International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


ORAL PRESENTATION

MONDAY 10 NOVEMBER
14:45 – 15:00 HRS

QUANTITATIVE TRAIT LOCI FOR HDL-CHOLESTEROL

Paigen B
The Jackson Laboratory

Co-Authors: Wang X, Lyons M, Korstanje R
Institutions: The Jackson Laboratory

During the past decade, 74 quantitative trait loci (QTL) have been reported for HDL cholesterol, 49 in mouse and 25 in humans. Most QTL have been found multiple times resulting in 23 confirmed locations and 7 locations found only once. Mouse and human QTL are found in homologous regions: 22 of the 25 human QTL have mouse QTL in homologous regions suggesting that the same genes may be involved. Previously hepatic lipase (Lipc) was identified as the gene for one of the human QTL. We report that Apoa2 is the gene for a mouse Chr 1 QTL found multiple times. By sequencing the Apoa2 gene from 42 strains, by using the data on HDL levels from the Mouse Phenome Database, and by noting which of 15 mouse crosses located or failed to locate the Chr 1 QTL, we found 6 different alleles of Apoa2 and identified the critical amino acid change that causes a difference in HDL. Using a combination of haplotype analysis, combining mouse crosses, and expression analysis, we have identified Abca1 as the gene underlying a mouse Chr 4 QTL found multiple times. Identifying the genes for the remaining confirmed QTL will increase our understanding of how HDL cholesterol is regulated.


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