Articles in 2013

Florent Soubrier and colleagues identify biallelic mutations in EIF2AK4 as a major cause of pulmonary veno-occlusive disease, a rare form of pulmonary hypertension. EIF2AK4 encodes a serine-threonine kinase, and the disease-causing mutations are predicted to result in loss of protein function.

Richard Houlston and colleagues report results of a genome-wide association study of chronic lymphocytic leukemia. They validate several new susceptibility loci for this disease, including variants near POT1, TERC and TERT.

Comprehensive sequencing of benign and malignant tumors has recently uncovered new driver mutations in childhood tumors. A new report now describes frequent histone H3.3 alterations in chondroblastoma and giant cell tumor of bone, emphasizing the importance of this histone variant in pediatric cancers.

The simple addition of vitamin C to cell culture medium can induce extensive remodeling of the cellular epigenome and facilitates reprogramming of somatic cells to pluripotency. A new study shows that the activity of the enzyme TET1 can inhibit or enhance reprogramming efficiency, dependent on the presence or absence of vitamin C.

Two new studies report the identification of activating ESR1 gene mutations in aromatase inhibitor–resistant metastatic breast cancers. This insight into therapeutic resistance suggests new approaches that may be useful in the management of endocrine-resistant breast cancer.

The assertions in a scientific article that invite testing can be specifically tagged for peer reviewers to evaluate relative to the experimental evidence offered. Isolated observations as well as theories that are not yet publishable can be tagged and immediately released like free-floating bubbles. These can then be considered as useful negative results when popped by experiment or as publishable advances when corroborated by further evidence gathered during attempts at refutation.

Margaret Goodell and colleagues report genome-wide mapping of 5-methylcytosine and 5-hydroxymethylcytosine in purified mouse hematopoietic stem cells. They identify large regions of low methylation with borders marked by 5-hydroxymethylcytosine. These borders become eroded in the absence of DNA methyltransferase 3a.

Augustine Kong, Kari Stefansson and colleagues report the discovery of common and low-frequency variants associated with genome-wide recombination rates. Most of the newly discovered variants exhibit differential effects on male and female recombination rates, and several map to genes with known roles in recombination, including RAD21L and MSH4.

Jung-Hyun Lee, Jong Bhak and their colleagues report the whole-genome sequencing and de novo assembly of a male minke whale genome, as well as the genome sequences of three additional minke whales, a fin whale, a bottlenose dolphin and a finless porpoise. Their comparative analysis across cetaceans provides insights into adaptation to an aquatic lifestyle.

Paul Meltzer and colleagues report the results of an exome sequencing study of variant and IGHV4-34–expressing hairy-cell leukemias. They identify a high frequency of activating MAP2K1 mutations in these malignancies, suggesting potential therapeutic strategies.

Klaus Bønnelykke and colleagues identify a common variant in CDHR3 associated with early childhood asthma with severe exacerbations. CDHR3 encodes a cell adhesion protein expressed at high levels in airway epithelium, suggesting a role for altered epithelial integrity in asthma pathogenesis.

Sérgio Sousa and colleagues show that Lenz-Majewski syndrome, a disorder featuring generalized craniotubular hyperostosis, results from de novo gain-of-function mutations in PTDSS1. The mutations lead to increased phophatidylserine synthesis, suggesting a link between phosphatidylserine production and bone metabolism.

Wolfgang Busch and colleagues report results of a genome-wide association study of developmental cell–type traits in Arabidopsis. They identify a new F-box gene, KUK, as a regulator of root meristem and cell length and show the feasibility of applying genome-wide association to the study of cellular traits.

Andrew Hattersley, Jorge Ferrer and colleagues use epigenomic annotation of pancreatic progenitor cells to guide the interpretation of whole-genome sequences from individuals with isolated pancreatic agenesis. They show that recessive mutations in a distal developmental enhancer of PTF1A cause pancreatic agenesis and abolish enhancer activity.