Brief Communications

Andrew Futreal and colleagues report inactivating somatic mutations in the histone lysine demethylase gene UTX in human cancers, including multiple myelomas, esophageal squamous carcinomas, renal clear cell carcinomas, acute and chronic myeloid leukemias, breast and colorectal cancers and glioblastomas, identifying UTX as a new tumor suppressor gene.

Yardena Samuels and colleagues report a mutational analysis of the matrix metalloproteinase gene family in cutaneous metastatic melanoma. They find frequent somatic mutations in MMP8 and present functional evidence that wild-type MMP-8 inhibits melanoma progression.

Stefan Schulte-Merker and colleagues report that ccbe1, a predicted secreted protein, is required for embryonic lymphangiogenesis in zebrafish. Ccbe1 acts at the same stage as Vegfc, and is required for lymphangioblast budding and angiogenic sprouting from the venous endothelium.

John Stamatoyannopoulos, Shamil Sunyaev and colleagues report a correlation between mutation rate and replication timing in the human genome, observing an increased mutation rate in later-replicating regions.

Jeanette Erdmann and colleagues identify a locus on chromosome 3q22.3 associated with coronary artery disease. The SNP with the strongest association is in MRAS, which encodes a membrane-anchored GTP-binding protein.

Using a haplotype-based approach, David-Alexandre Trégouët and colleagues report that the SLC22A3-LPAL2-LPA gene cluster is associated with risk of coronary artery disease.

Kari Stefansson and colleagues report association of a variant in LINGO1 with risk of essential tremor, a common progressive neurological disease. Mice lacking Lingo1 have impaired axonal integrity, which may be relevant to the pathophysiology of the human disease.

Laurie Ozelius and colleagues identify mutations in THAP1 in families with a mixed type (DYT6) of primary torsion dystonia, a movement disorder characterized by twisting movements and abnormal posture.

Ritsert Jansen and colleagues present an integrative analysis for genome-wide variation in transcript, protein and metabolite abundance in Arabidopsis, reporting six QTL hot spots with system-wide effects.

Philippe Froguel and colleauges present a genome-wide association study for early-onset and morbid adult obesity, reporting three new genetic associations to obesity.

Matthew Farrer and colleagues report missense mutations in DCTN1, encoding dynactin, in eight families with Perry syndrome, a neurodegenerative disorder marked by early-onset parkinsonism, depression, severe weight loss and hypoventilation.

Thomas Sander and colleagues identify 15q13.3 microdeletions in 1% of individuals with idiopathic generalized epilepsy (IGE). The majority of these individuals do not show intellectual disability, schizophrenia or other neuropsychiatric phenotypes, thus extending the phenotypic spectrum associated with 15q13.3 microdeletions.

Unnur Styrkarsdottir and Kari Stefansson and colleagues report the results of an expanded genome-wide association study for bone mineral density at the hip or the spine. New SNP associations were identified downstream of the SOST gene on 17q21, and in intron 1 of the MARK3 gene on 14q32.

Rogier Hintzen and colleagues report the results of a search for genetic variants associated with susceptibility to multiple sclerosis in a genetically isolated population that lead to identification of a new susceptibility locus in the region of the KIF1B gene on chromosome 1.

Stefan Mundlos and colleagues report the identification of mutations in SCYL1BP1 in families with gerodermia osteodysplastica, a disorder characterized by wrinkly skin and osteoporosis. SCYL1BP1 localizes to the Golgi apparatus and interacts with Rab6.

Richard Houlston and colleagues report a genome-wide association study for lung cancer susceptibility. In addition to confirming a previous association at 15q25.1, they identify and replicate two new risk loci at 6p21.33 and 5p15.33.

Paul Brennan and colleagues report a genome-wide association study for lung cancer susceptibility. In addition to a previously reported variant at 15q25, they detect and replicate a new association at 5p15.33.

Jason Cooper and colleagues identify four new risk loci for type 1 diabetes through a meta-analysis of data from three genome-wide association studies, with replication in additional case-control and family-based samples, providing further insights into the genetic risk factors underlying this disease.

Benjamin Blencowe and colleagues report the application of next-generation sequencing technology to alternative splicing in the human genome. They detect alternative splicing events in 85% of multiexon genes, and conclude that there are approximately 100,000 such events in major human tissues.

Stanislav Kmoch and colleagues identify mutations in TMEM70 in individuals with isolated mitochondrial ATP synthase deficiency, and demonstrate that complementation of cell lines of affected individuals with wild-type TMEM70 restores ATP synthase function.