Linkage of body mass index to chromosome 20 in Utah pedigrees

Abstract

Several linkage studies have hinted at the existence of an obesity predisposition locus on chromosome 20, but none of these studies has produced conclusive results. Therefore, we analyzed 48 genetic markers on chromosome 20 for linkage to severe obesity (BMI> or =35) in 103 extended Utah pedigrees (1,711 individuals), all of which had strong aggregation of severe obesity. A simple dominant model produced a maximum multipoint heterogeneity LOD score of 3.5 at D20S438 (55.1 cM). Two additional analyses were performed. First, a one-gene, two-mutation model (with one dominant mutation and one recessive mutation) increased the LOD score to 4.2. Second, a two-locus model (with one locus dominant and one recessive) generated a multipoint LOD score of 4.9. We conclude that one or more severe obesity predisposing genes lie within an interval of approx. 10 cM on chromosome 20. This study generated significant LOD scores which confirm suggestive linkage reports from previous studies. In addition, our analyses suggest that the predisposing gene(s) is localized very near the chromosome 20 centromere.

Fine Mapping Reveals Sex Bias in Quantitative Trait Loci Affecting Growth, Skeletal Size and Obesity-Related Traits on Mouse Chromosomes 2 and 11

“…Numerous linkages between HSA20 and obesity-related traits have been identified (Lembertas et al 1997;Hunt et al 2001;Dong et al 2003;Gorlova et al 2003;Collaku et al 2004). Additionally, the Mendelian syndromes Bardet-Biedl syndrome 6 (Katsanis et al 2001) and Albright hereditary osteodystrophy (Patten et al 1990), which are associated with obese states, are located on HSA20.…”

Major quantitative trait locus on chromosome 2 for glucose tolerance in diabetic SMXA-5 mouse established from non-diabetic SM/J and A/J strains

“…The chromosomal region with significant linkage of blood glucose concentration at 120 min during IPGTT is homologous to human chromosomes 2q11-q32, 9q33-34, 11p14-q12, 15q13-q21 and 20p13-11, and to rat chromosome 3. Human chromosomes 2 [35] and 20 [36][37][38][39] encompass the region associated with insulin resistance. In the WOKW rat, the homologous region on rat chromosome 3 contains a QTL that affects AUC during IPGTT [40].…”

Sex-Limited Genome-Wide Linkage Scan for Body Mass Index in an Unselected Sample of 933 Australian Twin Families

“…However, linkage analyses conducted on BMI have consistently identified regions located on chromosomes 7 Duggirala et al, 1996;Feitosa et al, 2002;Heijmans et al, 2004;Lapsys et al, 1997;Reed et al, 1996;Roth et al, 1997), 10 (Deng et al, 2002Hunt et al, 2001;Lee, 1999;Norman et al, 1998), 13 (Hager et al, 1998;Hinney et al, 2000;Price et al, 2001) and 20 (Feitosa et al, 2002;Lee, 1999). Furthermore, other findings suggest the influence of genes located on chromosomes 3 (Hsueh et al, 2001), 4 (Deng et al, 2002;Stone et al, 2002), 5 (Clement et al, 1999;Perola et al, 2001) and 11 (Atwood et al, 2002;Hanson et al, 1998) may play a role in the development of obesity.…”