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Research highlights

Nature Genetics 42, 737 (2010). doi:10.1038/ng0910-737

Variable evolutionary signatures at the heart of enhancers

Nature Genetics 42, 734 (2010). doi:10.1038/ng0910-734

Authors: Ross C Hardison

What is the best way to identify regulatory DNA sequences such as enhancers, promoters, insulators and silencers? A new study shows that specific binding by a coactivator protein identifies enhancers that are invisible to common detection methods based on evolutionary constraint.

Putting a finger on the switch

Nature Genetics 42, 733 (2010). doi:10.1038/ng0910-733

Authors: James J Bieker

The transition from fetal to adult β-like globin expression is a key step in the maturation of the red blood cell lineage. Two new studies show that the KLF1 zinc finger protein uses direct and indirect means to regulate the final switch from fetal to adult globin expression and that monoallelic loss of KLF1 expression leads to persistence of fetal hemoglobin.

Infectious diseases not immune to genome-wide association

Nature Genetics 42, 731 (2010). doi:10.1038/ng0910-731

Authors: Paul I W de Bakker & Amalio Telenti

Two genome-wide association studies for meningococcal disease and tuberculosis identify new loci associated with susceptibility to these infectious diseases. They highlight a role for the acquired and innate immune systems in host control of several human pathogens and demonstrate that denser genotyping platforms and population-specific reference panels are necessary for genetic studies in African populations.

Cite site

Nature Genetics 42, 729 (2010). doi:10.1038/ng0910-729

We now have adapted our preprint archive, Nature Precedings, to host project descriptions, community standards papers and funder policies. Citable project descriptions provide a guide to the resources available and create a mechanism to give data producers citation credit.

Research highlights

Nature Genetics 42, 653 (2010). doi:10.1038/ng0810-653

Preempting and preventing drug-induced liver injury

Nature Genetics 42, 650 (2010). doi:10.1038/ng0810-650

Authors: Guruprasad P Aithal & Ann K Daly

A new study reports that susceptibility to drug-induced liver injury by the cyclooxygenase 2 (COX-2) inhibitor lumiracoxib is associated with a human lymphocyte antigen (HLA) class II haplotype. This finding suggests that those at risk of hepatotoxicity can be identified by HLA genotyping, raising the possibility that lumiracoxib can be resurrected as a useful drug.

Variation across the allele frequency spectrum

Nature Genetics 42, 648 (2010). doi:10.1038/ng0810-648

Authors: Anna L Gloyn & Mark I McCarthy

A new study finds that individuals with high plasma triglyceride levels carry approximately twice as many rare, coding genetic variants within four candidate genes identified through genome-wide association studies than individuals without these high levels. This study demonstrates the overlap of rare and common variant signals at loci associated with lipid levels and shows the value of efforts to extend susceptibility variant discovery to embrace the full allele-frequency spectrum.

On the origin of prostate fusion oncogenes

Nature Genetics 42, 647 (2010). doi:10.1038/ng0810-647

Authors: Jiri Bartek, Petra Hamerlik & Jiri Lukas

A new study reports that androgen signaling induces DNA double-strand breaks and TMPRSS2-ERG rearrangements through androgen receptor–mediated recruitment of topoisomerase 2B. These findings shed light on the generation of the most common fusion oncogene in human cancer.

Collaborative genomics for human health and cooperation in the Mediterranean region

Nature Genetics 42, 641 (2010). doi:10.1038/ng0810-641

Authors: Tayfun Özçelik, Moien Kanaan, Karen B Avraham, Drakoulis Yannoukakos, André Mégarbané, Ghazi O Tadmouri, Lefkos Middleton, Giovanni Romeo, Mary-Claire King & Ephrat Levy-Lahad

Basin of attraction

Nature Genetics 42, 639 (2010). doi:10.1038/ng0810-639

A group of medical geneticists from the countries bordering the Mediterranean Sea are seeking support for an enduring cooperative research structure. Their research productivity and ability to collaborate are both proven. The expected value of the proposed organization is high.

Research highlights

Nature Genetics 42, 563 (2010). doi:10.1038/ng0710-563

Fungal pathogenicity and morphological switches

Nature Genetics 42, 560 (2010). doi:10.1038/ng0710-560

Author: P T Magee

The virulence of Candida albicans, a major human fungal pathogen, has been considered dependent on the ability to transition between different morphologies. A new study reports a screen of C. albicans mutants that demonstrates that pathogenesis can be dissociated from morphological switching and in vitro growth rate.

Hints of hidden heritability in GWAS

Nature Genetics 42, 558 (2010). doi:10.1038/ng0710-558

Author: Greg Gibson

Although susceptibility loci identified through genome-wide association studies (GWAS) typically explain only a small proportion of the heritability, a classical quantitative genetic analysis now argues that considering together all common SNPs can explain a large proportion of the heritability of these complex traits. A related study provides recommendations for the sample sizes needed in future GWAS to identify additional susceptibility loci.

Limits of sequence and functional conservation

Nature Genetics 42, 557 (2010). doi:10.1038/ng0710-557

Authors: Len A Pennacchio & Axel Visel

Sequence conservation of noncoding DNA across species can indicate functional conservation. However, a new study demonstrates notable differences between human and mouse stem cell regulatory networks, suggesting caution in generalizing from sequence to functional conservation.

Reply to “Associations of CFHR1–CFHR3 deletion and a CFH SNP to age-related macular degeneration are not independent”

Nature Genetics 42, 555 (2010). doi:10.1038/ng0710-555

Authors: Anne E Hughes, Nick Orr, Heather J Cordell & Timothy Goodship

Associations of CFHR1–CFHR3 deletion and a CFH SNP to age-related macular degeneration are not independent

Nature Genetics 42, 553 (2010). doi:10.1038/ng0710-553

Authors: Soumya Raychaudhuri, Stephan Ripke, Mingyao Li, Benjamin M Neale, Jesen Fagerness, Robyn Reynolds, Lucia Sobrin, Anand Swaroop, Gonçalo Abecasis, Johanna M Seddon & Mark J Daly

On beyond GWAS

Nature Genetics 42, 551 (2010). doi:10.1038/ng0710-551

Analyses of genome-wide association studies (GWAS) show that common SNPs can account for the majority of the heritability of complex traits, but that there are likely to be limits to the usefulness of the current strategy of accumulating common variants of small effect for risk prediction. The ongoing success of GWAS has implications for functional characterization of trait-associated loci.

Research highlights

Nature Genetics 42, 481 (2010). doi:10.1038/ng0610-481

Another piece of the autism puzzle

Nature Genetics 42, 478 (2010). doi:10.1038/ng0610-478

Author: Matthew W State

A new study has identified rare de novo mutations in SHANK2 in individuals with autism and/or mental retardation. SHANK2 encodes a scaffolding protein present in excitatory synapses. This finding sheds some light on the pathophysiology of social and cognitive disability.

Relics of selection in the mycobacterial genome

Nature Genetics 42, 476 (2010). doi:10.1038/ng0610-476

Authors: Christopher M Sassetti & Eric J Rubin

A new study reports the whole-genome sequences of 21 Mycobacterium tuberculosis complex strains, selected to represent geographically diverse isolates. Comparative genomic analyses identify surprising conservation of epitopes recognized by human T cells.

Shaping a better rice plant

Nature Genetics 42, 475 (2010). doi:10.1038/ng0610-475

Author: Nathan Springer

Two studies describe how regulatory variation at the rice gene OsSPL14 can lead to altered plant morphology and improve grain yield. These studies support the possibility of improving rice yield through changing plant architecture.

Reply to “Reassessing evidence for a postnatal mitochondrial genetic bottleneck”

Nature Genetics 42, 472 (2010). doi:10.1038/ng0610-472

Authors: Timothy Wai & Eric A Shoubridge

Reassessing evidence for a postnatal mitochondrial genetic bottleneck

Nature Genetics 42, 471 (2010). doi:10.1038/ng0610-471

Authors: David C Samuels, Passorn Wonnapinij, Lynsey M Cree & Patrick F Chinnery

Reply to “Lack of support for association between the KIF1B rs10492972[C] variant and multiple sclerosis”

Nature Genetics 42, 470 (2010). doi:10.1038/ng0610-470

Authors: Rogier Q Hintzen, Yurii S Aulchenko, Sriram Ramagopalan, George Ebers & Cornelia M van Duijn

Lack of support for association between the KIF1B rs10492972[C] variant and multiple sclerosis

Nature Genetics 42, 469 (2010). doi:10.1038/ng0610-469

Authors:

Primary research on existing data

Nature Genetics 42, 467 (2010). doi:10.1038/ng0610-467

Articles in the Analysis format report primary research carried out on publications, datasets or research practices. We see Analyses as a way to generate new hypotheses, test data integrity and promote research integration.

Research highlights

Nature Genetics 42, 371 (2010). doi:10.1038/ng0510-371

Fanconi anemia and breast cancer susceptibility meet again

Nature Genetics 42, 368 (2010). doi:10.1038/ng0510-368

Author: Ephrat Levy-Lahad

A new study reports biallelic mutations in RAD51C in a Fanconi anemia–like disorder, while a second study reports monoallelic mutations in the same gene associated with increased breast cancer risk. These findings strengthen the link between Fanconi anemia and breast cancer–associated pathways.

Chipping away at the genetics of smoking behavior

Nature Genetics 42, 366 (2010). doi:10.1038/ng0510-366

Authors: Christopher I Amos, Margaret R Spitz & Paul Cinciripini

Three large consortia present comprehensive analyses that identify genetic factors influencing smoking initiation, intensity and cessation. The genetic architecture of these three phases of smoking behavior appears to be largely distinct.

Copy number variation and human genome maps

Nature Genetics 42, 365 (2010). doi:10.1038/ng0510-365

Author: Steven A McCarroll

Maps of human genome copy number variation (CNV) are maturing into useful resources for complex disease genetics. Four new studies increase the resolution of CNV maps and seek to locate human phenotypic variation on these maps.

Conventional wisdom

Nature Genetics 42, 363 (2010). doi:10.1038/ng0510-363

Recent agreement on stable reference sequences for reporting human genetic variants now allows us to mandate the use of the allele naming conventions developed by the Human Genome Variation Society.

Research highlights

Nature Genetics 42, 287 (2010). doi:10.1038/ng0410-287

Protective hemoglobinopathies and Plasmodium falciparum transmission

Nature Genetics 42, 284 (2010). doi:10.1038/ng0410-284

Author: Geoffrey Pasvol

Human hemoglobin variants are known to protect the host against severe malaria due to P. falciparum. A new study demonstrates that such genetic variation may also be associated with increased transmission of this pathogen from the human host to the Anopheles vector.

Epigenetic marks identify functional elements

Nature Genetics 42, 282 (2010). doi:10.1038/ng0410-282

Author: Randall H Morse

Enhancers and transcription factor binding sites that control cell-specific transcription in higher eukaryotes can be found up to hundreds of kilobases from the promoters that they control, making their identification challenging. A new study uses a model based on histone modifications and chromatin dynamics to predict functional elements involved in androgen receptor response.

Unlocking the pathogenesis of celiac disease

Nature Genetics 42, 281 (2010). doi:10.1038/ng0410-281

Author: Robert M Plenge

A genome-wide association study reports more than a dozen new susceptibility loci for celiac disease. Analysis of eQTL data from these and previously established risk loci sheds light on the genetic pathways underlying this common autoimmune disease.

Genome-wide analysis of palindrome formation

Nature Genetics 42, 279 (2010). doi:10.1038/ng0410-279

Authors: Scott J Diede, Hisashi Tanaka, Donald A Bergstrom, Meng-Chao Yao & Stephen J Tapscott

Keeping the tires warm

Nature Genetics 42, 277 (2010). doi:10.1038/ng0410-277

Research is a necessity for the Middle Eastern countries currently growing their knowledge economies, and it is the key to their achieving autonomous control of their people's healthcare. To sustain knowledge growth, policymakers need to learn to trust researchers while also insisting upon evidence for the advice they get from them.

Research highlights

Nature Genetics 42, 195 (2010). doi:10.1038/ng0310-195

Author: Orli Bahcall, Pamela Colosimo, Emily Niemitz & Kyle Vogan

Understanding variable expressivity in microdeletion syndromes

Nature Genetics 42, 192 (2010). doi:10.1038/ng0310-192

Authors: Joris A Veltman & Han G Brunner

A new study reports an elevated frequency of second-site genomic alterations among children with severe developmental delay who carry a recurrent microdeletion at chromosome 16p12.1. The work highlights the complex relationship between genotype and phenotype and provides a model to explain the clinical variability associated with this and other common microdeletion syndromes.

Open chromatin and diabetes risk

Nature Genetics 42, 190 (2010). doi:10.1038/ng0310-190

Author: Leif Groop

A new study has identified a large number of open chromatin regions harboring active regulatory elements in human pancreatic islets. A type 2 diabetes–associated SNP in TCF7L2 was found to be located in a region of allele-specific open chromatin and shows allele-specific enhancer activity, suggesting a potential mechanism for this disease association.

Deciphering genetic susceptibility to frontotemporal lobar dementia

Nature Genetics 42, 189 (2010). doi:10.1038/ng0310-189

Authors: Jean-Charles Lambert & Philippe Amouyel

A genome-wide association study has identified a new genetic susceptibility factor for a subtype of frontotemporal lobar dementia characterized by TDP-43 inclusions. The work illustrates how high-quality phenotyping can increase power to detect risk alleles for rare heterogeneous diseases.

Proportional representation

Nature Genetics 42, 187 (2010). doi:10.1038/ng0310-187

The journal publishes papers from a very broad geographical catchment, and we invite peer referees from among the world's best genetics researchers in order to attract and publish papers of a uniformly high standard. We need to do more to recruit outstanding referees from under-represented regions.

Research highlights

Nature Genetics 42, 103 (2010). doi:10.1038/ng0210-103

Author: Orli Bahcall, Pamela Colosimo, Emily Niemitz & Kyle Vogan

Deregulation of H3K27 methylation in cancer

Nature Genetics 42, 100 (2010). doi:10.1038/ng0210-100

Authors: Eva Martinez-Garcia & Jonathan D Licht

A new study now reports recurrent somatic mutation of EZH2, a histone methyltransferase that modifies H3K27, in diffuse large B-cell lymphoma (DLBCL). There is now evidence for both increased and decreased activity of enzymes controlling H3K27 methylation in cancer, suggesting that a precise balance of this methylation is critical for normal cell growth.

Channelopathies converge on TRPV4

Nature Genetics 42, 98 (2010). doi:10.1038/ng0210-98

Authors: Bernd Nilius & Grzegorz Owsianik

scapuloperoneal spinal muscular atrophy and Charcot-Marie-Tooth disease type 2C are inherited neurodegenerative diseases characterized by sensory defects and muscle weakness. Three new studies demonstrate that they are allelic disorders caused by mutations in the vanilloid transient receptor potential cation-channel gene TRPV4.

Inborn variation in metabolism

Nature Genetics 42, 97 (2010). doi:10.1038/ng0210-97

Authors: Vamsi K Mootha & Joel N Hirschhorn

Advances in analytical biochemistry have recently made it possible to obtain global snapshots of metabolism. A new study couples such technology with genome-wide genetic analysis to explore inherited variation in human metabolism.

Conclusion by exclusion

Nature Genetics 42, 95 (2010). doi:10.1038/ng0210-95

Systems models and biomarker studies both pose the problem of wrangling high information content. Such publications can be made easier to review and to use if they propose explicit alternative hypotheses and show experimental exclusion of each competing explanation. In practice, we will need to be able to identify and independently cite multiple hypotheses and related experiments within a published work.

Research highlights

Nature Genetics 42, 19 (2010). doi:10.1038/ng0110-19

Author: Orli Bahcall, Pamela Colosimo, Emily Niemitz & Kyle Vogan

Getting connected in the globin interactome

Nature Genetics 42, 16 (2010). doi:10.1038/ng0110-16

Authors: Tobias Ragoczy & Mark Groudine

A new study provides compelling evidence that transcriptional regulation and three-dimensional genomic architecture are linked. The alpha- and beta-globin loci associate with hundreds of active genes across the genome at transcription factories in erythroid cells, and specialized Klf1-containing transcription factories mediate the association of Klf1-regulated genes.

Lung function and airway diseases

Nature Genetics 42, 14 (2010). doi:10.1038/ng0110-14

Author: Scott T Weiss

Two studies report genome-wide association studies for lung function, using cross-sectional spirometric measurements in healthy individuals. They identify six genetic loci newly associated to natural variation in lung function, which may have implications for the related airway diseases of asthma and chronic obstructive pulmonary disease.

Exome sequencing makes medical genomics a reality

Nature Genetics 42, 13 (2010). doi:10.1038/ng0110-13

Author: Leslie G Biesecker

Massively parallel sequencing of the exomes of four individuals with Miller syndrome, combined with filtering to exclude benign and unrelated variants, has identified causative mutations in DHODH. This approach will accelerate discovery of the genetic bases of hundreds of other rare mendelian disorders.

Reply to “Evolutionary flux of canonical microRNAs and mirtrons in Drosophila”

Nature Genetics 42, 9 (2010). doi:10.1038/ng0110-9

Authors: Jian Lu, Yang Shen, Richard W Carthew, San Ming Wang & Chung-I Wu

Evolutionary flux of canonical microRNAs and mirtrons in Drosophila

Nature Genetics 42, 6 (2010). doi:10.1038/ng0110-6

Authors: Eugene Berezikov, Na Liu, Alex S Flynt, Emily Hodges, Michelle Rooks, Gregory J Hannon & Eric C Lai

Reply to “Reassessing the abundance of H3K9me2 chromatin domains in embryonic stem cells”

Nature Genetics 42, 5 (2010). doi:10.1038/ng0110-5

Authors: Bo Wen, Hao Wu, Yoichi Shinkai, Rafael A Irizarry & Andrew P Feinberg

Reassessing the abundance of H3K9me2 chromatin domains in embryonic stem cells

Nature Genetics 42, 4 (2010). doi:10.1038/ng0110-4

Authors: Guillaume J Filion & Bas van Steensel

No evidence for a role of CLCN2 variants in idiopathic generalized epilepsy

Nature Genetics 42, 3 (2010). doi:10.1038/ng0110-3

Authors: María I Niemeyer, L Pablo Cid, Francisco V Sepúlveda, Judith Blanz, Muriel Auberson & Thomas J Jentsch

Integrating with integrity

Nature Genetics 42, 1 (2010). doi:10.1038/ng0110-1

Data worthy of integration with the results of other researchers need to be prepared to explicit export standards, linked to appropriate metadata and offered with field-specific caveats for use. Data exchange may need to be taught and discussed in handshaking workshops.

Research highlights

Nature Genetics 41, 1267 (2009). doi:10.1038/ng1209-1267

Putting leprosy on the map

Nature Genetics 41, 1264 (2009). doi:10.1038/ng1209-1264

Author: Martin C J Maiden

Sequencing of the genome of a second strain of Mycobacterium leprae and the development of a genome-wide typing scheme have provided deeper understanding of the evolution and epidemiology of the leprosy bacillus. A new study confirms that leprosy has a single clone origin and has spread around the globe, following human migration and trade over the last several thousand years.

Copy number variation and antigenic repertoire

Nature Genetics 41, 1263 (2009). doi:10.1038/ng1209-1263

Author: John A L Armour

The success of bone marrow transplantation depends on whether transplanted immune cells respond in graft versus host disease. A new study identifies a common gene deletion that is associated with immune response following transplantation.

Evidence for a common pathway linking neurodegenerative diseases

Nature Genetics 41, 1261 (2009). doi:10.1038/ng1209-1261

Authors: Joshua M Shulman & Philip L De Jager

In the largest Parkinson's disease genome-wide association studies to date, common variants in three familiar genes—SNCA, MAPT and LRRK2—and two new loci are found to increase disease susceptibility. The studies suggest genetic heterogeneity for Parkinson's disease risk in different human populations and lend support to the idea of a common pathway for Parkinson's and Alzheimer's diseases.

Cool as a cucumber

Nature Genetics 41, 1259 (2009). doi:10.1038/ng1209-1259

The genome of the seventh plant to be sequenced, Cucumis sativus L., was assembled using the conventional long-read Sanger sequencing and higher-throughput short-read technology. This genome is the entry point for exploring the diversity and function of the Cucurbitaceae family of agriculturally important plants. Its compact genome, without evidence of recent duplication, will be useful in comparative analysis of plant genome evolution.

Alzheimer’s disease beyond APOE

Nature Genetics 41, 1047 (2009). doi:10.1038/ng1009-1047

Authors: Michael A van Es & Leonard H van den Berg

Two genome-wide association studies together report three new susceptibility loci for late-onset Alzheimer’s disease. CLU, PICALM and CR1 may be involved in amyloid-β clearance from the brain.

Data producers deserve citation credit

Nature Genetics 41, 1045 (2009). doi:10.1038/ng1009-1045

Datasets released to public databases in advance of (or with) research publications should be given digital object identifiers to allow databases and journals to give quantitative citation credit to the data producers and curators.

Research Highlights

Nature Genetics 41, 962 (2009). doi:10.1038/ng0909-962

An uphill battle toward pluripotency

Nature Genetics 41, 960 (2009). doi:10.1038/ng0909-960

Author: Thomas Graf

The discovery that a cocktail of transcription factors can reprogram somatic cells into induced pluripotent stem (iPS) cells keeps revealing new secrets of cell fate specification. A new study with hematopoietic cells shows that progenitor cells are far more susceptible than differentiated cells to reprogramming.

Closing the gap between genotype and phenotype

Nature Genetics 41, 958 (2009). doi:10.1038/ng0909-958

Author: Peter K. Gregersen

Making causative connections between genotypic and phenotypic variation is a major challenge for geneticists engaged in the study of human disease. A study drawing this connection for a type 1 diabetes risk locus now demonstrates the importance of focusing on specific quantitative traits and studying them in normal subjects.

Inherited susceptibility to pediatric acute lymphoblastic leukemia

Nature Genetics 41, 957 (2009). doi:10.1038/ng0909-957

Author: Ross L Levine

Although genome-wide analyses have identified somatic alterations contributing to the pathogenesis of pediatric acute lymphoblastic leukemia (ALL), few studies have identified germline variants conferring risk of this disease. Two reports now provide the first genome-wide glimpse into the role of inherited alleles in ALL pathogenesis.

CLCN2 variants in idiopathic generalized epilepsy

Nature Genetics 41, 954 (2009). doi:10.1038/ng0909-954

Authors: Ailing Kleefuß-Lie, Waltraut Friedl, Sven Cichon, Karsten Haug, Maike Warnstedt, Alexi Alekov, Thomas Sander, Alfredo Ramirez, Barbara Poser, Snezana Maljevic, Simon Hebeisen, Christian Kubisch, Johannes Rebstock, Steve Horvath, Kerstin Hallmann, Jörn S Dullinger, Birgit Rau, Fritz Haverkamp, Stefan Beyenburg, Herbert Schulz, Dieter Janz, Bernd Giese, Gerhard Müller-Newen, Peter Propping, Christian E Elger, Christoph Fahlke & Holger Lerche

Twelve lords a-leaping

Nature Genetics 41, 953 (2009). doi:10.1038/ng0909-953

The UK House of Lords Science and Technology Committee reports that genomic medicine is already in practice but needs a coordinated set of infrastructural and training systems to allow the healthcare system to cope.

Research Highlights

Nature Genetics 41, 962 (2009). doi:10.1038/ng0909-962

An uphill battle toward pluripotency

Nature Genetics 41, 960 (2009). doi:10.1038/ng0909-960

Author: Thomas Graf

The discovery that a cocktail of transcription factors can reprogram somatic cells into induced pluripotent stem (iPS) cells keeps revealing new secrets of cell fate specification. A new study with hematopoietic cells shows that progenitor cells are far more susceptible than differentiated cells to reprogramming.

Closing the gap between genotype and phenotype

Nature Genetics 41, 958 (2009). doi:10.1038/ng0909-958

Author: Peter K. Gregersen

Making causative connections between genotypic and phenotypic variation is a major challenge for geneticists engaged in the study of human disease. A study drawing this connection for a type 1 diabetes risk locus now demonstrates the importance of focusing on specific quantitative traits and studying them in normal subjects.

Inherited susceptibility to pediatric acute lymphoblastic leukemia

Nature Genetics 41, 957 (2009). doi:10.1038/ng0909-957

Author: Ross L Levine

Although genome-wide analyses have identified somatic alterations contributing to the pathogenesis of pediatric acute lymphoblastic leukemia (ALL), few studies have identified germline variants conferring risk of this disease. Two reports now provide the first genome-wide glimpse into the role of inherited alleles in ALL pathogenesis.

CLCN2 variants in idiopathic generalized epilepsy

Nature Genetics 41, 954 (2009). doi:10.1038/ng0909-954

Authors: Ailing Kleefuß-Lie, Waltraut Friedl, Sven Cichon, Karsten Haug, Maike Warnstedt, Alexi Alekov, Thomas Sander, Alfredo Ramirez, Barbara Poser, Snezana Maljevic, Simon Hebeisen, Christian Kubisch, Johannes Rebstock, Steve Horvath, Kerstin Hallmann, Jörn S Dullinger, Birgit Rau, Fritz Haverkamp, Stefan Beyenburg, Herbert Schulz, Dieter Janz, Bernd Giese, Gerhard Müller-Newen, Peter Propping, Christian E Elger, Christoph Fahlke & Holger Lerche

Twelve lords a-leaping

Nature Genetics 41, 953 (2009). doi:10.1038/ng0909-953

The UK House of Lords Science and Technology Committee reports that genomic medicine is already in practice but needs a coordinated set of infrastructural and training systems to allow the healthcare system to cope.

Research highlights

Nature Genetics 41, 870 (2009). doi:10.1038/ng0809-870

Elucidating the role of 8q24 in colorectal cancer

Nature Genetics 41, 868 (2009). doi:10.1038/ng0809-868

Authors: Olivier Harismendy & Kelly A. Frazer

Two new reports highlight the power of genome-wide association (GWA) studies to guide the functional annotation of genetic variants contributing to common diseases. The studies show that a common risk variant for colorectal cancer on chromosome 8q24 affects TCF4 binding to an enhancer that interacts with the MYC promoter, providing a mechanistic explanation for the association of this variant with disease risk.

Life can be stressful without ATR

Nature Genetics 41, 866 (2009). doi:10.1038/ng0809-866

Author: Mark O'Driscoll

A new study reports the first mouse model for ATR-mutated Seckel syndrome. The mice show phenotypes recapitulating the human disorder and provide insights into how reduced ATR function affects normal embryonic development by increasing replicative stress, ultimately resulting in an accelerated aging phenotype postnatally.

Labile H3.3+H2A.Z nucleosomes mark 'nucleosome-free regions'

Nature Genetics 41, 865 (2009). doi:10.1038/ng0809-865

Author: Steven Henikoff

Chromatin marks, including histone modifications and variants, have become important tools for characterizing epigenomes, yet how they might interact with one another to facilitate gene expression and regulation has remained unclear. A new study maps unstable nucleosomes containing both H3.3 and H2A.Z histone variants to human promoters and regulatory elements and suggests that transient occupancy by double-variant nucleosomes is a general feature of eukaryotic gene regulation.

Duplications of noncoding elements 5′ of SOX9 are associated with brachydactyly-anonychia

Nature Genetics 41, 862 (2009). doi:10.1038/ng0809-862

Authors: Ingo Kurth, Eva Klopocki, Sigmar Stricker, Jolieke van Oosterwijk, Sebastian Vanek, Jens Altmann, Heliosa G Santos, Jeske J T van Harssel, Thomy de Ravel, Andrew O M Wilkie, Andreas Gal & Stefan Mundlos

What's so funny about peace, love and understanding?

Nature Genetics 41, 861 (2009). doi:10.1038/ng0809-861

The Mediterranean Medical Genetics Meeting 2009 at Bilkent University, in Ankara, Turkey, reaffirmed the commitment of a pragmatic group of scientifically excellent researchers to local problem solving and to the vision of borderless global collaboration in human genomics.

Research highlights

Nature Genetics 41, 770 (2009). doi:10.1038/ng0709-770

Tumors line up for a letdown

Nature Genetics 41, 768 (2009). doi:10.1038/ng0709-768

Author: Joshua T Mendell

MicroRNAs (miRNAs) and the pathways that regulate their expression have critical functions during normal development. A new study demonstrates that select cancer cells have appropriated one developmental mechanism of miRNA regulation, the inhibition of let-7 biogenesis by the Lin-28 and Lin-28B RNA binding proteins, to rid themselves of an antitumorigenic miRNA.

TET2 mutations in myelodysplasia and myeloid malignancies

Nature Genetics 41, 766 (2009). doi:10.1038/ng0709-766

Author: Charles G Mullighan

The genetic basis of myelodysplasia has long been enigmatic, with few common targets of mutation known. A new study reports common mutations in the TET2 gene in myelodysplasia and related myeloid malignancies, suggesting that TET2 has an important role in hematopoiesis and in the pathogenesis of this disease.

High marks for GWAS

Nature Genetics 41, 765 (2009). doi:10.1038/ng0709-765

Author: Stephen Chanock

Two genome-wide association studies for testicular cancer report associations at three new loci, including two candidate genes previously implicated in testicular development, KITLG (ligand for the receptor tyrosine kinase) and SPRY4 (sprouty 4). These studies are notable for the high effect sizes detected and the biological plausibility of the candidate genes.

Online Methods

Nature Genetics 41, 763 (2009). doi:10.1038/ng0709-763

Most of our readers access our articles online, in formats that deal well with increasingly complex research methods and the growing requirement for increased precision of citation. These considerations have now led us to publish Methods online.

Research highlights

Nature Genetics 41, 642 (2009). doi:10.1038/ng0609-642

Narcolepsy and the T-cell receptor

Nature Genetics 41, 640 (2009). doi:10.1038/ng0609-640

Author: Timothy J Vyse

The etiology of the sleep disorder narcolepsy has not been firmly established, although an autoimmune pathogenesis has been proposed and is supported by a strong genetic association with the HLA. A new genome-wide association study provides further support for the autoimmune basis of narcolepsy by uncovering a robust association at the T-cell receptor alpha locus.

Diversifying microtubules in brain development

Nature Genetics 41, 638 (2009). doi:10.1038/ng0609-638

Author: Andrew P Jackson

Tubulins are key structural components of all cells. A new study reveals roles in brain development for a specific β-tubulin isoform and highlights potential for functional diversity in the β-tubulin gene family.

Genetics of reproductive lifespan

Nature Genetics 41, 637 (2009). doi:10.1038/ng0609-637

Author: Patricia Hartge

Five genome-wide association studies of the timing of menarche and menopause have now taken us beyond the range of candidate gene and linkage studies. The list of new genetic associations identified for these two traits should shed light on the mechanisms of ovarian aging, as well as breast cancer and other diseases associated with reproductive lifespan.

The cup half empty

Nature Genetics 41, 635 (2009). doi:10.1038/ng0609-635

One-sixth of the world's population does not have enough food to sustain life, and the world's food supply needs to double by 2050 without increasing demand for water or fuel. Agricultural genetics is one of the easier parts of the solution.

Of flaky tails and itchy skin

Nature Genetics 41, 512 (2009). doi:10.1038/ng0509-512

Author: Donata Vercelli

A new study defines the flaky tail mouse as a model for human atopic dermatitis caused by a null mutation in the gene encoding filaggrin, a key component of the epidermal barrier. Research in these mice will help explain how a disrupted barrier contributes to the pathogenesis of atopic dermatitis and to asthma arising in the context of atopic skin disease.

TMPRSS2-ERG and PTEN loss in prostate cancer

Nature Genetics 41, 509 (2009). doi:10.1038/ng0509-509

Author: Jeremy A Squire

Two studies show that the common recurrent gene fusion between TMPRSS2 and ERG promotes prostate cancer in both mouse and humans when PTEN is concurrently lost. In human prostate cancer, the presence of both these aberrations may be indicative of poor prognosis, suggesting that preclinical therapeutic research should target both of these pathways.

X-cess of variants in XLMR

Nature Genetics 41, 510 (2009). doi:10.1038/ng0509-510

Authors: David L Nelson & Richard A Gibbs

A new study reports large-scale systematic resequencing of the coding exons of the X chromosome in males with X-linked mental retardation (XLMR), illustrating the challenge of sorting through large amounts of benign variation in order to identify disease-causing sequence changes.

Research Highlights

Nature Genetics 41, 514 (2009). doi:10.1038/ng0509-514

Endless forms most beautiful and wonderful

Nature Genetics 41, 507 (2009). doi:10.1038/ng0509-507

Author: Stephen C. Stearns

Systems biology unlimited

Nature Genetics 41, 505 (2009). doi:10.1038/ng0509-505

Sequencing technologies have unleashed more than enough quantitative data to test systems models of genome function, and sequence data are now driving a new systems biology. The new RNA entities uncovered may require new concepts of how genomes regulate their own expression.

Genetics of cardiac repolarization

Nature Genetics 41, 388 (2009). doi:10.1038/ng0409-388

Authors: Svati H Shah & Geoffrey S Pitt

Prolongation of the electrocardiographic QT interval, a measure of cardiac repolarization, is associated with arrhythmogenic disorders and is a risk factor for sudden cardiac death. Two genome-wide association studies (GWAS) of variation in the QT interval in population-based cohorts now report association with variants in a subset of ion channel genes and other new associations.