Volume 42 Issue 4, April 2010

A genome-wide association study reports more than a dozen new susceptibility loci for celiac disease. Analysis of eQTL data from these and previously established risk loci sheds light on the genetic pathways underlying this common autoimmune disease.

Enhancers and transcription factor binding sites that control cell-specific transcription in higher eukaryotes can be found up to hundreds of kilobases from the promoters that they control, making their identification challenging. A new study uses a model based on histone modifications and chromatin dynamics to predict functional elements involved in androgen receptor response.

Human hemoglobin variants are known to protect the host against severe malaria due to P. falciparum. A new study demonstrates that such genetic variation may also be associated with increased transmission of this pathogen from the human host to the Anopheles vector.

Hakon Hakonarson and colleagues identify variants near TSLP at 5q22 associated with pediatric eosinophilic esophagitis. They further show that TSLP is overexpressed in esophageal biopsies of cases compared to controls and that the risk variants are associated with elevated TSLP expression.

Andre Franke and colleagues report results of a genome-wide association and replication study of ulcerative colitis. They identify two new regions of association at 7q22 and at 22q13 in IL17REL.

David van Heel and colleagues report results of a large genome-wide association study of celiac disease. Most of the associated loci contain genes with immune functions, and over half harbor risk variants that are correlated with variation in cis gene expression.

Paul Gissen and colleagues show that mutations in VIPAR cause a syndrome marked by arthrogryposis, renal dysfunction and cholestasis accompanied by defects in epithelial polarization. Their functional studies suggest that VIPAR forms a functional complex with VPS33B that interacts with RAB11A.

Franco Taroni and colleagues report the identification of mutations in AFG3L2 that cause dominant spinocerebellar ataxia type 28. Along with paraplegin, AFG3L2 forms a protein complex with ATPase and metalloprotease activities and functions in the maintenance of the mitochondrial proteome.

Torbert Rocheford and colleagues show that variation at crtRB1 is associated with increased beta-carotene levels in maize. The most favorable crtRB1 allele is currently being introgressed into tropical germplasm, in order to address dietary vitamin A deficiency in the developing world.

David Modiano and colleagues report an epidemiological study examining the role of host genetic variation at the β-globin locus on transmission of malaria in cross-sectional and transmission surveys from West Africa. They find that individuals carrying HbC allele show increased gametocyte levels, and an increased rate of Plasmodium falciparum transmission to the Anopheles vector.

Mark Seielstad and colleagues report results of a large genome-wide association and replication study of ulcerative colitis. The work identifies several new risk loci for this disease and provides further insight into the shared pathogenesis of ulcerative colitis and Crohn's disease.

Adolfo Ferrando and colleagues identify frequent inactivating mutations and deletions in the X chromosome gene PHF6 in T-cell acute lymphoblastic leukemia. PHF6 mutations are found almost exclusively in males and are associated with leukemias driven by aberrant expression of TLX1 and TLX3.

Myles Brown and colleagues analyze chromatin organization of androgen receptor-responsive transcriptional enhancers in a prostate cancer cell line. The authors develop a model to identify other genomic regions showing similar dynamic changes in chromatin structure, and identify other transcription factors that are involved in cellular responses to androgen.

Eleazar Eskin and colleagues report a variance component model for correcting for sample structure in association studies. The EMMAX program is publicly available and may be used for analysis of genome-wide association study datasets.

Zhiwu Zhang and colleagues report a mixed linear model approach for correcting for population structure and family relatedness in genome-wide association studies.