Rapid and accurate large-scale genotyping of duplicated genes and discovery of interlocus gene conversions

Xander Nuttle, John Huddleston, Brian O'Roak, Francesca Antonacci, Marco Fichera, Corrado Romano, Jay Shendure, Evan E. Eichler

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Over 900 genes have been annotated within duplicated regions of the human genome, yet their functions and potential roles in disease remain largely unknown. One major obstacle has been the inability to accurately and comprehensively assay genetic variation for these genes in a high-throughput manner. We developed a sequencing-based method for rapid and high-throughput genotyping of duplicated genes using molecular inversion probes designed to target unique paralogous sequence variants. We applied this method to genotype all members of two gene families, SRGAP2 and RH, among a diversity panel of 1,056 humans. The approach could accurately distinguish copy number in paralogs having up to ∼99.6% sequence identity, identify small gene-disruptive deletions, detect single-nucleotide variants, define breakpoints of unequal crossover and discover regions of interlocus gene conversion. The ability to rapidly and accurately genotype multiple gene families in thousands of individuals at low cost enables the development of genome-wide gene conversion maps and 'unlocks' many previously inaccessible duplicated genes for association with human traits.

Original languageEnglish (US)
Pages (from-to)903-909
Number of pages7
JournalNature Methods
Volume10
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

Fingerprint

Gene Conversion
Genetic Association Studies
Genes
Genotype
Molecular Probes
Gene Deletion
Human Genome
Throughput
Nucleotides
Genome
Costs and Cost Analysis
Assays
Association reactions

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Biochemistry
  • Cell Biology

Cite this

Nuttle, X., Huddleston, J., O'Roak, B., Antonacci, F., Fichera, M., Romano, C., ... Eichler, E. E. (2013). Rapid and accurate large-scale genotyping of duplicated genes and discovery of interlocus gene conversions. Nature Methods, 10(9), 903-909. https://doi.org/10.1038/nmeth.2572

Rapid and accurate large-scale genotyping of duplicated genes and discovery of interlocus gene conversions. / Nuttle, Xander; Huddleston, John; O'Roak, Brian; Antonacci, Francesca; Fichera, Marco; Romano, Corrado; Shendure, Jay; Eichler, Evan E.

In: Nature Methods, Vol. 10, No. 9, 09.2013, p. 903-909.

Research output: Contribution to journalArticle

Nuttle, X, Huddleston, J, O'Roak, B, Antonacci, F, Fichera, M, Romano, C, Shendure, J & Eichler, EE 2013, 'Rapid and accurate large-scale genotyping of duplicated genes and discovery of interlocus gene conversions', Nature Methods, vol. 10, no. 9, pp. 903-909. https://doi.org/10.1038/nmeth.2572
Nuttle, Xander ; Huddleston, John ; O'Roak, Brian ; Antonacci, Francesca ; Fichera, Marco ; Romano, Corrado ; Shendure, Jay ; Eichler, Evan E. / Rapid and accurate large-scale genotyping of duplicated genes and discovery of interlocus gene conversions. In: Nature Methods. 2013 ; Vol. 10, No. 9. pp. 903-909.
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