The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol[S]
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 gen...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2011-06-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520313328 |
| _version_ | 1819127518634967040 |
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| author | Magalie S. Leduc Malcolm Lyons Katayoon Darvishi Kenneth Walsh Susan Sheehan Sarah Amend Allison Cox Marju Orho-Melander Sekar Kathiresan Beverly Paigen Ron Korstanje |
| author_facet | Magalie S. Leduc Malcolm Lyons Katayoon Darvishi Kenneth Walsh Susan Sheehan Sarah Amend Allison Cox Marju Orho-Melander Sekar Kathiresan Beverly Paigen Ron Korstanje |
| author_sort | Magalie S. Leduc |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T08:13:12Z |
| format | Article |
| id | doaj.art-e2516ad026464a8a95d9e7d542358a9c |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-22T08:13:12Z |
| publishDate | 2011-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-e2516ad026464a8a95d9e7d542358a9c2022-12-21T18:32:59ZengElsevierJournal of Lipid Research0022-22752011-06-0152611391149The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol[S]Magalie S. Leduc0Malcolm Lyons1Katayoon Darvishi2Kenneth Walsh3Susan Sheehan4Sarah Amend5Allison Cox6Marju Orho-Melander7Sekar Kathiresan8Beverly Paigen9Ron Korstanje10The Jackson Laboratory, Bar Harbor, METhe Jackson Laboratory, Bar Harbor, METhe Jackson Laboratory, Bar Harbor, METhe Jackson Laboratory, Bar Harbor, METhe Jackson Laboratory, Bar Harbor, METhe Jackson Laboratory, Bar Harbor, METhe Jackson Laboratory, Bar Harbor, MEUniversity Hospital Malmo, Lund University, Malmo, SwedenMassachussetts General Hospital, Boston, MAThe Jackson Laboratory, Bar Harbor, METo whom correspondence should be addressed. ron.korstanje@jax.org; The Jackson Laboratory, Bar Harbor, MEGenome-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.http://www.sciencedirect.com/science/article/pii/S0022227520313328genomicshigh density lipoproteincomparative genomicsquantitative trait locimouse model |
| spellingShingle | Magalie S. Leduc Malcolm Lyons Katayoon Darvishi Kenneth Walsh Susan Sheehan Sarah Amend Allison Cox Marju Orho-Melander Sekar Kathiresan Beverly Paigen Ron Korstanje The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol[S] Journal of Lipid Research genomics high density lipoprotein comparative genomics quantitative trait loci mouse model |
| title | The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol[S] |
| title_full | The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol[S] |
| title_fullStr | The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol[S] |
| title_full_unstemmed | The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol[S] |
| title_short | The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol[S] |
| title_sort | mouse qtl map helps interpret human genome wide association studies for hdl cholesterol s |
| topic | genomics high density lipoprotein comparative genomics quantitative trait loci mouse model |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520313328 |
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