Prioritization of positional candidate genes using multiple web-based software tools.

The prioritization of genes within a candidate genomic region is an important step in the identification of causal gene variants affecting complex traits. Surprisingly, there have been very few reports of bioinformatics tools to perform such prioritization. The purpose of this article is to investigate the performance of 3 positional candidate gene software tools available, PosMed, GeneSniffer and SUSPECTS.

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants.

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Association of genetic variation within UBL5 with phenotypes of metabolic syndrome.

The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat, and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON, UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity.

Genetic variation in selenoprotein S influences inflammatory response.

Chronic inflammation has a pathological role in many common diseases and is influenced by both genetic and environmental factors. Here we assess the role of genetic variation in selenoprotein S (SEPS1, also called SELS or SELENOS), a gene involved in stress response in the endoplasmic reticulum and inflammation control. After resequencing SEPS1, we genotyped 13 SNPs in 522 individuals from 92 families.

Genetic variation in BEACON influences quantitative variation in metabolic syndrome-related phenotypes.

The BEACON gene (also known as UBL5) was identified as differentially expressed between lean and obese Psammomys obesus, a polygenic animal model of obesity, type 2 diabetes, and dyslipidemia. The human homologue of BEACON is located on chromosome 19p, a region likely to contain genes affecting metabolic syndrome-related quantitative traits as established by linkage studies. To assess whether the human BEACON gene may be involved in influencing these traits, we exhaustively analyzed the complete gene for genetic variation in 40 unrelated individuals and identified four variants (three novel).