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.
Our ability to map trait-associated regulatory variation still vastly exceeds the prospects for dissecting allele-specific effects on gene expression and activity in vivo in relevant tissues and organs. A small number of intensive investigations into functional variants should pave the way for scaleable strategies using high-throughput techniques and genomic data integration.
Elucidating the molecular mechanisms responsible for changes in gene expression is important for understanding the evolution of morphological traits. A new study identifies the molecular basis of the association between KITLG and blond hair color, presenting an intriguing example of how a single DNA base-pair change in an upstream regulatory element can cause relatively large and specific downstream changes in phenotype.
Two new studies report genomic data on three species of whipworm, soil-transmitted parasitic worms responsible for trichuriasis. These genomes provide insights into host-pathogen interactions and potential for new drug targets for helminth therapy.
A new study reports the genome of common bean (Phaseolus vulgaris) and genome-wide resequencing data from both wild and domesticated accessions. These data confirm that common bean was domesticated at least twice, in Mesoamerica and South America, and also provide a framework to identify genes that contributed to the phenotypic changes associated with domestication.
André Oliveira and colleagues identify a recurrent translocation in biphenotypic sinonasal sarcomas generating a PAX3-MAML3 fusion gene. The resulting protein is a potent transcriptional activator of PAX3 response elements and is associated with aberrant expression of genes involved in neuroectodermal and myogenic differentiation.
Stephanie London, Martin Tobin and colleagues report meta-analyses of genome-wide association studies for forced vital capacity (FVC), a spirometric measure of pulmonary function that reflects lung volume. They identify six regions newly associated with FVC and demonstrate that candidate genes at these loci are expressed in lung tissue and primary lung cells.
Tomas Ganz and colleagues identify a new regulator of iron metabolism, erythroferrone, that is produced by erythroblasts in response to erythropoietin and suppresses hepcidin expression during stress erythropoiesis. They further show that erythroferrone levels are highly elevated in a mouse model of β-thalassemia, contributing to hepcidin suppression and iron overload in this model.
Alexander Stark and colleagues use STARR-seq, a quantitative enhancer assay, to determine enhancer activity profiles for the genomes of five Drosophila species in Drosophila melanogaster S2 cells. They find that a large fraction of D. melanogaster enhancers are functionally conserved and enhancer activity is frequently gained.
Matthew Berriman and colleagues report the whole-genome sequences of the human-infective whipworm Trichuris trichiura and the mouse-infective laboratory model Trichuris muris. Their transcriptome analyses and examination of T. muris infection in mice provide insights into host response to infection and potential drug targets for this major soil-transmitted helminth.
Aaron Jex and colleagues report whole-genome sequencing of adult male and female whipworm, Trichuris suis, from experimentally infected pigs. They also report stage-, sex- and tissue-specific transcriptomes and provide insights into host-parasite interactions.
Scott Jackson, Jeremy Schmutz, Phillip McClean and colleagues report the genome sequence of the common bean (Phaseolus vulgaris) and resequenced wild individuals and landraces from Mesoamerican and Andean gene pools, showing that common bean underwent two independent domestications.
Jie Luo, Xingming Lian and colleagues report results of a large genome-wide association study of metabolic variation in rice. They identify hundreds of common variants influencing metabolite levels and illustrate how this approach can complement classical trait mapping and provide insights into pathways of physiological and nutritional importance.
Robert West, Jonathan Pollack and colleagues identify mutations in either the Hedgehog pathway gene SMO or the MAPK gene BRAF in 24 of the 28 ameloblastoma samples studied. They found 9 of 11 SMO mutations were found in maxillary ameloblastomas, whereas 9 of 13 BRAF mutations were found in mandibular cases.
Kyle Walsh and colleagues identify a variant near TERC associated with glioma susceptibility. They further show that glioma risk alleles near TERC and TERT are associated with longer mean telomere length in leukocytes, implicating telomerase activity in gliomagenesis.
Stephen Scherer and colleagues report an inverse relationship between exon transcription levels in the developing brain and the burden of rare missense mutations. Using these data, they develop a contingency index that identifies critical exons harboring deleterious de novo mutations that are enriched in individuals with ASD relative to their unaffected siblings.
David Kingsley and colleagues functionally investigate a previously identified GWAS region in an enhancer of the KITLG gene (encoding KIT ligand) that is significantly associated with blond hair color in northern European populations. They show that a single regulatory SNP, located 350,000 bp upstream of the human gene, reduces the activity of a tissue-specific hair follicle enhancer and is sufficient to alter hair color in mice.
François Spitz and colleagues identify cis-acting enhancers of Myc in a region orthologous to human 8q24 that are required for normal development of the face in mice. Their results shed light on the role of this region in facial deformities in humans, including cleft lip and palate.