International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


ORAL PRESENTATION

MONDAY OCTOBER 18

5.30pm – 5.45pm

HAPLOTYPE ANALYSIS IN MULTIPLE CROSSES TO IDENTIFY A QTL GENE

Wang X, Korstanje R, Higgins D, Paigen B

The Jackson Laboratory, Bar Harbor, United States

Identifying quantitative trait locus (QTL) genes is a challenging task. Herein, we report using a two-step process to identify Apoa2 as the gene underlying Hdlq5, a major QTL for plasma high-density lipoprotein cholesterol (HDL) levels on mouse chromosome 1. First, we performed a sequence analysis of the Apoa2 coding region in 46 genetically diverse mouse strains and found five different APOA2 protein variants, which we named APOA2a to APOA2e. Second, we conducted a haplotype analysis of strains in 21 crosses that have so far detected HDL QTLs and found that Hdlq5 was detected only in the nine crosses where one parent had the APOA2b protein variant characterized by an Ala61 to Val61 substitution. We then found that strains with the APOA2b variant had significantly higher (P < 0.002) plasma HDL levels than those with either the APOA2a or the APOA2c variant. Thus, in addition to identifying Apoa2 as the gene underlying Hdlq5, our haplotype analysis identified the Apoa2 polymophism responsible for the Hdlq5 phenotype. Our haplotype analysis in multiple crosses proved to be a quick and cost-effective approach in testing a candidate QTL gene.

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