Volume 42 Issue 7, July 2010

Sequence conservation of noncoding DNA across species can indicate functional conservation. However, a new study demonstrates notable differences between human and mouse stem cell regulatory networks, suggesting caution in generalizing from sequence to functional conservation.

Although susceptibility loci identified through genome-wide association studies (GWAS) typically explain only a small proportion of the heritability, a classical quantitative genetic analysis now argues that considering together all common SNPs can explain a large proportion of the heritability of these complex traits. A related study provides recommendations for the sample sizes needed in future GWAS to identify additional susceptibility loci.

The virulence of Candida albicans, a major human fungal pathogen, has been considered dependent on the ability to transition between different morphologies. A new study reports a screen of C. albicans mutants that demonstrates that pathogenesis can be dissociated from morphological switching and in vitro growth rate.

Peter Visscher and colleagues report an analysis of the heritability explained by common variants identified through genome-wide association studies. They find that 45% of the variance for height can be explained by using a linear model to simultaneously consider the combined effect of common SNPs.

Nilanjan Chatterjee and colleagues report an analysis of the number and effect size distribution of susceptibility variants identified from current genome-wide association studies. They estimate the number of susceptibility loci expected to be discovered by GWAS over a range of sample sizes and compare to recent findings from GWAS for height, Crohn's disease and several cancers.

Richard Spritz and colleagues identify variants on 3p13 and 6q27 associated with generalized vitiligo, a common autoimmune disorder with loss of melanocytes and depigmentation.

Mark McCarthy and colleagues identify twelve new risk loci for type 2 diabetes through a large-scale genome-wide association and replication study in individuals of European ancestry. The identified loci affect both beta-cell function and insulin action and are enriched for genes involved in cell cycle regulation.

Suzanne Noble and colleagues present a library of ∼3,000 homozygous gene deletion strains of Candida albicans. The authors screened for infectivity in a mouse model and for yeast-to-hypha morphological switching. They identified 115 infectivity-attenuated mutants, half of which demonstrated normal morphological switching.

Yi-Xin Zeng and colleagues performed a genome-wide association study for nasopharyngeal cancer in Southern Chinese. The authors report three new susceptibility loci for nasopharyngeal cancer.

Clare Turnbull and colleagues identify three new risk loci for testicular germ cell cancer. The newly discovered risk variants reside near the telomere regulator genes TERT and ATF7IP and the sex determination gene DMRT1.

Andrew Johnson and colleagues report a genome-wide association study for platelet aggregation in response to three different agonists, ADP, collagen and epinephrine.

Youwen Zhou and Xue-Jun Zhang and colleagues report a genome-wide association study of generalized vitiligo, a common autoimmune disorder characterized by loss of melanocytes and depigmentation. The authors identify two independent associations within the MHC region and one new susceptibility locus on chromosome 6q27, which contains the genes RNASET2, FGFR1OP and CCR6.

Joseph Gleeson and colleagues report that mutations in TMEM216 cause Joubert, Meckel and related syndromes. They further show that TMEM216 localizes to the base of cilia and that its loss leads to defects in ciliogenesis and centrosome docking.

George Daley and colleagues show that transgenic mice expressing elevated levels of Lin28a have increased body size and delayed onset of puberty. These findings support human association studies implicating the LIN28B locus in height variation and timing of menarche.

Guillaume Bourque and colleagues report genome-wide binding profiles of the OCT4, NANOG and CTCF proteins in human ES cells as determined by ChIP-sequencing. They find that the binding profiles of OCT4 and NANOG are different in human and mouse ES cells, and some of the differences in bound sites are due to transposable elements.

Takeshi Izawa and colleagues report that the rice florigen gene Hd3a, which triggers photoperiodic flowering, is toggled by a 30-minute change in day length. They report that Hd3a transcription is controlled by two gating mechanisms involving the floral promoter Ehd1 and the floral repressor Ghd7.