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1. The DNA sequence and biological annotation of human chromosome 1

Author

Gregory, S. G., Barlow, K. F., McLay, K. E., Kaul, R., Swarbreck, D., Dunham, A., Scott, C. E., Howe, K. L., Woodfine, K., Spencer, C. C. A., Jones, M. C., Gillson, C., Searle, S., Zhou, Y., Kokocinski, F., McDonald, L., Evans, R., Phillips, K., Atkinson, A., Cooper, R., Jones, C., Hall, R. E., Andrews, T. D., Lloyd, C., Ainscough, R., Almeida, J. P., Ambrose, K. D., Anderson, F., Andrew, R. W., Ashwell, R. I. S., Aubin, K., Babbage, A. K., Bagguley, C. L., Bailey, J., Beasley, H., Bethel, G., Bird, C. P., Bray-Allen, S., Brown, J. Y., Brown, A. J., Buckley, D., Burton, J., Bye, J., Carder, C., Chapman, J. C., Clark, S. Y., Clarke, G., Clee, C., Cobley, V., Collier, R. E., Corby, N., Coville, G. J., Davies, J., Deadman, R., Dunn, M., Earthrowl, M., Ellington, A. G., Errington, H., Frankish, A., Frankland, J., French, L., Garner, P., Garnett, J., Gay, L., Ghori, M. R. J., Gibson, R., Gilby, L. M., Gillett, W., Glithero, R. J., Grafham, D. V., Griffiths, C., Griffiths-Jones, S., Grocock, R., Hammond, S., Harrison, E. S. I., Hart, E., Haugen, E., Heath, P. D., Holmes, S., Holt, K., Howden, P. J., Hunt, A. R., Hunt, S. E., Hunter, G., Isherwood, J., James, R., Johnson, C., Johnson, D., Joy, A., Kay, M., Kershaw, J. K., Kibukawa, M., Kimberley, A. M., King, A., Knights, A. J., Lad, H., Laird, G., Lawlor, S., Leongamornlert, D. A., Lloyd, D. M., Loveland, J., Lovell, J., Lush, M. J., Lyne, R., Martin, S., Mashreghi-Mohammadi, M., Matthews, L., Matthews, N. S. W., McLaren, S., Milne, S., Mistry, S., Nickerson, T., O'Dell, C. N., Oliver, K., Palmeiri, A., Palmer, S. A., Parker, A., Patel, D., Pearce, A. V., Peck, A. I., Pelan, S., Phelps, K., Phillimore, B. J., Plumb, R., Rajan, J., Raymond, C., Rouse, G., Saenphimmachak, C., Sehra, H. K., Sheridan, E., Shownkeen, R., Sims, S., Skuce, C. D., Smith, M., Steward, C., Subramanian, S., Sycamore, N., Tracey, A., Tromans, A., Van Helmond, Z., Wall, M., Wallis, J. M., White, S., Whitehead, S. L., Wilkinson, J. E., Willey, D. L., Williams, H., Wilming, L., Wray, P. W., Wu, Z., Coulson, A., Vaudin, M., Sulston, J. E., Durbin, R., Hubbard, T., Wooster, R., Dunham, I., Carter, N. P., McVean, G., Ross, M. T., Harrow, J., Olson, M. V., Beck, S., Rogers, J., and Bentley, D. R.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): S. G. Gregory (corresponding author) [1, 2]; K. F. Barlow [1]; K. E. McLay [1]; R. Kaul [3]; D. Swarbreck [1]; A. Dunham [1]; C. E. Scott [1]; K. [...]

Published
2006
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2. DNA sequence and analysis of human chromosome 9

Author

Humphray, S. J., Oliver, K., Hunt, A. R., Plumb, R. W., Loveland, J. E., Howe, K. L., Andrews, T. D., Searle, S., Hunt, S. E., Scott, C. E., Jones, M. C., Ainscough, R., Almeida, J. P., Ambrose, K. D., Ashwell, R. I. S., Babbage, A. K., Babbage, S., Bagguley, C. L., Bailey, J., Banerjee, R., Barker, D. J., Barlow, K. F., Bates, K., Beasley, H., Beasley, O., Bird, C. P., Bray-Allen, S., Brown, A. J., Brown, J. Y., Burford, D., Burrill, W., Burton, J., Carder, C., Carter, N. P., Chapman, J. C., Chen, Y., Clarke, G., Clark, S. Y., Clee, C. M., Clegg, S., Collier, R. E., Corby, N., Crosier, M., Cummings, A. T., Davies, J., Dhami, P., Dunn, M., Dutta, I., Dyer, L. W., Earthrowl, M. E., Faulkner, L., Fleming, C. J., Frankish, A., Frankland, J. A., French, L., Fricker, D. G., Garner, P., Garnett, J., Ghori, J., Gilbert, J. G. R., Glison, C., Grafham, D. V., Gribble, S., Griffiths, C., Griffiths-Jones, S., Grocock, R., Guy, J., Hall, R. E., Hammond, S., Harley, J. L., Harrison, E. S. I., Hart, E. A., Heath, P. D., Henderson, C. D., Hopkins, B. L., Howard, P. J., Howden, P. J., Huckle, E., Johnson, C., Johnson, D., Joy, A. A., Kay, M., Keenan, S., Kershaw, J. K., Kimberley, A. M., King, A., Knights, A., Laird, G. K., Langford, C., Lawlor, S., Leongamornlert, D. A., Leversha, M., Lloyd, C., Lloyd, D. M., Lovell, J., Martin, S., Mashreghi-Mohammadi, M., Matthews, L., McLaren, S., McLay, K. E., McMurray, A., Milne, S., Nickerson, T., Nisbett, J., Nordsiek, G., Pearce, A. V., Peck, A. I., Porter, K. M., Pandian, R., Pelan, S., Phillimore, B., Povey, S., Ramsey, Y., Rand, V., Scharfe, M., Sehra, H. K., Shownkeen, R., Sims, S. K., Skuce, C. D., Smith, M., Steward, C. A., Swarbreck, D., Sycamore, N., Tester, J., Thorpe, A., Tracey, A., Tromans, A., Thomas, D. W., Wall, M., Wallis, J. M., West, A. P., Whitehead, S. L., Willey, D. L., Williams, S. A., Wilming, L., Wray, P. W., Young, L., Ashurst, J. L., Coulson, A., Blocker, H., Durbin, R., Sulston, J. E., Hubbard, T., Jackson, M. J., Bentley, D. R., Beck, S., Rogers, J., and Dunham, I.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): S. J. Humphray (corresponding author) [1]; K. Oliver [1]; A. R. Hunt [1]; R. W. Plumb [1]; J. E. Loveland [1]; K. L. Howe [1]; T. D. Andrews [1]; [...]

Published
2004
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3. The DNA sequence and comparative analysis of human chromosome 10

Author

Deloukas, P., Earthrowl, M. E., Grafham, D. V., Rubenfield, M., French, L., Steward, C. A., Sims, S. K., Jones, M. C., Searle, S., Scott, C., Howe, K., Hunt, S. E., Andrews, T. D., Gilbert, J. G. R., Swarbreck, D., Ashurst, J. L., Taylor, A., Battles, J., Bird, C. P., Ainscough, R., Almeida, J. P., Ashwell, R. I. S., Ambrose, K. D., Babbage, A. K., Bagguley, C. L., Bailey, J., Banerjee, R., Bates, K., Beasley, H., Bray-Allen, S., Brown, A. J., Brown, J. Y., Burford, D. C., Burrill, W., Burton, J., Cahill, P., Camire, D., Carter, N. P., Chapman, J. C., Clark, S. Y., Clarke, G., Clee, C. M., Clegg, S., Corby, N., Coulson, A., Dhami, P., Dutta, I., Dunn, M., Faulkner, L., Frankish, A., Frankland, J. A., Garner, P., Garnett, J., Gribble, S., Griffiths, C., Grocock, R., Gustafson, E., Hammond, S., Harley, J. L., Hart, E., Heath, P. D., Ho, T. P., Hopkins, B., Horne, J., Howden, P. J., Huckle, E., Hynds, C., Johnson, C., Johnson, D., Kana, A., Kay, M., Kimberley, A. M., Kershaw, J. K., Kokkinaki, M., Laird, G. K., Lawlor, S., Lee, H. M., Leongamornlert, D. A., Laird, G., Lloyd, C., Lloyd, D. M., Loveland, J., Lovell, J., McLaren, S., McLay, K. E., McMurray, A., Mashreghi-Mohammadi, M., Matthews, L., Milne, S., Nickerson, T., Nguyen, M., Overton-Larty, E., Palmer, S. A., Pearce, A. V., Peck, A. I., Pelan, S., Phillimore, B., Porter, K., Rice, C. M., Rogosin, A., Ross, M. T., Sarafidou, T., Sehra, H. K., Shownkeen, R., Skuce, C. D., Smith, M., Standring, L., Sycamore, N., Tester, J., Thorpe, A., Torcasso, W., Tracey, A., Tromans, A., Tsolas, J., Wall, M., Walsh, J., Wang, H., Weinstock, K., West, A. P., Willey, D. L., Whitehead, S. L., Wilming, L., Wray, P. W., Young, L., Chen, Y., Lovering, R. C., Moschonas, N. K., Siebert, R., Fechtel, K., Bentley, D., Durbin, R., Hubbard, T., Doucette-Stamm, L., Beck, S., Smith, D. R., and Rogers, J.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): P. Deloukas (corresponding author) [1]; M. E. Earthrowl [1]; D. V. Grafham [1]; M. Rubenfield [2, 3]; L. French [1]; C. A. Steward [1]; S. K. Sims [1]; M. [...]

Published
2004
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4. NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease

Author

Schwerd, T., Bryant, R. V., Pandey, S., Capitani, M., Meran, L., Cazier, J. -B., Jung, J., Mondal, K., Parkes, M., Mathew, C. G., Fiedler, K., McCarthy, D. J., Sullivan, P. B., Rodrigues, A., Travis, S. P. L., Moore, C., Sambrook, J., Ouwehand, W. H., Roberts, D. J., Danesh, J., Russell, R. K., Wilson, D. C., Kelsen, J. R., Cornall, R., Denson, L. A., Kugathasan, S., Knaus, U. G., Serra, E. G., Anderson, C. A., Duerr, R. H., McGovern, D. P. B., Cho, J., Powrie, Fiona, Li, V. S. W., Muise, A. M., Uhlig, H. H., Donnelly, P., Bell, J., Bentley, D., McVean, G., Ratcliffe, P., Taylor, J., Wilkie, A. O. M., Broxholme, J., Buck, D., Gregory, L., Gregory, J., Lunter, G., Tomlinson, I., Allan, C., Attar, M., Green, A., Humphray, S., Kingsbury, Z., Lamble, S., Lonie, L., Pagnamenta, A., Piazza, P., Polanco, G., Trebes, A., Copley, R., Fiddy, S., Grocock, R., Hatton, E., Holmes, C., Hughes, L., Humburg, P., Kanapin, A., Lise, S., Martin, H., Murray, L., McCarthy, D., Rimmer, A., Sahgal, N., Wright, B., Yau, C., Arancibia, Carolina, Bailey, Adam, Barnes, Ellie, Bird-Lieberman, Beth, Brain, Oliver, Braden, Barbara, Collier, Jane, East, James, Geremia, Alessandra, Howarth, Lucy, Keshav, Satish, Klenerman, Paul, Leedham, Simon, Palmer, Rebecca, Rodrigues, Astor, Simmons, Alison, Sullivan, Peter B, Travis, Simon P L, Uhlig, Holm H, Heuschkel, Rob, Zilbauer, Matthias, Auth, Marcus K. H., Shah, Neil, Kammermeier, Jochen, Croft, Nick, Barakat, Farah, Russell, Richard K., Wilson, David C., Henderson, Paul, Braegger, Christian P., Posovszky, Carsten, Fyderek, Krzysztof, Wedrychowicz, Andrzej, Zurek, Marlen, Strisciuglio, Caterina, Elawad, Mamoun, Lo, Bernice, Parkes, Miles, Satsangi, Jack, Anderson, Carl A., Jostins, L., Kennedy, N. A., Lamb, C. A., Ahmad, T., Edwards, C., Hart, A., Hawkey, C., Mansfield, J. C., Mowat, C., Newman, W. G., Satsangi, J., Simmons, A., Tremelling, M., Lee, J. C., Prescott, N. J., Lees, C. W., Barrett, J. C., UK IBD Genetics Consortium, COLORS in IBD, Oxford IBD cohort study investigators, WGS500 Consortium, INTERVAL Study, Schwerd, T., Bryant, R. V., Pandey, S., Capitani, M., Meran, L., Cazier, J. -B., Jung, J., Mondal, K., Parkes, M., Mathew, C. G., Fiedler, K., Mccarthy, D. J., Sullivan, P. B., Rodrigues, A., Travis, S. P. L., Moore, C., Sambrook, J., Ouwehand, W. H., Roberts, D. J., Danesh, J., Russell, R. K., Wilson, D. C., Kelsen, J. R., Cornall, R., Denson, L. A., Kugathasan, S., Knaus, U. G., Serra, E. G., Anderson, C. A., Duerr, R. H., Mcgovern, D. P. B., Cho, J., Powrie, Fiona, Li, V. S. W., Muise, A. M., Uhlig, H. H., Donnelly, P., Bell, J., Bentley, D., Mcvean, G., Ratcliffe, P., Taylor, J., Wilkie, A. O. M., Broxholme, J., Buck, D., Gregory, L., Gregory, J., Lunter, G., Tomlinson, I., Allan, C., Attar, M., Green, A., Humphray, S., Kingsbury, Z., Lamble, S., Lonie, L., Pagnamenta, A., Piazza, P., Polanco, G., Trebes, A., Copley, R., Fiddy, S., Grocock, R., Hatton, E., Holmes, C., Hughes, L., Humburg, P., Kanapin, A., Lise, S., Martin, H., Murray, L., Mccarthy, D., Rimmer, A., Sahgal, N., Wright, B., Yau, C., Arancibia, Carolina, Bailey, Adam, Barnes, Ellie, Bird-Lieberman, Beth, Brain, Oliver, Braden, Barbara, Collier, Jane, East, Jame, Geremia, Alessandra, Howarth, Lucy, Keshav, Satish, Klenerman, Paul, Leedham, Simon, Palmer, Rebecca, Rodrigues, Astor, Simmons, Alison, Sullivan, Peter B, Travis, Simon P L, Uhlig, Holm H, Heuschkel, Rob, Zilbauer, Matthia, Auth, Marcus K. H., Shah, Neil, Kammermeier, Jochen, Croft, Nick, Barakat, Farah, Russell, Richard K., Wilson, David C., Henderson, Paul, Braegger, Christian P., Posovszky, Carsten, Fyderek, Krzysztof, Wedrychowicz, Andrzej, Zurek, Marlen, Strisciuglio, Caterina, Elawad, Mamoun, Lo, Bernice, Parkes, Mile, Satsangi, Jack, Anderson, Carl A., Jostins, L., Kennedy, N. A., Lamb, C. A., Ahmad, T., Edwards, C., Hart, A., Hawkey, C., Mansfield, J. C., Mowat, C., Newman, W. G., Satsangi, J., Simmons, A., Tremelling, M., Lee, J. C., Prescott, N. J., Lees, C. W., Barrett, J. C., UK IBD Genetics, Consortium, COLORS in, Ibd, Oxford IBD cohort study, Investigator, Wgs500, Consortium, and Interval, Study

Subjects
Male, Genotype, Colon, Immunology, Mutation, Missense, Genetic Association Studie, Polymorphism, Single Nucleotide, Article, Mice, Animals, Humans, Immunology and Allergy, Genetic Predisposition to Disease, Child, Genetic Association Studies, Genes, Modifier, Genome, Animal, Inflammatory Bowel Disease, High-Throughput Nucleotide Sequencing, Inflammatory Bowel Diseases, digestive system diseases, Host-Pathogen Interaction, Mice, Inbred C57BL, Child, Preschool, Host-Pathogen Interactions, NADPH Oxidase 1, Reactive Oxygen Species, Reactive Oxygen Specie, Human
Abstract

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes.

Published
2018

5. The relevance of alcohol to dental practice

Author

Grocock R

Subjects
Dental practice, medicine.medical_specialty, Alcohol Drinking, MEDLINE, Alcohol, Oral Health, Oral health, Dental Caries, chemistry.chemical_compound, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Periodontal disease, Oral and maxillofacial pathology, medicine, Relevance (law), Humans, 030212 general & internal medicine, General Dentistry, Periodontal Diseases, business.industry, Halitosis, 030206 dentistry, General Medicine, medicine.disease, stomatognathic diseases, chemistry, Tooth wear, 030220 oncology & carcinogenesis, Family medicine, Tooth Wear, business
Abstract

Alcohol is a very widely used drug which can cause dental disease and influence dental treatment. It is therefore important that dental professionals take an alcohol history from all patients and are aware of how to give alcohol reduction advice. This article discusses the impact of alcohol on oral health, including oral cancer, trauma, halitosis, tooth wear, periodontal disease and caries, with reference to the available literature. It also outlines current alcohol risk level advice and guidance regarding giving alcohol reduction advice in a dental setting.

Published
2018
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6. Human genomic regions with exceptionally high levels of population differentiation identified from 911 whole-genome sequences

Author

Colonna, V, Ayub, Q, Chen, Y, Pagani, L, Luisi, P, Pybus, M, Garrison, E, Xue, Y, Tyler-Smith, C, Abecasis, GR, Auton, A, Brooks, LD, Depristo, MA, Durbin, RM, Handsaker, RE, Kang, HM, Marth, GT, McVean, G, Altshuler, DM, Bentley, DR, Chakravarti, A, Clark, AG, Donnelly, P, Eichler, EE, Flicek, P, Gabriel, SB, Gibbs, RA, Green, ED, Hurles, ME, Knoppers, BM, Korbel, JO, Lander, ES, Lee, C, Lehrach, H, Mardis, ER, McVean, GA, Nickerson, DA, Schmidt, JP, Sherry, ST, Wang, J, Wilson, RK, Dinh, H, Kovar, C, Lee, S, Lewis, L, Muzny, D, Reid, J, Wang, M, Fang, X, Guo, X, Jian, M, Jiang, H, Jin, X, Li, G, Li, J, Li, Y, Li, Z, Liu, X, Lu, Y, Ma, X, Su, Z, Tai, S, Tang, M, Wang, B, Wang, G, Wu, H, Wu, R, Yin, Y, Zhang, W, Zhao, J, Zhao, M, Zheng, X, Zhou, Y, Gupta, N, Clarke, L, Leinonen, R, Smith, RE, Zheng-Bradley, X, Grocock, R, Humphray, S, James, T, Kingsbury, Z, Sudbrak, R, Albrecht, MW, Amstislavskiy, VS, Borodina, TA, Lienhard, M, Mertes, F, Sultan, M, Timmermann, B, Yaspo, ML, Fulton, L, Fulton, R, Weinstock, GM, Balasubramaniam, S, Burton, J, Danecek, P, Keane, TM, Kolb-Kokocinski, A, McCarthy, S, Molecular Dynamics, Biomimetics, Urban and Regional Studies Institute, Nanomedicine & Drug Targeting, Artificial Intelligence, Micromechanics, Molecular Cell Biology, Van Swinderen Institute for Particle Physics and G, Archaeology of Northwestern Europe, Polymer Chemistry and Bioengineering, Christianity and the History of Ideas, Scientific Visualization and Computer Graphics, Chemical Technology, Macromolecular Chemistry & New Polymeric Materials, Bernoulli Institute, Surfaces and Thin Films, Hemelrijk group, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Falcao Salles lab, Synthetic Organic Chemistry, Psychometrics and Statistics, Bio-inspired systems and circuits, Advanced Production Engineering, Drug Design, The 1000 Genomes Project Consortium, Faculteit Medische Wetenschappen/UMCG, Wellcome Trust, Consiglio Nazionale delle Ricerche, EMBO, and 1000 Genomes Project Consortium

Subjects
Historia y Arqueología, lactase persistence, POSITIVE SELECTION, BALANCING SELECTION, SOFT SWEEP, Biología, standing variation, Population, Biology, Balancing selection, Genome, Polymorphism, Single Nucleotide, Genètica de poblacions humanes, Ciencias Biológicas, purl.org/becyt/ford/1 [https], selective sweep, functional annotation cluster, Genética y Herencia, HUMANIDADES, Genetic drift, Gene Frequency, INDEL Mutation, Humans, Selection, Genetic, education, purl.org/becyt/ford/1.6 [https], Selection (genetic algorithm), education.field_of_study, purl.org/becyt/ford/6 [https], Genome, Human, Research, Genetic Drift, Levenshtein distance, Selecció natural, Sequence Analysis, DNA, Human genetics, Otras Historia y Arqueología, Evolutionary biology, Human genome, purl.org/becyt/ford/6.1 [https], Selective sweep, Genètica humana -- Variació, CIENCIAS NATURALES Y EXACTAS
Abstract

It contains associated material.-- The 1000 Genomes Project Consortium, [Background] Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes., [Results] We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively., [Conclusions] We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research. © 2014 Colonna et al., This work was supported by The Wellcome Trust (098051), an Italian National Research Council (CNR) short-term mobility fellowship from the 2013 program to VC, and an EMBO Short Term Fellowship ASTF 324–2010 to VC.

Published
2014
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7. Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

Author

Delaneau O., Marchini J., McVeanh G.A., Donnelly P., Lunter G., Marchini J.L., Myers, S., Gupta-Hinch, A., Iqbal, Z., Mathieson I., Rimmer, A., Xifara, D.K., Kerasidou, A., Churchhouse, C., Altshuler, D.M., Gabriel, S.B., Lander, E.S., Gupta, N., Daly, M.J., DePristo, M.A., Banks, E., Bhatia G., Carneiro, M.O., Del Angel G., Genovese G., Handsaker, R.E., Hartl, C., McCarroll, S.A., Nemesh J.C., Poplin, R.E., Schaffner, S.F., Shakir, K., Sabeti P.C., Grossman, S.R., Tabrizi, S., Tariyal, R., Li H., Reich, D., Durbin, R.M., Hurles, M.E., Balasubramaniam, S., Burton J., Danecek P., Keane, T.M., Kolb-Kokocinski, A., McCarthy, S., Stalker J., Quail, M., Ayub Q., Chen, Y., Coffey, A.J., Colonna V., Huang, N., Jostins L., Scally, A., Walter, K., Xue, Y., Zhang, Y., Blackburne, B., Lindsay, S.J., Ning, Z., Frankish, A., Harrow J., Chris, T.-S., Abecasis G.R., Kang H.M., Anderson P., Blackwell, T., Busonero F., Fuchsberger, C., Jun G., Maschio, A., Porcu, E., Sidore, C., Tan, A., Trost, M.K., Bentley, D.R., Grocock, R., Humphray, S., James, T., Kingsbury, Z., Bauer, M., Cheetham, R.K., Cox, T., Eberle, M., Murray L., Shaw, R., Chakravarti, A., Clark, A.G., Keinan, A., Rodriguez-Flores J.L., De LaVega F.M., Degenhardt J., Eichler, E.E., Flicek P., Clarke L., Leinonen, R., Smith, R.E., Zheng-Bradley X., Beal, K., Cunningham F., Herrero J., McLaren W.M., Ritchie G.R.S., Barker J., Kelman G., Kulesha, E., Radhakrishnan, R., Roa, A., Smirnov, D., Streeter I., Toneva I., Gibbs, R.A., Dinh H., Kovar, C., Lee, S., Lewis L., Muzny, D., Reid J., Wang, M., Yu F., Bainbridge, M., Challis, D., Evani, U.S., Lu J., Nagaswamy, U., Sabo, A., Wang, Y., Yu J., Fowler G., Hale W., Kalra, D., Green, E.D., Knoppers, B.M., Korbel J.O., Rausch, T., Sttz, A.M., Lee, C., Griffin L., Hsieh, C.-H., Mills, R.E., Von Grotthuss, M., Zhang, C., Shi X., Lehrach H., Sudbrak, R., Amstislavskiy V.S., Lienhard, M., Mertes F., Sultan, M., Timmermann, B., Yaspo, M.L., Herwig, S.R., Mardis, E.R., Wilson, R.K., Fulton L., Fulton, R., Weinstock G.M., Chinwalla, A., Ding L., Dooling, D., Koboldt, D.C., McLellan, M.D., Wallis J.W., Wendl, M.C., Zhang Q., Marth G.T., Garrison, E.P., Kural, D., Lee W.-P., Leong W.F., Ward, A.N., Wu J., Zhang, M., Nickerson, D.A., Alkan, C., Hormozdiari F., Ko, A., Sudmant P.H., Schmidt J.P., Davies, C.J., Gollub J., Webster, T., Wong, B., Zhan, Y., Sherry, S.T., Xiao, C., Church, D., Ananiev V., Belaia, Z., Beloslyudtsev, D., Bouk, N., Chen, C., Cohen, R., Cook, C., Garner J., Hefferon, T., Kimelman, M., Liu, C., Lopez J., Meric P., Ostapchuk, Y., Phan L., Ponomarov, S., Schneider V., Shekhtman, E., Sirotkin, K., Slotta, D., Zhang H., Wang J., Fang X., Guo X., Jian, M., Jiang H., Jin X., Li G., Li J., Li, Y., Liu X., Lu, Y., Ma X., Tai, S., Tang, M., Wang, B., Wang G., Wu H., Wu, R., Yin, Y., Zhang W., Zhao J., Zhao, M., Zheng X., Lachlan H., Fang L., Li Q., Li, Z., Lin H., Liu, B., Luo, R., Shao H., Xie, Y., Ye, C., Yu, C., Zheng H., Zhu H., Cai H., Cao H., Su, Y., Tian, Z., Yang H., Yang L., Zhu J., Cai, Z., Albrecht, M.W., Borodina, T.A., Auton, A., Yoon, S.C., Lihm J., Makarov V., Jin H., Kim W., Kim, K.C., Gottipati, S., Jones, D., Cooper, D.N., Ball, E.V., Stenson P.D., Barnes, B., Kahn, S., Ye, K., Batzer, M.A., Konkel, M.K., Walker J.A., MacArthur, D.G., Lek, M., Shriver, M.D., Bustamante, C.D., Gravel, S., Kenny, E.E., Kidd J.M., Lacroute P., Maples, B.K., Moreno-Estrada, A., Zakharia F., Henn, B., Sandoval, K., Byrnes J.K., Halperin, E., Baran, Y., Craig, D.W., Christoforides, A., Izatt, T., Kurdoglu, A.A., Sinari, S.A., Homer, N., Squire, K., Sebat J., Bafna V., Burchard, E.G., Hernandez, R.D., Gignoux, C.R., Haussler, D., Katzman, S.J., Kent W.J., Howie, B., Ruiz-Linares, A., Dermitzakis, E.T., Lappalainen, T., Devine, S.E., Maroo, A., Tallon L.J., Rosenfeld J.A., Michelson L.P., Angius, A., Cucca F., Sanna, S., Bigham, A., Jones, C., Reinier F., Lyons, R., Schlessinger, D., Awadalla P., Hodgkinson, A., Oleksyk, T.K., Martinez-Cruzado J.C., Fu, Y., Xiong, M., Jorde L., Witherspoon, D., Xing J., Browning, B.L., Hajirasouliha I., Chen, K., Albers, C.A., Gerstein, M.B., Abyzov, A., Chen J., Habegger L., Harmanci, A.O., Mu X.J., Sisu, C., Balasubramanian, S., Jin, M., Khurana, E., Clarke, D., Michaelson J.J., OSullivan, C., Barnes, K.C., Gharani, N., Toji L.H., Gerry, N., Kaye J.S., Kent, A., Mathias, R., Ossorio P.N., Parker, M., Rotimi, C.N., Royal, C.D., Tishkoff, S., Via, M., Bodmer W., Bedoya G., Yang G., You, C.J., Garcia-Montero, A., Orfao, A., Dutil J., Brooks L.D., Felsenfeld, A.L., McEwen J.E., Clemm, N.C., Guyer, M.S., Peterson J.L., Duncanson, A., Dunn, M., Peltonen L., and 1000 Genomes Project Consortium

Subjects
haplotype, genetic association, genotype, General Physics and Astronomy, Genome-wide association study, genetic analysis, gene sequence, Biology, gene frequency, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, polymorphism, Gene Frequency, single nucleotide polymorphism, Humans, chromosome, human, 1000 Genomes Project, indel mutation, genome, Alleles, Genetic association, Genetics, Whole genome sequencing, Multidisciplinary, accuracy, Genome, Human, Haplotype, allele, article, reference database, General Chemistry, Microarray Analysis, chromosome 20, Haplotypes, Human genome, microarray analysis, Imputation (genetics), Algorithms, SNP array, Genome-Wide Association Study
Abstract

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved.

Published
2014
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8. An integrated map of genetic variation from 1,092 human genomes

Author

Altshuler, DM, Durbin, RM, Abecasis, GR, Bentley, DR, Chakravarti, A, Clark, AG, Donnelly, P, Eichler, EE, Flicek, P, Gabriel, SB, Gibbs, RA, Green, ED, Hurles, ME, Knoppers, BM, Korbel, JO, Lander, ES, Lee, C, Lehrach, H, Mardis, ER, Marth, GT, McVean, GA, Nickerson, DA, Schmidt, JP, Sherry, ST, Wang, J, Wilson, RK, Dinh, H, Kovar, C, Lee, S, Lewis, L, Muzny, D, Reid, J, Wang, M, Fang, X, Guo, X, Jian, M, Jiang, H, Jin, X, Li, G, Li, J, Li, Y, Li, Z, Liu, X, Lu, Y, Ma, X, Su, Z, Tai, S, Tang, M, Wang, B, Wang, G, Wu, H, Wu, R, Yin, Y, Zhang, W, Zhao, J, Zhao, M, Zheng, X, Zhou, Y, Gupta, N, Clarke, L, Leinonen, R, Smith, RE, Zheng-Bradley, X, Grocock, R, Humphray, S, James, T, Kingsbury, Z, Sudbrak, R, Albrecht, MW, Amstislavskiy, VS, Borodina, TA, Lienhard, M, Mertes, F, Sultan, M, Timmermann, B, Yaspo, M-L, Fulton, L, Fulton, R, Weinstock, GM, Balasubramaniam, S, Burton, J, Danecek, P, Keane, TM, Kolb-Kokocinski, A, McCarthy, S, Stalker, J, Quail, M, Davies, CJ, Gollub, J, Webster, T, Wong, B, Zhan, Y, Auton, A, Yu, F, Bainbridge, M, Challis, D, Evani, US, Lu, J, Nagaswamy, U, Sabo, A, Wang, Y, Yu, J, Coin, LJM, Fang, L, Li, Q, Lin, H, Liu, B, Luo, R, Qin, N, Shao, H, Xie, Y, Ye, C, Yu, C, Zhang, F, Zheng, H, Zhu, H, Garrison, EP, Kural, D, Lee, W-P, Leong, WF, Ward, AN, Wu, J, Zhang, M, Griffin, L, Hsieh, C-H, Mills, RE, Shi, X, Von Grotthuss, M, Zhang, C, Daly, MJ, DePristo, MA, Banks, E, Bhatia, G, Carneiro, MO, Del Angel, G, Genovese, G, Handsaker, RE, Hartl, C, McCarroll, SA, Nemesh, JC, Poplin, RE, Schaffner, SF, Shakir, K, Yoon, SC, Lihm, J, Makarov, V, Jin, H, Kim, W, Kim, KC, Rausch, T, Beal, K, Cunningham, F, Herrero, J, McLaren, WM, Ritchie, GRS, Gottipati, S, Keinan, A, Rodriguez-Flores, JL, Sabeti, PC, Grossman, SR, Tabrizi, S, Tariyal, R, Cooper, DN, Ball, EV, Stenson, PD, Barnes, B, Bauer, M, Cheetham, RK, Cox, T, Eberle, M, Kahn, S, Murray, L, Peden, J, Shaw, R, Ye, K, Batzer, MA, Konkel, MK, Walker, JA, MacArthur, DG, Lek, M, Herwig, R, Shriver, MD, Bustamante, CD, Byrnes, JK, De la Vega, FM, Gravel, S, Kenny, EE, Kidd, JM, Lacroute, P, Maples, BK, Moreno-Estrada, A, Zakharia, F, Halperin, E, Baran, Y, Craig, DW, Christoforides, A, Homer, N, Izatt, T, Kurdoglu, AA, Sinari, SA, Squire, K, Xiao, C, Sebat, J, Bafna, V, Burchard, EG, Hernandez, RD, Gignoux, CR, Haussler, D, Katzman, SJ, Kent, WJ, Howie, B, Ruiz-Linares, A, Dermitzakis, ET, Lappalainen, T, Devine, SE, Maroo, A, Tallon, LJ, Rosenfeld, JA, Michelson, LP, Kang, HM, Anderson, P, Angius, A, Bigham, A, Blackwell, T, Busonero, F, Cucca, F, Fuchsberger, C, Jones, C, Jun, G, Lyons, R, Maschio, A, Porcu, E, Reinier, F, Sanna, S, Schlessinger, D, Sidore, C, Tan, A, Trost, MK, Awadalla, P, Hodgkinson, A, Lunter, G, Marchini, JL, Myers, S, Churchhouse, C, Delaneau, O, Gupta-Hinch, A, Iqbal, Z, Mathieson, I, Rimmer, A, Xifara, DK, Oleksyk, TK, Fu, Y, Xiong, M, Jorde, L, Witherspoon, D, Xing, J, Browning, BL, Alkan, C, Hajirasouliha, I, Hormozdiari, F, Ko, A, Sudmant, PH, Chen, K, Chinwalla, A, Ding, L, Dooling, D, Koboldt, DC, McLellan, MD, Wallis, JW, Wendl, MC, Zhang, Q, Tyler-Smith, C, Albers, CA, Ayub, Q, Chen, Y, Coffey, AJ, Colonna, V, Huang, N, Jostins, L, Li, H, Scally, A, Walter, K, Xue, Y, Zhang, Y, Gerstein, MB, Abyzov, A, Balasubramanian, S, Chen, J, Clarke, D, Habegger, L, Harmanci, AO, Jin, M, Khurana, E, Mu, XJ, Sisu, C, Degenhardt, J, Stuetz, AM, Church, D, Michaelson, JJ, Ben, B, Lindsay, SJ, Ning, Z, Frankish, A, Harrow, J, Fowler, G, Hale, W, Kalra, D, Barker, J, Kelman, G, Kulesha, E, Radhakrishnan, R, Roa, A, Smirnov, D, Streeter, I, Toneva, I, Vaughan, B, Ananiev, V, Belaia, Z, Beloslyudtsev, D, Bouk, N, Chen, C, Cohen, R, Cook, C, Garner, J, Hefferon, T, Kimelman, M, Liu, C, Lopez, J, Meric, P, O'Sullivan, C, Ostapchuk, Y, Phan, L, Ponomarov, S, Schneider, V, Shekhtman, E, Sirotkin, K, Slotta, D, Zhang, H, Barnes, KC, Beiswanger, C, Cai, H, Cao, H, Gharani, N, Henn, B, Jones, D, Kaye, JS, Kent, A, Kerasidou, A, Mathias, R, Ossorio, PN, Parker, M, Reich, D, Rotimi, CN, Royal, CD, Sandoval, K, Su, Y, Tian, Z, Tishkoff, S, Toji, LH, Via, M, Yang, H, Yang, L, Zhu, J, Bodmer, W, Bedoya, G, Ming, CZ, Yang, G, You, CJ, Peltonen, L, Garcia-Montero, A, Orfao, A, Dutil, J, Martinez-Cruzado, JC, Brooks, LD, Felsenfeld, AL, McEwen, JE, Clemm, NC, Duncanson, A, Dunn, M, Guyer, MS, Peterson, JL, 1000 Genomes Project Consortium, Dermitzakis, Emmanouil, Universitat de Barcelona, Massachusetts Institute of Technology. Department of Biology, Altshuler, David, and Lander, Eric S.

Subjects
Natural selection, LOCI, Genome-wide association study, Evolutionary biology, Continental Population Groups/genetics, Human genetic variation, VARIANTS, Genoma humà, Binding Sites/genetics, 0302 clinical medicine, RARE, Sequence Deletion/genetics, WIDE ASSOCIATION, ddc:576.5, Copy-number variation, MUTATION, Exome sequencing, transcription factor, Conserved Sequence, Human evolution, Sequence Deletion, Genetics, RISK, 0303 health sciences, Multidisciplinary, Continental Population Groups, 1000 Genomes Project Consortium, Genetic analysis, Genomics, Polymorphism, Single Nucleotide/genetics, Research Highlight, 3. Good health, Algorithm, Multidisciplinary Sciences, Genetic Variation/genetics, Map, Science & Technology - Other Topics, Conserved Sequence/genetics, Integrated approach, General Science & Technology, Genetics, Medical, Haplotypes/genetics, Biology, Polymorphism, Single Nucleotide, Evolution, Molecular, 03 medical and health sciences, Genetic variation, Humans, Transcription Factors/metabolism, POPULATION-STRUCTURE, 1000 Genomes Project, Polymorphism, Nucleotide Motifs, Alleles, 030304 developmental biology, COPY NUMBER VARIATION, Science & Technology, Binding Sites, Human genome, Genome, Human, Racial Groups, Genetic Variation, Genetics, Population, Haplotypes, Genome, Human/genetics, untranslated RNA, 030217 neurology & neurosurgery, Transcription Factors, Genome-Wide Association Study
Abstract

By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations., National Institutes of Health (U.S.) (Grant RC2HL102925), National Institutes of Health (U.S.) (Grant U54HG3067)

Published
2012

9. Erratum: The DNA sequence and biological annotation of human chromosome 1

Author

Gregory, S. G., primary, Barlow, K. F., additional, McLay, K. E., additional, Kaul, R., additional, Swarbreck, D., additional, Dunham, A., additional, Scott, C. E., additional, Howe, K. L., additional, Woodfine, K., additional, Spencer, C. C. A., additional, Jones, M. C., additional, Gillson, C., additional, Searle, S., additional, Zhou, Y., additional, Kokocinski, F., additional, McDonald, L., additional, Evans, R., additional, Phillips, K., additional, Atkinson, A., additional, Cooper, R., additional, Jones, C., additional, Hall, R. E., additional, Andrews, T. D., additional, Lloyd, C., additional, Ainscough, R., additional, Almeida, J. P., additional, Ambrose, K. D., additional, Anderson, F., additional, Andrew, R. W., additional, Ashwell, R. I. S., additional, Aubin, K., additional, Babbage, A. K., additional, Bagguley, C. L., additional, Bailey, J., additional, Banerjee, R., additional, Beasley, H., additional, Bethel, G., additional, Bird, C. P., additional, Bray-Allen, S., additional, Brown, J. Y., additional, Brown, A. J., additional, Bryant, S. P., additional, Buckley, D., additional, Burford, D. C., additional, Burrill, W. D. H., additional, Burton, J., additional, Bye, J., additional, Carder, C., additional, Chapman, J. C., additional, Clark, S. Y., additional, Clarke, G., additional, Clee, C., additional, Clegg, S. M., additional, Cobley, V., additional, Collier, R. E., additional, Corby, N., additional, Coville, G. J., additional, Davies, J., additional, Deadman, R., additional, Dhami, P., additional, Dovey, O., additional, Dunn, M., additional, Earthrowl, M., additional, Ellington, A. G., additional, Errington, H., additional, Faulkner, L. M., additional, Frankish, A., additional, Frankland, J., additional, French, L., additional, Garner, P., additional, Garnett, J., additional, Gay, L., additional, Ghori, M. R. J., additional, Gibson, R., additional, Gilby, L. M., additional, Gillett, W., additional, Glithero, R. J., additional, Grafham, D. V., additional, Gribble, S. M., additional, Griffiths, C., additional, Griffiths-Jones, S., additional, Grocock, R., additional, Hammond, S., additional, Harrison, E. S. I., additional, Hart, E., additional, Haugen, E., additional, Heath, P. D., additional, Holmes, S., additional, Holt, K., additional, Howden, P. J., additional, Hunt, A. R., additional, Hunt, S. E., additional, Hunter, G., additional, Isherwood, J., additional, James, R., additional, Johnson, C., additional, Johnson, D., additional, Joy, A., additional, Kay, M., additional, Kershaw, J. K., additional, Kibukawa, M., additional, Kimberley, A. M., additional, King, A., additional, Knights, A. J., additional, Lad, H., additional, Laird, G., additional, Langford, C. F., additional, Lawlor, S., additional, Leongamornlert, D. A., additional, Lloyd, D. M., additional, Loveland, J., additional, Lovell, J., additional, Lush, M. J., additional, Lyne, R., additional, Martin, S., additional, Mashreghi-Mohammadi, M., additional, Matthews, L., additional, Matthews, N. S. W., additional, McLaren, S., additional, Milne, S., additional, Mistry, S., additional, oore, M. J. F. M., additional, Nickerson, T., additional, O'Dell, C. N., additional, Oliver, K., additional, Palmeiri, A., additional, Palmer, S. A., additional, Pandian, R. D., additional, Parker, A., additional, Patel, D., additional, Pearce, A. V., additional, Peck, A. I., additional, Pelan, S., additional, Phelps, K., additional, Phillimore, B. J., additional, Plumb, R., additional, Porter, K. M., additional, Prigmore, E., additional, Rajan, J., additional, Raymond, C., additional, Rouse, G., additional, Saenphimmachak, C., additional, Sehra, H. K., additional, Sheridan, E., additional, Shownkeen, R., additional, Sims, S., additional, Skuce, C. D., additional, Smith, M., additional, Steward, C., additional, Subramanian, S., additional, Sycamore, N., additional, Tracey, A., additional, Tromans, A., additional, Van Helmond, Z., additional, Wall J. M. Wallis, M., additional, White, S., additional, Whitehead, S. L., additional, Wilkinson, J. E., additional, Willey, D. L., additional, Williams, H., additional, Wilming, L., additional, Wray, P. W., additional, Wu, Z., additional, Coulson, A., additional, Vaudin, M., additional, Sulston, J. E., additional, Durbin, R., additional, Hubbard, T., additional, Wooster, R., additional, Dunham, I., additional, Carter, N. P., additional, McVean, G., additional, Ross, M. T., additional, Harrow, J., additional, Olson, M. V., additional, Beck, S., additional, Rogers, J., additional, and Bentley, D. R., additional

Published
2006
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10. APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma.

Author

Leonard B, Hart SN, Burns MB, Carpenter MA, Temiz NA, Rathore A, Vogel RI, Nikas JB, Law EK, Brown WL, Li Y, Zhang Y, Maurer MJ, Oberg AL, Cunningham JM, Shridhar V, Bell DA, April C, Bentley D, Bibikova M, Cheetham RK, Fan JB, Grocock R, Humphray S, Kingsbury Z, Peden J, Chien J, Swisher EM, Hartmann LC, Kalli KR, Goode EL, Sicotte H, Kaufmann SH, and Harris RS

Subjects
Carcinoma, Ovarian Epithelial, Cell Line, Tumor, Cystadenocarcinoma, Serous enzymology, Cystadenocarcinoma, Serous pathology, Cytidine Deaminase biosynthesis, Cytidine Deaminase metabolism, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Genomics, Humans, Minor Histocompatibility Antigens, Neoplasms, Glandular and Epithelial enzymology, Neoplasms, Glandular and Epithelial pathology, Ovarian Neoplasms enzymology, Ovarian Neoplasms pathology, RNA, Messenger genetics, RNA, Messenger metabolism, Up-Regulation, Cystadenocarcinoma, Serous genetics, Cytidine Deaminase genetics, Mutation, Neoplasms, Glandular and Epithelial genetics, Ovarian Neoplasms genetics
Abstract

Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 5'-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 5'-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA "repair" enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability., (©2013 AACR.)

Published
2013
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11. Monitoring chronic lymphocytic leukemia progression by whole genome sequencing reveals heterogeneous clonal evolution patterns.

Author

Schuh A, Becq J, Humphray S, Alexa A, Burns A, Clifford R, Feller SM, Grocock R, Henderson S, Khrebtukova I, Kingsbury Z, Luo S, McBride D, Murray L, Menju T, Timbs A, Ross M, Taylor J, and Bentley D

Subjects
Alleles, Cell Transformation, Neoplastic genetics, Clonal Deletion, Clone Cells, DNA Mutational Analysis, Disease Progression, Evolution, Molecular, Gene Frequency, Humans, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Leukemia, Lymphocytic, Chronic, B-Cell physiopathology, Neoplasm Proteins genetics, Selection, Genetic, DNA, Neoplasm genetics, Genome-Wide Association Study, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Mutation, Sequence Analysis, DNA
Abstract

Chronic lymphocytic leukemia is characterized by relapse after treatment and chemotherapy resistance. Similarly, in other malignancies leukemia cells accumulate mutations during growth, forming heterogeneous cell populations that are subject to Darwinian selection and may respond differentially to treatment. There is therefore a clinical need to monitor changes in the subclonal composition of cancers during disease progression. Here, we use whole-genome sequencing to track subclonal heterogeneity in 3 chronic lymphocytic leukemia patients subjected to repeated cycles of therapy. We reveal different somatic mutation profiles in each patient and use these to establish probable hierarchical patterns of subclonal evolution, to identify subclones that decline or expand over time, and to detect founder mutations. We show that clonal evolution patterns are heterogeneous in individual patients. We conclude that genome sequencing is a powerful and sensitive approach to monitor disease progression repeatedly at the molecular level. If applied to future clinical trials, this approach might eventually influence treatment strategies as a tool to individualize and direct cancer treatment.

Published
2012
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12. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

Author

Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, and Nusbaum C

Subjects
Animals, Base Composition, Gene Duplication, Humans, Long Interspersed Nucleotide Elements genetics, Mice, Sequence Analysis, DNA, Short Interspersed Nucleotide Elements genetics, Synteny genetics, Chromosomes, Human, Pair 17 genetics, Evolution, Molecular
Abstract

Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.

Published
2006
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13. The DNA sequence of the human X chromosome.

Author

Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP, Frankish A, Lovell FL, Howe KL, Ashurst JL, Fulton RS, Sudbrak R, Wen G, Jones MC, Hurles ME, Andrews TD, Scott CE, Searle S, Ramser J, Whittaker A, Deadman R, Carter NP, Hunt SE, Chen R, Cree A, Gunaratne P, Havlak P, Hodgson A, Metzker ML, Richards S, Scott G, Steffen D, Sodergren E, Wheeler DA, Worley KC, Ainscough R, Ambrose KD, Ansari-Lari MA, Aradhya S, Ashwell RI, Babbage AK, Bagguley CL, Ballabio A, Banerjee R, Barker GE, Barlow KF, Barrett IP, Bates KN, Beare DM, Beasley H, Beasley O, Beck A, Bethel G, Blechschmidt K, Brady N, Bray-Allen S, Bridgeman AM, Brown AJ, Brown MJ, Bonnin D, Bruford EA, Buhay C, Burch P, Burford D, Burgess J, Burrill W, Burton J, Bye JM, Carder C, Carrel L, Chako J, Chapman JC, Chavez D, Chen E, Chen G, Chen Y, Chen Z, Chinault C, Ciccodicola A, Clark SY, Clarke G, Clee CM, Clegg S, Clerc-Blankenburg K, Clifford K, Cobley V, Cole CG, Conquer JS, Corby N, Connor RE, David R, Davies J, Davis C, Davis J, Delgado O, Deshazo D, Dhami P, Ding Y, Dinh H, Dodsworth S, Draper H, Dugan-Rocha S, Dunham A, Dunn M, Durbin KJ, Dutta I, Eades T, Ellwood M, Emery-Cohen A, Errington H, Evans KL, Faulkner L, Francis F, Frankland J, Fraser AE, Galgoczy P, Gilbert J, Gill R, Glöckner G, Gregory SG, Gribble S, Griffiths C, Grocock R, Gu Y, Gwilliam R, Hamilton C, Hart EA, Hawes A, Heath PD, Heitmann K, Hennig S, Hernandez J, Hinzmann B, Ho S, Hoffs M, Howden PJ, Huckle EJ, Hume J, Hunt PJ, Hunt AR, Isherwood J, Jacob L, Johnson D, Jones S, de Jong PJ, Joseph SS, Keenan S, Kelly S, Kershaw JK, Khan Z, Kioschis P, Klages S, Knights AJ, Kosiura A, Kovar-Smith C, Laird GK, Langford C, Lawlor S, Leversha M, Lewis L, Liu W, Lloyd C, Lloyd DM, Loulseged H, Loveland JE, Lovell JD, Lozado R, Lu J, Lyne R, Ma J, Maheshwari M, Matthews LH, McDowall J, McLaren S, McMurray A, Meidl P, Meitinger T, Milne S, Miner G, Mistry SL, Morgan M, Morris S, Müller I, Mullikin JC, Nguyen N, Nordsiek G, Nyakatura G, O'Dell CN, Okwuonu G, Palmer S, Pandian R, Parker D, Parrish J, Pasternak S, Patel D, Pearce AV, Pearson DM, Pelan SE, Perez L, Porter KM, Ramsey Y, Reichwald K, Rhodes S, Ridler KA, Schlessinger D, Schueler MG, Sehra HK, Shaw-Smith C, Shen H, Sheridan EM, Shownkeen R, Skuce CD, Smith ML, Sotheran EC, Steingruber HE, Steward CA, Storey R, Swann RM, Swarbreck D, Tabor PE, Taudien S, Taylor T, Teague B, Thomas K, Thorpe A, Timms K, Tracey A, Trevanion S, Tromans AC, d'Urso M, Verduzco D, Villasana D, Waldron L, Wall M, Wang Q, Warren J, Warry GL, Wei X, West A, Whitehead SL, Whiteley MN, Wilkinson JE, Willey DL, Williams G, Williams L, Williamson A, Williamson H, Wilming L, Woodmansey RL, Wray PW, Yen J, Zhang J, Zhou J, Zoghbi H, Zorilla S, Buck D, Reinhardt R, Poustka A, Rosenthal A, Lehrach H, Meindl A, Minx PJ, Hillier LW, Willard HF, Wilson RK, Waterston RH, Rice CM, Vaudin M, Coulson A, Nelson DL, Weinstock G, Sulston JE, Durbin R, Hubbard T, Gibbs RA, Beck S, Rogers J, and Bentley DR

Subjects
Animals, Antigens, Neoplasm genetics, Centromere genetics, Chromosomes, Human, Y genetics, Contig Mapping, Crossing Over, Genetic genetics, Dosage Compensation, Genetic, Female, Genetic Linkage genetics, Genetics, Medical, Humans, Male, Polymorphism, Single Nucleotide genetics, RNA genetics, Repetitive Sequences, Nucleic Acid genetics, Sequence Homology, Nucleic Acid, Testis metabolism, Chromosomes, Human, X genetics, Evolution, Molecular, Genomics, Sequence Analysis, DNA
Abstract

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.

Published
2005
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