News & Views

Two new studies show that the Fanconi anemia complementation group N results from biallelic mutations in PALB2, which encodes a recently identified interaction partner of the breast cancer susceptibility protein BRCA2. A third study shows that monoallelic PALB2 mutations are associated with breast cancer susceptibility, providing yet more links between Fanconi anemia, homologous recombination repair and cancer predisposition.

A new study identifies 'quantitative trait transcripts' for nicotine resistance in large populations of wild strains of Drosophila melanogaster by comparing global gene expression patterns, survival time and metabolite levels in the presence or absence of nicotine. The results provide proof-of-concept for a correlation-based statistical approach that can be used in personalized medicine.

A new study examines the agn43 epigenetic switch of Escherichia coli, providing an alternative to feedback regulation as a model for gene expression regulation. Through a combination of synthetic network construction and computational modeling, the authors show that the generated bistable gene expression involves transitions between several rarely occupied states between 'on' and 'off'.

Telomere dysfunction suppresses cancer through the p53 tumor suppressor pathway but also contributes to aging. A new study suggests that these effects of dysfunctional telomeres may be separable, such that aging—but not cancer suppression—depends on the p21 cell cycle inhibitor.

Noonan syndrome is a disease caused by aberrant signaling through the Ras GTPase, yet the underlying causal mutations remain unknown in many affected individuals. Two papers now identify gain-of-function mutations in the Ras nucleotide exchange factor SOS1 as a new player in this common developmental disorder.

Replication initiation factors are essential for cell proliferation and thus are not expected to be disrupted in cancers. Challenging this notion, a new study in mice shows that a hypomorphic mutation in the gene encoding the replication initiation factor Mcm4 leads to genetic instability and predisposes to mammary adenocarcinomas.

Three new studies provide a genome-wide snapshot of genetic variation in Plasmodium falciparum, the most pathogenic of the parasites causing human malaria. These studies pave the way for mapping of genes underlying important parasite traits such as drug resistance and pathogenesis as well as for evolutionary analysis of selection in a parasite genome.

The ability to digest lactose into adulthood is a recently evolved trait that has risen to high frequency in some human populations, coincident with the introduction of cattle domestication. A new study shows that variants responsible for this trait arose independently in Europeans and Africans, providing a striking example of convergent evolution.

Sequencing of genomes, including that of humans, has revolutionized our understanding of genome organization and accelerated the hunt for disease-causing mutations. New studies by the Human Epigenome Project (HEP) now highlight the importance and complexity of cytosine DNA methylation in tissue-specific regulation of gene expression.

Many clinical syndromes result from deletion or duplication of regions within the human genome. Two new studies demonstrate strong connections between such events and allelic recombination in humans, which in the future may enable researchers to better predict the locations of unstable genomic regions.

A new study reports mutations in PLCE1 responsible for an autosomal recessive nephrotic syndrome in children that presents with diffuse mesangial sclerosis or focal segmental glomerulosclerosis. Remarkably, two affected individuals treated at an early phase of life responded to either steroids or cyclosporin A, opening a window of opportunity for therapy.

Analysis of the phenotype of mouse germ cells deficient for the retinoic acid–responsive gene Stra8 provides insight into the timing of the commitment to enter meiosis in mammals. The observations suggest that, as in other eukaryotes, this commitment precedes (or coincides with) the commitment to premeiotic DNA replication.

The recently completed International HapMap Project has provided detailed information about patterns of genetic variation in four different population samples. Two new studies show that the patterns of variation documented in the HapMap can be applied to other human populations, suggesting it is time to establish a standardized platform for all whole-genome association studies.

A new study shows that during transcription, the T_H2 interleukin gene cluster is organized into several small chromatin loops connected at their base by the protein SATB1. This first detailed glimpse of chromatin folding provides a new perspective on the coordination of cell type–specific gene expression.