Volume 40 Issue 11, November 2008

A newly described Lgr5-expressing cell population is poised to depose the reigning monarch of the follicular hierarchy, the label-retaining cell, to claim the title as stem cell of the hair follicle.

Two new studies report the results of genome-wide association analysis for androgenetic alopecia. The two major genetic loci identified set the scene for understanding the molecular basis of common male-pattern baldness.

Constitutional epigenetic defects affecting the 11p15.5 imprinted region cause a number of syndromic conditions involving birth defects. Now, an analysis of a large cohort of individuals with nonsyndromic Wilms tumor demonstrates the presence of known and newly identified constitutional IGF2-H19 imprinting defects, extending the phenotype associated with soma-wide 11p15.5 imprinting disorders.

Two new studies identify PROG1, a gene underlying a quantitative trait locus that regulates rice tiller angle and that has likely been a target for artificial selection during rice domestication. Genetic manipulation of PROG1 has the potential to promote agronomically valuable traits.

A new study identifies the gene that, when mutated, causes autosomal recessive retinitis pigmentosa 25 (arRP25). The RP25 gene encodes an ortholog of Drosophila spacemaker (eyes shut), thus emphasizing common biological functions between Drosophila sensory systems and the human eye.

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.

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.

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.

Stanislav Kmoch and colleagues identify mutations in TMEM70 in individuals with isolated mitochondrial ATP synthase deficiency, and demonstrate that complementation of cell lines of affected individuals with wild-type TMEM70 restores ATP synthase function.

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.

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.

Kari Stefansson and colleagues report results of a genome-wide association study for urinary bladder cancer. The strongest association was with a variant on 8q24, located 30 kb upstream of MYC in a haplotype block distinct from previously reported 8q24 cancer risk variants.

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.

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.

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

Hannie Kremer and colleagues report the identification of mutations in LROMT associated with profound nonsyndromic hearing loss. LRTOMT has two alternative reading frames and encodes two different proteins, LRTOMT1 and LRTOMT2.

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.

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

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.

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.

Erik Jorgensen and colleagues report a highly efficient method for generating single-copy transgene insertions in C. elegans. Notably, these single-copy transgenes are expressed at endogenous levels and can be expressed in the female and male germlines.