Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders that often progress to chemotherapy-resistant secondary acute myeloid leukemia (sAML). We used whole-genome sequencing to perform an unbiased comprehensive screen to discover the somatic mutations in a sample from an individual with sAML and genotyped the loci containing these mutations in the matched MDS sample. Here we show that a missense mutation affecting the serine at codon 34 (Ser34) in U2AF1 was recurrently present in 13 out of 150 (8.7%) subjects with de novo MDS, and we found suggestive evidence of an increased risk of progression to sAML associated with this mutation. U2AF1 is a U2 auxiliary factor protein that recognizes the AG splice acceptor dinucleotide at the 3' end of introns, and the alterations in U2AF1 are located in highly conserved zinc fingers of this protein. Mutant U2AF1 promotes enhanced splicing and exon skipping in reporter assays in vitro. This previously unidentified, recurrent mutation in U2AF1 implicates altered pre-mRNA splicing as a potential mechanism for MDS pathogenesis.     

Occurrence of anisakid larvae (Nematoda: Ascardidia) in fishes from Alaska and Idaho

All 25 sablefish ( Anoplopoma fimbria ) examined from two bays near Sitka, Alaska, were infected with anisakid larvae. There were 1 to 11 larvae per infected fish, with worms encysted in the musculature of the body wall of 5 fish and in the liver of 4 fish. For the other hosts the viscera was the site of infection. Chinook salmon ( Onchorhynchus tshawytscha ) from Barrow, Alaska, and Obsidian, Idaho, were also infected with anisakid larvae. These data extend the known northern distribution of the anisakids along the Pacific Coast for sablefish and chinook salmon. The pathogenesis of the migratory pathway of anisakid larvae is described, and comments on human health implications are presented.     

Records of exotic fishes from Idaho and Wyoming

One exotic poeciliid ( Xiphophorus helleri ) and two cichlids ( Cichlasoma nigrofasciatum and Tilapia mossambica ) are recorded as recently established in thermal springs and their outflows in southern Idaho. Misgurnus anguillicaudatus was collected and is considered as established in the Boise River system. Poecilia mexicana and juvenile hybrid tilapias are recorded from the Bruneau River at Bruneau Hot Springs, Idaho. A reproducing population of X. helleri was found in a spring within the boundaries of Grand Teton National Park, Wyoming. Poecilia reticulata , previously reported from one spring each in Idaho and Wyoming, is recorded from a second spring outflow in Idaho.     

Chromosome races in Sarcobatus (Sarcobataceae, Caryophyllales)

Sarcobatus Nees., a genus of North American halophytic shrubs, consists of 2 species: S. vermiculatus (Hook.) Torr. ( n = 18, 36), which is widespread in North America, and S. baileyi Cov ( n = 54), endemic to Nevada. Within S. vermiculatus , populations of n = 36 are widely distributed, whereas populations of n = 18 are found only in the Sonoran Desert, northern California, and northwestern Great Plains, locations at the periphery of the species range. Although the chromosome number of n = 18 is apparently a tetraploid, failure to form and n = 27 race intermediate to those of n = 18 and n = 36 suggests than n = 18 S. vermiculatus is of significant age and that it behaves chromosomally as a diploid. Sacrobatus has a long fossil pollen record and endured Pleistocene climatic extremes with little range displacement.     

Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ～25% of the familial risk in this disease, have now been identified.     

Variants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature

We report mapping of a quantitative trait locus (QTL) with a major effect on bovine stature to a ～780-kb interval using a Hidden Markov Model-based approach that simultaneously exploits linkage and linkage disequilibrium. We re-sequenced the interval in six sires with known QTL genotype and identified 13 clustered candidate quantitative trait nucleotides (QTNs) out of >9,572 discovered variants. We eliminated five candidate QTNs by studying the phenotypic effect of a recombinant haplotype identified in a breed diversity panel. We show that the QTL influences fetal expression of seven of the nine genes mapping to the ～780-kb interval. We further show that two of the eight candidate QTNs, mapping to the PLAG1-CHCHD7 intergenic region, influence bidirectional promoter strength and affect binding of nuclear factors. By performing expression QTL analyses, we identified a splice site variant in CHCHD7 and exploited this naturally occurring null allele to exclude CHCHD7 as single causative gene.