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...

Full description

Bibliographic Details
Main Authors: Cheryl Ackert-Bicknell, Beverly Paigen, Ron Korstanje
Format: Article
Language:English
Published: Elsevier 2013-04-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520422035
_version_ 1818740440003772416
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.
first_indexed 2024-12-18T01:40:45Z
format Article
id doaj.art-eb36f85166f3476d8d8118112c59cd91
institution Directory Open Access Journal
issn 0022-2275
language English
last_indexed 2024-12-18T01:40:45Z
publishDate 2013-04-01
publisher Elsevier
record_format Article
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
work_keys_str_mv AT cherylackertbicknell recalculationof23mousehdlqtldatasetsimprovesaccuracyandallowsforbettercandidategeneanalysis
AT beverlypaigen recalculationof23mousehdlqtldatasetsimprovesaccuracyandallowsforbettercandidategeneanalysis
AT ronkorstanje recalculationof23mousehdlqtldatasetsimprovesaccuracyandallowsforbettercandidategeneanalysis