title: Lith6: a new QTL for cholesterol gallstones from an intercross of CAST/Ei and DBA/2J inbred mouse strains.
abstract: A complex genetic basis determines the individual predisposition to develop cholesterol gallstones in response to environmental factors. We employed quantitative trait locus/loci (QTL) analyses of an intercross between inbred strains CAST/Ei (susceptible) and DBA/2J (resistant) to determine the subset of gallstone susceptibility (Lith) genes these strains possess. Parental and first filial generation mice of both genders and male intercross offspring were evaluated for gallstone formation after feeding a lithogenic diet. Linkage analysis was performed using a form of multiple interval mapping. One significant QTL colocalized with Lith1 [chromosome (chr) 2, 50 cM], a locus identified previously. Significantly, new QTL were detected and named Lith10 (chr 6, 4 cM), Lith6 (chr 6, 54 cM), and Lith11 (chr 8, 58 cM). Statistical and genetic analyses suggest that Lith6 comprises two QTL in close proximity. Our molecular and genetic data support the candidacy of peroxisome proliferator-activated receptor gamma (Pparg) and Slc21a1, encoding Pparg, and the basolateral bile acid transporter SLC21A1 (Slc21a1/Oatp1), respectively, as genes underlying Lith6.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 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: Monika R
authors.initials: MR
authors.lastname: Leonard
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: D000483:Alleles; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D042882:Gallstones / Q000235:genetics* / Q000378:metabolism* / Q000662:veterinary; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010641:Phenotype; D015995:Prevalence; D040641:Quantitative Trait Loci / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D002784:Cholesterol