Volume 40 Issue 12, December 2008

Embryonic stem (ES) cells undergo rapid cell division without compromising their ability to differentiate into virtually all cell types. Using ES cells deficient for a microRNA biogenesis factor, Dgcr8, a new report uncovers the importance of specific microRNAs in the ES cell cycle transition from G1 to S phase.

Copy number variation has emerged as an important type of genetic risk factor for developmental disorders, including the neurodevelopmental disorders schizophrenia, autism and mental retardation. The highly pleiotropic effects observed for specific copy number variants (CNVs) challenge current classification of these disorders, but also provide opportunities to understand their origins and the relationships between them.

Fat accumulation in the liver is a common trait that may progress to severe liver disease. A new study identifies common and rare nonsynonymous variants in PNPLA3 that are associated with hepatic triglyceride content and that may explain some of the population differences in prevalence.

Jason Cooper and colleagues identify four new risk loci for type 1 diabetes through a meta-analysis of data from three genome-wide association studies, with replication in additional case-control and family-based samples, providing further insights into the genetic risk factors underlying this disease.

Rogier Hintzen and colleagues report the results of a search for genetic variants associated with susceptibility to multiple sclerosis in a genetically isolated population that lead to identification of a new susceptibility locus in the region of the KIF1B gene on chromosome 1.

Paul Brennan and colleagues report a genome-wide association study for lung cancer susceptibility. In addition to a previously reported variant at 15q25, they detect and replicate a new association at 5p15.33.

Richard Houlston and colleagues report a genome-wide association study for lung cancer susceptibility. In addition to confirming a previous association at 15q25.1, they identify and replicate two new risk loci at 6p21.33 and 5p15.33.

Stefan Mundlos and colleagues report the identification of mutations in SCYL1BP1 in families with gerodermia osteodysplastica, a disorder characterized by wrinkly skin and osteoporosis. SCYL1BP1 localizes to the Golgi apparatus and interacts with Rab6.

Benjamin Blencowe and colleagues report the application of next-generation sequencing technology to alternative splicing in the human genome. They detect alternative splicing events in 85% of multiexon genes, and conclude that there are approximately 100,000 such events in major human tissues.

Jason Johnson and colleagues present the first genome-scale compendium of human alternative splicing events in 48 tissues. These data constitute a rich resource for the study of splicing in the human genome and its impact on development, physiology and disease.

Richard Houlston and colleagues identify four new susceptibility loci for colorectal cancer through a meta-analysis of genome-wide association data, followed by replication testing in a large collection of independent samples. The study brings to ten the number of confirmed loci harboring low-penetrance risk alleles for this common malignancy.

Owen Sansom and colleagues show that conditional deletion of Pten specifically from the small intestinal epithelium in mice does not disrupt normal tissue architecture, but in the context of Apc deficiency leads to rapid development of adenocarcinoma. These findings suggest that Pten does not serve a rate-limiting, intrinsic role in regulating normal intestinal stem cell physiology.

Sudipto Roy and colleagues report that zebrafish homologs of the transcription factor Foxj1 are sufficient to induce the motile ciliogenic program by upregulating expression of genes encoding key components of the motile ciliary machinery. Similar findings are reported in a related study by Chris Kintner and colleagues.

Chris Kintner and colleagues report that a Xenopus homolog of the transcription factor Foxj1 is sufficient to induce motile cilia by upregulating expression of genes encoding key components of the motile ciliary machinery. Similar findings are reported in a related study by Sudipto Roy and colleagues.

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.

Ankita Patel and colleagues report microdeletions and microduplications on chromosome 1q21.1 in a series of individuals with features of microcephaly and macrocephaly, as well as developmental delay and neuropsychiatric abnormalities.

Richard Lifton and colleagues report the identification of three susceptibility loci for intracranial aneurysm. Two of the loci are new, with SNPs on chromosome 8q likely acting through SOX17, which is required for the formation and maintenance of endothelial cells.

Robert Blelloch and colleagues report the use of Dgcr8 knockout embryonic stem cells to identify ES cell-specific microRNAs that regulate the G1-S transition of the ES cell cycle.

Eric Shoubridge and colleagues report that the mitochondrial DNA genetic bottleneck occurs during postnatal ovarian folliculogenesis, when a subpopulation of mtDNAs is preferentially replicated.

Siegbert Melzer and colleagues report that in Arabidopsis the absence of MADS box proteins SOC1 and FUL leads to phenotypes of perennial woody plants, with indeterminate meristems, secondary growth with wood formation, and recurrent growth cycles.

Michael Elowitz and colleagues demonstrate that dynamic correlations in gene expression noise, as revealed using single-cell time-lapse microscopy showing time lags due to regulation, can be used to characterize active regulatory links in a synthetic and an endogenous network.

Gavin Sherlock and colleagues report an experimental genome evolution study in Saccharomyces cerevisiae demonstrating adaptive evolution by clonal interference.