title: Integration of QTL and bioinformatic tools to identify candidate genes for triglycerides in mice.
abstract: To identify genetic loci influencing lipid levels, we performed quantitative trait loci (QTL) analysis between inbred mouse strains MRL/MpJ and SM/J, measuring triglyceride levels at 8 weeks of age in F2 mice fed a chow diet. We identified one significant QTL on chromosome (Chr) 15 and three suggestive QTL on Chrs 2, 7, and 17. We also carried out microarray analysis on the livers of parental strains of 282 F2 mice and used these data to find cis-regulated expression QTL. We then narrowed the list of candidate genes under significant QTL using a "toolbox" of bioinformatic resources, including haplotype analysis; parental strain comparison for gene expression differences and nonsynonymous coding single nucleotide polymorphisms (SNP); cis-regulated eQTL in livers of F2 mice; correlation between gene expression and phenotype; and conditioning of expression on the phenotype. We suggest Slc25a7 as a candidate gene for the Chr 7 QTL and, based on expression differences, five genes (Polr3 h, Cyp2d22, Cyp2d26, Tspo, and Ttll12) as candidate genes for Chr 15 QTL. This study shows how bioinformatics can be used effectively to reduce candidate gene lists for QTL related to complex traits.
authors.affiliation: Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Magalie S
authors.initials: MS
authors.lastname: Leduc
authors.forename: Rachael S
authors.initials: RS
authors.lastname: Hageman
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Verdugo
authors.forename: Shirng-Wern
authors.initials: SW
authors.lastname: Tsaih
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.forename: Gary A
authors.initials: GA
authors.lastname: Churchill
authors.forename: Beverly
authors.initials: B
authors.lastname: Paigen
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods; D033481:Chromosomes, Mammalian / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006239:Haplotypes; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D014280:Triglycerides / Q000235:genetics* / Q000378:metabolism
chemical_list: D014280:Triglycerides