Nature Genetics publishes the very highest quality research in genetics. It encompasses genetic and functional genomic studies on human traits and on other model organisms, including mouse, fly, nematode and yeast. Current emphasis is on the genetic basis for common and complex diseases and on the functional mechanism, architecture and evolution of gene networks, studied by experimental perturbation.
Attention to accurate representation of claims within a research article together with the evidence and method supporting each claim can expedite peer review. Accurate citation of the claims of others is essential to avoid prematurely closing possibly productive research strategies.
For over 100 years, it has been known that polymorphic mimicry is often switched by simple mendelian factors, yet the physical nature of these loci had escaped characterization. Now, the genome sequences of two swallowtail butterfly (Papilio) species have enabled the precise identification of a locus underlying mimicry, adding to unprecedented recent discoveries in mimicry genetics.
Recent molecular classification of colorectal cancer (CRC) has identified a poor-prognosis transcriptional subtype associated with mesenchymal traits. New studies used CRC transcriptomic data to show that tumor-associated stroma mimics the gene signature of epithelial-to-mesenchymal transition (EMT) and found no evidence for EMT of colorectal tumor cells.
Mycorrhizal fungi live in the roots of host plants and are crucial components of all forest ecosystems. A large-scale study of fungal genomics provides new insights into the evolution of mycorrhizae and a deep exploration of mycorrhizal diversity that helps to uncover the molecular and genetic details of fungal symbiotic relationships with plants.
Claudio Isella and colleagues report an analysis of colorectal cancer (CRC) gene expression data from patient-derived xenografts, which they use to reconcile three commonly used CRC classification systems. They find that the stem/serrated/mesenchymal (SSM) transcriptional subtype of CRC, previously linked to poor prognosis, is driven by stromal cells rather than tumor cells.
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.
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.
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.
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.
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.
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.
Colin Cooper and colleagues report genome-wide sequences of multiple samples of multifocal cancer and morphologically normal tissue from the prostates of three men. They found high levels of mutations in morphologically normal tissue distant from the cancer, consistent with field effects.
Doug Easton and colleagues report the results of a large-scale genome-wide association study of breast cancer. They discover 15 new susceptibility loci and highlight likely target genes in several of the newly associated regions.
Stephen Rich and colleagues report the discovery and fine mapping of type 1 diabetes susceptibility loci using the Immunochip. They also perform comparative analyses with 15 other immune disorders and find evidence of colocalization of causal variants with lymphoid gene enhancers.
Tin Aung, Chiea-Chuen Khor and colleagues report the results of a genome-wide association study of exfoliation syndrome. They replicate a known association at LOXL1 and identify a previously unreported association at CACNA1A.
Johannes Lemke, Holger Lerche and colleagues report the identification of de novo mutations in the potassium channel gene KCNA2 in patients with epileptic encephalopathies. The authors confirm in vitro that two mutations cause dominant loss of channel function, whereas the other two mutations induce gain-of-function effects, leading to permanently open channels.
Philip Awadalla and colleagues report an analysis of the relationship between recombination and deleterious variation using high-coverage sequence data from over 1,400 individuals. They find that the recombination rate modulates the distribution of putatively deleterious variants across the human genome.
Haruhiko Fujiwara and colleagues report the genome sequences of two swallowtail butterfly species, Papilio xuthus and Papilio polytes, and the identification of a chromosomal inversion underlying the mimetic phenotype in P. polytes females. The inversion interacts with dsx to control mimetic coloration patterns in an allele-specific manner.
Francis Martin and colleagues report genome sequences for 18 species of mycorrhizal fungi and a phylogenomic analysis including 32 other fungal genomes. The study identifies cell wall-degradation genes lost in all true ectomycorrhizal species and, using gene expression data, finds candidate genes for the establishment of symbiosis.
Erich Schwarz and colleagues report whole-genome sequencing of the zoonotic hookworm Ancylostoma ceylanicum. They also analyze the transcriptome through the course of infection in golden hamsters and identify groups of genes showing differential regulation across different stages.