Research articles

Hadi Al-Hasani and colleagues report that a frameshift deletion in Tbc1d1 in lean SJL mice underlies a quantitative trait locus conferring protection against high-fat diet-induced obesity. TBC1D1 seems to influence metabolism by regulating fatty acid uptake and oxidation in skeletal muscle cells.

Erin O'Shea and colleagues present a quantitative model of the Hog1 MAPK-dependent osmotic stress response in budding yeast derived from gene expression analyses in single- and multiple-mutant strains. The network reveals interactions involved in signal integration and processing and could serve as model for investigations into other gene regulatory networks.

Tim Spector and colleagues report a genome-wide association study for androgenic alopecia, or male-pattern baldness. They confirm a previous association with the gene encoding the androgen receptor, and identify a new association at chromosome 20p11.22, between the PAX1 and FOXA2 genes.

Axel Hillmer and colleagues present a genome-wide association study for male-pattern baldness. They confirm a previous association with the gene encoding the androgen receptor, and report replicated associations for five SNPs on chromosome 20p11.

Rune Toftgård and colleagues report that Lgr5, a G protein-coupled receptor recently identified as a marker of intestinal stem cells, marks a population of hair follicle stem cells that is actively proliferating and able to give rise to all cell types in the mouse hair follicle.

Simon Stacey and colleagues report results of a genome-wide association study for cutaneous basal cell carcinoma. They identify two loci, at 1p36 and 1q42, associated with BCC risk, and show that neither is associated with melanoma or pigmentation traits.

Stefan Schreiber and colleagues report the results of a genome-wide association study for ulcerative colitis. Variants flanking the gene encoding the cytokine IL10 are associated with increased risk of disease, as are several other loci.

Shomi Bhattacharya and colleagues report the identification of six independent mutations in an ortholog of Drosophila eys in families with autosomal recessive retinitis pigmentosa from diverse ancestral origins. A phylogenetic analysis of this gene, which spans more than 2 Mb, suggests that it has a role in the modeling of retinal architecture.

Nonsyndromic cleft lip with or without cleft palate has been associated with SNPs in the IRF6 gene. Now Jeff Murray and colleagues report the identification of a common variant in a previously unknown IRF6 enhancer that shows strong evidence of association with cleft lip only and disrupts the binding site of transcription factor AP-2α.

Nazneen Rahman and colleagues report the identification of constitutional imprinting center mutations, epimutations and uniparental disomy in individuals with nonsyndromic Wilms tumors.

Doug Epstein and colleagues present biochemical and transgenic studies implicating Six3 in the regulation of Shh forebrain expression through direct binding to a remote enhancer. The work was driven by the discovery of a rare variant in this enhancer in an individual with holoprosencephaly

Katsushi Tokunaga and colleagues report the results of a genome-wide association study for narcolepsy. A variant on chromosome 22 between CPT1B and CHKB is associated with increased risk of the disorder. Both gene products have previously been linked to the physiology of sleep, making each a potential susceptibility factor.

Chuanqing Sun and colleagues show that the gene PROG1, encoding a zinc-finger protein, determines the erect growth habit in rice. Sequencing of 182 varieties of cultivated rice reveals an identical mutation in the PROG1 coding region, suggesting a common origin for erect growth during rice domestication.

Hong-Xuan Lin and colleagues report that the gene PROG1 has an important role in determining the architecture of wild rice, including tiller angle and number of tillers. PROG1 encodes a zinc-finger transcription factor, and the authors suggest that selection of an amino acid substitution in PROG1 during domestication facilitated the transition to the architecture of domesticated rice.

Zuhua He and colleagues identify the gene underlying a quantitative trait locus for grain-filling in rice, which contributes to grain weight. The gene, GIF1, encodes a protein with cell-wall invertase activity and may have been under selection during rice domestication.

Helen Hobbs and colleagues report an association between coding variation in PNPLA3 and susceptibility to nonalcoholic fatty liver disease. The associated alleles vary in frequency among Hispanics, African Americans and European Americans and contribute to differences in disease prevalence among these ancestry groups.

Thaddeus Dryja and colleagues identify homozygous loss-of-function mutations in IDH3B, encoding the beta subunit of the NAD-specific isocitrate dehydrogenase enzyme, in two families with retinitis pigmentosa. The absence of obvious clinical phenotypes outside of the retina suggests that the NADP-specific form of this enzyme can compensate for the absence of the NAD-specific form in most human tissues.

Edward Patterson and colleagues report that a missense mutation in the gene encoding dynamin 1 (DNM1) is associated with exercise-induced collapsed in Labrador retriever dogs. This is the first documented mutation in DNM1 in mammals and suggests a critical role for dynamin 1 in maintaining proper neurotransmission under conditions of high synaptic activity.

Ralf Sommer and colleagues present a draft genome sequence of the nematode Pristionchus pacificus, a species that lives in association with beetles and shows a major expansion of protein-coding genes. Comparative analysis with the genomes of the ecologically distinct nematodes C. elegans and B. malayi suggests insights into the association between their genome structures and differing lifestyles.

Jane Worthington and colleagues report that three SNPs, located on chromosomes 10p15, 12q13 and 22q13, are associated with susceptibility to rheumatoid arthritis. These SNPs had previously been putatively associated with rheumatoid arthritis in the genome-wide association study conducted by the Wellcome Trust Case Control Consortium.