ALBERT

Description: Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892339/" 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/PMC2892339/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wellcome Trust Case Control Consortium -- Craddock, Nick -- Hurles, Matthew E -- Cardin, Niall -- Pearson, Richard D -- Plagnol, Vincent -- Robson, Samuel -- Vukcevic, Damjan -- Barnes, Chris -- Conrad, Donald F -- Giannoulatou, Eleni -- Holmes, Chris -- Marchini, Jonathan L -- Stirrups, Kathy -- Tobin, Martin D -- Wain, Louise V -- Yau, Chris -- Aerts, Jan -- Ahmad, Tariq -- Andrews, T Daniel -- Arbury, Hazel -- Attwood, Anthony -- Auton, Adam -- Ball, Stephen G -- Balmforth, Anthony J -- Barrett, Jeffrey C -- Barroso, Ines -- Barton, Anne -- Bennett, Amanda J -- Bhaskar, Sanjeev -- Blaszczyk, Katarzyna -- Bowes, John -- Brand, Oliver J -- Braund, Peter S -- Bredin, Francesca -- Breen, Gerome -- Brown, Morris J -- Bruce, Ian N -- Bull, Jaswinder -- Burren, Oliver S -- Burton, John -- Byrnes, Jake -- Caesar, Sian -- Clee, Chris M -- Coffey, Alison J -- Connell, John M C -- Cooper, Jason D -- Dominiczak, Anna F -- Downes, Kate -- Drummond, Hazel E -- Dudakia, Darshna -- Dunham, Andrew -- Ebbs, Bernadette -- Eccles, Diana -- Edkins, Sarah -- Edwards, Cathryn -- Elliot, Anna -- Emery, Paul -- Evans, David M -- Evans, Gareth -- Eyre, Steve -- Farmer, Anne -- Ferrier, I Nicol -- Feuk, Lars -- Fitzgerald, Tomas -- Flynn, Edward -- Forbes, Alistair -- Forty, Liz -- Franklyn, Jayne A -- Freathy, Rachel M -- Gibbs, Polly -- Gilbert, Paul -- Gokumen, Omer -- Gordon-Smith, Katherine -- Gray, Emma -- Green, Elaine -- Groves, Chris J -- Grozeva, Detelina -- Gwilliam, Rhian -- Hall, Anita -- Hammond, Naomi -- Hardy, Matt -- Harrison, Pile -- Hassanali, Neelam -- Hebaishi, Husam -- Hines, Sarah -- Hinks, Anne -- Hitman, Graham A -- Hocking, Lynne -- Howard, Eleanor -- Howard, Philip -- Howson, Joanna M M -- Hughes, Debbie -- Hunt, Sarah -- Isaacs, John D -- Jain, Mahim -- Jewell, Derek P -- Johnson, Toby -- Jolley, Jennifer D -- Jones, Ian R -- Jones, Lisa A -- Kirov, George -- Langford, Cordelia F -- Lango-Allen, Hana -- Lathrop, G Mark -- Lee, James -- Lee, Kate L -- Lees, Charlie -- Lewis, Kevin -- Lindgren, Cecilia M -- Maisuria-Armer, Meeta -- Maller, Julian -- Mansfield, John -- Martin, Paul -- Massey, Dunecan C O -- McArdle, Wendy L -- McGuffin, Peter -- McLay, Kirsten E -- Mentzer, Alex -- Mimmack, Michael L -- Morgan, Ann E -- Morris, Andrew P -- Mowat, Craig -- Myers, Simon -- Newman, William -- Nimmo, Elaine R -- O'Donovan, Michael C -- Onipinla, Abiodun -- Onyiah, Ifejinelo -- Ovington, Nigel R -- Owen, Michael J -- Palin, Kimmo -- Parnell, Kirstie -- Pernet, David -- Perry, John R B -- Phillips, Anne -- Pinto, Dalila -- Prescott, Natalie J -- Prokopenko, Inga -- Quail, Michael A -- Rafelt, Suzanne -- Rayner, Nigel W -- Redon, Richard -- Reid, David M -- Renwick -- Ring, Susan M -- Robertson, Neil -- Russell, Ellie -- St Clair, David -- Sambrook, Jennifer G -- Sanderson, Jeremy D -- Schuilenburg, Helen -- Scott, Carol E -- Scott, Richard -- Seal, Sheila -- Shaw-Hawkins, Sue -- Shields, Beverley M -- Simmonds, Matthew J -- Smyth, Debbie J -- Somaskantharajah, Elilan -- Spanova, Katarina -- Steer, Sophia -- Stephens, Jonathan -- Stevens, Helen E -- Stone, Millicent A -- Su, Zhan -- Symmons, Deborah P M -- Thompson, John R -- Thomson, Wendy -- Travers, Mary E -- Turnbull, Clare -- Valsesia, Armand -- Walker, Mark -- Walker, Neil M -- Wallace, Chris -- Warren-Perry, Margaret -- Watkins, Nicholas A -- Webster, John -- Weedon, Michael N -- Wilson, Anthony G -- Woodburn, Matthew -- Wordsworth, B Paul -- Young, Allan H -- Zeggini, Eleftheria -- Carter, Nigel P -- Frayling, Timothy M -- Lee, Charles -- McVean, Gil -- Munroe, Patricia B -- Palotie, Aarno -- Sawcer, Stephen J -- Scherer, Stephen W -- Strachan, David P -- Tyler-Smith, Chris -- Brown, Matthew A -- Burton, Paul R -- Caulfield, Mark J -- Compston, Alastair -- Farrall, Martin -- Gough, Stephen C L -- Hall, Alistair S -- Hattersley, Andrew T -- Hill, Adrian V S -- Mathew, Christopher G -- Pembrey, Marcus -- Satsangi, Jack -- Stratton, Michael R -- Worthington, Jane -- Deloukas, Panos -- Duncanson, Audrey -- Kwiatkowski, Dominic P -- McCarthy, Mark I -- Ouwehand, Willem -- Parkes, Miles -- Rahman, Nazneen -- Todd, John A -- Samani, Nilesh J -- Donnelly, Peter -- 061858/Wellcome Trust/United Kingdom -- 083948/Wellcome Trust/United Kingdom -- 089989/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 17552/Arthritis Research UK/United Kingdom -- CZB/4/540/Chief Scientist Office/United Kingdom -- ETM/137/Chief Scientist Office/United Kingdom -- ETM/75/Chief Scientist Office/United Kingdom -- G0000934/Medical Research Council/United Kingdom -- G0400874/Medical Research Council/United Kingdom -- G0500115/Medical Research Council/United Kingdom -- G0501942/Medical Research Council/United Kingdom -- G0600329/Medical Research Council/United Kingdom -- G0600705/Medical Research Council/United Kingdom -- G0700491/Medical Research Council/United Kingdom -- G0701003/Medical Research Council/United Kingdom -- G0701420/Medical Research Council/United Kingdom -- G0701810/Medical Research Council/United Kingdom -- G0701810(85517)/Medical Research Council/United Kingdom -- G0800383/Medical Research Council/United Kingdom -- G0800509/Medical Research Council/United Kingdom -- G0800759/Medical Research Council/United Kingdom -- G19/9/Medical Research Council/United Kingdom -- G90/106/Medical Research Council/United Kingdom -- G9521010/Medical Research Council/United Kingdom -- MC_UP_A390_1107/Medical Research Council/United Kingdom -- RG/09/012/28096/British Heart Foundation/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Apr 1;464(7289):713-20. doi: 10.1038/nature08979.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360734" target="_blank"〉PubMed〈/a〉

Description: The HLA-C locus is distinct relative to the other classical HLA class I loci in that it has relatively limited polymorphism, lower expression on the cell surface, and more extensive ligand-receptor interactions with killer-cell immunoglobulin-like receptors. A single nucleotide polymorphism (SNP) 35 kb upstream of HLA-C (rs9264942; termed -35) associates with control of HIV, and with levels of HLA-C messenger RNA transcripts and cell-surface expression, but the mechanism underlying its varied expression is unknown. We proposed that the -35 SNP is not the causal variant for differential HLA-C expression, but rather is marking another polymorphism that directly affects levels of HLA-C. Here we show that variation within the 3' untranslated region (UTR) of HLA-C regulates binding of the microRNA hsa-miR-148 to its target site, resulting in relatively low surface expression of alleles that bind this microRNA and high expression of HLA-C alleles that escape post-transcriptional regulation. The 3' UTR variant associates strongly with control of HIV, potentially adding to the effects of genetic variation encoding the peptide-binding region of the HLA class I loci. Variation in HLA-C expression adds another layer of diversity to this highly polymorphic locus that must be considered when deciphering the function of these molecules in health and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084326/" 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/PMC3084326/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kulkarni, Smita -- Savan, Ram -- Qi, Ying -- Gao, Xiaojiang -- Yuki, Yuko -- Bass, Sara E -- Martin, Maureen P -- Hunt, Peter -- Deeks, Steven G -- Telenti, Amalio -- Pereyra, Florencia -- Goldstein, David -- Wolinsky, Steven -- Walker, Bruce -- Young, Howard A -- Carrington, Mary -- 5-M01-RR-00722/RR/NCRR NIH HHS/ -- HHSN261200800001E/CO/NCI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- N02-CP-55504/CP/NCI NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- R01-DA04334/DA/NIDA NIH HHS/ -- R01-DA12568/DA/NIDA NIH HHS/ -- U01-AI-35039/AI/NIAID NIH HHS/ -- U01-AI-35040/AI/NIAID NIH HHS/ -- U01-AI-35041/AI/NIAID NIH HHS/ -- U01-AI-35042/AI/NIAID NIH HHS/ -- U01-AI-35043/AI/NIAID NIH HHS/ -- U01-AI-37613/AI/NIAID NIH HHS/ -- U01-AI-37984/AI/NIAID NIH HHS/ -- UL1 RR024131/RR/NCRR NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2011 Apr 28;472(7344):495-8. doi: 10.1038/nature09914. Epub 2011 Apr 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21499264" target="_blank"〉PubMed〈/a〉

Description: Author(s): Martin P. Gelfand and R. Mark Bradley We introduce a fabrication method in which a mask with a long, narrow slit is placed between the source of an ion beam and the surface of a solid moving with constant speed. Numerical simulations reveal the method can generate surface ripples and arrays of nanoholes that are virtually defect free. I... [Phys. Rev. B 86, 121406] Published Fri Sep 21, 2012

Description: Author(s): M. Schwitters, D. S. Martin, P. Unsworth, T. Farrell, J. E. Butler, M. Marsili, O. Pulci, and P. Weightman We apply reflection anisotropy spectroscopy (RAS) to high-quality atomically smooth H/C(100) 2×1 surfaces. The optical signal of the H/C(100) 0^{°} flat surface, and of the H/C(100) 2^{°} and H/C(100) 4^{°} vicinal surfaces, is investigated in terms of single and double steps. A comparison of ex... [Phys. Rev. B 83, 085402] Published Wed Feb 09, 2011

Description: Author(s): Frerik van Beijnum, Jeroen Sirre, Chris Rétif, and Martin P. van Exter The optical intensity transmitted through a random pattern of subwavelength holes in a metal film exhibits a speckle pattern. We study the variation of this speckle pattern as a function of wavelength. We find that the resulting speckle correlation function (SCF) separates into a wavelength-dependen... [Phys. Rev. B 85, 035437] Published Mon Jan 23, 2012