Article
|
Open Access
Featured
-
-
Research Highlights |
Sisterhood of lymphoma
-
News |
A wake-up call for dormant genes
Anti-cancer drug holds potential as a treatment for genetic-imprinting disorder.
- Rebecca Hill
-
Outlook |
Genetics: Profiling a shape-shifter
Unlocking the genetic secrets of multiple myeloma could reveal new ways to attack this killer disease.
- Courtney Humphries
-
Outlook |
Atopy: Marching with allergies
They come not single spies, but in battalions. The latest research helps explain why an individual may experience the 'atopic march' from one allergic disorder to another.
- Paige Brown
-
News |
Sickle-cell mystery solved
Researchers discover how carriers of the sickle-cell anaemia gene are protected from malaria.
- Meredith Wadman
-
News |
More clues in the genetics of schizophrenia
Chinese researchers add three chromosomal regions to a slow-growing list of genetic links.
- David Cyranoski
-
Letter |
Somatic retrotransposition alters the genetic landscape of the human brain
- J. Kenneth Baillie
- , Mark W. Barnett
- & Geoffrey J. Faulkner
-
Article
| Open AccessA high-resolution map of human evolutionary constraint using 29 mammals
- Kerstin Lindblad-Toh
- , Manuel Garber
- & Manolis Kellis
-
Letter |
Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy
- Mariko Taniguchi-Ikeda
- , Kazuhiro Kobayashi
- & Tatsushi Toda
-
Letter |
Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia
- Mark A. Dawson
- , Rab K. Prinjha
- & Tony Kouzarides
-
Letter |
Sequence-based characterization of structural variation in the mouse genome
- Binnaz Yalcin
- , Kim Wong
- & Jonathan Flint
-
Letter |
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
- Georg B. Ehret
- , Patricia B. Munroe
- & Toby Johnson
-
Research Highlights |
Long-term fix for SCID kids
-
Letter |
Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus
- Sébastien Jacquemont
- , Alexandre Reymond
- & Philippe Froguel
-
Letter |
Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia
- Han-Xiang Deng
- , Wenjie Chen
- & Teepu Siddique
-
Review Article |
A continuum model for tumour suppression
- Alice H. Berger
- , Alfred G. Knudson
- & Pier Paolo Pandolfi
-
News |
Gene-therapy enzymes make unpredicted errors
Techniques show mistakes of 'highly specific' molecular tools.
- Heidi Ledford
-
News |
Lessons about Alzheimer's disease
Psychologist Margaret Gatz explains what 25 years of research have taught her about reducing the risk of dementia.
- Gwyneth Dickey Zakaib
-
Comment |
Growth of genome screening needs debate
There could be unexpected consequences if greater understanding of disease genetics gives parents more choice in what they pass to their children, says David B. Goldstein.
- David B. Goldstein
-
Letter |
RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
- Johannes Zuber
- , Junwei Shi
- & Christopher R. Vakoc
-
News |
Chinese depression survey holds surprises
Parenting style and level of education have different impact than in the West.
- David Cyranoski
-
Research Highlights |
Customer data aid Parkinson's study
-
News |
How to build a better mouse
The Collaborative Cross project will boost diversity and help the hunt for disease genes.
- Ewen Callaway
-
Outlook |
Genetics: Finding risk factors
Uncovering genes that are linked with Alzheimer's disease can help researchers understand what causes the disease. But it's not easy.
- Michael Eisenstein
-
Article |
Crystal structure of a copper-transporting PIB-type ATPase
- Pontus Gourdon
- , Xiang-Yu Liu
- & Poul Nissen
-
News |
Software pinpoints cause of mystery genetic disorder
Genome analysis tools speedily track down previously unknown mutation.
- Brendan Maher
-
News |
Genome study solves twins' mystery condition
Sequencing ends years of speculation over children's rare disorder.
- Erika Check Hayden
-
News |
Autism linked to hundreds of spontaneous genetic mutations
Analysis suggests that girls are partially shielded from effects of the changes.
- Heidi Ledford
-
Research Highlights |
Genetics of malaria severity
-
Letter |
Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells
- Luis F. Z. Batista
- , Matthew F. Pech
- & Steven E. Artandi
-
Research Highlights |
A search for depression genes
-
Review Article |
Lessons on the pathogenesis of aneurysm from heritable conditions
- Mark E. Lindsay
- & Harry C. Dietz
-
News |
Stress can shorten telomeres in childhood
Children in orphanages have chromosome changes that could affect future health.
- Marian Turner
-
Letter |
Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA
- Dong Wang
- , Ivan Garcia-Bassets
- & Xiang-Dong Fu
-
News |
Schizophrenia 'in a dish'
Researchers are making inroads in the daunting challenge of modelling mental illness, thanks to patients' cells.
- Ewen Callaway
-
Letter |
Suppression of lung adenocarcinoma progression by Nkx2-1
- Monte M. Winslow
- , Talya L. Dayton
- & Tyler Jacks
-
News & Views |
Zooming in on a gene
Genome-wide association studies are often criticized for providing little insight of immediate physiological relevance. The finding of one such study, which implicates a signalling molecule in schizophrenia, is welcome news. See Letter p.499
- Hugh D. Piggins
-
Article |
Mapping and analysis of chromatin state dynamics in nine human cell types
- Jason Ernst
- , Pouya Kheradpour
- & Bradley E. Bernstein
-
Article
| Open AccessInitial genome sequencing and analysis of multiple myeloma
Multiple myeloma, a malignancy of plasma cells, remains incurable and is poorly understood. Using next-generation sequencing of several multiple myeloma genomes reveals that this disease involves mutations of genes involved in protein translation, histone methylation and blood coagulation. The study suggests that BRAF inhibitors should be evaluated in multiple myeloma clinical trials.
- Michael A. Chapman
- , Michael S. Lawrence
- & Todd R. Golub
-
Letter |
The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset
Using a zebrafish model of melanoma, this study has searched for genes that can cooperate with mutated BRAF, a frequent oncogenic event in human melanomas. It is found that SETDB1 can accelerate melanoma formation in fish and resides in a region frequently amplified in human melanomas. SETDB1, a histone methylating enzyme, is also frequently overexpressed in human melanomas and functions at least in part by regulating the expression of HOX genes.
- Craig J. Ceol
- , Yariv Houvras
- & Leonard I. Zon
-
Letter |
Aberrant chromosome morphology in human cells defective for Holliday junction resolution
Exchange of sister chromatids to form four-stranded Holliday junctions occurs naturally during meiosis, to hold sister chromatids together, and during various repair events. In eukaryotes, double Holliday junctions that escape dissolution by a helicase/topoisomerase (BTR) complex are instead processed by one of several nucleases known as resolvases. This study defines the activities of the GEN1, MUS81-EME1 and SLX1-SLX4 resolvases in the absence of BLM, the helicase component of BTR that is mutated in Bloom's syndrome.
- Thomas Wechsler
- , Scott Newman
- & Stephen C. West
-
Letter |
Tumour evolution inferred by single-cell sequencing
Although it is known that tumours are genetically heterogeneous it has so far been difficult to dissect this heterogeneity at a single cell level. This paper combines whole-genome amplification and next-generation sequencing of flow-sorted nuclei from breast tumours to investigate their population structure and evolution. In contrast to gradual models of tumour progression, the results indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.
- Nicholas Navin
- , Jude Kendall
- & Michael Wigler
-
Letter |
CREBBP mutations in relapsed acute lymphoblastic leukaemia
In three different subtypes of B-cell lymphomas, two papers now report frequent somatic mutations in CREBBP and EP300, present in primary tumours or acquired at relapse. These genes encode related acetyltransferases that mainly function to regulate gene expression by acetylating histones and other transcriptional regulators. The mutations found inactivate these activities and thus alter chromatin regulation of gene expression, as well as proliferation and potentially the response to therapeutic drugs.
- Charles G. Mullighan
- , Jinghui Zhang
- & James R. Downing
-
Article |
Inactivating mutations of acetyltransferase genes in B-cell lymphoma
In three different subtypes of B-cell lymphomas, two papers now report frequent somatic mutations in CREBBP and EP300, present in primary tumours or acquired at relapse. These genes encode related acetyltransferases that mainly function to regulate gene expression by acetylating histones and other transcriptional regulators. The mutations found inactivate these activities and thus alter chromatin regulation of gene expression, as well as proliferation and potentially the response to therapeutic drugs.
- Laura Pasqualucci
- , David Dominguez-Sola
- & Riccardo Dalla-Favera
-
News & Views |
The dark side of induced pluripotency
Induced pluripotent stem cells have great therapeutic potential. But genomic and epigenomic analyses of these cells generated using current technology reveal abnormalities that may affect their safe use. See Articles p.58, p.63 & p.68
- Martin F. Pera
-
Letter |
MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers
Using whole-transcriptome sequencing, this paper identifies recurrent gene translocations in B-cell lymphomas that involve the MHC class II transactivator CIITA. These translocations lead to downregulation of cell surface HLA class II expression and, in the case of some fusion partners, overexpression of CD274/CD273 ligands, which have the potential to reduce the antitumour response against these lymphomas.
- Christian Steidl
- , Sohrab P. Shah
- & Randy D. Gascoyne
-
Letter |
The RAG2 C terminus suppresses genomic instability and lymphomagenesis
Misrepair of DNA double strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin and T-cell receptor loci has been implicated in the pathogenesis of lymphoid malignancies. Here, the RAG2 carboxy terminus is shown to be critical for maintaining genomic stability. Rag2c/c p53−/− mice, unlike Rag1c/c p53−/− and p53−/− mice, rapidly develop thymic lymphomas bearing complex chromosomal translocations, amplifications and deletions involving the Tcrα/δ and Igh loci. These results reveal a new 'genome guardian' role for RAG2 and suggest that similar 'end release/end persistence' mechanisms underlie genomic instability and lymphomagenesis in Rag2c/c p53−/− and Atm−/− mice.
- Ludovic Deriano
- , Julie Chaumeil
- & David B. Roth
-
Letter |
Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia
Substantial risk for schizophrenia is conferred by large copy number variants at a number of genomic loci. Here, a significant association between duplications on chromosome 7 and schizophrenia is reported. Importantly, microduplication analysis narrowed down the region to a region just upstream of a gene encoding vasoactive intestinal peptide receptor (VIPR2). Increased expression of VIPR2 in patients with schizophrenia implicates VIP signalling as a molecular mechanism underlying schizophrenia.
- Vladimir Vacic
- , Shane McCarthy
- & Jonathan Sebat
-
Article |
Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor
- Kerry J. Ressler
- , Kristina B. Mercer
- & Victor May