Volume 43 Issue 11, November 2011

Diversification and specialization of high-throughput technologies demand assay-specific treatment of data for reliable interpretation. A new study shows that data generated using the Hi-C approach contain hidden features of interchromosomal DNA interactions, which are revealed through analysis with an integrated probabilistic model that corrects for multiple sources of bias in the data.

A new study shows an inserted retroelement in the regulatory sequences of the maize tb1 gene, which controls shoot branching, was the target of human selection during the domestication of maize from its wild relative teosinte. The insertion allele was already present at low frequency in teosinte populations before selection, highlighting the significance of standing genetic variation in the evolution of morphological diversity.

The origin of DNA methylation patterns has been a mystery for many years. A new study identifies the DNA sequence itself as a key determinant and focuses attention on the role of transcription factors.

The Archon Genomics X Prize contest has been declared for January 2013. Larry Kedes and Grant Campany explain the selection of centenarian genomes for the contest and provide the rules by which the contestants will be judged.

Amos Tanay and Eitan Yaffe report methods to correct biases in the Hi-C method for mapping chromosomal contacts on a genome-wide scale. Their analysis of Hi-C data shows interchromosomal aggregation of hypersensitive sites, transcriptionally active foci and other epigenetic markers of active chromatin.

Mark Daly, Manuel Rivas and colleagues used next-generation sequencing to study the coding exons of 56 genes from regions previously associated with Crohn's disease. Follow-up analyses in independent case-control series confirmed association of many newly discovered rare variants with disease risk.

Jim Lupski and colleagues report characterization of complex genomic rearrangements at the MECP2 and PLP1 loci. They show that all the complex rearrangement products share a common genomic organization wherein the triplicated segment is inverted and located between directly oriented duplicated genomic segments; these structures are mediated by inverted repeats that can be separated by over 300 kb.

Martin Tobin and colleagues report a meta-analysis of 23 genome-wide association studies for pulmonary function. They identify 16 loci newly associated with variation in two cross-sectional measures of lung function, used to define airway obstruction and to grade the severity of obstruction.

Dirk Schübeler and colleagues report an experimental strategy to identify genetic elements that autonomously determine DNA methylation states in murine stem cells. They identified promoter sequences that supported proper de novo methylation during differentiation and determined that this activity is contained within small methylation-determining regions.

Simon Stacey, Kari Stefansson and colleagues show that a germline variant in the TP53 polyadenylation signal is associated with increased risk of basal cell carcinoma and other solid tumors.

Using a combination of whole-genome sequencing, haplotype sharing and the genealogies of the Icelandic population, Thorunn Rafnar, Kari Stefansson and colleagues identified a rare coding mutation in the gene of a BRCA1-interacting factor, BRIP1, that confers a high relative risk of ovarian cancer.

Timothy Bishop and colleagues of the GenoMEL Consortium report a genome-wide association study for melanoma, identifying three new susceptibility loci.

Stuart MacGregor and colleagues report the results of a genome-wide association study for melanoma susceptibility in an Australian population. They identify a new melanoma susceptibility locus on chromosome 1.

Yardena Samuels and colleagues sequenced G protein-coupled receptors in 11 melanoma samples and report a comprehensive map of somatic variants in the GPCR gene family. They find frequent mutations in GRM3, which promote proliferation and migration of melanoma cells.

Patrick Sulem, Daniel Gudbjartsson, Bragi Walters and colleagues identify two low-frequency variants associated with serum uric acid levels and gout in the Icelandic population. The variants were discovered by whole-genome sequencing and are associated with two- to threefold differences in disease risk.

John Chambers and colleagues report a genome-wide association study for markers of liver function. They identify 42 loci associated with concentrations of one or more liver enzymes in plasma, and use a range of functional genomic analyses to suggest candidate genes at these loci.

Martin Hibberd, Cameron Simmons and colleagues report a genome-wide association study for dengue shock syndrome, a severe complication of dengue, in pediatric cases and controls from Vietnam. They identify common variants at MICB within the broad MHC region on chromosome 6 and at PLCE1 on chromosome 10 associated with dengue shock syndrome in people with dengue.

Shireen Lamandé and colleagues report mutations in TRPV4 in familial digital arthropathy-brachydactyly (FDAB), which is characterized by osteoarthropathy of the fingers and toes. TRPV4 is a cation channel, and functional experiments suggest mutant proteins are not localized properly to the cell surface.

Fanni Gergely, Geoffrey Woods and colleagues identify a disease-associated CEP63 mutation in a family with primary microcephaly. They further show that CEP63 and CEP152 interact and form a discrete ring around the proximal end of the parental centriole, implicating this complex in the regulation of centrosome number.

Vincent Lynch and colleagues report the transcriptional landscapes of endometrial stromal cells from placental and marsupial mammals and identify 1,532 genes that are expressed in human and armadillo but not opossum. The authors suggest these genes were recruited into endometrial stromal cells during the evolution of pregnancy in placental mammals. Thirteen percent of these genes are located within 200 kb of a MER20 transposable element, and functional experiments show that MER20 elements regulate endometrial-specific gene expression response to progesterone and cAMP.

John Doebley and colleagues have identified a transposon insertion in the maize domestication gene, tb1, that acts as a regulatory enhancer. The transposon insertion appears to be a causative variant that partially explains major changes in plant architecture during maize domestication.