-554 - PubMed

MeSH terms

Publication Types

Grant support