Quantitative trait loci that determine lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and CAST/Ei inbred mice.
To identify genetic determinants of lipoprotein levels, we are performing quantitative trait locus (QTL) analysis on a series of mouse intercrosses in a "daisy chain" experimental design, to increase the power of detecting QTL and to identify common variants that should segregate in multiple intercrosses. In this study, we intercrossed strains CAST/Ei and 129S1/SvImJ, determined HDL, total, and non-HDL cholesterol levels, and performed QTL mapping using Pseudomarker software. For HDL cholesterol, we identified two significant QTL on chromosome (Chr) 1 (Hdlq5, 82 cM, 60-100 cM) and Chr 4 (Hdlq10, 20 cM, 10-30 cM). For total cholesterol, we identified three significant QTL on Chr 1 (Chol7, 74 cM, 65-80 cM), Chr 4 (Chol8, 12 cM, 0-30 cM), and Chr 17 (Chol9, 54 cM, 20-60 cM). For non-HDL cholesterol, we identified significant QTL on Chr 8 (Nhdlq1, 34 cM, 20-60 cM) and Chr X (Nhdlq2, 6 cM, 0-18 cM). Hdlq10 was the only QTL detected in two intercrosses involving strain CAST/Ei. Hdlq5, Hdlq10, Nhdlq1, and two suggestive QTL at D7Mit246 and D15Mit115 coincided with orthologous human lipoprotein QTL. Our analysis furthers the knowledge of the genetic control of lipoprotein levels and points to the importance of Hdlq10, which was detected repeatedly in multiple studies.
Lyons
Malcolm A
MA
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Wittenburg
Henning
H
Li
Renhua
R
Walsh
Kenneth A
KA
Korstanje
Ron
R
Churchill
Gary A
GA
Carey
Martin C
MC
Paigen
Beverly
B
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000483:Alleles; D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood*; D002874:Chromosome Mapping / Q000379:methods*; D002875:Chromosomes / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D040641:Quantitative Trait Loci / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014960:X Chromosome / Q000235:genetics
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D012333:RNA, Messenger; D008071:Lipoprotein Lipase