Volume 45 Issue 6, June 2013

A recent study in the New England Journal of Medicine reports the genomic and epigenomic changes in adult acute myeloid leukemia (AML). The patterns of somatic mutation suggest biologically relevant connections between the functional categories of genes driving AML.

Two new studies show that the known histone H3 alteration p.Lys27Met in pediatric glioma leads to globally diminished trimethylation at histone H3 lysine 27. The mutant histone H3 acts as a selective inhibitor of the PRC2 chromatin-modifying complex by binding and presumably sequestering it, shedding light on how this variant may contribute to the etiology of these highly malignant brain tumors.

Plasmodium falciparum in Southeast Asia are gradually becoming resistant to artemesinin, a standard first-line treatment for malaria. Whole-genome sequencing offers a chance to better understand and perhaps undermine the parasite's evolutionary response to this drug.

Gerald Crabtree and colleagues identify new subunits of the mSWI/SNF complex and perform a bioinformatic analysis of the mutation patterns of the mSWI/SNF complex members in human cancers. mSWI/SNF is the most frequently mutated chromatin-regulatory complex in human cancer.

David Ellison and colleagues report whole-genome sequencing of pediatric low-grade gliomas, the most common pediatric brain tumor. They identify a range of genomic alterations, including recurrent and mutually exclusive duplications of the FGFR1 region encoding the tyrosine kinase domain and rearrangements of MYB.

Tasha Fingerlin, David Schwartz and colleagues report a genome-wide association study of fibrotic idiopathic interstitial pneumonia. Their results confirm known risk variants at MUC5B and TERT and identify several new regions associated with disease susceptibility.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

Dongxin Lin and colleagues report a genome-wide association study identifying common variants in SLC39A6 associated with length of survival in individuals with esophageal squamous-cell carcinoma (ESCC). Higher expression of SLC39A6 in esophageal tissues was correlated reduced survival time in individuals with ESCC.

Jamel Chelly, Nicholas Cowan and colleagues report mutations in TUBG1, DYNC1H1, KIF2A and KIF5C in individuals with malformations of cortical development and microcephaly. Their findings emphasize the importance of centrosomal and microtubule-related proteins for normal brain development.

Dominic Kwiatkowski and colleagues report analysis of genetic variation in 826 Plasmodium falciparum samples collected from 10 locations in West Africa and southeast Asia. They characterize the population structure of this parasite in Cambodia and find evidence for multiple distinct subpopulations showing high levels of genetic differentiation and artemisinin resistance.

Nicholas Croucher and colleagues report whole-genome sequencing of 616 asymptomatically carried Streptococcus pneumoniae, a major cause of pneumonia, bacteremia and meningitis. They examine the impact of the introduction of the pneumococcal conjugate vaccine PCV7 on pneumococcal population dynamics.

Anne Hinks and colleagues identify 14 new susceptibility loci for juvenile idiopathic arthritis through targeted analyses of genomic regions implicated in immune function. Their study implicates several pathways, including IL-2 signaling, in the pathogenesis of this common childhood autoimmune disease.

Tom Karlsen and colleagues report an association study for primary sclerosing cholangitis (PSC), a severe liver disease, using the Immunochip array. They identify nine loci newly associated with PSC and examine pleiotropy with other autoimmune disorders.

Shiro Ikegawa and colleagues report a genome-wide association study for adolescent idiopathic scoliosis (AIS). They identify one locus associated with AIS on chromosome 6q24.1 in Japanese individuals, which was also replicated in individuals of Han Chinese and European ancestry.

Katherine Nathanson and colleagues report four new susceptibility loci for testicular germ cell tumor identified through a meta-analysis of genome-wide association studies with follow-up replication. The newly discovered risk regions include genes important for male germ cell development, chromosomal segregation and the DNA damage response.

Clare Turnbull and colleagues identify nine new susceptibility loci for testicular germ-cell tumor. The newly identified risk regions include variants near DAZL and PRDM14, genes known to be important for germ cell development.

Keri Monda, Kari North, Christopher Haiman and colleagues report a meta-analysis of GWAS for body mass index that is composed of 39,144 individuals of African ancestry, followed by further genotyping in 32,268 individuals of African ancestry. The study also includes analysis of publicly available data from the GIANT consortium of ~124,000 individuals of European ancestry. The paper reports evidence for two new loci near GALNT10 and MIR148A.

Min Deng, Kai Wang and colleagues report genome-wide association analyses of amyotrophic lateral sclerosis in the Han Chinese population. They identify two new risk loci at 1q32 and 22p11.

Naoki Irie and colleagues report the draft genomes of the soft-shell and green sea turtles. Their genome-wide phylogenetic analysis supports the hypothesis that turtles are a sister group of crocodilians and birds.

Ken Ishimaru and colleagues show that loss of function of the rice gene TGW6 enhances rice grain weight and increases yield. TGW6 encodes a protein with IAA-glucose hydrolase activity.