meta-analysis of quantitative trait loci associated with body weight and adiposity in mice

Objective: Cross-breeding experiments with different mouse strains have successfully been used by many groups to identify genetic loci that predispose for obesity. In order to provide a statistical assessment of these quantitative trait loci (QTL) as a basis for a systematic investigation of candida...

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Bibliographic Details
Published in:	International Journal of Obesity Vol. 31; no. 5; pp. 829 - 841
Main Authors:	Wuschke, S, Dahm, S, Schmidt, C, Joost, H.G, Al-Hasani, H
Format:	Journal Article
Language:	English
Published:	Basingstoke Nature Publishing 01-05-2007 Nature Publishing Group
Subjects:	Adipose Tissue animal models Animals Biological and medical sciences body fat Body weight Body Weight - genetics chromosome mapping Chromosomes Complications and side effects crossing Dehydrogenase Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology Gene expression Gene mapping Genetic aspects Genome - genetics Humans linkage (genetics) Medical sciences meta-analysis Metabolic diseases Mice nutrition Obesity Obesity - genetics Physiological aspects quantitative trait loci Quantitative Trait Loci - genetics Rodents Species Specificity Systematic review Vertebrates: anatomy and physiology, studies on body, several organs or systems Germany Adipose tissue Methodology genome-wide scan Anthropometry Body weight Metaanalysis Association Adiposity Genetics Candidate gene Nutritional status Obesity Nutrition Rodentia Nutrition disorder Metabolic diseases Corporal biometry Method Quantitative trait loci Vertebrata Mammalia Mouse candidate genes Animal Genetic linkage Truncated shape truncated product method
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Summary:	Objective: Cross-breeding experiments with different mouse strains have successfully been used by many groups to identify genetic loci that predispose for obesity. In order to provide a statistical assessment of these quantitative trait loci (QTL) as a basis for a systematic investigation of candidate genes, we have performed a meta-analysis of genome-wide linkage scans for body weight and body fat. Data: From a total of 34 published mouse cross-breeding experiments, we compiled a list of 162 non-redundant QTL for body weight and 117 QTL for fat weight and body fat percentage. Collectively, these studies include data from 42 different parental mouse strains and >14 500 individual mice. Methods: The results of the studies were analyzed using the truncated product method (TPM). Results: The analysis revealed significant evidence (logarithm of odds (LOD) score >4.3) for linkage of body weight and adiposity to 49 different segments of the mouse genome. The most prominent regions with linkage for body weight and body fat (LOD scores 14.8-21.8) on chromosomes 1, 2, 7, 11, 15, and 17 contain a total of 58 QTL for body weight and body fat. At least 34 candidate genes and genetic loci, which have been implicated in regulation of body weight and body composition in rodents and/or humans, are found in these regions, including CCAAT/enhancer-binding protein alpha (C/EBPA), sterol regulatory element-binding transcription factor 1 (SREBP-1), peroxisome proliferator activator receptor delta (PPARD), and hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1). Our results demonstrate the presence of numerous distinct consensus QTL regions with highly significant LOD scores that control body weight and body composition. An interactive physical map of the QTL is available online at http://www.obesitygenes.org.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 ObjectType-Review-3
ISSN:	0307-0565 1476-5497
DOI:	10.1038/sj.ijo.0803473