Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain.
Atherosclerosis is a complex disease resulting from the interaction of multiple genes, including those causing dyslipidemia. Relatively few of the causative genes have been identified. Previously, we identified Apoa2 as a major determinant of high-density lipoprotein cholesterol (HDL-C) levels in the mouse model. To identify additional HDL-C level quantitative trait loci (QTLs), while controlling for the effect of the Apoa2 locus, we performed linkage analysis in 179 standard diet-fed F(2) mice derived from strains BALB/cJ and B6.C-H25(c) (a congenic strain carrying the BALB/c Apoa2 allele). Three significant QTLs and one suggestive locus were identified. A female-specific locus mapping to chromosome 6 (Chr 6) also exhibited effects on plasma non-HDL-C, apolipoprotein AII (apoAII), apoB, and apoE levels. A Chr 6 QTL was independently isolated in a related congenic strain (C57BL/6J vs. B6.NODc6: P = 0.003 and P = 0.0001 for HDL-C and non-HDL-C levels, respectively). These data are consistent with polygenic inheritance of HDL-C levels in the mouse model and provide candidate loci for HDL-C and non-HDL-C level determination in humans.
Welch
Carrie L
CL
Division of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA. cbw13@columbia.edu
Bretschger
Sara
S
Wen
Ping-Zi
PZ
Mehrabian
Margarete
M
Latib
Nashat
N
Fruchart-Najib
Jamila
J
Fruchart
Jean Charles
JC
Myrick
Christy
C
Lusis
Aldons J
AJ
D000483:Alleles; D000818:Animals; D016633:Apolipoprotein A-II / Q000235:genetics*; D001947:Breeding; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D002874:Chromosome Mapping / Q000379:methods*; D002875:Chromosomes / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006937:Hypercholesterolemia / Q000235:genetics; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D020412:Multifactorial Inheritance / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*
D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; C079456:amyloidogenic apolipoprotein A-II, mouse; D002784:Cholesterol