journal
MENU ▼
Read by QxMD icon Read
search

Nature Genetics

journal
https://www.readbyqxmd.com/read/28920961/germline-mutations-affecting-the-histone-h4-core-cause-a-developmental-syndrome-by-altering-dna-damage-response-and-cell-cycle-control
#1
Federico Tessadori, Jacques C Giltay, Jane A Hurst, Maarten P Massink, Karen Duran, Harmjan R Vos, Robert M van Es, Richard H Scott, Koen L I van Gassen, Jeroen Bakkers, Gijs van Haaften
Covalent modifications of histones have an established role as chromatin effectors, as they control processes such as DNA replication and transcription, and repair or regulate nucleosomal structure. Loss of modifications on histone N tails, whether due to mutations in genes belonging to histone-modifying complexes or mutations directly affecting the histone tails, causes developmental disorders or has a role in tumorigenesis. More recently, modifications affecting the globular histone core have been uncovered as being crucial for DNA repair, pluripotency and oncogenesis...
September 18, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28892063/interpreting-short-tandem-repeat-variations-in-humans-using-mutational-constraint
#2
Melissa Gymrek, Thomas Willems, David Reich, Yaniv Erlich
Identifying regions of the genome that are depleted of mutations can distinguish potentially deleterious variants. Short tandem repeats (STRs), also known as microsatellites, are among the largest contributors of de novo mutations in humans. However, per-locus studies of STR mutations have been limited to highly ascertained panels of several dozen loci. Here we harnessed bioinformatics tools and a novel analytical framework to estimate mutation parameters for each STR in the human genome by correlating STR genotypes with local sequence heterozygosity...
September 11, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28892062/genome-wide-association-study-identifies-112-new-loci-for-body-mass-index-in-the-japanese-population
#3
Masato Akiyama, Yukinori Okada, Masahiro Kanai, Atsushi Takahashi, Yukihide Momozawa, Masashi Ikeda, Nakao Iwata, Shiro Ikegawa, Makoto Hirata, Koichi Matsuda, Motoki Iwasaki, Taiki Yamaji, Norie Sawada, Tsuyoshi Hachiya, Kozo Tanno, Atsushi Shimizu, Atsushi Hozawa, Naoko Minegishi, Shoichiro Tsugane, Masayuki Yamamoto, Michiaki Kubo, Yoichiro Kamatani
Obesity is a risk factor for a wide variety of health problems. In a genome-wide association study (GWAS) of body mass index (BMI) in Japanese people (n = 173,430), we found 85 loci significantly associated with obesity (P < 5.0 × 10(-8)), of which 51 were previously unknown. We conducted trans-ancestral meta-analyses by integrating these results with the results from a GWAS of Europeans and identified 61 additional new loci. In total, this study identifies 112 novel loci, doubling the number of previously known BMI-associated loci...
September 11, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28892061/linkage-disequilibrium-dependent-architecture-of-human-complex-traits-shows-action-of-negative-selection
#4
Steven Gazal, Hilary K Finucane, Nicholas A Furlotte, Po-Ru Loh, Pier Francesco Palamara, Xuanyao Liu, Armin Schoech, Brendan Bulik-Sullivan, Benjamin M Neale, Alexander Gusev, Alkes L Price
Recent work has hinted at the linkage disequilibrium (LD)-dependent architecture of human complex traits, where SNPs with low levels of LD (LLD) have larger per-SNP heritability. Here we analyzed summary statistics from 56 complex traits (average N = 101,401) by extending stratified LD score regression to continuous annotations. We determined that SNPs with low LLD have significantly larger per-SNP heritability and that roughly half of this effect can be explained by functional annotations negatively correlated with LLD, such as DNase I hypersensitivity sites (DHSs)...
September 11, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28892060/a-functional-genomics-predictive-network-model-identifies-regulators-of-inflammatory-bowel-disease
#5
Lauren A Peters, Jacqueline Perrigoue, Arthur Mortha, Alina Iuga, Won-Min Song, Eric M Neiman, Sean R Llewellyn, Antonio Di Narzo, Brian A Kidd, Shannon E Telesco, Yongzhong Zhao, Aleksandar Stojmirovic, Jocelyn Sendecki, Khader Shameer, Riccardo Miotto, Bojan Losic, Hardik Shah, Eunjee Lee, Minghui Wang, Jeremiah J Faith, Andrew Kasarskis, Carrie Brodmerkel, Mark Curran, Anuk Das, Joshua R Friedman, Yoshinori Fukui, Mary Beth Humphrey, Brian M Iritani, Nicholas Sibinga, Teresa K Tarrant, Carmen Argmann, Ke Hao, Panos Roussos, Jun Zhu, Bin Zhang, Radu Dobrin, Lloyd F Mayer, Eric E Schadt
A major challenge in inflammatory bowel disease (IBD) is the integration of diverse IBD data sets to construct predictive models of IBD. We present a predictive model of the immune component of IBD that informs causal relationships among loci previously linked to IBD through genome-wide association studies (GWAS) using functional and regulatory annotations that relate to the cells, tissues, and pathophysiology of IBD. Our model consists of individual networks constructed using molecular data generated from intestinal samples isolated from three populations of patients with IBD at different stages of disease...
September 11, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28892059/a-meta-analysis-of-genome-wide-association-studies-identifies-17-new-parkinson-s-disease-risk-loci
#6
Diana Chang, Mike A Nalls, Ingileif B Hallgrímsdóttir, Julie Hunkapiller, Marcel van der Brug, Fang Cai, Geoffrey A Kerchner, Gai Ayalon, Baris Bingol, Morgan Sheng, David Hinds, Timothy W Behrens, Andrew B Singleton, Tushar R Bhangale, Robert R Graham
Common variant genome-wide association studies (GWASs) have, to date, identified >24 risk loci for Parkinson's disease (PD). To discover additional loci, we carried out a GWAS comparing 6,476 PD cases with 302,042 controls, followed by a meta-analysis with a recent study of over 13,000 PD cases and 95,000 controls at 9,830 overlapping variants. We then tested 35 loci (P < 1 × 10(-6)) in a replication cohort of 5,851 cases and 5,866 controls. We identified 17 novel risk loci (P < 5 × 10(-8)) in a joint analysis of 26,035 cases and 403,190 controls...
September 11, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28869592/reconstruction-of-enhancer-target-networks-in-935-samples-of-human-primary-cells-tissues-and-cell-lines
#7
Qin Cao, Christine Anyansi, Xihao Hu, Liangliang Xu, Lei Xiong, Wenshu Tang, Myth T S Mok, Chao Cheng, Xiaodan Fan, Mark Gerstein, Alfred S L Cheng, Kevin Y Yip
We propose a new method for determining the target genes of transcriptional enhancers in specific cells and tissues. It combines global trends across many samples and sample-specific information, and considers the joint effect of multiple enhancers. Our method outperforms existing methods when predicting the target genes of enhancers in unseen samples, as evaluated by independent experimental data. Requiring few types of input data, we are able to apply our method to reconstruct the enhancer-target networks in 935 samples of human primary cells, tissues and cell lines, which constitute by far the largest set of enhancer-target networks...
September 4, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28869591/identification-of-153-new-loci-associated-with-heel-bone-mineral-density-and-functional-involvement-of-gpc6-in-osteoporosis
#8
John P Kemp, John A Morris, Carolina Medina-Gomez, Vincenzo Forgetta, Nicole M Warrington, Scott E Youlten, Jie Zheng, Celia L Gregson, Elin Grundberg, Katerina Trajanoska, John G Logan, Andrea S Pollard, Penny C Sparkes, Elena J Ghirardello, Rebecca Allen, Victoria D Leitch, Natalie C Butterfield, Davide Komla-Ebri, Anne-Tounsia Adoum, Katharine F Curry, Jacqueline K White, Fiona Kussy, Keelin M Greenlaw, Changjiang Xu, Nicholas C Harvey, Cyrus Cooper, David J Adams, Celia M T Greenwood, Matthew T Maurano, Stephen Kaptoge, Fernando Rivadeneira, Jonathan H Tobias, Peter I Croucher, Cheryl L Ackert-Bicknell, J H Duncan Bassett, Graham R Williams, J Brent Richards, David M Evans
Osteoporosis is a common disease diagnosed primarily by measurement of bone mineral density (BMD). We undertook a genome-wide association study (GWAS) in 142,487 individuals from the UK Biobank to identify loci associated with BMD as estimated by quantitative ultrasound of the heel. We identified 307 conditionally independent single-nucleotide polymorphisms (SNPs) that attained genome-wide significance at 203 loci, explaining approximately 12% of the phenotypic variance. These included 153 previously unreported loci, and several rare variants with large effect sizes...
September 4, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28869590/identification-of-new-susceptibility-loci-for-type-2-diabetes-and-shared-etiological-pathways-with-coronary-heart-disease
#9
Wei Zhao, Asif Rasheed, Emmi Tikkanen, Jung-Jin Lee, Adam S Butterworth, Joanna M M Howson, Themistocles L Assimes, Rajiv Chowdhury, Marju Orho-Melander, Scott Damrauer, Aeron Small, Senay Asma, Minako Imamura, Toshimasa Yamauch, John C Chambers, Peng Chen, Bishwa R Sapkota, Nabi Shah, Sehrish Jabeen, Praveen Surendran, Yingchang Lu, Weihua Zhang, Atif Imran, Shahid Abbas, Faisal Majeed, Kevin Trindade, Nadeem Qamar, Nadeem Hayyat Mallick, Zia Yaqoob, Tahir Saghir, Syed Nadeem Hasan Rizvi, Anis Memon, Syed Zahed Rasheed, Fazal-Ur-Rehman Memon, Khalid Mehmood, Naveeduddin Ahmed, Irshad Hussain Qureshi, Tanveer-Us-Salam, Wasim Iqbal, Uzma Malik, Narinder Mehra, Jane Z Kuo, Wayne H-H Sheu, Xiuqing Guo, Chao A Hsiung, Jyh-Ming J Juang, Kent D Taylor, Yi-Jen Hung, Wen-Jane Lee, Thomas Quertermous, I-Te Lee, Chih-Cheng Hsu, Erwin P Bottinger, Sarju Ralhan, Yik Ying Teo, Tzung-Dau Wang, Dewan S Alam, Emanuele Di Angelantonio, Steve Epstein, Sune F Nielsen, Børge G Nordestgaard, Anne Tybjaerg-Hansen, Robin Young, Marianne Benn, Ruth Frikke-Schmidt, Pia R Kamstrup, J Wouter Jukema, Naveed Sattar, Roelof Smit, Ren-Hua Chung, Kae-Woei Liang, Sonia Anand, Dharambir K Sanghera, Samuli Ripatti, Ruth J F Loos, Jaspal S Kooner, E Shyong Tai, Jerome I Rotter, Yii-Der Ida Chen, Philippe Frossard, Shiro Maeda, Takashi Kadowaki, Muredach Reilly, Guillaume Pare, Olle Melander, Veikko Salomaa, Daniel J Rader, John Danesh, Benjamin F Voight, Danish Saleheen
To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D-CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D...
September 4, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28846101/line-1-activation-after-fertilization-regulates-global-chromatin-accessibility-in-the-early-mouse-embryo
#10
Joanna W Jachowicz, Xinyang Bing, Julien Pontabry, Ana Bošković, Oliver J Rando, Maria-Elena Torres-Padilla
After fertilization, to initiate development, gametes are reprogramed to become totipotent. Approximately half of the mammalian genome consists of repetitive elements, including retrotransposons, some of which are transcribed after fertilization. Retrotransposon activation is generally assumed to be a side effect of the extensive chromatin remodeling underlying the epigenetic reprogramming of gametes. Here, we used a targeted epigenomic approach to address whether specific retrotransposon families play a direct role in chromatin organization and developmental progression...
August 28, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28846100/composition-and-dosage-of-a-multipartite-enhancer-cluster-control-developmental-expression-of-ihh-indian-hedgehog
#11
Anja J Will, Giulia Cova, Marco Osterwalder, Wing-Lee Chan, Lars Wittler, Norbert Brieske, Verena Heinrich, Jean-Pierre de Villartay, Martin Vingron, Eva Klopocki, Axel Visel, Darío G Lupiáñez, Stefan Mundlos
Copy number variations (CNVs) often include noncoding sequences and putative enhancers, but how these rearrangements induce disease is poorly understood. Here we investigate CNVs involving the regulatory landscape of IHH (encoding Indian hedgehog), which cause multiple, highly localized phenotypes including craniosynostosis and synpolydactyly. We show through transgenic reporter and genome-editing studies in mice that Ihh is regulated by a constellation of at least nine enhancers with individual tissue specificities in the digit anlagen, growth plates, skull sutures and fingertips...
August 28, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28825729/a-children-s-oncology-group-and-target-initiative-exploring-the-genetic-landscape-of-wilms-tumor
#12
Samantha Gadd, Vicki Huff, Amy L Walz, Ariadne H A G Ooms, Amy E Armstrong, Daniela S Gerhard, Malcolm A Smith, Jaime M Guidry Auvil, Daoud Meerzaman, Qing-Rong Chen, Chih Hao Hsu, Chunhua Yan, Cu Nguyen, Ying Hu, Leandro C Hermida, Tanja Davidsen, Patee Gesuwan, Yussanne Ma, Zusheng Zong, Andrew J Mungall, Richard A Moore, Marco A Marra, Jeffrey S Dome, Charles G Mullighan, Jing Ma, David A Wheeler, Oliver A Hampton, Nicole Ross, Julie M Gastier-Foster, Stefan T Arold, Elizabeth J Perlman
We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A...
August 21, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28825728/cis-and-trans-determinants-of-epigenetic-silencing-by-polycomb-repressive-complex-2-in-arabidopsis
#13
Jun Xiao, Run Jin, Xiang Yu, Max Shen, John D Wagner, Armaan Pai, Claire Song, Michael Zhuang, Samantha Klasfeld, Chongsheng He, Alexandre M Santos, Chris Helliwell, Jose L Pruneda-Paz, Steve A Kay, Xiaowei Lin, Sujuan Cui, Meilin Fernandez Garcia, Oliver Clarenz, Justin Goodrich, Xiaoyu Zhang, Ryan S Austin, Roberto Bonasio, Doris Wagner
Disruption of gene silencing by Polycomb protein complexes leads to homeotic transformations and altered developmental-phase identity in plants. Here we define short genomic fragments, known as Polycomb response elements (PREs), that direct Polycomb repressive complex 2 (PRC2) placement at developmental genes regulated by silencing in Arabidopsis thaliana. We identify transcription factor families that bind to these PREs, colocalize with PRC2 on chromatin, physically interact with and recruit PRC2, and are required for PRC2-mediated gene silencing in vivo...
August 21, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28825727/condensin-mediated-remodeling-of-the-mitotic-chromatin-landscape-in-fission-yeast
#14
Yasutaka Kakui, Adam Rabinowitz, David J Barry, Frank Uhlmann
The eukaryotic genome consists of DNA molecules far longer than the cells that contain them. They reach their greatest compaction during chromosome condensation in mitosis. This process is aided by condensin, a structural maintenance of chromosomes (SMC) family member. The spatial organization of mitotic chromosomes and how condensin shapes chromatin architecture are not yet fully understood. Here we use chromosome conformation capture (Hi-C) to study mitotic chromosome condensation in the fission yeast Schizosaccharomyces pombe...
August 21, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28825726/a-mutational-signature-reveals-alterations-underlying-deficient-homologous-recombination-repair-in-breast-cancer
#15
Paz Polak, Jaegil Kim, Lior Z Braunstein, Rosa Karlic, Nicholas J Haradhavala, Grace Tiao, Daniel Rosebrock, Dimitri Livitz, Kirsten Kübler, Kent W Mouw, Atanas Kamburov, Yosef E Maruvka, Ignaty Leshchiner, Eric S Lander, Todd R Golub, Aviad Zick, Alexandre Orthwein, Michael S Lawrence, Rajbir N Batra, Carlos Caldas, Daniel A Haber, Peter W Laird, Hui Shen, Leif W Ellisen, Alan D D'Andrea, Stephen J Chanock, William D Foulkes, Gad Getz
Biallelic inactivation of BRCA1 or BRCA2 is associated with a pattern of genome-wide mutations known as signature 3. By analyzing ∼1,000 breast cancer samples, we confirmed this association and established that germline nonsense and frameshift variants in PALB2, but not in ATM or CHEK2, can also give rise to the same signature. We were able to accurately classify missense BRCA1 or BRCA2 variants known to impair homologous recombination (HR) on the basis of this signature. Finally, we show that epigenetic silencing of RAD51C and BRCA1 by promoter methylation is strongly associated with signature 3 and, in our data set, was highly enriched in basal-like breast cancers in young individuals of African descent...
August 21, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28805829/lineage-specific-dynamic-and-pre-established-enhancer-promoter-contacts-cooperate-in-terminal-differentiation
#16
Adam J Rubin, Brook C Barajas, Mayra Furlan-Magaril, Vanessa Lopez-Pajares, Maxwell R Mumbach, Imani Howard, Daniel S Kim, Lisa D Boxer, Jonathan Cairns, Mikhail Spivakov, Steven W Wingett, Minyi Shi, Zhixin Zhao, William J Greenleaf, Anshul Kundaje, Michael Snyder, Howard Y Chang, Peter Fraser, Paul A Khavari
Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer-promoter contact remodeling during cellular differentiation remains poorly understood. To address this, genome-wide promoter capture Hi-C (CHi-C) was performed during epidermal differentiation. Two classes of enhancer-promoter contacts associated with differentiation-induced genes were identified. The first class ('gained') increased in contact strength during differentiation in concert with enhancer acquisition of the H3K27ac activation mark...
August 14, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28805828/mutations-in-keops-complex-genes-cause-nephrotic-syndrome-with-primary-microcephaly
#17
Daniela A Braun, Jia Rao, Geraldine Mollet, David Schapiro, Marie-Claire Daugeron, Weizhen Tan, Olivier Gribouval, Olivia Boyer, Patrick Revy, Tilman Jobst-Schwan, Johanna Magdalena Schmidt, Jennifer A Lawson, Denny Schanze, Shazia Ashraf, Jeremy F P Ullmann, Charlotte A Hoogstraten, Nathalie Boddaert, Bruno Collinet, Gaëlle Martin, Dominique Liger, Svjetlana Lovric, Monica Furlano, I Chiara Guerrera, Oraly Sanchez-Ferras, Jennifer F Hu, Anne-Claire Boschat, Sylvia Sanquer, Björn Menten, Sarah Vergult, Nina De Rocker, Merlin Airik, Tobias Hermle, Shirlee Shril, Eugen Widmeier, Heon Yung Gee, Won-Il Choi, Carolin E Sadowski, Werner L Pabst, Jillian K Warejko, Ankana Daga, Tamara Basta, Verena Matejas, Karin Scharmann, Sandra D Kienast, Babak Behnam, Brendan Beeson, Amber Begtrup, Malcolm Bruce, Gaik-Siew Ch'ng, Shuan-Pei Lin, Jui-Hsing Chang, Chao-Huei Chen, Megan T Cho, Patrick M Gaffney, Patrick E Gipson, Chyong-Hsin Hsu, Jameela A Kari, Yu-Yuan Ke, Cathy Kiraly-Borri, Wai-Ming Lai, Emmanuelle Lemyre, Rebecca Okashah Littlejohn, Amira Masri, Mastaneh Moghtaderi, Kazuyuki Nakamura, Fatih Ozaltin, Marleen Praet, Chitra Prasad, Agnieszka Prytula, Elizabeth R Roeder, Patrick Rump, Rhonda E Schnur, Takashi Shiihara, Manish D Sinha, Neveen A Soliman, Kenza Soulami, David A Sweetser, Wen-Hui Tsai, Jeng-Daw Tsai, Rezan Topaloglu, Udo Vester, David H Viskochil, Nithiwat Vatanavicharn, Jessica L Waxler, Klaas J Wierenga, Matthias T F Wolf, Sik-Nin Wong, Sebastian A Leidel, Gessica Truglio, Peter C Dedon, Annapurna Poduri, Shrikant Mane, Richard P Lifton, Maxime Bouchard, Peter Kannu, David Chitayat, Daniella Magen, Bert Callewaert, Herman van Tilbeurgh, Martin Zenker, Corinne Antignac, Friedhelm Hildebrandt
Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue...
August 14, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28805827/transcriptional-risk-scores-link-gwas-to-eqtls-and-predict-complications-in-crohn-s-disease
#18
Urko M Marigorta, Lee A Denson, Jeffrey S Hyams, Kajari Mondal, Jarod Prince, Thomas D Walters, Anne Griffiths, Joshua D Noe, Wallace V Crandall, Joel R Rosh, David R Mack, Richard Kellermayer, Melvin B Heyman, Susan S Baker, Michael C Stephens, Robert N Baldassano, James F Markowitz, Mi-Ok Kim, Marla C Dubinsky, Judy Cho, Bruce J Aronow, Subra Kugathasan, Greg Gibson
Gene expression profiling can be used to uncover the mechanisms by which loci identified through genome-wide association studies (GWAS) contribute to pathology. Given that most GWAS hits are in putative regulatory regions and transcript abundance is physiologically closer to the phenotype of interest, we hypothesized that summation of risk-allele-associated gene expression, namely a transcriptional risk score (TRS), should provide accurate estimates of disease risk. We integrate summary-level GWAS and expression quantitative trait locus (eQTL) data with RNA-seq data from the RISK study, an inception cohort of pediatric Crohn's disease...
August 14, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28783165/tmprss2-erg-fusion-co-opts-master-transcription-factors-and-activates-notch-signaling-in-primary-prostate-cancer
#19
Ken J Kron, Alexander Murison, Stanley Zhou, Vincent Huang, Takafumi N Yamaguchi, Yu-Jia Shiah, Michael Fraser, Theodorus van der Kwast, Paul C Boutros, Robert G Bristow, Mathieu Lupien
TMPRSS2-ERG (T2E) structural rearrangements typify ∼50% of prostate tumors and result in overexpression of the ERG transcription factor. Using chromatin, genomic and expression data, we show distinct cis-regulatory landscapes between T2E-positive and non-T2E primary prostate tumors, which include clusters of regulatory elements (COREs). This difference is mediated by ERG co-option of HOXB13 and FOXA1, implementing a T2E-specific transcriptional profile. We also report a T2E-specific CORE on the structurally rearranged ERG locus arising from spreading of the TMPRSS2 locus pre-existing CORE, assisting in its overexpression...
September 2017: Nature Genetics
https://www.readbyqxmd.com/read/28783164/effect-of-sequence-variants-on-variance-in-glucose-levels-predicts-type-2-diabetes-risk-and-accounts-for-heritability
#20
Erna V Ivarsdottir, Valgerdur Steinthorsdottir, Maryam S Daneshpour, Gudmar Thorleifsson, Patrick Sulem, Hilma Holm, Snaevar Sigurdsson, Astradur B Hreidarsson, Gunnar Sigurdsson, Ragnar Bjarnason, Arni V Thorsson, Rafn Benediktsson, Gudmundur Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, Sirous Zeinali, Fereidoun Azizi, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Kari Stefansson
Sequence variants that affect mean fasting glucose levels do not necessarily affect risk for type 2 diabetes (T2D). We assessed the effects of 36 reported glucose-associated sequence variants on between- and within-subject variance in fasting glucose levels in 69,142 Icelanders. The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance (5.7% per allele, P = 4.2 × 10(-10)), whereas variants in GCK and G6PC2 that increase fasting glucose levels decrease between-subject variance (7...
September 2017: Nature Genetics
journal
journal
31198
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"