Volume 44 Issue 9, September 2012

Plasmodium vivax has received less attention and study than Plasmodium falciparum, due in part to difficulties in culturing this pathogen. Whole-genome sequencing of both P. vivax and Plasmodium cynomolgi and characterization of genetic variation in these species provide a genetic toolbox for tertian malaria and new insights into the monkey malaria clade.

Shigella sonnei is an important cause of bacterial dysentery in the developed world and has also recently emerged in transitional countries. Phylogenetic analysis based on whole-genome sequencing of a global sample has detailed the recent evolutionary history of this pathogen and shed light on the genetic changes associated with this epidemiological shift.

The cloning of Dolly the sheep was a remarkable demonstration of the oocyte's ability to reprogram a specialized nucleus. However, embryos derived from such somatic cell nuclear transfer (SCNT) very rarely result in live births—a fate that may be linked to observed epigenetic defects. A new genome-wide study shows that epigenetic reprogramming in SCNT embryos does not fully recapitulate the natural DNA demethylation events occurring at fertilization, resulting in aberrant methylation at some promoters and repetitive elements that may contribute to developmental failure.

Elisabeth Mangold and colleagues report a genome-wide meta-analyses of non-syndromic cleft lip with or without cleft palate (NSCL/P). They report six new genetic loci associated with risk for NSCL/P.

Ming Qi and colleagues report that compound heterozygous mutations in NMNAT1 cause Leber congenital amaurosis, a childhood form of retinal dystrophy. NMNAT1 encodes an enzyme previously implicated in protection against axonal degeneration.

Josseline Kaplan, Jean-Michel Rozet and colleagues show that biallelic mutations in NMNAT1 cause an autosomal recessive form of Leber congenital amaurosis characterized by early-onset severe macular atrophy and optic atrophy.

Alex Meissner and colleagues report base pair–resolution methylation maps from donor fibroblasts and nuclear transfer–reconstructed mouse embryos. They compare methylation profiles to that present during normal fertilization and find that specific promoters and repeat elements exhibit differential dynamics.

Mark McCarthy, Michael Boehnke, Andrew Morris and colleagues perform large-scale association analyses using the Metabochip to gain insights into the genetic architecture of type 2 diabetes. They report several new susceptibility loci, including two that show sex-differentiated effects on disease risk.

Jose Florez, Claudia Langenberg, Erik Ingelsson, Inga Prokopenko, Inês Barroso and colleagues perform large-scale association analyses using the Metabochip to gain further insights into the genetic architecture of glucose regulation. They identify 38 new loci influencing 1 or more glycemic traits and show that many of these loci also modify risk of type 2 diabetes.

Ruth Halaban and colleagues report exome sequences of 147 melanoma tumors. They identified a recurrent somatic activating alteration in the Rho GTPase RAC1 in sun-exposed melanomas.

Joel Hirschhorn and colleagues examine height-associated SNPs in northern- and southern-European populations. They report evidence of widespread weak selection on standing variation for height in humans.

Zi-Jiang Chen and colleagues report a genome-wide association analysis for polycystic ovary syndrome (PCOS) in Han Chinese. They identify eight new susceptibility loci for PCOS in this population.

Ching-Lung Cheung and colleagues report a genome-wide association study for thyrotoxic periodic paralysis (TPP), a life-threatening complication of thyrotoxicosis, in a Chinese population. They identify associated variants at 17q24.3 near KCNJ2.

David Goldstein, Mohamad Mikati and colleagues report identification of de novo mutations in ATP1A3 in alternating hemiplegia of childhood, which is a rare neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurologic manifestations.

Rui Chen and colleagues identify mutations in NMNAT1 as a new cause of Leber congenital amaurosis. They further show that all examined individuals with NMNAT1 mutations have macular colobomas, a condition marked by severe degeneration of the central retina.

Eric Pierce, Xiaowu Gai and colleagues identify mutations in NMNAT1 as a new cause of Leber congenital amaurosis, an early-onset form of retinal degeneration. NMNAT1 encodes an isoform of nicotinamide mononucleotide adenylyltransferase, which is required for nicotinamide adenine dinucleotide (NAD⁺) biosynthesis.

Jane Carlton and colleagues report the genome sequencing, de novo assembly and annotation of four Plasmodium vivax reference strains from diverse geographic locations. Their cross-species comparisons show that P. vivax has greater genetic diversity than Plasmodium falciparum.

Jane Carlton, Kazuyuki Tanabe and colleagues report the draft genome sequences of three Plasmodium cynomolgi strains isolated from infected monkeys. Their comparative genomic analysis with P. vivax and P. knowlesi offers insights into these simian malaria parasites.

Nicholas Thomson and colleagues report whole-genome sequencing of 132 globally distributed isolates of Shigella sonnei, a cause of human dysentery. Their phylogeographic analyses suggest that the current S. sonnei population is under 500 years old, and the authors are able to trace several distinct lineages that have spread out of Europe to other continents over the last few decades.

Richard O'Connell and colleagues report the genomes and transcriptomes of two Colletotrichum plant fungal pathogens. C. higginsianum infects Arabidopsis thaliana, and C. graminicola infects maize (Zea mays); comparative genomics in both species lead to molecular insights into the transition from biotrophic to necrotrophic life stages.

Magnus Nordborg and colleagues report a parameterized multi-trait mixed model (MTMM) method applied to genome-wide association studies of correlated phenotypes. They test this approach, using both human and Arabidopsis thaliana data sets, and demonstrate how it can be used to identify pleiotropic loci and gene by environment interactions.