title: The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol.
abstract: Genome-wide association (GWA) studies represent a powerful strategy for identifying susceptibility genes for complex diseases in human populations but results must be confirmed and replicated. Because of the close homology between mouse and human genomes, the mouse can be used to add evidence to genes suggested by human studies. We used the mouse quantitative trait loci (QTL) map to interpret results from a GWA study for genes associated with plasma HDL cholesterol levels. We first positioned single nucleotide polymorphisms (SNPs) from a human GWA study on the genomic map for mouse HDL QTL. We then used mouse bioinformatics, sequencing, and expression studies to add evidence for one well-known HDL gene (Abca1) and three newly identified genes (Galnt2, Wwox, and Cdh13), thus supporting the results of the human study. For GWA peaks that occur in human haplotype blocks with multiple genes, we examined the homologous regions in the mouse to prioritize the genes using expression, sequencing, and bioinformatics from the mouse model, showing that some genes were unlikely candidates and adding evidence for candidate genes Mvk and Mmab in one haplotype block and Fads1 and Fads2 in the second haplotype block. Our study highlights the value of mouse genetics for evaluating genes found in human GWA studies.
authors: The Jackson Laboratory, Bar Harbor, ME.
authors: Magalie S
authors: MS
authors: Leduc
authors: The Jackson Laboratory, Bar Harbor, ME.
authors: Malcolm
authors: M
authors: Lyons
authors: The Jackson Laboratory, Bar Harbor, ME.
authors: Katayoon
authors: K
authors: Darvishi
authors: The Jackson Laboratory, Bar Harbor, ME.
authors: Kenneth
authors: K
authors: Walsh
authors: The Jackson Laboratory, Bar Harbor, ME.
authors: Susan
authors: S
authors: Sheehan
authors: The Jackson Laboratory, Bar Harbor, ME.
authors: Sarah
authors: S
authors: Amend
authors: The Jackson Laboratory, Bar Harbor, ME.
authors: Allison
authors: A
authors: Cox
authors: University Hospital Malmo, Lund University, Malmo, Sweden.
authors: Marju
authors: M
authors: Orho-Melander
authors: Massachussetts General Hospital, Boston, MA.
authors: Sekar
authors: S
authors: Kathiresan
authors: The Jackson Laboratory, Bar Harbor, ME.
authors: Beverly
authors: B
authors: Paigen
authors: The Jackson Laboratory, Bar Harbor, ME. Electronic address: ron.korstanje@jax.org.
authors: Ron
authors: R
authors: Korstanje
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D002874:Chromosome Mapping; D019295:Computational Biology; D000090943:Delta-5 Fatty Acid Desaturase; D020869:Gene Expression Profiling; D016678:Genome; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D051379:Mice / Q000235:genetics*; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D040641:Quantitative Trait Loci; D017385:Sequence Homology
chemical_list: D008076:Cholesterol, HDL; D000090943:Delta-5 Fatty Acid Desaturase; C000716847:FADS1 protein, human