Articles in 2015

Ian Krantz, Katsuhiko Shirahige and colleagues report the genetic characterization of a new clinical syndrome characterized by cognitive impairment, heart and pulmonary defects, and skeletal dysplasia, among other symptoms. They identify gain-of-function mutations in the super elongation complex gene AFF4 as causing the disorder.

Fernando Pardo-Manuel de Villena and colleagues generate a 3 × 3 diallel cross of three inbred mouse lines and examine gene expression in multiple tissues. They identify allelic imbalance favoring the expression of the paternal allele across the genome.

Anna Andersson, Tanja Gruber, James Downing and colleagues report a genomic analysis of infant acute lymphoblastic leukemias with MLL rearrangements. They identify recurrent activating mutations in tyrosine kinase, phosphatidylinositol 3-kinase and RAS pathway genes but find that these mutations were often present in minor subclones and lost at the time of relapse.

Eduard Batlle and colleagues find that poor-outcome subgroups of colorectal cancer are driven by genes expressed in tumor-associated stromal cells. They show that TGF-β expression is a common feature of poor-prognosis subtypes and demonstrate the use of anti–TGF-β molecules in patient-derived tumoroids and xenografts.

José Penadés and colleagues examine host adaptation and specificity for Staphylococcus aureus with analysis of the whole-genome sequences of strains isolated from humans or rabbits. They find that a rabbit-specific clone evolved through a human-to-rabbit host jump, enabled by a single mutation in dltB.

Christopher O'Donnell and colleagues report a genome-wide screen for splicing quantitative trait loci (sQTLs) in 5,257 human blood samples. They identify cis sQTLs affecting mRNA isoform variation for over 2,000 genes, 367 of which are linked to trait-associated GWAS SNPs that overlapped with the sQTLs.

Daniel Jeffares, Jürg Bähler and colleagues report the genome sequences of 161 natural isolates of Schizosaccharomyces pombe, finding moderate genetic diversity and weak global population structure. They also report genome-wide association studies for 223 quantitative traits.

Christina Curtis, Darryl Shibata and colleagues report genomic profiling of 349 individual glands sampled from 15 human colorectal tumors. They observe high within-tumor heterogeneity and mixing of subclones in distant tumor regions, supporting a model whereby tumor growth occurs predominantly as a single expansion, with most detectable subclonal mutations arising during the earliest phases of tumor growth.

Lusheng Huang, Jun Ren and colleagues report the genome sequences of 69 pigs, representing 11 geographically distinct breeds and 3 wild boar populations, from within China. They identify loci related to high- and low-latitude adaptation and infer a likely ancient introgression event in northern Chinese pigs.

Dominic Kwiatkowski and colleagues report a large multicenter genome-wide association study of Plasmodium falciparum resistance to artemisinin. They identify markers of a genetic background on which kelch13 mutations conferring artemisinin resistance are likely to emerge.

Thierry Wirth, Philip Supply, Stefan Niemann and colleagues analyze 4,987 Mycobacterium tuberculosis strains of the Beijing lineage isolated from 99 countries. They report whole-genome sequencing of 110 representative strains, characterize global population structure and reconstruct the evolutionary history of this lineage.

Nancy Jenkins and colleagues report the use of Sleeping Beauty transposon mutagenesis screens in mice to identify new genes involved in tumor progression in colorectal cancer. They identify 111 common transposon insertion sites present in all cohorts, including Znf292, a new tumor suppressor whose human counterpart is also mutated in human colorectal cancer.