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dinsdag 10 april 2018

Nature Genetics Contents: April 2018 Volume 50 Number 4

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Nature Genetics

  • Efficient labeling of limited genomic material using CYTAG® SuperCGH
  • High quality data for previously undetected CNVs in amniotic fluid and postnatal samples
  • Results indicating superior DLR scores

April 2018 Volume 50, Issue 4

News & Views
Brief Communications

Speeding up the sequencing

In the age of genomic big data, the worlds of medicine and IT are rapidly colliding. 

Access free online >>


Focal Point on Japan's Designated National University Initiative

Japan's radical new program to boost just a handful of universities has precedents across the world 

Access free online

Genome Variation in Precision Medicine 2018 

The aim of this conference is to take advantage of the past decade of enormous progress in understanding the human genome and the flourishing discoveries in clinical genetics and genetic epidemiology in order to identify and match therapeutic strategies more accurately to the people and populations that are best suited to benefit from them.

May 25-27, 2018 | Chengdu, China



FAIR to the community    p473



Plain-language medical vocabulary for precision diagnosis    pp474 - 476
Nicole A. Vasilevsky, Erin D. Foster, Mark E. Engelstad, Leigh Carmody, Matt Might et al.

News & Views


Repeat expansions in myoclonic epilepsy    pp477 - 478
Marka van Blitterswijk & Rosa Rademakers

Switching from fetal to adult hemoglobin    pp478 - 480
Xunde Wang & Swee Lay Thein

Evaluating tumor-suppressor gene combinations    pp480 - 482
James Kim & John D. Minna

JOBS of the week
New Postdoctoral Positions
The University of Texas MD Anderson Cancer Center, Department of Genertics
Postdoctoral Research Scholar
UT Southwestern Medical Center
Postdoctoral Fellow / Pediatrics - 180000006J
The University of Tennessee Health Science Center (UTHSC)
Post-doctoral fellow
Washington University School of Medicine, St. Louis
Postdoctoral Fellow Positions in RNA Biology / Neurobiology Lab
University of California, Riverside
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Machines on Genes
Snowmass Village, USA
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Brief Communications


Mapping the in vivo fitness landscape of lung adenocarcinoma tumor suppression in mice    pp483 - 486
Zoë N. Rogers, Christopher D. McFarland, Ian P. Winters, Jose A. Seoane, Jennifer J. Brady et al.

In vivo analysis of pairwise combinations of tumor suppressor losses using a barcode-based assay in mice identifies unpredicted genetic interactions and shows that the effects of tumor suppressor alterations can be context-dependent.




Germline de novo mutation clusters arise during oocyte aging in genomic regions with high double-strand-break incidence    pp487 - 492
Jakob M. Goldmann, Vladimir B. Seplyarskiy, Wendy S. W. Wong, Thierry Vilboux, Pieter B. Neerincx et al.

Analysis of whole-genome sequencing data from 1,291 parent–offspring trios identifies patterns of clustered de novo mutations. Clusters increase in number with maternal age and are associated with DNA double-strand-break processes.


Single-cell RNA sequencing identifies celltype-specific cis-eQTLs and co-expression QTLs    pp493 - 497
Monique G. P. van der Wijst, Harm Brugge, Dylan H. de Vries, Patrick Deelen, Morris A. Swertz et al.

Single-cell RNA sequencing (scRNA-seq) of ~25,000 peripheral blood mononuclear cells from 45 donors identifies new celltype-specific cis-eQTLs and genetic variants that significantly alter co-expression relationships ('co-expression QTLs').


Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding    pp498 - 503
Gabriella E. Martyn, Beeke Wienert, Lu Yang, Manan Shah, Laura J. Norton et al.

The fetal globin gene repressors BCL11A and ZBTB7A directly bind ?-globin gene promoter regions. Repressor binding is disrupted by naturally occurring point mutations located upstream of the transcriptional start site that are associated with hereditary persistence of fetal hemoglobin.


A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins    pp504 - 509
Joaquín Letelier, Elisa de la Calle-Mustienes, Joyce Pieretti, Silvia Naranjo, Ignacio Maeso et al.

The authors study the cis-regulatory evolution of the Shh locus in vertebrates. Using genomic editing and chromatin profiling, they conclude that paired fins emerged through the co-option of developmental programs for the median fins of gnathostomes.


Highly parallel genome variant engineering with CRISPR–Cas9    pp510 - 514
Meru J. Sadhu, Joshua S. Bloom, Laura Day, Jake J. Siegel, Sriram Kosuri et al.

The authors present a CRISPR-library-based approach for highly efficient and precise genome-wide variant engineering. They examine the functional consequences of premature termination codons within all annotated essential genes in yeast.


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The Naturejobs podcast features one-on-one Q&As, panel discussions and other exclusive content to help scientists with their careers. Hosted on the Naturejobs blog, the podcast is also available on iTunes and Soundcloud. 

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Enhancer invasion shapes MYCN-dependent transcriptional amplification in neuroblastoma    pp515 - 523
Rhamy Zeid, Matthew A. Lawlor, Evon Poon, Jaime M. Reyes, Mariateresa Fulciniti et al.

This study investigates the effects of MYCN on the chromatin and transcriptional landscape of neuroblastoma. The authors find that, at oncogenic levels, MYCN binds to canonical E-boxes at promoters and invades enhancers, leading to transcriptional amplification.


Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes    pp524 - 537
Rainer Malik, Ganesh Chauhan, Matthew Traylor, Muralidharan Sargurupremraj, Yukinori Okada et al.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.


Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights    pp538 - 548
Alexander Gusev, Nicholas Mancuso, Hyejung Won, Maria Kousi, Hilary K. Finucane et al.

A transcriptome-wide association study integrating genome-wide association data with expression data from brain, blood and adipose tissues identifies new candidate susceptibility genes for schizophrenia, providing a step toward understanding the underlying biology.


Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis    pp549 - 558
Eleni Zengini, Konstantinos Hatzikotoulas, Ioanna Tachmazidou, Julia Steinberg, Fernando P. Hartwig et al.

Genome-wide association study for osteoarthritis using data from UK Biobank identifies loci for knee- and hip-specific disease. Functional analyses of chondrocytes provide further insight into candidate causal genes.


Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes    pp559 - 571
Anubha Mahajan, Jennifer Wessel, Sara M. Willems, Wei Zhao, Neil R. Robertson et al.

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.


Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition    pp572 - 580
Kerrin S. Small, Marijana Todorcevic, Mete Civelek, Julia S. El-Sayed Moustafa, Xiao Wang et al.

Analysis of the imprinted KLF14 locus shows that the type 2 diabetes risk alleles in this region act in adipocytes to reduce KLF14 expression and modulate the expression of almost 400 genes in trans, leading to a shift in body-fat distribution and insulin resistance specifically in females.


Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy    pp581 - 590
Hiroyuki Ishiura, Koichiro Doi, Jun Mitsui, Jun Yoshimura, Miho Kawabe Matsukawa et al.

This study identifies TTTCA- and TTTTA-repeat expansions in benign adult familial myoclonic epilepsy. Cortical neurons from affected people exhibit RNA foci containing these expanded repeats, suggesting RNA toxicity as the mechanism underlying disease pathogenesis.


DNA methylation loss in late-replicating domains is linked to mitotic cell division    pp591 - 602
Wanding Zhou, Huy Q. Dinh, Zachary Ramjan, Daniel J. Weisenberger, Charles M. Nicolet et al.

Whole-genome DNA methylation profiling and analysis of normal tissues from both human and mouse reveal that hypomethylation within partially methylated, late-replicating domains depends on sequence context, starts early in development, accumulates with cell divisions and progresses with organismal aging.


CRISPR–Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity    pp603 - 612
Nicholas J. Kramer, Michael S. Haney, David W. Morgens, Ana Jovicic, Julien Couthouis et al.

A genome-wide CRISPR screen for suppressors and enhancers of C9ORF72 dipeptide-repeat protein toxicity identifies candidate genes involved in nucleocytoplasmic transport and other pathways including RNA processing and chromatin modification.


A global transcriptional network connecting noncoding mutations to changes in tumor gene expression    pp613 - 620
Wei Zhang, Ana Bojorquez-Gomez, Daniel Ortiz Velez, Guorong Xu, Kyle S. Sanchez et al.

Analysis of whole-genome sequences and transcription data from tumors identifies noncoding loci in which mutations affect target gene expression. These somatic eQTLs can classify tumors into pathway-based subtypes and are disrupted in 88% of tumors.




Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types    pp621 - 629
Hilary K. Finucane, Yakir A. Reshef, Verneri Anttila, Kamil Slowikowski, Alexander Gusev et al.

A new method tests whether disease heritability is enriched near genes with high tissue-specific expression. The authors use gene expression data together with GWAS summary statistics for 48 diseases and traits to identify disease-relevant tissues.


Ionis Pharmaceuticals, Nature Structural and Molecular Biology & Nature Biotechnology present:

RNA at the Bench & Bedside
October 8-10, La Jolla, USA

RNA therapeutics is poised to deliver major advances. This conference will discuss the many roles of RNAs and the translation of basic science into new therapies. It will address the opportunities, current status and future of this exciting field.
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