Volume 40 Issue 8, August 2008

A new study of pigmentation in mice has revealed a surprising link between dark skin and defects in ribosomal proteins. The demonstration that this phenotype is mediated via cell-specific stabilization of p53 suggests insights into the pathogenesis of human diseases such as Diamond-Blackfan anemia caused by similar defects in ribosomal proteins.

The linked maternally expressed H19 and paternally expressed Igf2 genes use a CTCF-dependent DNA methylation–sensitive insulator to govern their allele-specific imprinting patterns. Contrary to expectations, a new study shows that the noncoding H19 RNA has a marsupial ortholog and that key features of the locus are similar, indicating that the imprinting regulation of this locus is conserved among therian mammals.

Developmentally regulated expression of the transcriptional repressor Prdm1 (Blimp1) in the early mammalian embryo controls global epigenetic changes required for specification of primordial germ cells. A new study demonstrates that a close family member, Prdm14, similarly activated in response to Bmp and Smad signals, also has an essential role during establishment of the germ cell lineage.

Pervasive genome-wide transcription is widespread in eukaryotic cells, but key features of the transcriptome have yet to be fully characterized. A new study using antibody-based detection of RNA-DNA duplexes on tiling arrays now reveals a complex, strand-specific transcriptional world in fission yeast.

Colleen McBride and colleagues argue that progress on a multifaceted research agenda is necessary to reap the full benefits and avoid the potential pitfalls of the emerging area of personalized genomics. They also outline one element of this agenda, the Multiplex Initiative, which has been underway since 2006.

Philippe Froguel and colleagues report that common nonsynonymous variants in PCSK1, encoding a prohormone convertase, confer risk of obesity in individuals of European ancestry.

Juliane Winkelmann and colleagues report that two common variants in the 5′ UTR of PTPRD are independently associated with restless legs syndrome. PTPRD encodes a receptor-like protein tyrosine phosphatase previously implicated in axon guidance and motor neuron development.

Deborah Mackay and colleagues identify mutations in ZFP57, encoding a zinc-finger transcription factor, in families with transient neonatal diabetes and additional clinical features. Affected individuals have a variable pattern of DNA hypomethylation at multiple imprinted loci.

Theodore Kurtz and colleagues report that Cd36 expression in the kidney underlies a quantitative trait locus for essential hypertension in the rat. Cd36 affects levels of cyclic GMP, a downstream effector of nitric oxide signaling, consistent with published data that reduced nitric oxide activity in the kidney is associated with hypertension.

Mark Daly and colleagues present results of a combined analysis of data from three recent genome-wide association studies for Crohn's disease, followed by replication in a large independent sample collection. Their results confirm 11 previously reported risk loci and provide genome-wide significant evidence for 21 new loci associated with the disease.

Greg Barsh and colleagues show that two loci for dark skin in mice result from mutations in Rps19 and Rps20, encoding the ribosomal proteins S19 and S20. They further show that the dark skin phenotype and other pleiotropic effects of these mutations, including reduced erythrocyte count and body size, are mediated through stabilization of p53.

Wolf Reik and Ian Dunham and colleagues cloned and sequenced the complete IGF2-H19 locus in tammar wallaby, a marsupial. Functional analyses revealed conservation of imprinting mechanisms, including germline DNA methylation, between marsupials and eutherians.

Bradley Cairns and colleagues report a high-resolution strand-specific transcriptome of the fission yeast Schizosaccharomyces pombe. They survey the transcriptome under multiple growth conditions using an RNA-DNA hybridization mapping (HybMap) technique, and find that most of the euchromatic genome is transcribed.

Isolates of Salmonella enterica serovar Typhi (Typhi), a human-restricted bacterial pathogen that causes typhoid, show limited genetic variation. Kathryn Holt and colleagues now compare whole-genome sequences of 19 Typhi isolates dispersed throughout the phylogenetic tree of this pathogen, revealing notably little evidence of purifying selection, antigenic variation or recombination between isolates.

Shiro Ikegawa and colleagues identify a variant in a newly identified gene, DVWA, that is associated with susceptibility to knee osteoarthritis. DVWA contains von Willebrand factor domains and is expressed specifically in cartilage.

Daniel Cohn and colleagues identify mutations in the gene encoding the calcium-permeable cation channel TRPV4 in families with autosomal dominant brachyolmia. Functional studies show that the mutations result in gain-of-function of channel activation.

Gray horses are born colored but gradually lose hair pigmentation and become white, a trait that is transmitted in an autosomal dominant manner. Leif Andersson and colleagues report that the the mutation causing the Gray phenotype is a 4.6-kb duplication in intron 6 of STX17, which promotes overexpression of both STX17 and the neighboring gene NR4A3 in melanomas from Gray horses.

Helen McNeill and colleagues show that loss of Fat4, a homolog of the Drosophila planar cell polarity protein Fat, disrupts oriented cell division, leading to a failure of tubule elongation and cystic kidney disease in mice. The findings suggest that loss of planar cell polarity may underlie some forms of cystic kidney disease in humans.

Mitinori Saitou and colleagues report that Prdm14, which encodes a transcription factor expressed exclusively in the germ cell lineage, is essential for re-acquisition of pluripotency and epigenetic reprogramming of primordial germ cells.

Takeshi Izawa and colleagues report the cloning of a gene underlying a rice quantitative trait locus influencing grain width. A deletion in qSW5 increases yield of rice grains, and the authors show that this mutation has likely been selected for during the domestication of rice.