News & Views

Several devastating genetic diseases illustrate that peroxisomes are essential to the development and functioning of the central nervous system. New work using a mouse model now shows that peroxisome integrity in oligodendrocytes is essential for axonal maintenance.

Two genome-wide association studies report three loci predisposing to restless legs syndrome, a common sleep disorder also associated with periodic limb movements during sleep. The identified variants account for a large portion of population-attributable risk in individuals of European ancestry and may preferentially affect various symptoms of the disorder.

Genome-wide association studies, exemplified by the Wellcome Trust Case Control Consortium and follow-up studies, have identified dozens of common variants robustly associated with common diseases, providing new clues about genetic architecture in humans. Finding all such loci, and fully defining genotype-phenotype correlation, will be a key to translating initial clues into pathophysiological understanding and clinical prediction.

Human genome-wide association studies pose a challenge in identifying significant disease associations from nearly half a million statistical tests. A new report describes an especially promising approach, recently applied to the Wellcome Trust Case Control Consortium data sets, that uses the correlated structure of genomic variation to impute genotypes at missing sites and to test association with both observed and imputed SNPs.

The much-anticipated publication of the ENCODE pilot project, representing a detailed and comprehensive characterization of 1% of the human genome, has demonstrated how little we truly understand about how our genes are regulated. Transcripts are nearly everywhere, regulatory sequences remain poorly defined and evolutionary conservation is a surprisingly inadequate predictor of transcriptional features.

Wnt signaling regulates several aspects of development and tissue homeostasis. Two new studies in this issue uncover the underlying mechanism for focal dermal hypoplasia, a multiorgan developmental disorder, and underscore the important role of Wnt proteins in ectodermal-mesodermal communication.

The list of genetic diseases associated with dysfunction of primary cilia continues to expand. Two new studies add to this growing body of literature and provide a fascinating example of the clinical variability associated with ciliary disorders.

Although common obesity has a strong genetic component, there has been little success in the discovery of the underlying genetic causes. This has now changed, as two independent studies demonstrate strong association between variants in a gene called FTO and obesity.

A new study reports that specific combinations of killer immunoglobulin-like receptor and HLA-B alleles influence AIDS progression and plasma HIV RNA levels in HIV-infected individuals. These results suggest that natural killer cells have an important role in recognizing and limiting HIV infection.

The p53-inducible small subunit of ribonucleotide reductase (p53R2) was originally assumed to be involved in DNA repair. A new study finds mutations in the gene encoding p53R2 (RRM2B) in individuals with severe mitochondrial DNA depletion in muscle, demonstrating its central role in mitochondrial DNA synthesis.

Spontaneous, replication-induced DNA breaks are likely to be a primary source of chromosomal rearrangements typical of cancer, but it is unknown how often these breaks occur in normal cells. A new study suggests that they are exceedingly rare but probably up to 100-fold more potent in causing genome instability than previously estimated.

The fusion of myoblasts into myofibers has been studied extensively in Drosophila, but it is not known if the same mechanisms operate in vertebrates. A new study suggests an unanticipated degree of similarity in zebrafish.

Human cancers are characterized by widespread reduction in microRNA gene expression, but what role does this have in the pathobiology of the disease? A new study proves that reduction in microRNA expression does indeed promote tumorigenesis, changing the way we think about cancer.

The genetic basis of aggression may be conserved from lobsters to humans. A new study uses the genetics of Drosophila melanogaster to explore the underlying neurochemical mechanisms.

Three new reports leverage genome-wide studies to localize and replicate multiple independent variants strongly associated with prostate cancer on chromosome 8q24. These findings provide a significant advance toward deciphering the genetic basis of this disease, although further work is needed to clarify the biological mechanisms underlying these associations.

Understanding the molecular genetic mechanisms governing agronomic traits such as grain yield is important for genetics as well as agriculture. A newly discovered quantitative trait locus, GW2, which encodes a new RING-type E3 ubiquitin ligase, has been found to regulate rice grain width. This insight should prove useful for improving the yield of staple grains.