Submitted on January 30, 2008
Revised on March 13, 2008
Accepted on March 24, 2008
Candidate genes for plasma triglyceride, free fatty acid, and glucose revealed from an intercross between inbred mouse strains NZB/B1NJ x NZW/LacJ
Zhiguang Su, Shirng-Wern Tsaih, Jin Szatkiewicz, Yuan Shen, and Beverly Paigen
The Jackson Laboratory, Bar Harbor, ME 04609
Corresponding Author: bev.paigen{at}jax.org
To identify the genes controlling plasma concentrations of triglycerides, free fatty acids, and glucose, we carried out a quantitative trait loci (QTL) analysis of the closely related mouse strains New Zealand Black (NZB/B1NJ) and New Zealand White (NZW/LacJ), which share 63% of their genomes. The (NZB x NZW) F2 progeny were genotyped and phenotyped to detect QTL and then comparative genomics, bioinformatics, and sequencing were used to narrow the QTL and reduce the number of candidate genes. Triglyceride concentrations were linked to loci on chromosomes (Chr) 4, 7, 8, 10, and 18. Free fatty acid concentrations were affected by a significant locus on Chr 4, a suggestive locus on Chr 16, and two interacting loci on Chr 2 and 15. Plasma glucose concentrations were affected by QTL on Chr 2, 4, 7, 8, 10, 15, 17, and 18. Comparative genomics narrowed the QTL by 31% to 86%; haplotype analysis was usually able to further narrow by 80%. We suggest several candidate genes: Gba2 on Chr 4, Irs2 on Chr 8, and Ppargc1b on Chr 18 for triglycerides; A2bp1 on Chr 16 for free fatty acids; and G6pc2 on Chr 2 and Timp3 on Chr 10 for glucose.
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