title: Quantitative trait loci that determine lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and CAST/Ei inbred mice.
abstract: 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.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Lyons
authors.forename: Henning
authors.initials: H
authors.lastname: Wittenburg
authors.forename: Renhua
authors.initials: R
authors.lastname: Li
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Walsh
authors.forename: Ron
authors.initials: R
authors.lastname: Korstanje
authors.forename: Gary A
authors.initials: GA
authors.lastname: Churchill
authors.forename: Martin C
authors.initials: MC
authors.lastname: Carey
authors.forename: Beverly
authors.initials: B
authors.lastname: Paigen
mesh_terms: 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
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D012333:RNA, Messenger; D008071:Lipoprotein Lipase