Articles in 2009

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.

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.

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.

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.

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.

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.

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.

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.

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.

Julius Gudmundsson and colleagues report the association of two SNPs on chromosomes 9 and 14 with thyroid cancer in European populations. The variants are near FOXE1 and NKX2-1, both good biological candidates, and individuals who are homozygous for both risk variants have a 5.7-fold greater risk of thyroid cancer.

High-throughput datasets and analysis protocols are intrinsically difficult to referee. Community standards enforced by journals may be less effective than is widely appreciated. Greater awareness of the needs and value of secondary data users can result in higher-impact papers.

A new study identifies mutations in the HR gene as the cause of Marie Unna hereditary hypotrichosis (MUHH). The mutations seem to disrupt an unusual leader sequence–based mechanism of translational repression, making MUHH the first example of a disease linked to this form of repression.

Obesity genetics is making progress, as evidenced by the recent discovery of 15 new loci associated with body mass index. The function of the likely candidate genes in associated regions suggests a key role for the hypothalamus in the genetics of weight control.

Experimental reverse evolution, in which a population is readapted to an ancestral environment, can probe the nature and extent of evolutionary memory. A new study shows that standing genetic variation is key to this memory in experimental Drosophila populations, where selection drives rapid but incomplete convergence to ancestral genotypes.

An integrative genetical genomics study in Arabidopsis reports that six QTL hot spots have system-wide effects on a wide range of molecular and phenotypic traits, providing empirical evidence for phenotypic buffering.

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.