Volume 41 Issue 3, March 2009

Studies of rare genetic disorders in humans have yielded important insights into the function of the hypothalamic-pituitary-gonadal axis. A new study now establishes a fundamental role for the neurokinin B pathway in normal reproductive function.

The global patterning of histone lysine methylation has been scrutinized over the years in an effort to uncover unique features indicative of chromatin function. A study in Caenorhabditis elegans now shows that nucleosomes covering exons and introns on active genes are differentially marked by H3K36 trimethylation, suggesting a new mode of communication between chromatin and pre-mRNA processing.

FGF receptors have been implicated in a number of syndromes that involve skeletal disorders. A new study in mice has identified a spontaneous mutation in Fgf9 with reduced activity but increased diffusion through tissues resulting in a gain-of-function phenotype comparable to those due to activating mutations in genes encoding FGF receptors.

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.

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.

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.

Haruhiko Koseki and colleagues identify a gain-of-function mutation in Fgf9 in mice with elbow knee synostosis. They further show that this mutation prevents homodimerization of Fgf9, allowing increased diffusion of the altered protein through developing tissues.

Trudy Mackay and colleagues present a resource of 40 Drosophila melanogaster wild-derived inbred lines. The authors quantify genome-wide variation in transcript abundance for six ecologically relevant traits, characterize the transcriptome and identify transcriptional modules.

Susan Lindquist and colleagues report a genetic interaction between α-synuclein and the ortholog of human ATP13A2 (PARK9) in yeast, two genes that when mutated cause Parkinson's disease. They further show that yeast PARK9 protects cells from manganese toxicity, a known environmental risk factor for Parkinson's disease.

Ernest Fraenkel and colleagues present ResponseNet, a method used to integrate analysis of genetic and transcriptional datasets, and its application characterizing yeast cellular responses to alpha-synuclein toxicity.

Wei Zheng and colleagues carried out a genome-wide association study of breast cancer in Chinese women and discovered risk variants on 6q25.1 located upstream of the gene encoding estrogen receptor 1 (ESR1). They also found a similar association between the 6q25.1 locus and breast cancer in samples of European ancestry.

Toshihiro Tanaka and colleagues report the identification of variants in BRAP, which encodes a galectin-2–binding protein, that are associated with risk of myocardial infarction in two Asian populations.

The Myocardial Infarction Genetics Consortium reports results of a genome-wide association study of early-onset myocardial infarction. The study analyzed common SNPs, common CNVs and rare CNVs and identified SNP alleles at three new loci associated with disease risk.

Daniel Gudbjartsson and colleagues report results of a genome-wide association study for loci influencing eosinophil counts. Follow-up studies showed that a subset of the variants identified in this screen were associated with risk of asthma or myocardial infarction.

Christopher Newton-Cheh and colleagues report the identification of common variants at the NPPA-NPPB locus associated with plasma atrial natriuretic peptide concentration, as well as with lower systolic and diastolic blood pressure, and reduced risk of hypertension.

A. Kemal Topaloglu and colleagues report the identification of mutations in the neurokinin B receptor and its ligand in families with severe congenital gonadotropin deficiency and pubertal failure. These findings indicate that neurokinin B is a central regulator of human gonadal function.

Stanislas Lyonnet and colleagues report a new locus associated with Pierre Robin sequence, an important subgroup of cleft palate. They find that translocations, deletions and point mutation affecting highly conserved noncoding elements (HCNEs) found at distances on either side of SOX9 are associated with PRS.

Manel Esteller and colleagues report truncating mutations in TARBP2, an integral component of a DICER1-containing complex, in human colorectal cancers. This is the first report of a mutation in one of the genes involved in miRNA processing in human cancer.

Trudy Mackay and colleagues measure sleep phenotypes in 40 wild-derived Drosophila lines, and report candidate genes and transcriptional networks associated with sleep regulation.

Julie Ahringer and colleagues show that, in C. elegans, exons are preferentially marked with H3K36me3 relative to introns, and that the difference in H3K36me3 marking between exons and introns is evolutionarily conserved in human and mouse.