Volume 41 Issue 12, December 2009

In the largest Parkinson's disease genome-wide association studies to date, common variants in three familiar genes—SNCA, MAPT and LRRK2—and two new loci are found to increase disease susceptibility. The studies suggest genetic heterogeneity for Parkinson's disease risk in different human populations and lend support to the idea of a common pathway for Parkinson's and Alzheimer's diseases.

The success of bone marrow transplantation depends on whether transplanted immune cells respond in graft versus host disease. A new study identifies a common gene deletion that is associated with immune response following transplantation.

Sequencing of the genome of a second strain of Mycobacterium leprae and the development of a genome-wide typing scheme have provided deeper understanding of the evolution and epidemiology of the leprosy bacillus. A new study confirms that leprosy has a single clone origin and has spread around the globe, following human migration and trade over the last several thousand years.

Arthur Beaudet and colleagues report a recurrent 680-kb deletion within chromosome 15q13.3 associated with a range of neurodevelopmental phenotypes, including developmental delay, mental retardation and seizures. The deletion lies within the previously reported 1.5-Mb 15q13.3 deletion and spans only two genes, CHRNA7 and OTUD7A.

Raoul Hennekam and colleagues report the identification of mutations in CCBE1 that cause Hennekam syndrome in humans. Features of Hennekam syndrome include lymphedema, lymphangiectasias, mental retardation and unusual facial characteristics. CCBE1 encodes Collagen and Calcium-Binding EGF domain-1, a secreted protein that has been shown to be required for embryonic lymphangiogenesis in zebrafish.

Jun Wang and colleagues report the genome sequence of the cucumber. The cucumber genome is the seventh plant genome sequence to be reported and was assembled with a combination of traditional Sanger and next-generation sequencing methods.

Stewart Cole and colleagues report the genome sequence and comparative analyses of Brazilian, Indian, North American and Thai strains of Mycobacterium leprae, the etiologial agent of leprosy. They define 16 sub-types of M. leprae and examine their geographical distribution.

Mary Carrington and colleagues follow up on an earlier association of a variant upstream of HLA-C to HIV viral load setpoint, showing that this variant is associated with high HLA-C cell surface expression and demonstrating a protective effect of the variant in viral load and disease progression.

Frank Costantini and colleagues report the identification of the ETS transcription factors, Etv4 and Etv5, as key targets of Ret signaling during kidney branching morphogenesis. Loss of Etv4 and Etv5 function in mice leads to complete failure of kidney development.

Tatsushi Toda and colleagues report results of a genome-wide association study of Parkinson's disease in the Japanese population. They identify four loci harboring common variants associated with Parkinson's disease, including two newly discovered risk regions on 1q32 and 4p15.

Andrew Singleton, Thomas Gasser and colleagues report results of a genome-wide association study of Parkinson's disease among individuals of European ancestry. They find genome-wide significant associations at two loci, SNCA and MAPT, and provide supporting evidence for a new risk locus on 1q32.

Soumya Raychaudhuri and colleagues demonstrate the utility of GRAIL, a software program used to prioritize results from genome-wide association studies for further replication, applied here to rheumatoid arthritis. The authors seek replication of their predictions in additional independent cohorts and report three new genetic loci associated with RA susceptibility.

Karin Lundberg and colleagues explore gene-gene and gene-environment interactions in susceptibility to rheumatoid arthritis, reporting an association of HLA-DRB1, PTPN22 and smoking stratified by the autoantigen CEP-1.

Michiaki Kubo and colleagues report results of a genome-wide association study of ulcerative colitis in the Japanese population. Their study identifies three new susceptibility loci for this common inflammatory bowel disease, including FCGR2A, which has previously been implicated in other autoimmune diseases.

The UK IBD Genetics Consortium and the Wellcome Trust Case Control Consortium 2 report results of a genome-wide association study of ulcerative colitis. They identify three new loci associated with the disease, including the HNF4A region on 20q13.

Hakon Hakonarson and colleagues report the discovery of five new regions associated with susceptibility to early-onset inflammatory bowel disease. They also identify multiple loci previously implicated in the etiology of adult-onset Crohn's disease and/or ulcerative colitis as risk factors for early-onset forms of these diseases.

Steven McCarroll and colleagues examine common gene deletions in individuals that have undergone bone marrow transplantation. They find that risk of acute graft-versus-host disease is greater when the donor and recipient are mismatched for a homozygous deletion of UGT2B17.

Colin Ross and colleagues report the association of variants in TPMT and COMT to cisplatin-induced hearing loss in children.

Andrew Feinberg and colleagues show that differential methylation of CpG island shores distinguish human induced pluripotent stem cells from the fibroblasts from which they were derived. These differentially methylated regions of the genome can also distinguish normal colon tissue from colorectal cancer.