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Nature Genetics



Publishes the very highest quality research in genetics.



 



Remembrance of epigenomes past

2017-05-26

Understanding of how epigenetic information is acquired, processed and transmitted through cell division, and potentially across generations, remains limited. Mechanistic studies aiming to elucidate the molecular underpinnings of these phenomena may provide insights into development, disease susceptibility and evolution.






Starting embryonic transcription for the first time

2017-05-26

Three studies highlight DUX proteins as key transcription factors regulating embryonic genome activation in early mammalian development.



Of giraffes' necks and the inheritance of chromatin states

2017-05-26

New work reports that both derepressed and hyper-repressed chromatin states in animals can be transmitted to progeny for many generations. Transmission depends on genomic architecture and histone modifications.



Adenine N6-methylation in diverse fungi

2017-05-26

A DNA modification—methylation of cytosines and adenines—has important roles in diverse processes such as regulation of gene expression and genome stability, yet until recently adenine methylation had been considered to be only a hallmark of prokaryotes. A new study identifies abundant adenine methylation of transcriptionally active genes in early-diverging fungi that, together with recent other work, emphasizes the importance of adenine methylation in eukaryotes.



Recurrent noncoding regulatory mutations in pancreatic ductal adenocarcinoma

2017-05-08

Michael Schatz, David Tuveson and colleagues analyze somatic noncoding alterations in 308 pancreatic ductal adenocarcinomas. They find recurrent noncoding regulatory mutations that correlate with differential expression of proximal genes and find that the strongest regulatory elements are more frequently mutated, suggesting a selective advantage for mutations in these regions.



Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

2017-04-24

John Perry, Ken Ong and colleagues analyze genotype data on ∼370,000 women and identify 389 independent signals that associate with age at menarche, implicating ∼250 genes. Their analyses suggest causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men.



Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci

2017-04-24

Jonathan Cohen, Helen Hobbs and colleagues show that adiposity significantly amplifies the effects of PNPLA3, TM6SF2, and GCKR sequence variants on nonalcoholic fatty liver disease. They find that synergy between adiposity and genotype influences the full spectrum of the disease, from steatosis to hepatic inflammation and cirrhosis.



Pathogenic variants that alter protein code often disrupt splicing

2017-04-17

William Fairbrother and colleagues use a massively parallel splicing assay (MaPSy) to analyze 4,964 exonic, disease-causing mutations for splicing defects in vivo and in vitro. They find that 10% of these exonic mutations affect splicing, and they classify these alterations by the stage of spliceosome assembly that is disrupted.



Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes

2017-04-24

Sohrab Shah, David Huntsman and colleagues report the genomic analysis of 133 ovarian cancers spanning different subtypes. They identify seven subgroups using point mutation and structural variation signatures and use these genomic features to stratify ovarian cancers both between and within histotypes.



Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells

2017-04-24

Michael Kharas and colleagues characterize the MSI2 protein interactome in leukemia cells and subsequently perform a functional screen identifying 24 genes required for leukemia in vivo. They focus on the RNA-binding protein SYNCRIP, showing that it regulates Hoxa9 and other transcripts involved in a myeloid leukemia stem cell program.



Stable Polycomb-dependent transgenerational inheritance of chromatin states in Drosophila

2017-04-24

Giacomo Cavalli, Frédéric Bantignies and colleagues report the establishment of stable and isogenic Drosophila lines carrying alternative epialleles, defined by different levels of H3K27me3. They show that environmental changes modulate the expressivity of the epialleles and that epilines can be reset to a naive state, thus indicating that the inheritance of this phenotypic variability is epigenetic.



DNA sequence homology induces cytosine-to-thymine mutation by a heterochromatin-related pathway in Neurospora

2017-05-01

Eugene Gladyshev and Nancy Kleckner report that the DNMT1-like cytosine methylase DIM-2 can mediate RIP (repeat-induced point mutation) through cytosine-to-thymine mutation of repetitive DNA in Neurospora crassa. They show that this process requires heterochromatin factors and propose a model whereby direct interactions between homologous double-stranded DNA can initiate the formation of heterochromatin.



The Nephila clavipes genome highlights the diversity of spider silk genes and their complex expression

2017-05-01

Benjamin Voight and colleagues report the annotated genome of the golden orb-weaver spider. They describe 28 spider silk genes (spidroins), characterize their expression in distinct silk gland types and identify non-spidroin genes with expression patterns suggesting potential roles in silk production.



Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch

2017-05-08

Victor Albert, Petri Auvinen, Ykä Helariutta, Jaakko Kangasjärvi and colleagues report the reference genome of the silver birch (Betula pendula) and resequencing of 150 birch individuals. They infer past population size crashes consistent with historical periods of climatic change and identify candidate targets of more recent positive selection.



Contrasting evolutionary genome dynamics between domesticated and wild yeasts

2017-04-17

Jia-Xing Yue, Gianni Liti and colleagues use long-read sequencing to generate complete genome assemblies of 7 Saccharomyces cerevisiae and 5 Saccharomyces paradoxus strains. They use these data to define boundaries between chromosomal core and subtelomeric regions and to compare the evolutionary dynamics between these domesticated and wild yeast species.



Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons

2017-05-01

Bradley Cairns, Douglas Carrell, Stephen Tapscott and colleagues transcriptionally profile human oocytes and preimplantation embryos and highlight DUX4-family proteins as activators of cleavage-stage genes and repetitive elements. They show that Dux expression converts mouse embryonic stem cells into two-cell (2C) embryo-like cells, thus suggesting mouse DUX and human DUX4 as drivers of the mammalian cleavage/2C state.



Conservation and innovation in the DUX4-family gene network

2017-05-01

Stephen Tapscott and colleagues report that human DUX4, which is linked to facioscapulohumeral dystrophy, and mouse DUX activate genes associated with cleavage-stage embryos, including retrotransposons, in muscle cells. They suggest that the ancestral DUX4-regulated genes characteristic of cleavage-stage embryos are driven by conventional promoters, whereas divergence of the DUX4 and DUX homeodomains correlates with retrotransposon specificity.



DUX-family transcription factors regulate zygotic genome activation in placental mammals

2017-05-01

Didier Trono and colleagues show that both human DUX4 and mouse Dux are expressed before zygotic genome activation (ZGA) and lead to activation of ZGA-associated genes. Dux knockout in mouse embryonic stem cells prevents cycling through a 2-cell-like state, and zygotic depletion of Dux impairs embryonic development.



Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

2017-04-17

Patrick Ellinor and colleagues report meta-analyses of common and rare variant association studies for atrial fibrillation across multiple populations. They identify 12 new loci, some of which implicate genes in atrial electrical and mechanical function.



Identification of six new genetic loci associated with atrial fibrillation in the Japanese population

2017-04-17

Kaoru Ito, Yoichiro Kamatani, Toshihiro Tanaka and colleagues report a genome-wide association study for atrial fibrillation in the Japanese population. They identify six new loci, five of which are not associated with atrial fibrillation in individuals of European ancestry, suggesting that they may be specific to the Japanese population.



Cassava haplotype map highlights fixation of deleterious mutations during clonal propagation

2017-04-17

Fei Lu, Punna Ramu and colleagues construct a cassava haplotype map (HapMapII) by using deep-sequencing data from 241 accessions and identify over 28 million segregating variants. They find that clonal propagation has led to fixation of deleterious mutations, which have been ineffectively purged, owing to limited recombination



Widespread adenine N6-methylation of active genes in fungi

2017-05-08

Igor Grigoriev and colleagues perform single-molecule real-time sequencing on 16 diverse fungal species to evaluate levels of adenine methylation (6mA). They find that almost 3% of all adenines are methylated in early-diverging fungi, and they identify clusters of methylated adenines that are enriched at transcription start sites of active genes.