Genetics Articles

News and Views: Deciphering genetic susceptibility to frontotemporal lobar dementia

A genome-wide association study has identified a new genetic susceptibility factor for a subtype of frontotemporal lobar dementia characterized by TDP-43 inclusions. The work illustrates how high-quality phenotyping can increase power to detect risk alleles for rare heterogeneous diseases.

Nature Genetics, vol. 42 #3, pp189-190

News and Views: Open chromatin and diabetes risk

A new study has identified a large number of open chromatin regions harboring active regulatory elements in human pancreatic islets. A type 2 diabetes?associated SNP in TCF7L2 was found to be located in a region of allele-specific open chromatin and shows allele-specific enhancer activity, suggesting a potential mechanism for this disease association.

Nature Genetics, vol. 42 #3, pp190-192

News and Views: Understanding variable expressivity in microdeletion syndromes

A new study reports an elevated frequency of second-site genomic alterations among children with severe developmental delay who carry a recurrent microdeletion at chromosome 16p12.1. The work highlights the complex relationship between genotype and phenotype and provides a model to explain the clinical variability associated with this and other common microdeletion syndromes.

Nature Genetics, vol. 42 #3, pp192-193

Letter: A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

Stephen Chanock and colleagues identify three new susceptibility loci for pancreatic cancer on chromosomes 13q22.1, 1q32.1 and 5p15.33. The association signal at 13q22.1 maps to a large nongenic region, whereas the signals at 1q32.1 and 5p15.33 map near the NR5A2 gene and CPTM1L-TERT region, respectively.

Nature Genetics, vol. 42 #3, pp224-228

Letter: Germline mutations in TMEM127 confer susceptibility to pheochromocytoma

Patricia Dahia and colleagues show that germline mutations in TMEM127 confer susceptibility to pheochromocytomas. Their functional studies suggest that TMEM127 acts as a negative regulator of mTOR signaling.

Nature Genetics, vol. 42 #3, pp229-233

Letter: Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions

Vivianna Van Deerlin and colleagues report that common variants at 7p21 are associated with a subtype of frontotemporal lobar degeneration marked by TDP-43 inclusions. They further show that the risk alleles are associated with elevated brain expression of TMEM106B, which resides at the peak of association on 7p21.

Nature Genetics, vol. 42 #3, pp234-239

Letter: Common variants in KCNN3 are associated with lone atrial fibrillation

Patrick Ellinor and colleagues report a genome-wide association study identifying variants in KCNN3 associated to lone atrial fibrillation.

Nature Genetics, vol. 42 #3, pp240-244

Letter: Mutations in PNKP cause microcephaly, seizures and defects in DNA repair

Christopher Walsh and colleagues describe a new recessive genetic disease characterized by microcephaly, early-onset intractable seizures and developmental delay (MCSZ). The authors identify mutations in PNKP that result in this severe disease and show that PNKP mutations disrupt DNA repair.

Nature Genetics, vol. 42 #3, pp245-249

Letter: Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex

Kerstin Lindblad-Toh and colleagues use genome-wide association mapping to identify risk loci for a canine systemic lupus erythematosus-related disease complex in Nova Scotia duck tolling retrievers. The study illustrates the power of using dog breeds for complex trait mapping.

Nature Genetics, vol. 42 #3, pp250-254

Letter: A map of open chromatin in human pancreatic islets

Jorge Ferrer, Jason Lieb, and Karen Mohlke and colleagues identify regulatory DNA active in human pancreatic islets by formaldehyde-assisted isolation of regulatory elements (FAIRE) coupled with high-throughput sequencing. They identified 80,000 open chromatin sites and 3,300 islet-selective open chromatin sites and found that a TCF7L2 intronic variant associated with type 2 diabetes is located in islet-selective open chromatin.

Nature Genetics, vol. 42 #3, pp255-259

Letter: Population resequencing reveals local adaptation of Arabidopsis lyrata to serpentine soils

Thomas Turner and colleagues have applied next-generation sequencing technology to investigate the genetic basis of adaptive variation. They sequenced pools of DNA from geographically distinct Arabidopsis lyrata populations that are locally adapted to serpentine soils and analyzed 8 million polymorphisms, identifying a putative example of convergent evolution.

Nature Genetics, vol. 42 #3, pp260-263

Letter: A basic helix-loop-helix transcription factor controls cell growth and size in root hairs

Liam Dolan and colleagues report discovery of a basic helix-loop-helix transcription factor, RSL4, that is necessary and sufficient to promote postmitotic cell growth in Arabidopsis thaliana root hair cells.

Nature Genetics, vol. 42 #3, pp264-267

Letter: Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs

Xin-zhuan Su and colleagues report genome-wide SNP genotyping of 189 culture-adapted Plasmodium falciparum parasites and examine population structure, selection and recombination hotspots. They also conduct genome-wide association studies for resistance to seven different antimalarial drugs.

Nature Genetics, vol. 42 #3, pp268-271

Letter: Prevalent positive epistasis in Escherichia coli and Saccharomyces cerevisiae metabolic networks

Jianzhi Zhang and colleagues examine epistasis within the metabolic networks of Escherichia coli and Saccharomyces cerevisiae using flux balance analysis. They find a strong bias towards positive epistasis amongst essential genes and show that these only rarely include genes involved in biochemical reactions with related functions.

Nature Genetics, vol. 42 #3, pp272-276



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