Feinkartierung einer Kopplungsregion auf Chromosom 10p für frühmanifeste Adipositas mittels sieben Mikrosatellitenmarkern an 123 Familien bestehend aus mindestens zwei adipösen Geschwistern und ihren Eltern.

Im Rahmen der Suche nach genetischen Ursachen des komplexen Phänotyps Adipositas wurde von einer französischen Arbeitsgruppe eine Kopplungsregion für extreme Adipositas auf Chromosom 10p12 identifiziert (Hager et al. 1998). Dieser Befund konnte kurz darauf bestätigt werden (Hinney et al. 2000). Ziel...

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Bibliographic Details
Main Author: Vogel, Markus
Contributors: Hebebrand, Johannes Prof. Dr. med. (Thesis advisor)
Format: Dissertation
Language:German
Published: Philipps-Universität Marburg 2002
Medizin
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Table of Contents: In the context of the search for genetic causes of the complex phenotype obesity a linkage region for extreme adiposity on chromosom 10p12 was identified by a french group (Hager et al 1998). This findings could be confirmed shortly after (Hinney et al 2000). A goal of this work was the initial fine mapping of the region. For that purpose seven microsatellite markers spanning approximately 5 cM were used (LDB (Collins et al 1996)). The genotyping was made at one in relation to the preliminary investigations (Hinney et al 2000) extended patient collective. The available study concentrated on early onset obesity. 123 families participated in the study consisting of at least two obese brothers and sisters and their parents (509 individuals). All extremely concordant sib-pairs (n=263) had a BMI > 90th percentile. The BMI of 128 children and adolescents (48.67%) was > 99th BMI percentile (Coners et al 1996; Hebebrand et al 1996). Both parents were genotyped in all families. The markers D10S1639, D10S1732, D10S1426, D10S208, D10S183, D10S1654 and D10S1768 were used in order to do a fine mapping by means of IBD linkage analysis as well as testing for transmission disequilibrium (Spielman et al 1993). Two point and multipoint analysis by means of maximum likelihood binomial (MLB) were conducted (Ziegler 1999). In order to perform the TDT 263 trios were formed out of the 123 families consisting of obese children (sex and age specific BMI > 90th percentile) and their two parents. The findings of Hager (Hager et al. 1998) and Hinney (Hinney et al. 2000) could be confirmed, the gene region however could not be narrowed down further in the context of the fine mapping with the available data. The maximum MLB of 1,26 was obtained for the most distal marker D10S1639. TDT tests for all studied markers were negative both for alleles and haplotypes after correction for multiple testing.