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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



 






The road to precision oncology

2017-02-24

The ultimate goal of precision medicine is to use population-based molecular, clinical and other data to make individually tailored clinical decisions for patients, although the path to achieving this goal is not entirely clear. A new study shows how knowledge banks of patient data can be used to make individual treatment decisions in acute myeloid leukemia.



Convergence and divergence in sex-chromosome evolution

2017-02-24

A sequence assembly of the chicken W chromosome enables reconstruction of the gene content of the W chromosome across 14 bird species and shows striking similarities in the maintenance of broadly expressed and dosage-sensitive genes on highly degenerate sex chromosomes in both birds and mammals. However, the chicken W chromosome is not enriched for genes with expression in female-specific tissues, providing an intriguing contrast to the acquisition and amplification of genes with testis-specific expression on mammalian Y chromosomes and suggesting that the inheritance of chromosomes solely through females or males can lead to different evolutionary outcomes.



Untangling the genetics from the epigenetics in pancreatic cancer metastasis

2017-02-24

Comparative genomic analyses of primary tumors and metastases within individuals with pancreatic cancer have exposed the complex clonal dynamics that underlie the dissemination of cancer cells to distant sites. Recent studies implicate non-genetic mechanisms in this process, particularly fluctuations in chromatin states and metabolism, which can endow rare cells within a primary tumor with metastatic potential.



Case–control association mapping by proxy using family history of disease

2017-01-16

Jimmy Liu and colleagues perform genome-wide association by proxy (GWAX) in a large population cohort by replacing cases with their first-degree relatives. They apply GWAX to 12 common diseases and show its utility by identifying new risk loci for Alzheimer's disease, coronary artery disease and type 2 diabetes.



Precision oncology for acute myeloid leukemia using a knowledge bank approach

2017-01-16

Peter Campbell, Hartmut Döhner and colleagues present an analysis of genetic mutations and clinical information from 1,540 patients with acute myeloid leukemia, demonstrating the utility of clinical knowledge banks for personalized medicine. They show that use of their approach could reduce the number of hematopoietic cell transplants in patients with AML by up to 25% while maintaining survival rates.



A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers

2017-01-23

Serena Nik-Zainal and colleagues present a detailed analysis of somatic rearrangements in 560 breast cancers. They highlight 33 rearrangement hotspots characterized mainly by large tandem duplications and show that these hotspots are enriched in breast cancer germline susceptibility loci and breast-specific super-enhancer elements.



Systematic analysis of telomere length and somatic alterations in 31 cancer types

2017-01-30

Siyuan Zheng, Roel Verhaak and colleagues report an analysis of telomere lengths and somatic alterations in telomere-related pathways across 31 cancer types. Their study provides an overview of the molecular mechanisms driving TERT expression and activation of the ALT pathway, and identifies a subset of tumors with neither detectable TERT expression nor somatic alterations in ATRX or DAXX.



Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer

2017-01-16

Christine Iacobuzio-Donahue and colleagues report a detailed analysis of whole-genome sequencing data from primary and metastatic tumors in four patients with pancreatic cancer. They find that in each patient primary tumors and metastases have identical mutations in known driver genes.



Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis

2017-01-16

Andrew Feinberg, Christine Iacobuzio-Donahue and colleagues describe the epigenomic reprogramming that occurs during pancreatic cancer progression. They also show that hematogenous metastases co-evolve a dependence on the oxidative branch of the pentose phosphate pathway (oxPPP) and that oxPPP inhibition reverses chromatin reprogramming and blocks tumorigenic potential.



Landscape of monoallelic DNA accessibility in mouse embryonic stem cells and neural progenitor cells

2017-01-23

Howard Chang and colleagues use allele-specific ATAC–seq to profile active regulatory DNA across the genome in mouse embryonic stem cells and neural progenitor cells. They find that monoallelic DNA accessibility across autosomes is pervasive, developmentally programmed and composed of several patterns.



Avian W and mammalian Y chromosomes convergently retained dosage-sensitive regulators

2017-01-30

David Page and colleagues report the sequence of the chicken W sex chromosome and compare ancestral W-linked genes across bird species. They find that the W chromosome did not acquire genes expressed exclusively in reproductive tissue, but retained genes through selection to maintain appropriate dosage levels of broadly expressed genes.



Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance

2017-01-16

Ashlee Earl and colleagues analyze whole-genome sequences from 5,310 Mycobacterium tuberculosis isolates from five continents. They find that resistance to isoniazid arises before rifampicin resistance across all of the lineages, geographical regions and time periods.



Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

2017-01-30

Mark Caulfield, Paul Elliott and colleagues use data from the UK Biobank to perform genome-wide association analysis for blood pressure traits. They identify and validate 107 novel loci and highlight new biological pathways for potential therapeutic intervention for hypertension.



Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

2017-02-06

Louise Wain, Ian Hall, Martin Tobin and colleagues report genome-wide association analyses of lung function, identifying 43 new signals associated with one or more lung function traits. A genetic risk score derived from these results was significantly associated with risk for chronic obstructive pulmonary disease in independent populations.



Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis

2017-02-06

Michael Cho and colleagues report a genome-wide association study of risk for chronic obstructive pulmonary disease (COPD) in a large, multi-ancestry cohort. They identify 22 genome-wide significant loci, including 13 not previously associated with COPD and 4 not previously associated with any lung function trait.



A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases

2017-01-30

Betty Tsao, Jian Zhao, Nan Shen and colleagues show that a common missense variant in NCF1 confers susceptibility to multiple autoimmune diseases. This variant, which leads to reduced production of reactive oxygen species, accounts for the strong association signal previously identified in the GTF2IRD1–GTF2I region at 7q11.23.



Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet's disease susceptibility

2017-02-06

Daniel Kastner, Elaine Remmers and colleagues perform an association study of Behçet's disease based on dense genotyping of immune-related loci. They identify new association signals near genes involved in host response to microbial exposure and extend evidence for shared susceptibility loci with Crohn's disease and leprosy.



Acquired CYP19A1 amplification is an early specific mechanism of aromatase inhibitor resistance in ERα metastatic breast cancer

2017-01-23

Saverio Minucci, Giancarlo Pruneri, Luca Magnani and colleagues identify acquired CYP19A1 amplification as a mechanism of resistance to aromatase inhibitors in ERα metastatic breast cancer. Mechanistically, they show that CYP19A1 amplification results in increased aromatase activity and estrogen-independent ERα binding to target genes.



Pediatric non–Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes

2017-01-23

Franco Locatelli, Dirk Reinhardt, Marry van den Heuvel-Eibrink, C Michel Zwaan, Maarten Fornerod, Tanja Gruber and colleagues report whole-exome and transcriptome sequencing of acute megakaryoblastic leukemia from pediatric and adult patients without Down syndrome (non-DS-AMKL). They find that pediatric non-DS-AMKL can be divided into seven subgroups characterized by chimeric oncogenes with cooperating mutations in epigenetic and kinase signaling genes.



Biallelic mutations in the 3′ exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing

2017-01-16

Jens Lykke-Andersen, Frank Baas, Joseph Gleeson and colleagues report that mutations in the 3′ exonuclease TOE1 cause pontocerebellar hypoplasia type 7. They further show that these mutations result in the accumulation of incompletely processed small nuclear RNAs, leading to severe, early-onset neurodegeneration.



Divergent effects of intrinsically active MEK variants on developmental Ras signaling

2017-02-06

Stanislav Shvartsman and colleagues quantify signaling changes caused by disease-associated mutations in MAP2K1 (encoding MEK) in fruit fly and zebrafish embryos. They find that intrinsically active MEK variants can both increase and reduce the levels of pathway activation depending on cellular context.



Whole-genome analysis of introgressive hybridization and characterization of the bovine legacy of Mongolian yaks

2017-01-30

Ivica Medugorac, Aurélien Capitan and colleagues use high-density SNP genotyping and whole-genome sequencing to infer bovine haplotypes in the genomes of 76 Mongolian yaks. They show that these introgressed regions are enriched for genes involved in nervous system development and function, supporting the idea that introgressive hybridization contributed to the improvement of yak management and breeding.



A study of allelic diversity underlying flowering-time adaptation in maize landraces

2017-02-06

Edward Buckler, Sarah Hearne and colleagues integrate two approaches to characterize the genetic diversity of a large number of geographically distributed maize landraces. They examine flowering time and adaptation to altitude and find that the majority of the associated SNPs overlap both traits.