Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysis
In the past 15 years, the quantitative trait locus (QTL) mapping approach has been applied to crosses between different inbred mouse strains to identify genetic loci associated with plasma HDL cholesterol levels. Although successful, a disadvantage of this method is low mapping resolution, as often...
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Format: | Article |
Language: | English |
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Elsevier
2013-04-01
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Series: | Journal of Lipid Research |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520422035 |
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author | Cheryl Ackert-Bicknell Beverly Paigen Ron Korstanje |
author_facet | Cheryl Ackert-Bicknell Beverly Paigen Ron Korstanje |
author_sort | Cheryl Ackert-Bicknell |
collection | DOAJ |
description | In the past 15 years, the quantitative trait locus (QTL) mapping approach has been applied to crosses between different inbred mouse strains to identify genetic loci associated with plasma HDL cholesterol levels. Although successful, a disadvantage of this method is low mapping resolution, as often several hundred candidate genes fall within the confidence interval for each locus. Methods have been developed to narrow these loci by combining the data from the different crosses, but they rely on the accurate mapping of the QTL and the treatment of the data in a consistent manner. We collected 23 raw datasets used for the mapping of previously published HDL QTL and reanalyzed the data from each cross using a consistent method and the latest mouse genetic map. By utilizing this approach, we identified novel QTL and QTL that were mapped to the wrong part of chromosomes. Our new HDL QTL map allows for reliable combining of QTL data and candidate gene analysis, which we demonstrate by identifying Grin3a and Etv6, as candidate genes for QTL on chromosomes 4 and 6, respectively. In addition, we were able to narrow a QTL on Chr 19 to five candidates. |
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institution | Directory Open Access Journal |
issn | 0022-2275 |
language | English |
last_indexed | 2024-12-18T01:40:45Z |
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publisher | Elsevier |
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series | Journal of Lipid Research |
spelling | doaj.art-eb36f85166f3476d8d8118112c59cd912022-12-21T21:25:21ZengElsevierJournal of Lipid Research0022-22752013-04-01544984994Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysisCheryl Ackert-Bicknell0Beverly Paigen1Ron Korstanje2The Jackson Laboratory, Bar Harbor, METhe Jackson Laboratory, Bar Harbor, METo whom correspondence should be addressed ron.korstanje@jax.org; To whom correspondence should be addressed ron.korstanje@jax.org; The Jackson Laboratory, Bar Harbor, MEIn the past 15 years, the quantitative trait locus (QTL) mapping approach has been applied to crosses between different inbred mouse strains to identify genetic loci associated with plasma HDL cholesterol levels. Although successful, a disadvantage of this method is low mapping resolution, as often several hundred candidate genes fall within the confidence interval for each locus. Methods have been developed to narrow these loci by combining the data from the different crosses, but they rely on the accurate mapping of the QTL and the treatment of the data in a consistent manner. We collected 23 raw datasets used for the mapping of previously published HDL QTL and reanalyzed the data from each cross using a consistent method and the latest mouse genetic map. By utilizing this approach, we identified novel QTL and QTL that were mapped to the wrong part of chromosomes. Our new HDL QTL map allows for reliable combining of QTL data and candidate gene analysis, which we demonstrate by identifying Grin3a and Etv6, as candidate genes for QTL on chromosomes 4 and 6, respectively. In addition, we were able to narrow a QTL on Chr 19 to five candidates.http://www.sciencedirect.com/science/article/pii/S0022227520422035high-density lipoproteinquantitative trait locusmeta-analysis |
spellingShingle | Cheryl Ackert-Bicknell Beverly Paigen Ron Korstanje Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysis Journal of Lipid Research high-density lipoprotein quantitative trait locus meta-analysis |
title | Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysis |
title_full | Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysis |
title_fullStr | Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysis |
title_full_unstemmed | Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysis |
title_short | Recalculation of 23 mouse HDL QTL datasets improves accuracy and allows for better candidate gene analysis |
title_sort | recalculation of 23 mouse hdl qtl datasets improves accuracy and allows for better candidate gene analysis |
topic | high-density lipoprotein quantitative trait locus meta-analysis |
url | http://www.sciencedirect.com/science/article/pii/S0022227520422035 |
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