Comment
|
Open Access
Featured
-
-
Article
| Open AccessMultiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function
Pulmonary function is influenced by environmental factors, lifestyle, and genetics. Here, in a multiethnic GWAS meta-analysis for pulmonary function traits, the authors identify over 50 additional genetic loci, a subset of which are specific for European, African, Asian, or Hispanic/Latino ancestry.
- Annah B. Wyss
- , Tamar Sofer
- & Stephanie J. London
-
Article
| Open AccessGenome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes
GWAS have so far identified 129 loci associated with type 2 diabetes (T2D). Here, the authors meta-analyse three large T2D GWA studies which uncovers 42 additional loci, further prioritize 33 functional genes using eQTL and mQTL data and propose regulatory mechanisms for three putative T2D genes.
- Angli Xue
- , Yang Wu
- & Jian Yang
-
Perspective
| Open AccessA framework for enhancing ethical genomic research with Indigenous communities
Indigenous peoples are still underrepresented in genetic research. Here, the authors propose an ethical framework consisting of six major principles that encourages researchers and Indigenous communities to build strong and equal partnerships to increase trust, engagement and diversity in genomic studies.
- Katrina G. Claw
- , Matthew Z. Anderson
- & Joseph M. Yracheta
-
Article
| Open AccessSpindle tubulin and MTOC asymmetries may explain meiotic drive in oocytes
During ‘meiotic drive’, some chromosomes can bias their spindle orientation and thus be retained in the egg. Here, the authors find that this phenomenon can be driven by microtubule force asymmetry on chromosomes with differently sized centromeres and kinetochores.
- Tianyu Wu
- , Simon I. R. Lane
- & Keith T. Jones
-
Article
| Open AccessPairwise library screen systematically interrogates Staphylococcus aureus Cas9 specificity in human cells
A rigorous understanding of off-target effects is necessary for SaCas9 to be used in therapeutic genome editing. Here the authors measure SaCas9 mismatch tolerance across a pairwise library screen of 88,000 guides and targets in human cells and develop a model which ranks off-target sites.
- Josh Tycko
- , Luis A. Barrera
- & Patrick D. Hsu
-
Article
| Open AccessHorse Y chromosome assembly displays unique evolutionary features and putative stallion fertility genes
The rapidly evolving Y chromosome accumulates male-benefit genes but is often poorly characterized in many mammals. Here, the authors assemble the male specific region of the horse Y chromosome and investigate its evolution and function.
- Jan E. Janečka
- , Brian W. Davis
- & Terje Raudsepp
-
Article
| Open AccessEpigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1
Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by aggregation of Tau, encoded by MAPT. Here, the authors perform an EWAS for PSP in prefrontal lobe tissue and find hypermethylation of DLX1 and its antisense transcript DLX1AS to associate with MAPT expression.
- Axel Weber
- , Sigrid C. Schwarz
- & Ulrich Müller
-
Article
| Open AccessEnhancer histone-QTLs are enriched on autoimmune risk haplotypes and influence gene expression within chromatin networks
Disease risk variants can exert their influence on phenotypes by altering epigenome function. Here, Pelikan et al. show that variants inducing allelic imbalance in histone marks in lymphoblastoid cell lines from lupus patients are enriched in autoimmune disease haplotypes and influence gene expression.
- Richard C. Pelikan
- , Jennifer A. Kelly
- & Patrick M. Gaffney
-
Article
| Open AccessUnperturbed expression bias of imprinted genes in schizophrenia
This study analyzes allelic expression bias in post-mortem brains of healthy individuals and those diagnosed with schizophrenia or bipolar disorder. The study shows that the number of imprinted genes is consistent with low estimates, and that allelic bias is independent of psychiatric disease status.
- Attila Gulyás-Kovács
- , Ifat Keydar
- & Andrew Chess
-
Article
| Open AccessPR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
Abnormal PR interval duration is associated with risk for atrial fibrillation and heart block. Here, van Setten et al. identify 44 PR interval loci in a genome-wide association study of over 92,000 individuals and find genetic overlap with QRS duration, heart rate and atrial fibrillation.
- Jessica van Setten
- , Jennifer A. Brody
- & Nona Sotoodehnia
-
Article
| Open AccessWidespread anti-CRISPR proteins in virulent bacteriophages inhibit a range of Cas9 proteins
Some phages carry genes coding for anti-CRISPR (Acr) proteins that interfere with the activity of bacterial CRISPR-Cas systems. Here, Hynes et al. characterize a new Acr family from streptococcal phages and investigate its potential in genome-editing applications.
- Alexander P. Hynes
- , Geneviève M. Rousseau
- & Sylvain Moineau
-
Article
| Open AccessFoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence
Evidence for mitotic decline in aged cells and for aneuploidy-driven progression into full senescence is limited. Here, the authors find that in aged cells, mitotic gene repression leads to increased chromosome mis-segregation and aneuploidy that triggers permanent cell cycle arrest and full senescence.
- Joana Catarina Macedo
- , Sara Vaz
- & Elsa Logarinho
-
Article
| Open AccessNucleoporin 107, 62 and 153 mediate Kcnq1ot1 imprinted domain regulation in extraembryonic endoderm stem cells
Genomic imprinting restricts transcription to predominantly one parental allele. Here the authors perform a screen for epigenetic factors involved in paternal allelic silencing at the Kcnq1ot1 imprinted domain in mouse extraembryonic endoderm stem cells and characterize a role for specific nucleoporins in mediating Kcnq1ot1 imprinted regulation.
- Saqib S. Sachani
- , Lauren S. Landschoot
- & Mellissa R. W. Mann
-
Article
| Open AccessAn intercross population study reveals genes associated with body size and plumage color in ducks
Ducks, one of the most common domestic fowls, originated from mallards. Here, the authors perform whole-genome sequencing of mallards, indigenous-breed ducks, and Pekin ducks, as well as 1026 ducks from a population generated by wild × domestic crosses to identify selection signals and map variants associated with body size and plumage color.
- Zhengkui Zhou
- , Ming Li
- & Yu Jiang
-
Article
| Open AccessSquamate reptiles challenge paradigms of genomic repeat element evolution set by birds and mammals
Large-scale patterns of genomic repeat element evolution have been studied mainly in birds and mammals. Here, the authors analyze the genomes of over 60 squamate reptiles and show high variation in repeat elements compared to mammals and birds, and particularly high microsatellite seeding in snakes.
- Giulia I. M. Pasquesi
- , Richard H. Adams
- & Todd A. Castoe
-
Article
| Open AccessDirect observation of DNA target searching and cleavage by CRISPR-Cas12a
Cas12a is a RNA-guided DNA endonuclease whose detailed mechanisms of target searching and DNA cleavage remained unclear. Here authors use single-molecule fluorescence assays to show that Cas12a searches for their on-target site.
- Yongmoon Jeon
- , You Hee Choi
- & Sangsu Bae
-
Article
| Open AccessIntegrated genetic and epigenetic analysis of myxofibrosarcoma
Myxofibrosarcoma occurs in adults and is associated with high local relapse. Here, based on exome/transcriptome sequencing and DNA methylation analysis, the authors identify driver genes and methylation clusters associated with unique combinations of mutations, outcomes, and immune cell compositions.
- Koichi Ogura
- , Fumie Hosoda
- & Tatsuhiro Shibata
-
Article
| Open AccessGene expression drives the evolution of dominance
Dominance is difficult to measure in natural populations as it is confounded with fitness. Here, Huber et al. developed a new approach to co-estimate dominance and selection coefficients, and found that the observed relationship is best fit by a new model of dominance based on gene expression level.
- Christian D. Huber
- , Arun Durvasula
- & Kirk E. Lohmueller
-
Article
| Open AccessIn vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer
KRAS-driven lung cancers represent an aggressive form of NSCLC. In this study the authors perform an in vivo functional screening and identify GATAD2B as a driver of tumor growth and metastasis in KRAS-driven lung cancer.
- Caitlin L. Grzeskowiak
- , Samrat T. Kundu
- & Kenneth L. Scott
-
Article
| Open AccessMutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis
ASXL1 gene is often mutated in myeloid malignancies. Here, the authors show that mutant ASXL1 and BAP1 are in a positive feedback loop such that BAP1 induces monoubiquitination of mutant ASXL1, which in turn enhances BAP1 activity to potentiate myeloid transformation via HOXA clusters and IRF8.
- Shuhei Asada
- , Susumu Goyama
- & Toshio Kitamura
-
Article
| Open AccessHighly efficient RNA-guided base editing in rabbit
Base editors can make targeted changes without inducing a double-stranded break. Here, the authors apply the BE3 and ABE7.10 systems to rabbit to create highly efficient targeted base substitutions and various mutation types, and show reduced frequency of undesired by-products with the updated BE4-Gam system.
- Zhiquan Liu
- , Mao Chen
- & Zhanjun Li
-
Article
| Open AccessHHEX is a transcriptional regulator of the VEGFC/FLT4/PROX1 signaling axis during vascular development
VEGFC, its receptor FLT4, and transcriptional effector PROX1 control formation of the lymphatic system but how is unclear. Here, the authors show that the transcription factor hematopoietically expressed homeobox (HHEX) regulates VEGFC, FLT4 and PROX1 in fish and mammals during angiogenic sprouting and lymphatic formation.
- Sébastien Gauvrit
- , Alethia Villasenor
- & Didier Y. R. Stainier
-
Article
| Open AccessThe origin and adaptive evolution of domesticated populations of yeast from Far East Asia
An understanding of the domestication of the yeast Saccharomyces cerevisiae has important implications for studying its evolution and diversity. Here, the authors show that Far East Asia is likely the center of origin of the domesticated populations of the yeast based on genomic and phenotypic characterization of a large collection of isolates.
- Shou-Fu Duan
- , Pei-Jie Han
- & Feng-Yan Bai
-
Article
| Open AccessLarge-scale gene losses underlie the genome evolution of parasitic plant Cuscuta australis
Dodders (Cuscuta spp., Convolvulaceae) are root- and leafless parasitic plants. Here, the authors sequence the genome of Cuscuta australis and find remarkable gene loss associated with parasitic lifestyle and large changes in body plan.
- Guiling Sun
- , Yuxing Xu
- & Jianqiang Wu
-
Article
| Open AccessSystemic control of immune cell development by integrated carbon dioxide and hypoxia chemosensation in Drosophila
In mammals, crosstalk between O2 and CO2 sensing central and peripheral chemoreceptors has been linked to functions of the hematopoietic system. Here, the authors show an evolutionarily relevant cascade involving multiple organs that links CO2- and O2-chemosensation to immune cell maturation in Drosophila.
- Bumsik Cho
- , Carrie M. Spratford
- & Jiwon Shim
-
Correspondence
| Open AccessReply to ‘Inconclusive evidence for rapid adaptive evolution’
- Camilla Lo Cascio Sætre
- , Charles Coleiro
- & Fabrice Eroukhmanoff
-
Correspondence
| Open AccessInconclusive evidence for rapid adaptive evolution
- Júlio Manuel Neto
- , Staffan Bensch
- & Bengt Hansson
-
Article
| Open AccessPatterns of genomic evolution in advanced melanoma
As melanoma progresses, it evolves. Here, in advanced melanoma the authors study genomic evolution, highlighting trunk mutations dominated by the ultraviolet damage signature, common late truncal whole-genome duplication events, as well as selective copy number gain of mutant BRAF.
- E. Birkeland
- , S. Zhang
- & P. E. Lønning
-
Article
| Open AccessDeficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish
The functions of the class III PI3-kinase (PIK3C3) in gut homeostasis and innate immunity are poorly understood. Here the authors show that PIK3C3-deficient zebrafishes develop intestinal injury and inflammation due to mislocalization of cell junction proteins.
- Shaoyang Zhao
- , Jianhong Xia
- & Xiaodong Shu
-
Article
| Open AccessA mosaic monoploid reference sequence for the highly complex genome of sugarcane
Sugarcane (Saccharum spp.) is a crop of major economic significance but has complex genome structure. Here, the authors generate a BAC-based monoploid sugarcane reference sequence.
- Olivier Garsmeur
- , Gaetan Droc
- & Angélique D’Hont
-
Article
| Open AccessETS transcription factors induce a unique UV damage signature that drives recurrent mutagenesis in melanoma
Many factors contribute to mutation hotspots in cancer cells. Here the authors map UV damage at single-nucleotide resolution across the human genome and find that binding sites of ETS transcription factors are especially prone to forming UV lesions, leading to mutation hotspots in melanoma.
- Peng Mao
- , Alexander J. Brown
- & John J. Wyrick
-
Article
| Open AccessDeep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries
Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.
- Seyedeh M. Zekavat
- , Sanni Ruotsalainen
- & Sebastian Zoellner
-
Article
| Open AccessSystematic discovery of germline cancer predisposition genes through the identification of somatic second hits
Inherited germline variants and somatic mutations contribute to cancer. Here, the authors present the statistical method ALFRED that tests the two-hit hypothesis of tumorigenesis and apply it to ~10,000 tumor exomes to identify rare germline variants that affect putative cancer predisposition genes, contributing substantially to cancer risk.
- Solip Park
- , Fran Supek
- & Ben Lehner
-
Article
| Open AccessXPC is an RNA polymerase II cofactor recruiting ATAC to promoters by interacting with E2F1
XPC plays an important role in the nuclear exicision repair pathways. Here the authors show that in addition, XPC plays a role in transcription regulation by interacting with KAT2A and E2F1 and recruiting the ATAC coactivator complex to promoters.
- B. Bidon
- , I. Iltis
- & N. Le May
-
Article
| Open AccessElucidating the genetic basis of social interaction and isolation
Little is known about the genetic determinants of social isolation and loneliness despite their well-established importance for health. Here, using multi-trait GWAS, Day et al. identify 15 genomic loci for loneliness and further show a bidirectional causal relationship between BMI and loneliness by MR.
- Felix R. Day
- , Ken K. Ong
- & John R. B. Perry
-
Article
| Open AccessUhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a
Uhrf1 is a known regulator of heterochromatin and DNA methylation in embryonic stem cells (ESCs). Here, the authors demonstrate that Uhrf1 acts together with the Set1/COMPASS complex regulator of active transcription to promote H3K4 methylation at bivalent loci and Uhrf1 loss results in disruption of differentiation.
- Kun-Yong Kim
- , Yoshiaki Tanaka
- & In-Hyun Park
-
Article
| Open AccessGenomic analysis of a pre-elimination Malaysian Plasmodium vivax population reveals selective pressures and changing transmission dynamics
Plasmodium vivax incidence in Malaysia has declined markedly over the last decade, despite evidence of chloroquine resistance. Here, Auburn et al. compare population structure of P. vivax in Malaysia to regions with intermediate and high transmission and identify genetic regions under putative selection.
- Sarah Auburn
- , Ernest D. Benavente
- & Ric N. Price
-
Article
| Open AccessNuclear microtubule filaments mediate non-linear directional motion of chromatin and promote DNA repair
Following DNA damage, different processes come to action to aid repair. The authors here find that microtubule filaments within the cell nucleus capture and non-randomly mobilize damaged chromatin to mediate DNA repair.
- Roxanne Oshidari
- , Jonathan Strecker
- & Karim Mekhail
-
Article
| Open AccessPlacental H3K27me3 establishes female resilience to prenatal insults
Sex differences in placental O-linked N-acetylglucosamine transferase (OGT) activity mediate the effects of prenatal stress on neurodevelopmental programming. Here authors provide evidence that OGT confers variation in vulnerability to prenatal insults by establishing sex-specific trophoblast gene expression via regulation of H3K27me3.
- Bridget M. Nugent
- , Carly M. O’Donnell
- & Tracy L. Bale
-
Article
| Open AccessDedicated surveillance mechanism controls G-quadruplex forming non-coding RNAs in human mitochondria
G-rich RNAs encoded in mitochondrial DNA are prone to form four-stranded structures called G-quadruplexes (G4s). Here the authors show using in vitro and in vivo approaches that GRSF1 promotes melting of G4 RNA structures in mtRNAs, thus leading to their decay by the hSuv3–PNPase complex.
- Zbigniew Pietras
- , Magdalena A. Wojcik
- & Roman J. Szczesny
-
Correspondence
| Open AccessReply to ‘Misestimation of heritability and prediction accuracy of male-pattern baldness’
- Nicola Pirastu
- , Peter K. Joshi
- & James F. Wilson
-
Correspondence
| Open AccessMisestimation of heritability and prediction accuracy of male-pattern baldness
- Chloe X. Yap
- , Julia Sidorenko
- & Peter M. Visscher
-
Article
| Open AccessPervasive genetic interactions modulate neurodevelopmental defects of the autism-associated 16p11.2 deletion in Drosophila melanogaster
The 16p11.2 deletion leads to a range of neurodevelopmental phenotypes, but to date, sequencing studies have not been able to pinpoint individual genes that are causative for the disease on their own. Here, using Drosophila homologs of 14 16p11.2 genes, the authors take a combinatorial approach to show that gene interactions contribute to a neurological phenotype.
- Janani Iyer
- , Mayanglambam Dhruba Singh
- & Santhosh Girirajan
-
Article
| Open AccessPromoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks
Human embryonic stem cell-derived cardiomyocytes (hESC-CM) are a widely used model to study cardiac genomics. Here, Choy et al. perform promoter capture Hi-C to map long-range chromosomal interactions of hESC-CMs and to study overlap of such regions with genetic loci associated with cardiac phenotypes.
- Mun-Kit Choy
- , Biola M. Javierre
- & Bernard D. Keavney
-
Article
| Open AccessFootprints of parasitism in the genome of the parasitic flowering plant Cuscuta campestris
Parasitic lifestyles leave unique genomic footprints. Here, the authors describe the genome sequence of a parasitic plant, Cuscuta campestris, and find that gene losses and host gene acquisitions reflect the independence from photosynthesis and the ability to retain and express chunks of foreign genomic DNA.
- Alexander Vogel
- , Rainer Schwacke
- & Kirsten Krause
-
Article
| Open AccessThe mitochondrial DNA polymerase gamma degrades linear DNA fragments precluding the formation of deletions
Mitochondrial DNA fragments are rapidly degraded when double strand breaks occur. Here the authors reveal that the exonuclease activity of polymerase gamma is important for efficient degradation of these fragments and to avoid formation of large deletions.
- Nadee Nissanka
- , Sandra R. Bacman
- & Carlos T. Moraes
-
Article
| Open AccessLarge-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations
Mitochondrial populations in cells may consist of heteroplasmic mixtures of mtDNA types, and their evolution through development, aging and generations is central to genetic diseases. Here the authors dissect these population dynamics using a large mouse-based data set to characterise the dynamics of heteroplasmy mean and variance throughout life and across generations.
- Joerg P. Burgstaller
- , Thomas Kolbe
- & Iain G. Johnston
-
Article
| Open AccessKMT2D/MLL2 inactivation is associated with recurrence in adult-type granulosa cell tumors of the ovary
Adult-type granulosa cell tumors of the ovary (aGCTs) are rare and recurrence is difficult to treat. Here, the authors observe in aGCT a novel recurrent somatic truncating mutation of KMT2D, more frequent in recurrent aGCT, and also non-genetic loss of KMT2D expression.
- R. Tyler Hillman
- , Joseph Celestino
- & P. Andrew Futreal
-
Article
| Open AccessPooled CRISPR interference screening enables genome-scale functional genomics study in bacteria with superior performance
Systemic investigation of the bacterial genome is essential for both basic microbiology and bioengineering. Here the authors demonstrate CRISPRi pooled screening as a high-throughput tool for identifying gene and phenotype associations in bacteria.
- Tianmin Wang
- , Changge Guan
- & Xin-Hui Xing
Browse broader subjects
Browse narrower subjects
- Agricultural genetics
- Animal breeding
- Behavioural genetics
- Cancer genetics
- Cancer genomics
- Clinical genetics
- Consanguinity
- CRISPR-Cas systems
- Cytogenetics
- Development
- Epigenetics
- Epigenomics
- Eukaryote
- Evolutionary biology
- Functional genomics
- Gene expression
- Gene regulation
- Genetic association study
- Genetic hybridization
- Genetic interaction
- Genetic linkage study
- Genetic markers
- Genome
- Genomic instability
- Genomics
- Genotype
- Haplotypes
- Heritable quantitative trait
- Immunogenetics
- Inbreeding
- Medical genetics
- Microbial genetics
- Mutation
- Neurodevelopmental disorders
- Plant breeding
- Plant genetics
- Polyploidy
- Population genetics
- Prokaryote
- Quantitative trait
- RNA splicing
- RNAi
- Sequencing