Bulk segregation mapping of mutations in closely related strains of mice

Yu Xia, Sungyong Won, Xin Du, Pei Lin, Charles Ross, Diantha La Vine, Sean Wiltshire, Gabriel Leiva, Silvia M. Vidal, Belinda Whittle, Christopher C. Goodnow, James Koziol, Eva Marie Y Moresco, Bruce Beutler

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27 Scopus citations

Abstract

Phenovariance may be obscured when genetic mapping is performed using highly divergent strains, and closely similar strains are preferred if adequate marker density can be established. We sequenced the C57BL/10J mouse genome using the Applied Biosystems SOLiD platform and here describe a genomewide panel of informative markers that permits the mapping of mutations induced on the closely related C57BL/6J background by outcrossing to C57BL/10J, and backcrossing or intercrossing. The panel consists of 127 single nucleotide polymorphisms validated by capillary sequencing: 124 spaced at ∼20-Mb intervals across the 19 autosomes, and three markers on the X chromosome. We determined the genetic relationship between four C57BL-derived substrains and used the panel to map two N-ethyl-N-nitrosourea (ENU)-induced mutations responsible for visible phenotypes in C57BL/6J mice through bulk segregation analysis. Capillary sequencing, with computation of relative chromatogram peak heights, was used to determine the proportion of alleles from each strain at each marker.

Original languageEnglish (US)
Pages (from-to)1139-1145
Number of pages7
JournalGenetics
Volume186
Issue number4
DOIs
StatePublished - Dec 1 2010

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ASJC Scopus subject areas

  • Genetics

Cite this

Xia, Y., Won, S., Du, X., Lin, P., Ross, C., La Vine, D., Wiltshire, S., Leiva, G., Vidal, S. M., Whittle, B., Goodnow, C. C., Koziol, J., Moresco, E. M. Y., & Beutler, B. (2010). Bulk segregation mapping of mutations in closely related strains of mice. Genetics, 186(4), 1139-1145. https://doi.org/10.1534/genetics.110.121160