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The coevolution of staple crops and human society can be traced in the relics of ancient genomes and in population genetic signatures that our interdependence has left on our genomes and those of our crop plants. Patterns of geographical adaptation in the genomes of local crop varieties connect millennia of survival strategies of subsistence farmers with future agricultural improvement in the face of challenges from environmental changes.
A new analysis has characterized a fundamental building block of complex transcribed loci. Constellations of core promoters can generally be reduced to pairs of divergent transcription units, where the distance between the pairs of transcription units correlates with constraints on genomic context, which in turn contribute to transcript fate.
A genome-wide study in Samoans has identified a protein-altering variant (p.Arg475Gln) in CREBRF as being associated with 1.3-fold increased risk of obesity and, intriguingly, 1.6-fold decreased risk of type 2 diabetes. This variant, which is common among Samoans (minor allele frequency = 26%) but extremely rare in other populations, promotes fat storage and reduces energy use in cellular models.
Study of the Greater Middle East (GME), home to approximately 10% of the world's population, has made invaluable contributions to the characterization of rare genetic disease, especially recessive conditions arising from the tradition of consanguinity and large families with multiple children. A new study now reports 1,111 unrelated exomes from the GME and provides a comprehensive view of genetic variation for enhanced discovery of disease-associated genes.
Albert Tenesa and colleagues report an analysis of the heritability of 12 complex diseases in 1,555,906 individuals from the UK Biobank. They find that SNP heritability explains a higher proportion of estimated heritability when shared familial environmental factors are taken into account.
Yun Chen, Albin Sandelin, Torben Heick Jensen and colleagues describe general rules governing the expression of reverse-oriented promoter upstream transcripts (PROMPTs) based on the orientation and proximity of promoter pairs. They characterize how the distance between promoters affects the expression of PROMPTs and the usage of alternate mRNA transcription start sites.
Jonathan Pritchard, Christopher Garcia and colleagues examine associations between different T cell receptor V genes and MHC alleles by eQTL mapping. They find that there are strong associations between MHC variation and T cell receptor gene usage and map these signals to specific MHC amino acids, many of which physically interact with germline-encoded amino acids on the T cell receptor.
Yongfeng Shang and colleagues report that the pioneering factor FOXA1 associates with DNA repair complexes and regulates DNA demethylation at its genomic targets in a DNA polymerase β–dependent manner. They show that FOXA1-associated DNA demethylation is coupled with genomic targeting of estrogen receptor α and estrogen responsiveness in a breast cancer cell line.
Margaret Goodell, Wei Li and colleagues use double-knockout mice for Dnmt3a and Tet2 to model leukemia development. Through epigenetic and transcriptional analyses, they show that loss of DNMT3A and TET2 upregulates lineage-specific transcription factors such as KLF1 in hematopoietic stem cells and accelerates malignancy.
Robbie Waugh, Nils Stein, Gary Muehlbauer and colleagues report the exome sequencing of 267 landraces and wild accessions of barley from diverse regions to study adaptations to different agricultural environments. They observe correlations of days to heading and height with environment and find that variation in flowering-associated genes has strong geographical structuring.
Ashley Winslow, Roy Perlis, David Hinds and colleagues report the identification of 15 genetic loci associated with risk of major depressive disorder in individuals of European descent. They find that several loci are also associated with risk of other psychiatric traits, including schizophrenia and neuroticism.
Jan Veldink and colleagues show that loss-of-function variants in NEK1 are associated with susceptibility to amyotrophic lateral sclerosis (ALS). In addition to finding an excess of rare loss-of-function NEK1 variants in ALS cases, they report a significant association between a specific NEK1 missense variant (p.Arg261His) and disease risk.
Ammar Al-Chalabi, Jan Veldink and colleagues perform a genome-wide association study for amyotrophic lateral sclerosis (ALS) in 15,156 cases and 26,242 controls. They identify three new genome-wide-significant variants and establish ALS as a complex trait with a polygenic architecture, but with a distinct and important role for low-frequency variants.
Stephen McGarvey and colleagues identify a missense variant in CREBRF strongly associated with body mass index in Samoans. This variant is rare in other populations but is common in Samoans and has a much larger effect size than other known common obesity risk variants, including variation in FTO.
Ewan Pearson, Kathleen Giacomini and the Metformin Genetics Consortium perform a genome-wide association study for glycemic response to the antidiabetic drug metformin. They find an intronic allele of the GLUT2 glucose transporter gene that associates with greater metformin action, an effect that is more pronounced in obese individuals.
Matthew Hurles and colleagues report exome sequencing of 1,891 individuals with syndromic or nonsyndromic congenital heart defects (CHD). They found that nonsyndromic CHD patients were enriched for protein-truncating variants in CHD-associated genes inherited from unaffected parents and identified three new syndromic CHD disorders caused by de novo mutations.
Jaume Bertranpetit, Partha Majumder and colleagues analyze whole-genome sequences from Andamanese individuals and compare them to sequences from mainland Indian and other geographically diverse populations. They find evidence of ancestry from an unknown extinct hominin in South Asian populations and show that distinct Andamanese characteristics derive from strong natural selection.
Joseph Gleeson and colleagues report whole-exome sequencing of a cohort of over 1,000 individuals from the Greater Middle East, characterizing common and rare variants. They find evidence of subregional diversity and historical migrations and use the GME Variome to identify disease-causing mutations.
Magnus Nordborg and colleagues report a genomic analysis of all 27 known species in the genus Arabidopsis. They find evidence for a complex speciation history that is not accurately reflected by a traditional bifurcating species tree and identify widespread shared polymorphisms between species.
Rachel Meyer and colleagues use whole-genome resequencing of 93 African rice landraces to generate a SNP map used for population analysis and a genome-wide association study for salt tolerance traits. They find 11 significant loci, some with signatures of positive selection, and evidence for a population bottleneck beginning around 15,000 years ago.
Nils Stein, Ehud Weiss, Tzion Fahima, Johannes Krause and colleagues report the genome sequences of 6,000-year-old barley grains obtained from desert caves in Israel. They compare these to whole-exome sequences of a modern barley diversity panel to explore domestication and migration patterns, finding evidence for prehistoric gene flow between wild and cultivated populations.
Victoria Hore, Jonathan Marchini and colleagues present a method for multiple-tissue gene expression studies aimed at uncovering gene networks linked to genetic variation. They apply their method to RNA sequencing data from adipose, skin and lymphoblastoid cell lines and identify several biologically relevant gene networks with a genetic basis.
