Articles in 2009

Han-Xiang Deng, Teepu Siddique and colleagues report that scapuloperoneal spinal muscular atrophy and hereditary motor and sensory neuropathy type IIC are allelic disorders caused by mutations in TRPV4. Their functional studies indicate that the mutations result in increased calcium channel activity.

Michaela Auer-Grumbach and colleagues report that missense alterations in the N-terminal ankyrin domain of TRPV4 underlie three distinct autosomal dominant disorders of the peripheral nervous system. Alterations in other regions of TRPV4 have been shown to underlie a family of autosomal dominant skeletal dysplasias, underscoring the marked clinical heterogeneity associated with mutations in this channel.

Charlotte Sumner and colleagues report that mutations in the ankyrin repeat region of TRPV4 cause Charcot-Marie-Tooth disease type 2C. Their functional studies indicate that the mutations result in increased channel activity.

Karsten Suhre and colleagues report a genome-wide association study to 163 metabolic traits in human serum.

Elisabeth Mangold and colleagues report a genome-wide association study for non-syndromic cleft lip with or without cleft palate.

Martin Pollak and colleagues show that missense mutations in the diaphanous inhibitory domain of INF2 cause focal segmental glomerular sclerosis. INF2 encodes a member of the formin family of actin-regulating proteins, highlighting an important role for actin dynamics in podocyte function.

Nicholas Hastie and colleagues show that Wt1 is required for the epithelial-to-mesenchymal (EMT) transition in the developing epicardium and the formation of mesenchymal cardiovascular progenitors. Wt1 directly regulates the transcription of Snail and E-cadherin, two well-known mediators of EMT.

Stephanie London and colleagues from the CHARGE Consortium report genome-wide association studies for pulmonary function.

Peter Fraser and colleagues report a genome-wide analysis of transcription interactions involving the globin genes in mouse erythroid cells. They demonstrate that the transcription factor Klf1 mediates preferential co-associations between genes it regulates.

Martin Tobin and colleagues present genome-wide association studies for pulmonary function as part of the SpiroMeta consortium.

Martin Zenker, Marco Tartaglia, Reza Ahmadian and colleagues report the identification of a restricted spectrum of NRAS mutations in individuals with Noonan syndrome. Functional testing revealed that the mutations confer enhanced stimulus-dependent MAPK activation.

Liang Zhu and colleagues report that inactivation of Skp2, a target of the pRb tumor suppressor, completely prevented tumorigenesis in tumor-prone mice with loss of one Rb1 allele. This work nominates Skp2 as a drug target to combat Rb1-deficient tumors.

Chris Wallace and colleagues report the identification of a new locus on chromosome 14q32.3 that alters susceptibility to type 1 diabetes with a parent-of-origin effect. The region contains imprinted genes including DLK1 and MEG3.

Greg Gibson and colleagues report an analysis of gene expression variation in relation to environmental geography and ethnicity in blood leukocyte samples from individuals in rural and urban southern Morocco. The study determined the contributions of geography and ethnicity to associations between genotypes and transcript abundance.

The genome of the seventh plant to be sequenced, Cucumis sativus L., was assembled using the conventional long-read Sanger sequencing and higher-throughput short-read technology. This genome is the entry point for exploring the diversity and function of the Cucurbitaceae family of agriculturally important plants. Its compact genome, without evidence of recent duplication, will be useful in comparative analysis of plant genome evolution.

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.

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.

David Hinds and colleagues report that a non-synonymous variant in PNPLA3 is associated with alcoholic liver disease and liver cirrhosis. This result follows previously reported associations of this variant with nonalcoholic fatty liver disease.