Articles in 2010

Patricia Dahia and colleagues show that germline mutations in TMEM127 confer susceptibility to pheochromocytomas. Their functional studies suggest that TMEM127 acts as a negative regulator of mTOR signaling.

Evan Eichler and colleagues identify a recurrent microdeletion on 16p12.1 associated with developmental, cognitive and neuropsychiatric phenotypes. They also show that more severe phenotypes are frequently correlated with the presence of a second large genomic rearrangement, supporting a complex model of pathogenesis that may underlie the variable expressivity typical of many microdeletion syndromes.

Vivianna Van Deerlin and colleagues report that common variants at 7p21 are associated with a subtype of frontotemporal lobar degeneration marked by TDP-43 inclusions. They further show that the risk alleles are associated with elevated brain expression of TMEM106B, which resides at the peak of association on 7p21.

Liam Dolan and colleagues report discovery of a basic helix-loop-helix transcription factor, RSL4, that is necessary and sufficient to promote postmitotic cell growth in Arabidopsis thaliana root hair cells.

Nilesh Samani and colleagues report a genome-wide association study that identifies variants near the TERC locus associated to variance in mean telomere length.

Pier Paolo Pandolfi and colleagues report that Dok family members, Dok1, Dok2 and Dok3, are lung tumor suppressors, as loss of Dok genes in mice leads to spontaneous lung adenocarcinoma. DOK2 is frequently deleted in human lung cancer and suppresses lung cancer cell growth.

Naoyuki Kamatani and colleagues report genome-wide association studies for 8 hematological traits and 12 biochemical traits in a Japanese population.

Systems models and biomarker studies both pose the problem of wrangling high information content. Such publications can be made easier to review and to use if they propose explicit alternative hypotheses and show experimental exclusion of each competing explanation. In practice, we will need to be able to identify and independently cite multiple hypotheses and related experiments within a published work.

Scapuloperoneal spinal muscular atrophy and Charcot-Marie-Tooth disease type 2C are inherited neurodegenerative diseases characterized by sensory defects and muscle weakness. Three new studies demonstrate that they are allelic disorders caused by mutations in the vanilloid transient receptor potential cation-channel gene TRPV4.

A new study now reports recurrent somatic mutation of EZH2, a histone methyltransferase that modifies H3K27, in diffuse large B-cell lymphoma (DLBCL). There is now evidence for both increased and decreased activity of enzymes controlling H3K27 methylation in cancer, suggesting that a precise balance of this methylation is critical for normal cell growth.

Advances in analytical biochemistry have recently made it possible to obtain global snapshots of metabolism. A new study couples such technology with genome-wide genetic analysis to explore inherited variation in human metabolism.

Kerstin Lindblad-Toh and colleagues use genome-wide association mapping to identify risk loci for a canine systemic lupus erythematosus-related disease complex in Nova Scotia duck tolling retrievers. The study illustrates the power of using dog breeds for complex trait mapping.

Xin-zhuan Su and colleagues report genome-wide SNP genotyping of 189 culture-adapted Plasmodium falciparum parasites and examine population structure, selection and recombination hotspots. They also conduct genome-wide association studies for resistance to seven different antimalarial drugs.

Christopher Walsh and colleagues describe a new recessive genetic disease characterized by microcephaly, early-onset intractable seizures and developmental delay (MCSZ). The authors identify mutations in PNKP that result in this severe disease and show that PNKP mutations disrupt DNA repair.

Jorge Ferrer, Jason Lieb, and Karen Mohlke and colleagues identify regulatory DNA active in human pancreatic islets by formaldehyde-assisted isolation of regulatory elements (FAIRE) coupled with high-throughput sequencing. They identified 80,000 open chromatin sites and 3,300 islet-selective open chromatin sites and found that a TCF7L2 intronic variant associated with type 2 diabetes is located in islet-selective open chromatin.

Thomas Turner and colleagues have applied next-generation sequencing technology to investigate the genetic basis of adaptive variation. They sequenced pools of DNA from geographically distinct Arabidopsis lyrata populations that are locally adapted to serpentine soils and analyzed 8 million polymorphisms, identifying a putative example of convergent evolution.

Stephen Chanock and colleagues identify three new susceptibility loci for pancreatic cancer on chromosomes 13q22.1, 1q32.1 and 5p15.33. The association signal at 13q22.1 maps to a large nongenic region, whereas the signals at 1q32.1 and 5p15.33 map near the NR5A2 gene and CPTM1L-TERT region, respectively.

Jianzhi Zhang and colleagues examine epistasis within the metabolic networks of Escherichia coli and Saccharomyces cerevisiae using flux balance analysis. They find a strong bias towards positive epistasis amongst essential genes and show that these only rarely include genes involved in biochemical reactions with related functions.

Francis McMahon and colleagues report a meta-analysis of genome-wide association data sets for major mood disorders, including bipolar disorder and major depressive disorder.