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A Genetical Genomics Approach to Genome Scans Increases Power for QTL Mapping  

2011-09-16 10:28:57|  分类: 文献学习 |  标签: |举报 |字号 订阅

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Abstract:
We describe a method for integrating gene expression information into genome scans and show that this can substantially increase the statistical power of QTL mapping. The method has three stages. First, standard clustering methods identify small (size 5-20) groups of genes with similar expression patterns. Second, each gene group is tested for a causative genetic locus shared with the clinical trait of interest. This is done using an EM algorithm approach that treats genotype at the putative causative locus as an unobserved variable and combines expression information from all of the genes in the group to infer genotype information at the locus. Finally, expression QTL (eQTL) are mapped for each gene group that shares a causative locus with the clinical trait. Such eQTL are candidates for the causative locus. Simulation results show that this method has far superior power to standard QTL mapping techniques in many circumstances. We applied this method to existing data on mouse obesity. Our method identified 27 putative body weight QTL, whereas standard QTL mapping produced only one. Furthermore, most gene groups with body weight QTL included cis genes, so candidate genes could be immediately identified. Eleven body weight QTL produced 16 candidate genes that have been previously associated with body weight or body weight-related traits, thus validating our method. In addition, 15 of the 16 other loci produced 32 candidate genes that have not been associated with body weight. Thus, this method shows great promise for finding new causative loci for complex traits.
DOI:
DOI 10.1534/genetics.110.123968
Date:
MAR 2011
Type of Article:
Article
ISSN:
0016-6731
Accession Number:
ISI:000288457800024
Keywords:
QUANTITATIVE TRAIT LOCI;NATURAL-POPULATIONS;EXPRESSION;DISEASE;IDENTIFICATION;ASSOCIATION;ALGORITHM;NETWORKS;PATHWAY;MOUSE
URL:
GENETICS SOC AM转到该网页
Author Address:
Schliekelman, P (reprint author), Univ Georgia, Dept Stat, 203 Stat Bldg, Athens, GA 30602 USA;Univ Georgia, Dept Stat, Athens, GA 30602 USA
Language:
English
Times Cited:0
Notes:
Cited References Count:43; GENETICS SOC AM; 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
Added to Library:16 Sep 2011
Last Updated:16 Sep 2011
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