International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 60 - IDENTIFICATION OF POSITIONAL CANDIDATE GENES FOR GROWTH AND OBESITY

Aksu S, Neuschl C, Renne U, Koczan D, Thiesen HJ, Brockmann GA

Humboldt-University of Berlin, Berlin, Germany

One of the major challenges in modern biology is to understand the genetic basis of complex traits, such as body weight and fat accumulation. Obesity is often associated with many other severe diseases, for example, hypertension, diabetes, cardiovascular diseases, osteoarthritis, and certain cancers. In our study, we have used the high body weight selected mouse line DU6 and its inbred derivate DU6i, which contain the biggest mice known world-wide, and the mouse lines DBA/2 and DUKs as unselected controls. High body weight selected mice are twice as heavy and three times as fat as unselected control mice. Furthermore, the selection strain DU6 has highly elevated serum concentrations of insulin, leptin, IGF-I and IGF binding proteins. So far, many QTLs have been mapped for body weight, body composition and subcomponents of the endocrine control of growth in the cross between the lines DU6i and DBA/2. Microarray expression analysis showed, that 77 genes are differentially expressed in fat tissues between the selected and non-selected mouse lines. 10 out of 77 genes are located in QTL regions which affect body weight and fat accumulation. Semi-quantitative real-time PCR analysis of these 10 positional candidate genes confirmed the data obtained from microarray GeneChip analyses. Therefore we used these genes for further analyses. We comparatively sequenced promotor regions of 10 positional candidate genes in selected and control mouse lines to find DNA variants which could contribute to differences in gene-expression levels. We found polymorphisms which are identical for DU6 and DU6i. Some of these polymorphisms are located within potential transcription factor binding sites. There are candidate polymorphisms which could underlie the detected QTL effects.

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