ALBERT

Description: Genetic crosses in many organisms have shown that alleles of unlinked genes generally assort independently of one another during gamete formation. However, variation in chromosome size may affect the process of meiosis and lead to nonindependent assortment of chromosomes. We therefore examined chromosomes with insertions and found that they preferentially segregated away from the X chromosome during meiosis in Caenorhabditis elegans males. Conversely, chromosomes with deletions preferentially segregated with the X chromosome. The degree of segregation bias was significantly associated with the length of the insertion or deletion. Simulations revealed that this segregation bias leads to genome size reduction in hermaphroditic species, a pattern consistent with differences in genome sizes in the genus Caenorhabditis. These results suggest that insertions and deletions may affect chromosome segregation patterns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, John -- Chen, Pei-Jiun -- Wang, George J -- Keller, Laurent -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jul 16;329(5989):293. doi: 10.1126/science.1190130.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolution, University of Lausanne, CH-1015 Lausanne, Switzerland. John.Wang@unil.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20647459" target="_blank"〉PubMed〈/a〉

Description: Mutations of the breast cancer susceptibility gene BRCA1 confer increased risk for breast, ovarian, and prostatic cancers, but it is not clear why the mutations are associated with these particular tumor types. In transient transfection assays, BRCA1 was found to inhibit signaling by the ligand-activated estrogen receptor (ER-alpha) through the estrogen-responsive enhancer element and to block the transcriptional activation function AF-2 of ER-alpha. These results raise the possibility that wild-type BRCA1 suppresses estrogen-dependent transcriptional pathways related to mammary epithelial cell proliferation and that loss of this ability contributes to tumorigenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fan, S -- Wang, J -- Yuan, R -- Ma, Y -- Meng, Q -- Erdos, M R -- Pestell, R G -- Yuan, F -- Auborn, K J -- Goldberg, I D -- Rosen, E M -- R01-CA75503/CA/NCI NIH HHS/ -- R01-ES09169/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1999 May 21;284(5418):1354-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Radiation Oncology, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, 270-05 76th Avenue, New Hyde Park, NY 11040, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10334989" target="_blank"〉PubMed〈/a〉

Description: A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Venter, J C -- Adams, M D -- Myers, E W -- Li, P W -- Mural, R J -- Sutton, G G -- Smith, H O -- Yandell, M -- Evans, C A -- Holt, R A -- Gocayne, J D -- Amanatides, P -- Ballew, R M -- Huson, D H -- Wortman, J R -- Zhang, Q -- Kodira, C D -- Zheng, X H -- Chen, L -- Skupski, M -- Subramanian, G -- Thomas, P D -- Zhang, J -- Gabor Miklos, G L -- Nelson, C -- Broder, S -- Clark, A G -- Nadeau, J -- McKusick, V A -- Zinder, N -- Levine, A J -- Roberts, R J -- Simon, M -- Slayman, C -- Hunkapiller, M -- Bolanos, R -- Delcher, A -- Dew, I -- Fasulo, D -- Flanigan, M -- Florea, L -- Halpern, A -- Hannenhalli, S -- Kravitz, S -- Levy, S -- Mobarry, C -- Reinert, K -- Remington, K -- Abu-Threideh, J -- Beasley, E -- Biddick, K -- Bonazzi, V -- Brandon, R -- Cargill, M -- Chandramouliswaran, I -- Charlab, R -- Chaturvedi, K -- Deng, Z -- Di Francesco, V -- Dunn, P -- Eilbeck, K -- Evangelista, C -- Gabrielian, A E -- Gan, W -- Ge, W -- Gong, F -- Gu, Z -- Guan, P -- Heiman, T J -- Higgins, M E -- Ji, R R -- Ke, Z -- Ketchum, K A -- Lai, Z -- Lei, Y -- Li, Z -- Li, J -- Liang, Y -- Lin, X -- Lu, F -- Merkulov, G V -- Milshina, N -- Moore, H M -- Naik, A K -- Narayan, V A -- Neelam, B -- Nusskern, D -- Rusch, D B -- Salzberg, S -- Shao, W -- Shue, B -- Sun, J -- Wang, Z -- Wang, A -- Wang, X -- Wang, J -- Wei, M -- Wides, R -- Xiao, C -- Yan, C -- Yao, A -- Ye, J -- Zhan, M -- Zhang, W -- Zhang, H -- Zhao, Q -- Zheng, L -- Zhong, F -- Zhong, W -- Zhu, S -- Zhao, S -- Gilbert, D -- Baumhueter, S -- Spier, G -- Carter, C -- Cravchik, A -- Woodage, T -- Ali, F -- An, H -- Awe, A -- Baldwin, D -- Baden, H -- Barnstead, M -- Barrow, I -- Beeson, K -- Busam, D -- Carver, A -- Center, A -- Cheng, M L -- Curry, L -- Danaher, S -- Davenport, L -- Desilets, R -- Dietz, S -- Dodson, K -- Doup, L -- Ferriera, S -- Garg, N -- Gluecksmann, A -- Hart, B -- Haynes, J -- Haynes, C -- Heiner, C -- Hladun, S -- Hostin, D -- Houck, J -- Howland, T -- Ibegwam, C -- Johnson, J -- Kalush, F -- Kline, L -- Koduru, S -- Love, A -- Mann, F -- May, D -- McCawley, S -- McIntosh, T -- McMullen, I -- Moy, M -- Moy, L -- Murphy, B -- Nelson, K -- Pfannkoch, C -- Pratts, E -- Puri, V -- Qureshi, H -- Reardon, M -- Rodriguez, R -- Rogers, Y H -- Romblad, D -- Ruhfel, B -- Scott, R -- Sitter, C -- Smallwood, M -- Stewart, E -- Strong, R -- Suh, E -- Thomas, R -- Tint, N N -- Tse, S -- Vech, C -- Wang, G -- Wetter, J -- Williams, S -- Williams, M -- Windsor, S -- Winn-Deen, E -- Wolfe, K -- Zaveri, J -- Zaveri, K -- Abril, J F -- Guigo, R -- Campbell, M J -- Sjolander, K V -- Karlak, B -- Kejariwal, A -- Mi, H -- Lazareva, B -- Hatton, T -- Narechania, A -- Diemer, K -- Muruganujan, A -- Guo, N -- Sato, S -- Bafna, V -- Istrail, S -- Lippert, R -- Schwartz, R -- Walenz, B -- Yooseph, S -- Allen, D -- Basu, A -- Baxendale, J -- Blick, L -- Caminha, M -- Carnes-Stine, J -- Caulk, P -- Chiang, Y H -- Coyne, M -- Dahlke, C -- Mays, A -- Dombroski, M -- Donnelly, M -- Ely, D -- Esparham, S -- Fosler, C -- Gire, H -- Glanowski, S -- Glasser, K -- Glodek, A -- Gorokhov, M -- Graham, K -- Gropman, B -- Harris, M -- Heil, J -- Henderson, S -- Hoover, J -- Jennings, D -- Jordan, C -- Jordan, J -- Kasha, J -- Kagan, L -- Kraft, C -- Levitsky, A -- Lewis, M -- Liu, X -- Lopez, J -- Ma, D -- Majoros, W -- McDaniel, J -- Murphy, S -- Newman, M -- Nguyen, T -- Nguyen, N -- Nodell, M -- Pan, S -- Peck, J -- Peterson, M -- Rowe, W -- Sanders, R -- Scott, J -- Simpson, M -- Smith, T -- Sprague, A -- Stockwell, T -- Turner, R -- Venter, E -- Wang, M -- Wen, M -- Wu, D -- Wu, M -- Xia, A -- Zandieh, A -- Zhu, X -- New York, N.Y. -- Science. 2001 Feb 16;291(5507):1304-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA. humangenome@celera.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11181995" target="_blank"〉PubMed〈/a〉

Description: DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from 〉30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581791/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581791/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bentley, David R -- Balasubramanian, Shankar -- Swerdlow, Harold P -- Smith, Geoffrey P -- Milton, John -- Brown, Clive G -- Hall, Kevin P -- Evers, Dirk J -- Barnes, Colin L -- Bignell, Helen R -- Boutell, Jonathan M -- Bryant, Jason -- Carter, Richard J -- Keira Cheetham, R -- Cox, Anthony J -- Ellis, Darren J -- Flatbush, Michael R -- Gormley, Niall A -- Humphray, Sean J -- Irving, Leslie J -- Karbelashvili, Mirian S -- Kirk, Scott M -- Li, Heng -- Liu, Xiaohai -- Maisinger, Klaus S -- Murray, Lisa J -- Obradovic, Bojan -- Ost, Tobias -- Parkinson, Michael L -- Pratt, Mark R -- Rasolonjatovo, Isabelle M J -- Reed, Mark T -- Rigatti, Roberto -- Rodighiero, Chiara -- Ross, Mark T -- Sabot, Andrea -- Sankar, Subramanian V -- Scally, Aylwyn -- Schroth, Gary P -- Smith, Mark E -- Smith, Vincent P -- Spiridou, Anastassia -- Torrance, Peta E -- Tzonev, Svilen S -- Vermaas, Eric H -- Walter, Klaudia -- Wu, Xiaolin -- Zhang, Lu -- Alam, Mohammed D -- Anastasi, Carole -- Aniebo, Ify C -- Bailey, David M D -- Bancarz, Iain R -- Banerjee, Saibal -- Barbour, Selena G -- Baybayan, Primo A -- Benoit, Vincent A -- Benson, Kevin F -- Bevis, Claire -- Black, Phillip J -- Boodhun, Asha -- Brennan, Joe S -- Bridgham, John A -- Brown, Rob C -- Brown, Andrew A -- Buermann, Dale H -- Bundu, Abass A -- Burrows, James C -- Carter, Nigel P -- Castillo, Nestor -- Chiara E Catenazzi, Maria -- Chang, Simon -- Neil Cooley, R -- Crake, Natasha R -- Dada, Olubunmi O -- Diakoumakos, Konstantinos D -- Dominguez-Fernandez, Belen -- Earnshaw, David J -- Egbujor, Ugonna C -- Elmore, David W -- Etchin, Sergey S -- Ewan, Mark R -- Fedurco, Milan -- Fraser, Louise J -- Fuentes Fajardo, Karin V -- Scott Furey, W -- George, David -- Gietzen, Kimberley J -- Goddard, Colin P -- Golda, George S -- Granieri, Philip A -- Green, David E -- Gustafson, David L -- Hansen, Nancy F -- Harnish, Kevin -- Haudenschild, Christian D -- Heyer, Narinder I -- Hims, Matthew M -- Ho, Johnny T -- Horgan, Adrian M -- Hoschler, Katya -- Hurwitz, Steve -- Ivanov, Denis V -- Johnson, Maria Q -- James, Terena -- Huw Jones, T A -- Kang, Gyoung-Dong -- Kerelska, Tzvetana H -- Kersey, Alan D -- Khrebtukova, Irina -- Kindwall, Alex P -- Kingsbury, Zoya -- Kokko-Gonzales, Paula I -- Kumar, Anil -- Laurent, Marc A -- Lawley, Cynthia T -- Lee, Sarah E -- Lee, Xavier -- Liao, Arnold K -- Loch, Jennifer A -- Lok, Mitch -- Luo, Shujun -- Mammen, Radhika M -- Martin, John W -- McCauley, Patrick G -- McNitt, Paul -- Mehta, Parul -- Moon, Keith W -- Mullens, Joe W -- Newington, Taksina -- Ning, Zemin -- Ling Ng, Bee -- Novo, Sonia M -- O'Neill, Michael J -- Osborne, Mark A -- Osnowski, Andrew -- Ostadan, Omead -- Paraschos, Lambros L -- Pickering, Lea -- Pike, Andrew C -- Pike, Alger C -- Chris Pinkard, D -- Pliskin, Daniel P -- Podhasky, Joe -- Quijano, Victor J -- Raczy, Come -- Rae, Vicki H -- Rawlings, Stephen R -- Chiva Rodriguez, Ana -- Roe, Phyllida M -- Rogers, John -- Rogert Bacigalupo, Maria C -- Romanov, Nikolai -- Romieu, Anthony -- Roth, Rithy K -- Rourke, Natalie J -- Ruediger, Silke T -- Rusman, Eli -- Sanches-Kuiper, Raquel M -- Schenker, Martin R -- Seoane, Josefina M -- Shaw, Richard J -- Shiver, Mitch K -- Short, Steven W -- Sizto, Ning L -- Sluis, Johannes P -- Smith, Melanie A -- Ernest Sohna Sohna, Jean -- Spence, Eric J -- Stevens, Kim -- Sutton, Neil -- Szajkowski, Lukasz -- Tregidgo, Carolyn L -- Turcatti, Gerardo -- Vandevondele, Stephanie -- Verhovsky, Yuli -- Virk, Selene M -- Wakelin, Suzanne -- Walcott, Gregory C -- Wang, Jingwen -- Worsley, Graham J -- Yan, Juying -- Yau, Ling -- Zuerlein, Mike -- Rogers, Jane -- Mullikin, James C -- Hurles, Matthew E -- McCooke, Nick J -- West, John S -- Oaks, Frank L -- Lundberg, Peter L -- Klenerman, David -- Durbin, Richard -- Smith, Anthony J -- B05823/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0701805/Medical Research Council/United Kingdom -- MOL04534/Biotechnology and Biological Sciences Research Council/United Kingdom -- Z01 HG200330-03/Intramural NIH HHS/ -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2008 Nov 6;456(7218):53-9. doi: 10.1038/nature07517.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Illumina Cambridge Ltd. (Formerly Solexa Ltd), Chesterford Research Park, Little Chesterford, Nr Saffron Walden, Essex CB10 1XL, UK. dbentley@illumina.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987734" target="_blank"〉PubMed〈/a〉

Description: Cellular senescence has been recently shown to have an important role in opposing tumour initiation and promotion. Senescence induced by oncogenes or by loss of tumour suppressor genes is thought to critically depend on induction of the p19(Arf)-p53 pathway. The Skp2 E3-ubiquitin ligase can act as a proto-oncogene and its aberrant overexpression is frequently observed in human cancers. Here we show that although Skp2 inactivation on its own does not induce cellular senescence, aberrant proto-oncogenic signals as well as inactivation of tumour suppressor genes do trigger a potent, tumour-suppressive senescence response in mice and cells devoid of Skp2. Notably, Skp2 inactivation and oncogenic-stress-driven senescence neither elicit activation of the p19(Arf)-p53 pathway nor DNA damage, but instead depend on Atf4, p27 and p21. We further demonstrate that genetic Skp2 inactivation evokes cellular senescence even in oncogenic conditions in which the p19(Arf)-p53 response is impaired, whereas a Skp2-SCF complex inhibitor can trigger cellular senescence in p53/Pten-deficient cells and tumour regression in preclinical studies. Our findings therefore provide proof-of-principle evidence that pharmacological inhibition of Skp2 may represent a general approach for cancer prevention and therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928066/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928066/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Hui-Kuan -- Chen, Zhenbang -- Wang, Guocan -- Nardella, Caterina -- Lee, Szu-Wei -- Chan, Chia-Hsin -- Yang, Wei-Lei -- Wang, Jing -- Egia, Ainara -- Nakayama, Keiichi I -- Cordon-Cardo, Carlos -- Teruya-Feldstein, Julie -- Pandolfi, Pier Paolo -- R01 CA082328/CA/NCI NIH HHS/ -- R01 CA082328-13/CA/NCI NIH HHS/ -- R01 MD004038/MD/NIMHD NIH HHS/ -- England -- Nature. 2010 Mar 18;464(7287):374-9. doi: 10.1038/nature08815.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Biology and Genetics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237562" target="_blank"〉PubMed〈/a〉

Description: The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Ling -- Chen, Xiang-Jun -- Zhu, Jie -- Xi, Yi-Bo -- Yang, Xu -- Hu, Li-Dan -- Ouyang, Hong -- Patel, Sherrina H -- Jin, Xin -- Lin, Danni -- Wu, Frances -- Flagg, Ken -- Cai, Huimin -- Li, Gen -- Cao, Guiqun -- Lin, Ying -- Chen, Daniel -- Wen, Cindy -- Chung, Christopher -- Wang, Yandong -- Qiu, Austin -- Yeh, Emily -- Wang, Wenqiu -- Hu, Xun -- Grob, Seanna -- Abagyan, Ruben -- Su, Zhiguang -- Tjondro, Harry Christianto -- Zhao, Xi-Juan -- Luo, Hongrong -- Hou, Rui -- Perry, J Jefferson P -- Gao, Weiwei -- Kozak, Igor -- Granet, David -- Li, Yingrui -- Sun, Xiaodong -- Wang, Jun -- Zhang, Liangfang -- Liu, Yizhi -- Yan, Yong-Bin -- Zhang, Kang -- England -- Nature. 2015 Jul 30;523(7562):607-11. doi: 10.1038/nature14650. Epub 2015 Jul 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [3] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. ; BGI-Shenzhen, Shenzhen 518083, China. ; 1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; 1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China. ; Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. ; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] CapitalBio Genomics Co., Ltd., Dongguan 523808, China. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 20080, China. ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, USA. ; Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China. ; Department of Biochemistry, University of California Riverside, Riverside, California 92521, USA. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA. ; King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia. ; Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 20080, China. ; Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. ; 1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [3] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [4] Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA [5] Veterans Administration Healthcare System, San Diego, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26200341" target="_blank"〉PubMed〈/a〉

Description: Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (〈/=50 years in males and 〈/=60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol 〉 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319990/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319990/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Do, Ron -- Stitziel, Nathan O -- Won, Hong-Hee -- Jorgensen, Anders Berg -- Duga, Stefano -- Angelica Merlini, Pier -- Kiezun, Adam -- Farrall, Martin -- Goel, Anuj -- Zuk, Or -- Guella, Illaria -- Asselta, Rosanna -- Lange, Leslie A -- Peloso, Gina M -- Auer, Paul L -- NHLBI Exome Sequencing Project -- Girelli, Domenico -- Martinelli, Nicola -- Farlow, Deborah N -- DePristo, Mark A -- Roberts, Robert -- Stewart, Alexander F R -- Saleheen, Danish -- Danesh, John -- Epstein, Stephen E -- Sivapalaratnam, Suthesh -- Hovingh, G Kees -- Kastelein, John J -- Samani, Nilesh J -- Schunkert, Heribert -- Erdmann, Jeanette -- Shah, Svati H -- Kraus, William E -- Davies, Robert -- Nikpay, Majid -- Johansen, Christopher T -- Wang, Jian -- Hegele, Robert A -- Hechter, Eliana -- Marz, Winfried -- Kleber, Marcus E -- Huang, Jie -- Johnson, Andrew D -- Li, Mingyao -- Burke, Greg L -- Gross, Myron -- Liu, Yongmei -- Assimes, Themistocles L -- Heiss, Gerardo -- Lange, Ethan M -- Folsom, Aaron R -- Taylor, Herman A -- Olivieri, Oliviero -- Hamsten, Anders -- Clarke, Robert -- Reilly, Dermot F -- Yin, Wu -- Rivas, Manuel A -- Donnelly, Peter -- Rossouw, Jacques E -- Psaty, Bruce M -- Herrington, David M -- Wilson, James G -- Rich, Stephen S -- Bamshad, Michael J -- Tracy, Russell P -- Cupples, L Adrienne -- Rader, Daniel J -- Reilly, Muredach P -- Spertus, John A -- Cresci, Sharon -- Hartiala, Jaana -- Tang, W H Wilson -- Hazen, Stanley L -- Allayee, Hooman -- Reiner, Alex P -- Carlson, Christopher S -- Kooperberg, Charles -- Jackson, Rebecca D -- Boerwinkle, Eric -- Lander, Eric S -- Schwartz, Stephen M -- Siscovick, David S -- McPherson, Ruth -- Tybjaerg-Hansen, Anne -- Abecasis, Goncalo R -- Watkins, Hugh -- Nickerson, Deborah A -- Ardissino, Diego -- Sunyaev, Shamil R -- O'Donnell, Christopher J -- Altshuler, David -- Gabriel, Stacey -- Kathiresan, Sekar -- 090532/Wellcome Trust/United Kingdom -- 095552/Wellcome Trust/United Kingdom -- 5U54HG003067-11/HG/NHGRI NIH HHS/ -- G-0907/Parkinson's UK/United Kingdom -- K08 HL114642/HL/NHLBI NIH HHS/ -- K08HL114642/HL/NHLBI NIH HHS/ -- P01 HL076491/HL/NHLBI NIH HHS/ -- P01 HL098055/HL/NHLBI NIH HHS/ -- R01 HL107816/HL/NHLBI NIH HHS/ -- R01HL107816/HL/NHLBI NIH HHS/ -- RC2 HL-102923/HL/NHLBI NIH HHS/ -- RC2 HL-102924/HL/NHLBI NIH HHS/ -- RC2 HL-102925/HL/NHLBI NIH HHS/ -- RC2 HL-102926/HL/NHLBI NIH HHS/ -- RC2 HL-103010/HL/NHLBI NIH HHS/ -- T32 HL007208/HL/NHLBI NIH HHS/ -- T32HL00720/HL/NHLBI NIH HHS/ -- T32HL007604/HL/NHLBI NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2015 Feb 5;518(7537):102-6. doi: 10.1038/nature13917. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [2] Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA. [4] Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; 1] Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Division of Statistical Genomics, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Department of Clinical Biochemistry KB3011, Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Copenhagen 1165, Denmark. ; Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Universita degli Studi di Milano, Milano 20122, Italy. ; Division of Cardiology, Ospedale Niguarda, Milano 20162, Italy. ; Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2J, UK. ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; University of Verona School of Medicine, Department of Medicine, Verona 37129, Italy. ; John &Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada. ; Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 1TN, UK. ; MedStar Health Research Institute, Cardiovascular Research Institute, Hyattsville, Maryland 20782, USA. ; Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands. ; Department of Cardiovascular Sciences, University of Leicester, and Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK. ; DZHK (German Research Centre for Cardiovascular Research), Munich Heart Alliance, Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Berlin 13347, Germany. ; Medizinische Klinik II, University of Lubeck, Lubeck 23562, Germany. ; 1] Center for Human Genetics, Duke University, Durham, North Carolina 27708, USA. [2] Department of Cardiology and Center for Genomic Medicine, Duke University School of Medicine, Durham, North Carolina 27708, USA. ; Department of Cardiology and Center for Genomic Medicine, Duke University School of Medicine, Durham, North Carolina 27708, USA. ; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada. ; Department of Biochemistry, Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada. ; 1] Department of Biochemistry, Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada. [2] Department of Medicine, Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada. ; 1] Medical Faculty Mannheim, Mannheim Institute of Public Health, Social and Preventive Medicine, Heidelberg University, Ludolf Krehl Strasse 7-11, Mannheim D-68167, Germany. [2] Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria. [3] Synlab Academy, Mannheim 68259, Germany. ; Medical Faculty Mannheim, Mannheim Institute of Public Health, Social and Preventive Medicine, Heidelberg University, Ludolf Krehl Strasse 7-11, Mannheim D-68167, Germany. ; The National Heart, Lung, Blood Institute's Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; National Heart, Lung, and Blood Institute Center for Population Studies, The Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; Department of Biostatistics and Epidemiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Department of Epidemiology, University of Alabama-Birmingham, Birmingham, Alabama 35233, USA. ; Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27106, USA. ; Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; 1] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. [2] Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota 55455, USA. ; University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. ; Atherosclerosis Research Unit, Department of Medicine, and Center for Molecular Medicine, Karolinska Institutet, Stockholm 171 77, Sweden. ; Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford OX1 2JD, UK. ; Merck Sharp &Dohme Corporation, Rahway, New Jersey 08889, USA. ; The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK. ; 1] The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK. [2] Department of Statistics, University of Oxford, Oxford OX1 2JD, UK. ; National Heart, Lung, and Blood Institute, Bethesda, Maryland 20824, USA. ; 1] Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington 98195, USA. [2] Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98101, USA. ; Section on Cardiology, and Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27106, USA. ; Jackson Heart Study, University of Mississippi Medical Center, Jackson State University, Jackson, Mississippi 39217, USA. ; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22904, USA. ; 1] Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA. [2] Seattle Children's Hospital, Seattle, Washington 98105, USA. [3] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Department of Biochemistry, University of Vermont, Burlington, Vermont 05405, USA. ; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; St Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri 64111, USA. ; 1] Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Department of Genetics, Washington University in St Louis, Missouri 63130, USA. ; Department of Preventive Medicine and Institute for Genetic Medicine, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA. ; Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA. ; 1] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. [2] Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA. ; Ohio State University, Columbus, Ohio 43210, USA. ; Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA. ; 1] Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA. [2] Department of Medicine, School of Medicine, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Clinical Biochemistry KB3011, Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Copenhagen 1165, Denmark. [2] Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Kobenhavn N, Denmark. ; Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Missouri 48109, USA. ; 1] Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2J, UK. [2] The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Department of Cardiology, Parma Hospital, Parma 43100, Italy. ; 1] Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [2] Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487149" target="_blank"〉PubMed〈/a〉

Description: The Dobzhansky-Muller model proposes that hybrid incompatibilities are caused by the interaction between genes that have functionally diverged in the respective hybridizing species. Here, we show that Lethal hybrid rescue (Lhr) has functionally diverged in Drosophila simulans and interacts with Hybrid male rescue (Hmr), which has functionally diverged in D. melanogaster, to cause lethality in F1 hybrid males. LHR localizes to heterochromatic regions of the genome and has diverged extensively in sequence between these species in a manner consistent with positive selection. Rapidly evolving heterochromatic DNA sequences may be driving the evolution of this incompatibility gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brideau, Nicholas J -- Flores, Heather A -- Wang, Jun -- Maheshwari, Shamoni -- Wang, Xu -- Barbash, Daniel A -- R01 GM074737-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2006 Nov 24;314(5803):1292-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17124320" target="_blank"〉PubMed〈/a〉

Description: A single-base pair resolution silkworm genetic variation map was constructed from 40 domesticated and wild silkworms, each sequenced to approximately threefold coverage, representing 99.88% of the genome. We identified ~16 million single-nucleotide polymorphisms, many indels, and structural variations. We find that the domesticated silkworms are clearly genetically differentiated from the wild ones, but they have maintained large levels of genetic variability, suggesting a short domestication event involving a large number of individuals. We also identified signals of selection at 354 candidate genes that may have been important during domestication, some of which have enriched expression in the silk gland, midgut, and testis. These data add to our understanding of the domestication processes and may have applications in devising pest control strategies and advancing the use of silkworms as efficient bioreactors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951477/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951477/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xia, Qingyou -- Guo, Yiran -- Zhang, Ze -- Li, Dong -- Xuan, Zhaoling -- Li, Zhuo -- Dai, Fangyin -- Li, Yingrui -- Cheng, Daojun -- Li, Ruiqiang -- Cheng, Tingcai -- Jiang, Tao -- Becquet, Celine -- Xu, Xun -- Liu, Chun -- Zha, Xingfu -- Fan, Wei -- Lin, Ying -- Shen, Yihong -- Jiang, Lan -- Jensen, Jeffrey -- Hellmann, Ines -- Tang, Si -- Zhao, Ping -- Xu, Hanfu -- Yu, Chang -- Zhang, Guojie -- Li, Jun -- Cao, Jianjun -- Liu, Shiping -- He, Ningjia -- Zhou, Yan -- Liu, Hui -- Zhao, Jing -- Ye, Chen -- Du, Zhouhe -- Pan, Guoqing -- Zhao, Aichun -- Shao, Haojing -- Zeng, Wei -- Wu, Ping -- Li, Chunfeng -- Pan, Minhui -- Li, Jingjing -- Yin, Xuyang -- Li, Dawei -- Wang, Juan -- Zheng, Huisong -- Wang, Wen -- Zhang, Xiuqing -- Li, Songgang -- Yang, Huanming -- Lu, Cheng -- Nielsen, Rasmus -- Zhou, Zeyang -- Wang, Jian -- Xiang, Zhonghuai -- Wang, Jun -- R01 HG003229/HG/NHGRI NIH HHS/ -- R01 HG003229-05/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 16;326(5951):433-6. doi: 10.1126/science.1176620. Epub 2009 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Sericultural Laboratory of Agricultural Ministry, College of Biotechnology, Southwest University, Chongqing 400715, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19713493" target="_blank"〉PubMed〈/a〉

Description: Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involved in response to hypoxia. One single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP's association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus in genetic adaptation to high altitude.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711608/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711608/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yi, Xin -- Liang, Yu -- Huerta-Sanchez, Emilia -- Jin, Xin -- Cuo, Zha Xi Ping -- Pool, John E -- Xu, Xun -- Jiang, Hui -- Vinckenbosch, Nicolas -- Korneliussen, Thorfinn Sand -- Zheng, Hancheng -- Liu, Tao -- He, Weiming -- Li, Kui -- Luo, Ruibang -- Nie, Xifang -- Wu, Honglong -- Zhao, Meiru -- Cao, Hongzhi -- Zou, Jing -- Shan, Ying -- Li, Shuzheng -- Yang, Qi -- Asan -- Ni, Peixiang -- Tian, Geng -- Xu, Junming -- Liu, Xiao -- Jiang, Tao -- Wu, Renhua -- Zhou, Guangyu -- Tang, Meifang -- Qin, Junjie -- Wang, Tong -- Feng, Shuijian -- Li, Guohong -- Huasang -- Luosang, Jiangbai -- Wang, Wei -- Chen, Fang -- Wang, Yading -- Zheng, Xiaoguang -- Li, Zhuo -- Bianba, Zhuoma -- Yang, Ge -- Wang, Xinping -- Tang, Shuhui -- Gao, Guoyi -- Chen, Yong -- Luo, Zhen -- Gusang, Lamu -- Cao, Zheng -- Zhang, Qinghui -- Ouyang, Weihan -- Ren, Xiaoli -- Liang, Huiqing -- Zheng, Huisong -- Huang, Yebo -- Li, Jingxiang -- Bolund, Lars -- Kristiansen, Karsten -- Li, Yingrui -- Zhang, Yong -- Zhang, Xiuqing -- Li, Ruiqiang -- Li, Songgang -- Yang, Huanming -- Nielsen, Rasmus -- Wang, Jun -- Wang, Jian -- R01 HG003229/HG/NHGRI NIH HHS/ -- R01 MH084695/MH/NIMH NIH HHS/ -- R01HG003229/HG/NHGRI NIH HHS/ -- R01MHG084695/PHS HHS/ -- New York, N.Y. -- Science. 2010 Jul 2;329(5987):75-8. doi: 10.1126/science.1190371.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BGI-Shenzhen, Shenzhen 518083, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20595611" target="_blank"〉PubMed〈/a〉