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Integration of QTL and bioinformatic tools to identify candidate genes for triglycerides in mice. J Lipid Res 2011 Sep;52(9):1672-82

Date

05/31/2011

Pubmed ID

21622629

Pubmed Central ID

PMC3151687

DOI

10.1194/jlr.M011130

Scopus ID

2-s2.0-80051824901 (requires institutional sign-in at Scopus site)   21 Citations

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.

Author List

Leduc MS, Hageman RS, Verdugo RA, Tsaih SW, Walsh K, Churchill GA, Paigen B

Author

Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Chromosome Mapping
Chromosomes, Mammalian
Computational Biology
Female
Gene Expression Profiling
Gene Expression Regulation
Haplotypes
Humans
Male
Mice
Mice, Inbred Strains
Microarray Analysis
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Triglycerides