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1. Estimating the birth prevalence and pregnancy outcomes of congenital malformations worldwide

Author

Moorthie, Sowmiya, Blencowe, Hannah, Darlison, Matthew W., Lawn, Joy, Morris, Joan K., Modell, Bernadette, Congenital Disorders Expert Group, Bittles, A. H., Blencowe, H., Christianson, A., Cousens, S., Darlison, M. W., Gibbons, S., Hamamy, H., Khoshnood, B., Howson, C. P., Lawn, J., Mastroiacovo, P., Modell, B., Moorthie, S., Morris, J. K., Mossey, P. A., Neville, A. J., Petrou, M., Povey, S., Rankin, J., Schuler-Faccini, L., Wren, C., and Yunnis, K. A.

Published
2018
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2. REPORT on the Fifth International Workshop on Chromosome 9 held at Eynsham, Oxfordshire, UK, September 4–6, 1996

Author

POVEY, S, ATTWOOD, J, CHADWICK, B, FREZAL, J, HAINES, JL, KNOWLES, M, KWIATKOWSKI, DJ, OLOPADE, OI, SLAUGENHAUPT, S, SPURR, NK, SMITH, M, STEEL, K, WHITE, JA, and PERICAK‐VANCE, MA

Subjects
Genetics, Animals, Chromosome Aberrations, Chromosome Disorders, Chromosome Mapping, Chromosomes, Human, Pair 9, Computational Biology, Humans, Mice, Rats, Species Specificity, algorithm, animal cell, basal cell carcinoma, bladder cancer, cancer genetics, cardiomyopathy, chromosome 9, chromosome analysis, chromosome map, conference paper, consensus sequence, data analysis, ehlers danlos syndrome, friedreich ataxia, gene location, gene locus, gene mapping, hearing loss, human, human cell, hypoplasia, lymphatic leukemia, marker gene, meiosis, mouse, muscular dystrophy, neuropathy, nomenclature, nonhuman, priority journal, sex determination, tuberous sclerosis, tumor suppressor gene, workshop, Clinical Sciences, Genetics & Heredity
Abstract

The Fifth International workshop on chromosome 9 comprised a gathering of 36 scientists from seven countries and included a fairly even distribution of interests along chromosome 9 as well as a strong input from more global activities and from comparative mapping. At least eight groups had participated in the goal set at the previous workshop which was to improve the fine genetic mapping in different regions of chromosome 9 by meiotic breakpoint mapping in allocated regions and this has resulted in some greatly improved order information. Excellent computing facilities were available and all contributed maps were entered not only into SIGMA (and thence submitted to GDB) but also into a dedicated version of ACEDB which can be accessed on the Web in the form of one of 28 slices into which the chromosome has been arbitrarily divided. It was generally agreed that the amount of data is now overwhelming and that the integration and validation of all data is not only unrealistic in a short meeting but probably impossible until the whole chromosome has been sequenced and fully annotated. Sequence-ready contigs presented at the meeting totalled about 3 MB which is about one fiftieth of the estimated length. The single biggest barrier to integration of maps is the problem of non-standard nomenclature of loci. In the past 2 workshops efforts have been made to compare traditional 'consensus' maps made by human insight (still probably best for small specific regions) with those generated with some computer assistance (such as SIGMA) and those generated objectively by defined computer algorithms such as ldb. Since no single form of map or representation is entirely satisfactory for all purposes the maps reproduced in the published version of the report are confined to one of the genetic maps, in which Genethon and older markers have been incorporated, a Sigma map of the genes as symbols together with a listing of known 'disease' genes on chromosome 9, and a revised assessment of the mouse map together with a list of mouse loci predicted to be on human chromosome 9. One of the 25 ACEDB slices is also shown to illustrate strengths and weaknesses of this approach. Workshop files include not only all maps available at the time but also details of loci and details of the meiotic breakpoints in the CEPH families.

Published
1997

3. Report on the 1996 International chromosome 9 workshop

Author

Povey, S, Attvvood, J, Chadwick, B, Frezal, J, Haines, JL, Knowles, M, Kwiatkowski, DJ, Olopade, OI, Slaugenhaupt, S, Spurr, NK, Smith, M, Steel, K, White, JA, and Pericak-Vance, MA

Subjects
Genetics, algorithm, animal cell, basal cell carcinoma, bladder cancer, cancer genetics, cardiomyopathy, chromosome 9, chromosome analysis, chromosome map, conference paper, consensus sequence, data analysis, ehlers danlos syndrome, friedreich ataxia, gene location, gene locus, gene mapping, hearing loss, human, human cell, hypoplasia, lymphatic leukemia, marker gene, meiosis, mouse, muscular dystrophy, neuropathy, nomenclature, nonhuman, priority journal, sex determination, tuberous sclerosis, tumor suppressor gene, workshop, Genetics & Heredity, Clinical Sciences
Abstract

The Fifth International workshop on chromosome 9 comprised a gathering of 36 scientists from seven countries and included a fairly even distribution of interests along chromosome 9 as well as a strong input from more global activities and from comparative mapping. At least eight groups had participated in the goal set at the previous workshop which was to improve the fine genetic mapping in different regions of chromosome 9 by meiotic breakpoint mapping in allocated regions and this has resulted in some greatly improved order information. Excellent computing facilities were available and all contributed maps were entered not only into SIGMA (and thence submitted to GDB) but also into a dedicated version of ACEDB which can be accessed on the Web in the form of one of 28 slices into which the chromosome has been arbitrarily divided. It was generally agreed that the amount of data is now overwhelming and that the integration and validation of all data is not only unrealistic in a short meeting but probably impossible until the whole chromosome has been sequenced and fully annotated. Sequence-ready contigs presented at the meeting totalled about 3 MB which is about one fiftieth of the estimated length. The single biggest barrier to integration of maps is the problem of non-standard nomenclature of loci. In the past 2 workshops efforts have been made to compare traditional 'consensus' maps made by human insight (still probably best for small specific regions) with those generated with some computer assistance (such as SIGMA) and those generated objectively by defined computer algorithms such as ldb. Since no single form of map or representation is entirely satisfactory for all purposes the maps reproduced in the published version of the report are confined to one of the genetic maps, in which Genethon and older markers have been incorporated, a Sigma map of the genes as symbols together with a listing of known 'disease' genes on chromosome 9, and a revised assessment of the mouse map together with a list of mouse loci predicted to be on human chromosome 9. One of the 25 ACEDB slices is also shown to illustrate strengths and weaknesses of this approach. Workshop files include not only all maps available at the time but also details of loci and details of the meiotic breakpoints in the CEPH families.

Published
1997

4. Report and abstracts of the First International Workshop on Chromosome 9. Held at Girton College Cambridge, UK, 22-24 March, 1992.

Author

Povey, S, Smith, M, Haines, J, Kwiatkowski, D, Fountain, J, Bale, A, Abbott, C, Jackson, I, Lawrie, M, and Hultén, M

Subjects
DNA, Single Stranded, single stranded DNA, animal, chromosome 9, chromosome map, comparative study, conference paper, genetic linkage, genetics, human, molecular genetics, mouse, nucleotide sequence, tuberous sclerosis, Animal, Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 9, Comparative Study, DNA, Single-Stranded, Human, Linkage, Mice, Molecular Sequence Data, Support, Non-U.S. Gov't, Support, U.S. Gov't, Non-P.H.S., Support, U.S. Gov't, P.H.S., Tuberous Sclerosis, Clinical Sciences, Genetics & Heredity, Genetics
Published
1992

5. REPORT on the First International Workshop on Chromosome 9 held at Girton College Cambridge, UK, 22–24 March, 1992

Author

POVEY, S, SMITH, M, HAINES, J, KWIATKOWSKI, D, FOUNTAIN, J, BALE, A, ABBOTT, C, JACKSON, I, LAWRIE, M, and HULTÉN, M

Subjects
Biological Sciences, Genetics, Animals, Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 9, DNA, Single-Stranded, Genetic Linkage, Humans, Mice, Molecular Sequence Data, Tuberous Sclerosis, chromosomal localization, chromosome 9, chromosome 9p, chromosome 9q, chromosome analysis, chromosome map, conference paper, friedreich ataxia, gene, gene mapping, genetic linkage, genetic polymorphism, human, major clinical study, normal human, priority journal, pulsed field gel electrophoresis, telomere, torsion dystonia, tuberous sclerosis, Clinical Sciences, Genetics & Heredity
Published
1992

6. An Attempt to Map Two Genes for Tuberous Sclerosis Using Novel Two‐Point Methodsa

Author

POVEY, S, ATTWOOD, J, JANSSEN, LAJ, BURLEY, M, SMITH, M, FLODMAN, P, MORTON, NE, EDWARDS, JH, SAMPSON, JR, YATES, JRW, HAINES, JL, AMOS, J, SHORT, MP, SANDKUYL, LA, HALLEY, DJJ, FRYER, AE, BECH‐HANSEN, T, MUELLER, R, AL‐GHAZALI, L, SUPER, M, and OSBORNE, J

Subjects
Adult, Chromosome Mapping, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 9, Genetic Linkage, Humans, Likelihood Functions, Polymorphism, Restriction Fragment Length, Tuberous Sclerosis, conference paper, family study, female, gene mapping, human, major clinical study, male, marker gene, priority journal, tuberous sclerosis, Human, Linkage, Support, Non-U.S. Gov't, General Science & Technology
Published
1991

7. A Comparative Study on Genetic Heterogeneity in Tuberous Sclerosis: Evidence for One Gene on 9q34 and a Second Gene on 11q22–23a

Author

JANSSEN, LAJ, POVEY, S, ATTWOOD, J, SANDKUYL, LA, LINDHOUT, D, FLODMAN, P, SMITH, M, SAMPSON, JR, HAINES, JL, MERKENS, EC, FLEURY, P, SHORT, P, AMOS, J, and HALLEY, DJJ

Subjects
Biological Sciences, Genetics, Chromosome Mapping, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 9, Genes, Genetic Linkage, Humans, Likelihood Functions, Tuberous Sclerosis, chromosome 11q, chromosome 9q, conference paper, female, genetic heterogeneity, genetic linkage, human, male, priority journal, tuberous sclerosis, Genes, Structural, Human, Linkage, Support, Non-U.S. Gov't, General Science & Technology
Published
1991

11. Comparison of the functional and structural characteristics of rare TSC2 variants with clinical and genetic findings

Author

Dufner de Almeida, Luiz, Nanhoe, Santoesha, Zonta, A, Hosseinzadeh, M, Kom-Gortat, RP (Regina), Elfferich, Peter, Schaaf, Gerben, Kenter, Annegien, Kümmel, D, Migone, N, Povey, S, Ekong, R, Nellist, Mark, Dufner de Almeida, Luiz, Nanhoe, Santoesha, Zonta, A, Hosseinzadeh, M, Kom-Gortat, RP (Regina), Elfferich, Peter, Schaaf, Gerben, Kenter, Annegien, Kümmel, D, Migone, N, Povey, S, Ekong, R, and Nellist, Mark

Published
2020

12. 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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13. Recommendations for Locus-Specific Databases and Their Curation

Author

Cotton, R. G.H., Auerbach, A. D., Beckmann, J. S., Blumenfeld, O. O., Brookes, A. J., Brown, A. F., Carrera, P., Cox, D. W., Gottlieb, B., Greenblatt, M. S., Hilbert, P., Lehvaslaiho, H., Liang, P., Marsh, S., Nebert, D. W., Povey, S., Rossetti, S., Scriver, C. R., Summar, M., Tolan, D. R., Verma, I. C., Vihinen, M., and den Dunnen, J. T.

Published
2008
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14. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author

Haworth, S, Shapland, CY, Hayward, C, Prins, BP, Felix, JF, Medina-Gomez, C, Rivadeneira, F, Wang, C, Ahluwalia, TS, Vrijheid, M, Guxens, M, Sunyer, J, Tachmazidou, I, Walter, K, Iotchkova, V, Jackson, A, Cleal, L, Huffmann, J, Min, JL, Sass, L, Timmers, PRHJ, Al Turki, S, Anderson, CA, Anney, R, Antony, D, Artigas, MS, Ayub, M, Bala, S, Barrett, JC, Barroso, I, Beales, P, Bentham, J, Bhattacharya, S, Birney, E, Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G, Calissano, M, Carss, K, Charlton, R, Chatterjee, K, Chen, L, Ciampi, A, Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, DA, Cosgrove, C, Cox, T, Craddock, N, Crooks, L, Curran, S, Curtis, D, Daly, A, Danecek, P, Day, INM, Day-Williams, A, Dominiczak, A, Down, T, Du, Y, Dunham, I, Durbin, R, Edkins, S, Ekong, R, Ellis, P, Evans, DM, Farooqi, IS, Fitzpatrick, DR, Flicek, P, Floyd, J, Foley, AR, Franklin, CS, Futema, M, Gallagher, L, Gaunt, TR, Geihs, M, Geschwind, D, Greenwood, CMT, Griffin, H, Grozeva, D, Guo, X, Gurling, H, Hart, D, Hendricks, AE, Holmans, P, Howie, B, Huang, J, Huang, L, Hubbard, T, Humphries, SE, Hurles, ME, Hysi, P, Jackson, DK, Jamshidi, Y, Joyce, C, Karczewski, KJ, Kaye, J, Keane, T, Kemp, JP, Kennedy, K, Kent, A, Keogh, J, Khawaja, F, van Kogelenberg, M, Kolb-Kokocinski, A, Lachance, G, Langford, C, Lawson, D, Lee, I, Lek, M, Li, R, Li, Y, Liang, J, Lin, H, Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M, MacArthur, DG, Mangino, M, Marchini, J, Marenne, G, Maslen, J, Mathieson, I, McCarthy, S, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Memari, Y, Metrustry, S, Migone, N, Mitchison, HM, Moayyeri, A, Morris, A, Morris, J, Muddyman, D, Muntoni, F, Northstone, K, O'Donovan, MC, O'Rahilly, S, Onoufriadis, A, Oualkacha, K, Owen, MJ, Palotie, A, Panoutsopoulou, K, Parker, V, Parr, JR, Paternoster, L, Paunio, T, Payne, F, Payne, SJ, Perry, JRB, Pietilainen, O, Plagnol, V, Pollitt, RC, Porteous, DJ, Povey, S, Quail, MA, Quaye, L, Raymond, FL, Rehnstrom, K, Richards, JB, Ridout, CK, Ring, S, Ritchie, GRS, Roberts, N, Robinson, RL, Savage, DB, Scambler, P, Schiffels, S, Schmidts, M, Schoenmakers, N, Scott, RH, Semple, RK, Serra, E, Sharp, SI, Shaw, A, Shihab, HA, Shin, S-Y, Skuse, D, Small, KS, Smee, C, Smith, BH, Soranzo, N, Southam, L, Spasic-Boskovic, O, Spector, TD, St Clair, D, Stalker, J, Stevens, E, Sun, J, Surdulescu, G, Suvisaari, J, Syrris, P, Taylor, R, Tian, J, Tobin, MD, Valdes, AM, Vandersteen, AM, Vijayarangakannan, P, Visscher, PM, Wain, LV, Walters, JTR, Wang, G, Wang, J, Wang, Y, Ward, K, Wheeler, E, Whyte, T, Williams, HJ, Williamson, KA, Wilson, C, Wilson, SG, Wong, K, Xu, C, Yang, J, Zhang, F, Zhang, P, Zheng, H-F, Smith, GD, Fisher, SE, Wilson, JF, Cole, TJ, Fernandez-Orth, D, Bonnelykke, K, Bisgaard, H, Pennell, CE, Jaddoe, VWV, Dedoussis, G, Timpson, N, Zeggini, E, Vitart, V, St Pourcain, B, UK10K Consortium, Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, and Child and Adolescent Psychiatry / Psychology

Abstract

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.

Published
2019

16. Biochemical genetic analysis of human and rodent aldehyde dehydrogenase (ALDH).

Author

Hopkinson, DA, Santisteban, I, Povey, S, and Smith, M

Subjects
Animals, Humans, Rats, Isoenzymes, Aldehyde Dehydrogenase, Chromosome Mapping, Species Specificity, Genetic Variation, Aldehyde dehydrogenase, ALDH isozymes, Biochemical genetic analysis, aldehyde dehydrogenase, isoenzyme, animal cell, electrophoresis, enzyme specificity, human, human cell, hybrid cell, liver, nonhuman, rat, thermostability, tissue distribution, Animal, Human, Variation, Public Health and Health Services, Neurosciences, Substance Abuse
Abstract

ALDH isozymes have been characterized in terms of substrate and coenzyme specificity, heat stability, tissue distribution and electrophoretic properties. The activity of the isozymes has also been examined in rodent-human somatic cell hybrids in order to map the structural genes to specific chromosomes and to study the control of gene expression. One isozyme, designated ALDH3, which is very active against benzaldehyde, was found to show variable expression in hybrids made between rat hepatoma cells and human fibroblasts or fetal liver. Segregation analysis of these hybrids indicates that the structural locus for human ALDH3 may be on chromosome 17. The expression of rodent ALDH3 in these hybrids was extremely variable and not correlated with the appearance of the human enzyme. In hybrids expressing human and rodent ALDH3 no heteromeric isozymes were observed. The human "cytosolic" ALDH1 and "mitochondrial" ALDH2 isozymes did not appear to be expressed in any of the somatic cell hybrids examined.

Published
1985

17. Comparison of the functional and structural characteristics of rare TSC2 variants with clinical and genetic findings

Author

Dufner de Almeida, L.G. (Luiz), Nanhoe, S. (Santoesha), Zonta, A. (Andrea), Hosseinzadeh, M. (Mitra), Kom-Gortat, R. (Regina), Elfferich, P.C., Schaaf, G. (Gerben), Kenter, A.T. (Annegien), Kümmel, D. (Daniel), Migone, N. (Nicola), Povey, S. (Sue), Ekong, R. (Rosemary), Nellist, M.D. (Mark), Dufner de Almeida, L.G. (Luiz), Nanhoe, S. (Santoesha), Zonta, A. (Andrea), Hosseinzadeh, M. (Mitra), Kom-Gortat, R. (Regina), Elfferich, P.C., Schaaf, G. (Gerben), Kenter, A.T. (Annegien), Kümmel, D. (Daniel), Migone, N. (Nicola), Povey, S. (Sue), Ekong, R. (Rosemary), and Nellist, M.D. (Mark)

Abstract

The TSC1 and TSC2 gene products interact to form the tuberous sclerosis complex (TSC), an important negative regulator of the mechanistic target of rapamycin complex 1 (TORC1). Inactivating mutations in TSC1 or TSC2 cause TSC, and the identification of a pathogenic TSC1 or TSC2 variant helps establish a diagnosis of TSC. However, it is not always clear whether TSC1 and TSC2 variants are inactivating. To determine whether TSC1 and TSC2 variants of uncertain clinical significance affect TSC complex function and cause TSC, in vitro assays of TORC1 activity can be employed. Here we combine genetic, functional, and structural approaches to try and classify a series of 15 TSC2 VUS. We investigated the effects of the variants on the formation of the TSC complex, on TORC1 activity and on TSC2 pre-mRNA splicing. In 13 cases (87%), the functional data supported the hypothesis that the identified TSC2 variant caused TSC. Our results illustrate the benefits and limitations of functional testing for TSC.

Published
2019
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18. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author

Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), Pourcain, B.S. (Beate), Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), and Pourcain, B.S. (Beate)

Abstract

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for lowfrequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carrie

Published
2019
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24. Rare single gene disorders: Estimating baseline prevalence and outcomes worldwide

Author

Blencowe, H., Moorthie, S., Petrou, M., Hamamy, H., Povey, S., Bittles, A., Gibbons, S., Darlison, M., Modell, B., Blencowe, H., Moorthie, S., Petrou, M., Hamamy, H., Povey, S., Bittles, A., Gibbons, S., Darlison, M., and Modell, B.

Abstract

As child mortality rates overall are decreasing, non-communicable conditions, such as genetic disorders, constitute an increasing proportion of child mortality, morbidity and disability. To date, policy and public health programmes have focused on common genetic disorders. Rare single gene disorders are an important source of morbidity and premature mortality for affected families. When considered collectively, they account for an important public health burden, which is frequently under-recognised. To document the collective frequency and health burden of rare single gene disorders, it is necessary to aggregate them into large manageable groupings and take account of their family implications, effective interventions and service needs. Here, we present an approach to estimate the burden of these conditions up to 5 years of age in settings without empirical data. This approaches uses population-level demographic data, combined with assumptions based on empirical data from settings with data available, to provide population-level estimates which programmes and policy-makers when planning services can use.

Published
2018

26. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Author

Hendricks, A.E. Bochukova, E.G. Marenne, G. Keogh, J.M. Atanassova, N. Bounds, R. Wheeler, E. Mistry, V. Henning, E. Körner, A. Muddyman, D. McCarthy, S. Hinney, A. Hebebrand, J. Scott, R.A. Langenberg, C. Wareham, N.J. Surendran, P. Howson, J.M. Butterworth, A.S. Danesh, J. Nordestgaard, Bø.G. Nielsen, S.F. Afzal, S. Papadia, S. Ashford, S. Garg, S. Millhauser, G.L. Palomino, R.I. Kwasniewska, A. Tachmazidou, I. O'Rahilly, S. Zeggini, E. Barroso, I. Farooqi, I.S. Benzeval, M. Burton, J. Buck, N. Jäckle, A. Kumari, M. Laurie, H. Lynn, P. Pudney, S. Rabe, B. Wolke, D. Overvad, K. Tjønneland, A. Clavel-Chapelon, F. Kaaks, R. Boeing, H. Trichopoulou, A. Ferrari, P. Palli, D. Krogha, V. Panico, S. Tuminoa, R. Matullo, G. Boer, J. Van Der Schouw, Y. Weiderpass, E. Quiros, J.R. Sánchez, M.-J. Navarro, C. Moreno-Iribas, C. Arriola, L. Melander, O. Wennberg, P. Key, T.J. Riboli, E. Turki, S.A. Anderson, C.A. Anney, R. Antony, D. Soler Artigas, M. Ayub, M. Bala, S. Barrett, J.C. Beales, P. Bentham, J. Bhattacharyaa, S. Birney, E. Blackwooda, D. Bobrow, M. Bolton, P.F. Boustred, C. Breen, G. Calissanoa, M. Carss, K. Charlton, R. Chatterjee, K. Chen, L. Ciampia, A. Cirak, S. Clapham, P. Clement, G. Coates, G. Coccaa, M. Collier, D.A. Cosgrove, C. Coxa, T. Craddock, N. Crooks, L. Curran, S. Curtis, D. Daly, A. Danecek, P. Day, I.N.M. Day-Williams, A. Dominiczak, A. Down, T. Du, Y. Dunham, I. Durbin, R. Edkins, S. Ekong, R. Ellis, P. Evansa, D.M. Fitzpatrick, D.R. Flicek, P. Floyd, J. Foley, A.R. Franklin, C.S. Futema, M. Gallagher, L. Gaunt, T.R. Geihs, M. Geschwind, D. Greenwood, C.M.T. Griffin, H. Grozeva, D. Guo, X. Guo, X. Gurling, H. Hart, D. Holmans, P. Howie, B. Huang, J. Huang, L. Hubbard, T. Humphries, S.E. Hurles, M.E. Hysi, P. Iotchkova, V. Jackson, D.K. Jamshidi, Y. Joyce, C. Karczewski, K.J. Kaye, J. Keane, T. Kemp, J.P. Kennedy, K. Kent, A. Khawaja, F. Van Kogelenberg, M. Kolb-Kokocinski, A. Lachance, G. Langford, C. Lawson, D. Lee, I. Lek, M. Li, R. Li, Y. Liang, J. Lin, H. Liu, R. Lönnqvist, J. Lopes, L.R. Lopes, M. MacArthur, D.G. Mangino, M. Marchini, J. Maslen, J. Mathieson, I. McGuffin, P. McIntosh, A.M. McKechanie, A.G. McQuillin, A. Memari, Y. Metrustry, S. Migone, N. Min, J.L. Mitchison, H.M. Moayyeri, A. Morris, A. Morris, J. Muntoni, F. Northstone, K. O'Donovan, M.C. Onoufriadis, A. Oualkacha, K. Owen, M.J. Palotie, A. Panoutsopoulou, K. Parker, V. Parr, J.R. Paternoster, L. Paunio, T. Payne, F. Payne, S.J. Perry, J.R.B. Pietilainen, O. Plagnol, V. Pollitt, R.C. Porteous, D.J. Povey, S. Quail, M.A. Quaye, L. Raymond, F.L. Rehnström, K. Richards, J.B. Ridout, C.K. Ring, S. Ritchie, G.R.S. Roberts, N. Robinson, R.L. Savage, D.B. Scambler, P. Schiffels, S. Schmidts, M. Schoenmakers, N. Scott, R.H. Semple, R.K. Serra, E. Sharp, S.I. Shaw, A. Shihab, H.A. Shin, S.-Y. Skuse, D. Small, K.S. Smee, C. Smith, B.H. Davey Smith, G. Soranzo, N. Southam, L. Spasic-Boskovic, O. Spector, T.D. St Clair, D. St Pourcain, B. Stalker, J. Stevens, E. Sun, J. Surdulescu, G. Suvisaari, J. Syrris, P. Taylor, R. Tian, J. Timpson, N.J. Tobin, M.D. Valdes, A.M. Vandersteen, A.M. Vijayarangakannan, P. Visscher, P.M. Wain, L.V. Walter, K. Walters, J.T.R. Wang, G. Wang, J. Wang, Y. Ward, K. Whyte, T. Williams, H.J. Williamson, K.A. Wilson, C. Wilson, S.G. Wong, K. Xu, C. Yang, J. Zhang, F. Zhang, P. Zheng, H.-F.

Abstract

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies. © 2017 The Author(s).

Published
2017

28. Abstracts of Selected Posters

Author

Albanese, R., Antoine, J. L., Dutrillaux, B., Ashley, T., Avivi, L., Kariv, I., Barigozzi, C., Baratelli, L., Profeta, S., Bartram, C. R., de Klein, A., Hagemeijer, A., Grosveld, G., Bootsma, D., Bennett, Michael D., Smith, J. B., Ward, J. P., Heslop-Harrison, J. S., Blin, N., Kopun, M., Buys, C. H. C. M., Koerts, T., van der Veen, A. Y., de Leij, L., Civitelli, M. V., Capanna, E., Couturier, J., Arnason, U., Mandahl, N., Créau-Goldberg, N., Turleau, C., Cochet, C., de Grouchy, J., Dietrich, A. J. J., Delhanty, J. D. A., Mazzullo, H. A., Cooke, H. M. G., Dotan, A., Dresser, M. E., Moses, M. J., Evans, E. P., Burgoyne, P. B., Ferraro, M., Lavia, P., Fonatsch, C., Kirchner, H. H., Pajunk, A., Schaadt, M., Burrichter, H., Diehl, V., Ford, J. H., Roberts, C. G., Friebe, B., Vogel, R., Friedländer, M., Gamperl, R., Amtmann, E., Pfister, H., Gebhart, E., Wagner, H., Goetz, P., Chandley, A. C., Speed, R. M., Goyanes, V. J., Schvartzman, J. B., Graeven, U., Weh, H. J., Hossfeld, D. K., Greenblatt, I. M., Gripenberg, U., Söderlund, V., Wahlberg, C., Blomqvist, L., Guichaoua, M. R., Delafontaine, D., Taillemite, J. L., Luciani, J. M., Naaf, T., Grunert, D., Schmid, M., Hameister, H., Sperling, K., Hamers, A., Jongbloet, P., Peeters, G., Geraedts, J., Hartley-Asp, B., Heneen, W. K., Hens, L., Kirsch-Volders, M., Susanne, C., Herbst, E. W., Winking, H., Claussen, C. P., Putz, B., Sellin, D., Kolbus, U., Gropp, A., Bennett, M. D., Heyting, C., Koperdraad, F., Redeker, E. J. W., Holmquist, G., Goldman, M., Jaworska, Halina, Johannisson, R., Kerem, B., Goitein, R., Richier, C., Marcus, M., Cedar, H., Koch, H., Hoehn, H., Kubbies, Manfred, Rabinovitch, Peter S., Kunz, W., Franz, G., Lacadena, J. R., Cermeno, M. C., Orellana, J., Santos, J. L., Lemeunier, F., Derbin, C., Lin, C. C., Hoar, D. I., Hoo, J. J., Macgregor, H. C., Sims, S., Horner, H. A., Pellatt, P., Mackay, J. M., Fox, D. P., Brunt, P. W., Johnston, A. W., Magenis, R. E., Chamberlin, J., Allen, L., Tomar, D., Olson, S., Donlon, T., Marlekaj, P., Balcini, A., Fantoni, A., de Capoa, A., Martinsson, T., Dahllöf, B., Levan, G., Matsukuma, S., Utakoji, T., del Mazo, J., Avila, J., Miller, D. A., Feinstein, S. I., Miller, O. J., Morita, T., Delarbre, C., Gachelin, G., Kourilsky, P., Moritz, K., Moriwaki, K., Miyashita, N., Imai, H. T., Wang, C. H., Bonhomme, F., Murer-Orlando, M., Peterson, A. C., Neitzel, H., Bogenberger, J., Fittler, F., Gaenge, M., Schulze, C., Nietzel, H., Nürnberger, F., Höhn, H., van Ommen, G. J. B., Baas, F., Arnberg, A. C., Pearson, P. L., De Vijilder, J. J. M., Bakker, E., Hofker, M., Wapenaar, M. C., Parrington, J. M., West, L. F., Povey, S., Pasquali, F., Casalone, R., Bernasconi, P., Paul, J., Froster-Iskenius, U., Schwinger, E., Moje, W., Pearson, P. O., Beverstock, G. C., Veenema, H., v.d Kamp, J. J., Petitpierre, E., Philip, J., Lundsteen, C., van der Ploeg, M., van Prooijen-Knegt, A. C., Bauman, J. G. J., van Duijn, P., Puertas, M. J., de la Pena, A., Estades, B., Merino, F., Rao, S. R. V., Vasantha, K., Thelma, B. K., Juyal, R. C., Jhanwar, S. C., Ratomponirina, Ch, Hamilton, A., Rumpler, Y., Moses, M., Raveh, D., Ben-Zeoev, A., Redi, C. A., Garagna, S., Italy, C. N. R., Robert-Nicoud, M., Streichhan, I., Möhr, E., Westermann, R., Grossbach, U., Sandberg, P., Levan, A., Schäfer, Mireille, Schempp, W., Scheres, J. M. J. C., Hustinx, T. W. J., Holdrinet, R. S. G., Tice, R. R., Schwarzacher, T., Finch, R. A., Searle, J. B., Sharma, T., Sen, S., Cheong, N., Siebert, E., Loidl, J., Slater, R. M., de Kraker, J., Voute, P. A., Delemarre, J. F. M., Smeets, D. F. C. M., Smits, A. P. T., Solleder, E., Inglin, B., Geile, B., Somssich, I., Schwarz, E., Speit, G., Mehnert, K., Vogel, W., Stahl, A., Hartung, M., Devictor, M., Guichaoua, M., Stoll, C., Roth, M.-P., Dott, B., Tabor, A., Madsen, M., Tommerup, N., Traut, W., Chavin-Colin, F., Junien, C., Vekemans, M., Esseltine, D., Venegas, W., Lasne, Cl, Chouroulinkov, I., Vidal, F., Navarro, J., Templado, C., Egozcue, J., Viegas-Péquignot, E., Malfoy, B., Taillandier, E., Leng, M., Viinikka, Y., Spielmann, H., Boldin, S., Volobouev, V. T., Webb, G. C., Krumins, E., Wegner, R.-D., Lüdtke, E.-L., Weith, A., Westerman, M., Thomson, R., Sinclair, A., Yacobi, Y. Z., Feldman, M., Yoon, J. S., Bennett, M. D., editor, Gropp, A., editor, and Wolf, U., editor

Published
1984
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29. Expression and Characterization of Leucocyte Antigens

Author

Allen, R., Ferrone, S., Hoch, J., Bankhurst, A., Spellmann, J., Burmester, G. R., Dimitriu-Bona, A., Gregersen, P., Waters, S. J., Winchester, R. J., Burrone, O. R., Calabi, F., Gilmore, D., Wright, B., Milstein, C., Clark, E., Martin, P., Hansen, J., Ledbetter, J., de Leij, L., Poppema, S., The, T. H., De Vries, J. E., Vaessen, R., Janssens, P., Tan, B., Heiman, A., Figdor, C. G., Dörken, B., Pfreundschuh, M., Moldenhauer, G., Schwarz, E., Hämmerling, G., Frisman, D., Baird, S., Gazit, E., Gothelf, Y., Gil, R., Orgad, S., Yunis, E. J., Girardet, Ch., Heumann, D., Mach, J.-P., von Fliedner, V., Carrel, S., Goyert, S. M., Silver, J., Hogg, N., Hokland, P., Schlossman, S. F., Ritz, J., Kalil, J., Abita, J. P., Chomienne, C., Poirier, O., Besluau, D., Dastot, H., Reboul, M., Fellous, M., Colombani, J., Kater, L., Brekelmans, P., Daemen, T., Schuurman, H. J., Katz, F., Povey, S., Stanley, K., Schneider, C., Greaves, M., Lemonnier, F. A., Le Bouteiller, P. P., Malissen, B., Golstein, P., Malissen, M., Mishal, Z., Caillol, D. H., Jordan, B. R., Kourilsky, F., Lennert, K., Stein, H., Miiller-Hermelink, H. K., Vollenweider, R., Karol, R. A., Eng, J., Dennison, D., Faris, E., Marcus, D. M., Piatier-Tonneau, D., Boyer, B., Debre, P., Charron, D., Reuben, J. M., Hersh, E. M., Mansell, P. W. A., Newell, G., Rios, A., Rumpold, H., Kraft, D., Förster, O., Schulz, T. F., Alsenz, J., Scheiner, O., Lambris, J., Dierich, M. P., Van Laarhoven, J. P. R. M., Broekhuizen, R., Spierenburg, G. Th., De Bruyn, C. H. M. M., Solbach, W., Röllinghoff, M., Wagner, H., Szer, I. S., Irani, A., Tax, W. J. M., Janossy, G., Jonker, M., Willems, R., Leeuwenberg, J., Capel, P. J. A., Koene, R. A. P., Leeuwenberg, H. F. M., Willems, H. M., Tetteroo, P. A. T., Visser, F., Landsdorp, P., von dem Borne, A. E. G. Kr., Thompson, J. S., Goeken, N. E., Brown, S. A., Rhoades, J. R., Yamamoto, K., Nakauchi, H., Karasuyama, H., Kitamura, K., Tanimoto, K., Okumura, K., Bernard, Alain, editor, Boumsell, Laurence, editor, Dausset, Jean, editor, Milstein, César, editor, and Schlossman, Stuart F., editor

Published
1984
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31. EagI and NotI linking clones from human chromosomes 11 and Xp

Author

Pook, MA, Thakrar, R, Pottinger, B, Harding, B, Porteous, D, van Heyningen, V, Cowell, J, Jones, C, Povey, S, Davies, KE, and Thakker, RV

Abstract

EagI and NotI linking libraries were prepared in the lambda vector, EMBL5, from the mouse-human somatic cell hybrid 1W1LA4.9, which contains human chromosomes 11 and Xp as the only human component. Individual clones containing human DNA were isolated by their ability to hybridise with total human DNA and digested with SalI and EcoRI to identify the human insert size and single-copy fragments. The mean (+/- SD) insert sizes of the EagI and NotI clones were 18.3 +/- 3.2 kb and 16.6 +/- 3.6 kb, respectively. Regional localisation of 66 clones (52 EagI, 14 NotI) was achieved using a panel of 20 somatic cell hybrids that contained different overlapping deletions of chromosomes 11 or Xp. Thirty-nine clones (36 EagI, 3 NotI) were localised to chromosome 11; 17 of these were clustered in 11q13 and another nine were clustered in 11q14-q23.1. Twenty-seven clones (16 EagI, 11 NotI) were localised to Xp and 10 of these were clustered in Xp11. The 66 clones were assessed for seven different microsatellite repetitive sequences; restriction fragment length polymorphisms for five clones from 11q13 were also identified. These EagI and NotI clones, which supplement those previously mapped to chromosome 11 and Xp, should facilitate the generation of more detailed maps and the identification of genes that are associated with CpG-rich islands.

Published
2016

32. Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Author

Huang, J, Howie, B, Mccarthy, S, Memari, Y, Walter, K, Min, Jl, Danecek, P, Malerba, Giovanni, Trabetti, Elisabetta, Zheng, Hf, Gambaro, G, Richards, Jb, Durbin, R, Timpson, Nj, Marchini, J, Soranzo, N, Al Turki, S, Amuzu, A, Anderson, Ca, Anney, R, Antony, D, Artigas, Ms, Ayub, M, Bala, S, Barrett, Jc, Barroso, I, Beales, P, Benn, M, Bentham, J, Bhattacharya, S, Birney, E, Blackwood, D, Bobrow, M, Bochukova, E, Bolton, Pf, Bounds, R, Boustred, C, Breen, G, Calissano, M, Carss, K, Casas, Jp, Chambers, Jc, Charlton, R, Chatterjee, K, Chen, L, Ciampi, A, Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, Da, Cosgrove, C, Cox, T, Craddock, N, Crooks, L, Curran, S, Curtis, D, Daly, A, Day, In, Day Williams, A, Dedoussis, G, Down, T, Du, Y, van Duijn, Cm, Dunham, I, Edkins, S, Ekong, R, Ellis, P, Evans, Dm, Farooqi, Is, Fitzpatrick, Dr, Flicek, P, Floyd, J, Foley, Ar, Franklin, Cs, Futema, M, Gallagher, L, Gasparini, P, Gaunt, Tr, Geihs, M, Geschwind, D, Greenwood, C, Griffin, H, Grozeva, D, Guo, X, Gurling, H, Hart, D, Hendricks, Ae, Holmans, P, Huang, L, Hubbard, T, Humphries, Se, Hurles, Me, Hysi, P, Iotchkova, V, Isaacs, A, Jackson, Dk, Jamshidi, Y, Johnson, J, Joyce, C, Karczewski, Kj, Kaye, J, Keane, T, Kemp, Jp, Kennedy, K, Kent, A, Keogh, J, Khawaja, F, Kleber, Me, van Kogelenberg, M, Kolb Kokocinski, A, Kooner, Js, Lachance, G, Langenberg, C, Langford, C, Lawson, D, Lee, I, van Leeuwen, Em, Lek, M, Li, R, Li, Y, Liang, J, Lin, H, Liu, R, Lönnqvist, J, Lopes, Lr, Lopes, M, Luan, J, Macarthur, Dg, Mangino, M, Marenne, G, März, W, Maslen, J, Matchan, A, Mathieson, I, Mcguffin, P, Mcintosh, Am, Mckechanie, Ag, Mcquillin, A, Metrustry, S, Migone, N, Mitchison, Hm, Moayyeri, A, Morris, J, Morris, R, Muddyman, D, Muntoni, F, Nordestgaard, Bg, Northstone, K, O'Donovan, Mc, O'Rahilly, S, Onoufriadis, A, Oualkacha, K, Owen, Mj, Palotie, A, Panoutsopoulou, K, Parker, V, Parr, Jr, Paternoster, L, Paunio, T, Payne, F, Payne, Sj, Perry, Jr, Pietilainen, O, Plagnol, V, Pollitt, Rc, Povey, S, Quail, Ma, Quaye, L, Raymond, L, Rehnström, K, Ridout, Ck, Ring, S, Ritchie, Gr, Roberts, N, Robinson, Rl, Savage, Db, Scambler, P, Schiffels, S, Schmidts, M, Schoenmakers, N, Scott, Rh, Scott, Ra, Semple, Rk, Serra, E, Sharp, Si, Shaw, A, Shihab, Ha, Shin, Sy, Skuse, D, Small, Ks, Smee, C, Smith, Gd, Southam, L, Spasic Boskovic, O, Spector, Td, St Clair, D, St Pourcain, B, Stalker, J, Stevens, E, Sun, J, Surdulescu, G, Suvisaari, J, Syrris, P, Tachmazidou, I, Taylor, R, Tian, J, Tobin, Md, Toniolo, D, Traglia, M, Tybjaerg Hansen, A, Valdes, Am, Vandersteen, Am, Varbo, A, Vijayarangakannan, P, Visscher, Pm, Wain, Lv, Walters, Jt, Wang, G, Wang, J, Wang, Y, Ward, K, Wheeler, E, Whincup, P, Whyte, T, Williams, Hj, Williamson, Ka, Wilson, C, Wilson, Sg, Wong, K, Xu, C, Yang, J, Zaza, Gianluigi, Zeggini, E, Zhang, F, Zhang, P, Zhang, W., Clinicum, Department of Psychiatry, Jie, Huang, Bryan, Howie, Shane, Mccarthy, Yasin, Memari, Klaudia, Walter, Josine L., Min, Petr, Danecek, Giovanni, Malerba, Elisabetta, Trabetti, Hou Feng, Zheng, Saeed Al, Turki, Antoinette, Amuzu, Carl A., Anderson, Richard, Anney, Dinu, Antony, María Soler, Artiga, Muhammad, Ayub, Senduran, Bala, Jeffrey C., Barrett, Inês, Barroso, Phil, Beale, Marianne, Benn, Jamie, Bentham, Shoumo, Bhattacharya, Ewan, Birney, Douglas, Blackwood, Martin, Bobrow, Elena, Bochukova, Patrick F., Bolton, Rebecca, Bound, Chris, Boustred, Gerome, Breen, Mattia, Calissano, Keren, Car, Juan Pablo, Casa, John C., Chamber, Ruth, Charlton, Krishna, Chatterjee, Lu, Chen, Antonio, Ciampi, Sebahattin, Cirak, Peter, Clapham, Gail, Clement, Guy, Coate, Cocca, Massimiliano, David A., Collier, Catherine, Cosgrove, Tony, Cox, Nick, Craddock, Lucy, Crook, Sarah, Curran, David, Curti, Allan, Daly, Ian N. M., Day, Aaron Day, William, George, Dedoussi, Thomas, Down, Yuanping, Du, Cornelia M., van Duijn, Ian, Dunham, Sarah, Edkin, Rosemary, Ekong, Peter, Elli, David M., Evan, I., Sadaf Farooqi, David R., Fitzpatrick, Paul, Flicek, James, Floyd, A., Reghan Foley, Christopher S., Franklin, Marta, Futema, Louise, Gallagher, Gasparini, Paolo, Tom R., Gaunt, Matthias, Geih, Daniel, Geschwind, Celia, Greenwood, Heather, Griffin, Detelina, Grozeva, Xiaosen, Guo, Xueqin, Guo, Hugh, Gurling, Deborah, Hart, Audrey E., Hendrick, Peter, Holman, Liren, Huang, Tim, Hubbard, Steve E., Humphrie, Matthew E., Hurle, Pirro, Hysi, Valentina, Iotchkova, Aaron, Isaac, David K., Jackson, Yalda, Jamshidi, Jon, Johnson, Chris, Joyce, Konrad J., Karczewski, Jane, Kaye, Thomas, Keane, John P., Kemp, Karen, Kennedy, Alastair, Kent, Julia, Keogh, Farrah, Khawaja, Marcus E., Kleber, Margriet van, Kogelenberg, Anja Kolb, Kokocinski, Jaspal S., Kooner, Genevieve, Lachance, Claudia, Langenberg, Cordelia, Langford, Daniel, Lawson, Irene, Lee, Elisabeth M., van Leeuwen, Monkol, Lek, Rui, Li, Yingrui, Li, Jieqin, Liang, Hong, Lin, Ryan, Liu, Jouko, Lönnqvist, Luis R., Lope, Margarida, Lope, Jian'An, Luan, Daniel G., Macarthur, Massimo, Mangino, Gaëlle, Marenne, Winfried, März, John, Maslen, Angela, Matchan, Iain, Mathieson, Peter, Mcguffin, Andrew M., Mcintosh, Andrew G., Mckechanie, Andrew, Mcquillin, Sarah, Metrustry, Nicola, Migone, Hannah M., Mitchison, Alireza, Moayyeri, James, Morri, Richard, Morri, Dawn, Muddyman, Francesco, Muntoni, Børge G., Nordestgaard, Kate, Northstone, Michael C., O'Donovan, Stephen, O'Rahilly, Alexandros, Onoufriadi, Karim, Oualkacha, Michael J., Owen, Aarno, Palotie, Kalliope, Panoutsopoulou, Victoria, Parker, Jeremy R., Parr, Lavinia, Paternoster, Tiina, Paunio, Felicity, Payne, Stewart J., Payne, John R. B., Perry, Olli, Pietilainen, Vincent, Plagnol, Rebecca C., Pollitt, Sue, Povey, Michael A., Quail, Lydia, Quaye, Lucy, Raymond, Karola, Rehnström, Cheryl K., Ridout, Susan, Ring, Graham R. S., Ritchie, Nicola, Robert, Rachel L., Robinson, David B., Savage, Peter, Scambler, Stephan, Schiffel, Miriam, Schmidt, Nadia, Schoenmaker, Richard H., Scott, Robert A., Scott, Robert K., Semple, Eva, Serra, Sally I., Sharp, Adam, Shaw, Hashem A., Shihab, So Youn, Shin, David, Skuse, Kerrin S., Small, Carol, Smee, George Davey, Smith, Lorraine, Southam, Olivera Spasic, Boskovic, Timothy D., Spector, David St, Clair, Beate St, Pourcain, Jim, Stalker, Elizabeth, Steven, Jianping, Sun, Gabriela, Surdulescu, Jaana, Suvisaari, Petros, Syrri, Ioanna, Tachmazidou, Rohan, Taylor, Jing, Tian, Martin D., Tobin, Daniela, Toniolo, Michela, Traglia, Anne Tybjaerg, Hansen, Ana M., Valde, Anthony M., Vandersteen, Anette, Varbo, Parthiban, Vijayarangakannan, Peter M., Visscher, Louise V., Wain, James T. R., Walter, Guangbiao, Wang, Jun, Wang, Yu, Wang, Kirsten, Ward, Eleanor, Wheeler, Peter, Whincup, Tamieka, Whyte, Hywel J., William, Kathleen A., Williamson, Crispian, Wilson, Scott G., Wilson, Kim, Wong, Changjiang, Xu, Jian, Yang, Gianluigi, Zaza, Eleftheria, Zeggini, Feng, Zhang, Pingbo, Zhang, Weihua, Zhang, Giovanni, Gambaro, J., Brent Richard, Richard, Durbin, Nicholas J., Timpson, Jonathan, Marchini, and Nicole, Soranzo

Subjects
Computer science, General Physics and Astronomy, Genome-wide association study, 0302 clinical medicine, Gene Frequency, Haplotype, Genetics,Biological sciences, Settore MED/14 - NEFROLOGIA, Aged, 80 and over, Genetics, 0303 health sciences, education.field_of_study, Multidisciplinary, TWINSUK, Middle Aged, single-nucleotide polymorphism, Whole-genome sequencing, WGS imputation panel, single-nucleotide polymorphism, Biological sciences, Italy, MAP, Adult, Adolescent, Genotype, WGS imputation panel, Population, Single-nucleotide polymorphism, FORMAT, Computational biology, GENOTYPE IMPUTATION, Polymorphism, Single Nucleotide, Article, White People, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, Humans, GENOME-WIDE ASSOCIATION, 1000 Genomes Project, education, Allele frequency, Alleles, Aged, 030304 developmental biology, Whole-genome sequencing, Models, Statistical, Models, Genetic, Genome, Human, Genetic Variation, General Chemistry, United Kingdom, Minor allele frequency, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Haplotypes, 3111 Biomedicine, 030217 neurology & neurosurgery, Imputation (genetics)
Abstract

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants., Imputation uses genotype information from SNP arrays to infer the genotypes of missing markers. Here, the authors show that an imputation reference panel derived from whole-genome sequencing of 3,781 samples from the UK10K project improves the imputation accuracy and coverage of low frequency variants compared to existing methods.

Published
2015

33. Variants Within TSC2 Exons 25 and 31 Are Very Unlikely to Cause Clinically Diagnosable Tuberous Sclerosis

Author

Ekong, R. (Rosemary), Nellist, M.D. (Mark), Hoogeveen-Westerveld, M. (Marianne), Wentink, M.W.J. (Marjolein), Panzer, J. (Jessica), Sparagana, S.P. (Steven), Emmett, W. (Warren), Dawson, N.L. (Natalie L.), Malinge, M.C. (Marie Claire), Nabbout, R. (Rima), Carbonara, C. (Caterina), Barberis, M. (Marco), Padovan, S. (Sergio), Futema, M. (Marta), Plagnol, V. (Vincent), Humphries, S.E. (Steve E.), Migone, N. (Nicola), Povey, S. (Sue), Ekong, R. (Rosemary), Nellist, M.D. (Mark), Hoogeveen-Westerveld, M. (Marianne), Wentink, M.W.J. (Marjolein), Panzer, J. (Jessica), Sparagana, S.P. (Steven), Emmett, W. (Warren), Dawson, N.L. (Natalie L.), Malinge, M.C. (Marie Claire), Nabbout, R. (Rima), Carbonara, C. (Caterina), Barberis, M. (Marco), Padovan, S. (Sergio), Futema, M. (Marta), Plagnol, V. (Vincent), Humphries, S.E. (Steve E.), Migone, N. (Nicola), and Povey, S. (Sue)

Abstract

Inactivating mutations in TSC1 and TSC2 cause tuberous sclerosis complex (TSC). The 2012 international consensus meeting on TSC diagnosis and management agreed that the identification of a pathogenic TSC1 or TSC2 variant establishes a diagnosis of TSC, even in the absence of clinical signs. However, exons 25 and 31 of TSC2 are subject to alternative splicing. No variants causing clinically diagnosed TSC have been reported in these exons, raising the possibility that such variants would not cause TSC. We present truncating and in-frame variants in exons 25 and 31 in three individuals unlikely to fulfil TSC diagnostic criteria and examine the importance of these exons in TSC using different approaches. Amino acid conservation analysis suggests significantly less conservation in these exons compared with the majority of TSC2 exons, and TSC2 expression data demonstrates that the majority of TSC2 transcripts lack exons 25 and/or 31 in many human adult tissues. In vitro assay of both exons shows that neither exon is essential for TSC complex function. Our evidence suggests that variants in TSC2 exons 25 or 31 are very unlikely to cause classical TSC, although a role for these exons in tissue/stage specific development cannot be excluded.

Published
2016
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34. Variants Within TSC2 Exons 25 and 31 Are Very Unlikely to Cause Clinically Diagnosable Tuberous Sclerosis

Author

Ekong, R, Nellist, Mark, Hoogeveen - Westerveld, Marianne, Wentink, Marjolein, Panzer, J, Sparagana, S, Emmett, W, Dawson, N L, Malinge, M C, Nabbout, R, Carbonara, C, Barberis, M, Padovan, S, Futema, M, Plagnol, V, Humphries, SE, Migone, N, Povey, S, Ekong, R, Nellist, Mark, Hoogeveen - Westerveld, Marianne, Wentink, Marjolein, Panzer, J, Sparagana, S, Emmett, W, Dawson, N L, Malinge, M C, Nabbout, R, Carbonara, C, Barberis, M, Padovan, S, Futema, M, Plagnol, V, Humphries, SE, Migone, N, and Povey, S

Published
2016

37. Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Author

Huang, J. (Jie), Howie, B. (Bryan), McCarthy, S. (Shane), Memari, Y. (Yasin), Walter, K. (Klaudia), Min, J.L. (Josine L.), Danecek, P. (Petr), Malerba, G. (Giovanni), Trabetti, E. (Elisabetta), Zheng, H.-F. (Hou-Feng), Gambaro, G. (Giovanni), Richards, J.B. (Brent), Durbin, R. (Richard), Timpson, N.J. (Nicholas), Marchini, J. (Jonathan), Soranzo, N. (Nicole), Al Turki, S.H. (Saeed), Amuzu, A. (Antoinette), Anderson, C. (Carl), Anney, R. (Richard), Antony, D. (Dinu), Artigas, M.S., Ayub, M. (Muhammad), Bala, S. (Senduran), Barrett, J.C. (Jeffrey), Barroso, I.E. (Inês), Beales, P.L. (Philip), Benn, M. (Marianne), Bentham, J. (Jamie), Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D.H.R. (Douglas), Bobrow, M. (Martin), Bochukova, E. (Elena), Bolton, P.F. (Patrick F.), Bounds, R. (Rebecca), Boustred, C. (Chris), Breen, G. (Gerome), Calissano, M. (Mattia), Carss, K. (Keren), Casas, J.P. (Juan Pablo), Chambers, J.C. (John C.), Charlton, R. (Ruth), Chatterjee, K. (Krishna), Chen, L. (Lu), Ciampi, A. (Antonio), Cirak, S. (Sebahattin), Clapham, P. (Peter), Clement, G. (Gail), Coates, G. (Guy), Cocca, M. (Massimiliano), Collier, D.A. (David), Cosgrove, C. (Catherine), Cox, T. (Tony), Craddock, N.J. (Nick), Crooks, L. (Lucy), Curran, S. (Sarah), Curtis, D. (David), Daly, A. (Allan), Day, I.N.M. (Ian N.M.), Day-Williams, A.G. (Aaron), Dedoussis, G.V. (George), Down, T. (Thomas), Du, Y. (Yuanping), Duijn, C.M. (Cornelia) van, Dunham, I. (Ian), Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Peter), Evans, D.M. (David), Farooqi, I.S. (I. Sadaf), Fitzpatrick, D.R. (David R.), Flicek, P. (Paul), Floyd, J. (James), Foley, A.R. (A. Reghan), Franklin, C.S. (Christopher S.), Futema, M. (Marta), Gallagher, L. (Louise), Gasparini, P. (Paolo), Gaunt, T.R. (Tom), Geihs, M. (Matthias), Geschwind, D. (Daniel), Greenwood, C.M.T. (Celia), Griffin, H. (Heather), Grozeva, D. (Detelina), Guo, X. (Xiaosen), Guo, X. (Xueqin), Gurling, H. (Hugh), Hart, D. (Deborah), Hendricks, A.E. (Audrey E.), Holmans, P.A. (Peter A.), Huang, L. (Liren), Hubbard, T. (Tim), Humphries, S.E. (Steve E.), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Iotchkova, V. (Valentina), Isaacs, A. (Aaron), Jackson, D.K. (David K.), Jamshidi, Y. (Yalda), Johnson, J. (Jon), Joyce, C. (Chris), Karczewski, K.J. (Konrad), Kaye, J. (Jane), Keane, T. (Thomas), Kemp, J.P. (John), Kennedy, K. (Karen), Kent, A. (Alastair), Keogh, J. (Julia), Khawaja, F. (Farrah), Kleber, M.E. (Marcus), Van Kogelenberg, M. (Margriet), Kolb-Kokocinski, A. (Anja), Kooner, J.S. (Jaspal S.), Lachance, G. (Genevieve), Langenberg, C. (Claudia), Langford, C. (Cordelia), Lawson, D. (Daniel), Lee, I. (Irene), Leeuwen, E.M. (Elisa) van, Lek, M. (Monkol), Li, R. (Rui), Li, Y. (Yingrui), Liang, J. (Jieqin), Lin, H. (Hong), Liu, R. (Ryan), Lönnqvist, J. (Jouko), Lopes, L.R. (Luis R.), Lopes, M.C. (Margarida), Luan, J., MacArthur, D.G. (Daniel G.), Mangino, M. (Massimo), Marenne, G. (Gaëlle), März, W. (Winfried), Maslen, J. (John), Matchan, A. (Angela), Mathieson, I. (Iain), McGuffin, P. (Peter), McIntosh, A.M. (Andrew), McKechanie, A.G. (Andrew G.), McQuillin, A. (Andrew), Metrustry, S. (Sarah), Migone, N. (Nicola), Mitchison, H.M. (Hannah M.), Moayyeri, A. (Alireza), Morris, J. (James), Morris, R.W. (Richard), Muddyman, D. (Dawn), Muntoni, F., Nordestgaard, B.G. (Børge G.), Northstone, K. (Kate), O'donovan, M.C. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A. (Alexandros), Oualkacha, K. (Karim), Owen, M.J. (Michael J.), Palotie, A. (Aarno), Panoutsopoulou, K. (Kalliope), Parker, V. (Victoria), Parr, J.R. (Jeremy R.), Paternoster, L. (Lavinia), Paunio, T. (Tiina), Payne, F. (Felicity), Payne, S.J. (Stewart J.), Perry, J.R.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V. (Vincent), Pollitt, R.C. (Rebecca C.), Povey, S. (Sue), Quail, M.A. (Michael A.), Quaye, L. (Lydia), Raymond, L. (Lucy), Rehnström, K. (Karola), Ridout, C.K. (Cheryl K.), Ring, S.M. (Susan), Ritchie, G.R.S. (Graham R.S.), Roberts, N. (Nicola), Robinson, R.L. (Rachel L.), Savage, D.B. (David), Scambler, P.J. (Peter), Schiffels, S. (Stephan), Schmidts, M. (Miriam), Schoenmakers, N. (Nadia), Scott, R.H. (Richard H.), Scott, R.A. (Robert), Semple, R.K. (Robert K.), Serra, E. (Eva), Sharp, S.I. (Sally I.), Shaw, A.C. (Adam C.), Shihab, H.A. (Hashem A.), Shin, S.-Y. (So-Youn), Skuse, D. (David), Small, K.S. (Kerrin), Smee, C. (Carol), Smith, A.V. (Davey), Southam, L. (Lorraine), Spasic-Boskovic, O. (Olivera), Spector, T.D. (Timothy), St. Clair, D. (David), St Pourcain, B. (Beate), Stalker, J. (Jim), Stevens, E. (Elizabeth), Sun, J. (Jianping), Surdulescu, G. (Gabriela), Suvisaari, J. (Jaana), Syrris, P. (Petros), Tachmazidou, I. (Ioanna), Taylor, R. (Rohan), Tian, J. (Jing), Tobin, M.D. (Martin), Toniolo, D. (Daniela), Traglia, M. (Michela), Tybjaerg-Hansen, A. (Anne), Valdes, A.M., Vandersteen, A.M. (Anthony M.), Varbo, A. (Anette), Vijayarangakannan, P. (Parthiban), Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, J.T. (James), Wang, G. (Guangbiao), Wang, J. (Jun), Wang, Y. (Yu), Ward, K. (Kirsten), Wheeler, E. (Eleanor), Whincup, P.H. (Peter), Whyte, T. (Tamieka), Williams, H.J. (Hywel J.), Williamson, K.A. (Kathleen), Wilson, C. (Crispian), Wilson, S.G. (Scott), Wong, K. (Kim), Xu, C. (Changjiang), Yang, J. (Jian), Zaza, G. (Gianluigi), Zeggini, E. (Eleftheria), Zhang, F. (Feng), Zhang, P. (Pingbo), Zhang, W. (Weihua), Huang, J. (Jie), Howie, B. (Bryan), McCarthy, S. (Shane), Memari, Y. (Yasin), Walter, K. (Klaudia), Min, J.L. (Josine L.), Danecek, P. (Petr), Malerba, G. (Giovanni), Trabetti, E. (Elisabetta), Zheng, H.-F. (Hou-Feng), Gambaro, G. (Giovanni), Richards, J.B. (Brent), Durbin, R. (Richard), Timpson, N.J. (Nicholas), Marchini, J. (Jonathan), Soranzo, N. (Nicole), Al Turki, S.H. (Saeed), Amuzu, A. (Antoinette), Anderson, C. (Carl), Anney, R. (Richard), Antony, D. (Dinu), Artigas, M.S., Ayub, M. (Muhammad), Bala, S. (Senduran), Barrett, J.C. (Jeffrey), Barroso, I.E. (Inês), Beales, P.L. (Philip), Benn, M. (Marianne), Bentham, J. (Jamie), Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D.H.R. (Douglas), Bobrow, M. (Martin), Bochukova, E. (Elena), Bolton, P.F. (Patrick F.), Bounds, R. (Rebecca), Boustred, C. (Chris), Breen, G. (Gerome), Calissano, M. (Mattia), Carss, K. (Keren), Casas, J.P. (Juan Pablo), Chambers, J.C. (John C.), Charlton, R. (Ruth), Chatterjee, K. (Krishna), Chen, L. (Lu), Ciampi, A. (Antonio), Cirak, S. (Sebahattin), Clapham, P. (Peter), Clement, G. (Gail), Coates, G. (Guy), Cocca, M. (Massimiliano), Collier, D.A. (David), Cosgrove, C. (Catherine), Cox, T. (Tony), Craddock, N.J. (Nick), Crooks, L. (Lucy), Curran, S. (Sarah), Curtis, D. (David), Daly, A. (Allan), Day, I.N.M. (Ian N.M.), Day-Williams, A.G. (Aaron), Dedoussis, G.V. (George), Down, T. (Thomas), Du, Y. (Yuanping), Duijn, C.M. (Cornelia) van, Dunham, I. (Ian), Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Peter), Evans, D.M. (David), Farooqi, I.S. (I. Sadaf), Fitzpatrick, D.R. (David R.), Flicek, P. (Paul), Floyd, J. (James), Foley, A.R. (A. Reghan), Franklin, C.S. (Christopher S.), Futema, M. (Marta), Gallagher, L. (Louise), Gasparini, P. (Paolo), Gaunt, T.R. (Tom), Geihs, M. (Matthias), Geschwind, D. (Daniel), Greenwood, C.M.T. (Celia), Griffin, H. (Heather), Grozeva, D. (Detelina), Guo, X. (Xiaosen), Guo, X. (Xueqin), Gurling, H. (Hugh), Hart, D. (Deborah), Hendricks, A.E. (Audrey E.), Holmans, P.A. (Peter A.), Huang, L. (Liren), Hubbard, T. (Tim), Humphries, S.E. (Steve E.), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Iotchkova, V. (Valentina), Isaacs, A. (Aaron), Jackson, D.K. (David K.), Jamshidi, Y. (Yalda), Johnson, J. (Jon), Joyce, C. (Chris), Karczewski, K.J. (Konrad), Kaye, J. (Jane), Keane, T. (Thomas), Kemp, J.P. (John), Kennedy, K. (Karen), Kent, A. (Alastair), Keogh, J. (Julia), Khawaja, F. (Farrah), Kleber, M.E. (Marcus), Van Kogelenberg, M. (Margriet), Kolb-Kokocinski, A. (Anja), Kooner, J.S. (Jaspal S.), Lachance, G. (Genevieve), Langenberg, C. (Claudia), Langford, C. (Cordelia), Lawson, D. (Daniel), Lee, I. (Irene), Leeuwen, E.M. (Elisa) van, Lek, M. (Monkol), Li, R. (Rui), Li, Y. (Yingrui), Liang, J. (Jieqin), Lin, H. (Hong), Liu, R. (Ryan), Lönnqvist, J. (Jouko), Lopes, L.R. (Luis R.), Lopes, M.C. (Margarida), Luan, J., MacArthur, D.G. (Daniel G.), Mangino, M. (Massimo), Marenne, G. (Gaëlle), März, W. (Winfried), Maslen, J. (John), Matchan, A. (Angela), Mathieson, I. (Iain), McGuffin, P. (Peter), McIntosh, A.M. (Andrew), McKechanie, A.G. (Andrew G.), McQuillin, A. (Andrew), Metrustry, S. (Sarah), Migone, N. (Nicola), Mitchison, H.M. (Hannah M.), Moayyeri, A. (Alireza), Morris, J. (James), Morris, R.W. (Richard), Muddyman, D. (Dawn), Muntoni, F., Nordestgaard, B.G. (Børge G.), Northstone, K. (Kate), O'donovan, M.C. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A. (Alexandros), Oualkacha, K. (Karim), Owen, M.J. (Michael J.), Palotie, A. (Aarno), Panoutsopoulou, K. (Kalliope), Parker, V. (Victoria), Parr, J.R. (Jeremy R.), Paternoster, L. (Lavinia), Paunio, T. (Tiina), Payne, F. (Felicity), Payne, S.J. (Stewart J.), Perry, J.R.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V. (Vincent), Pollitt, R.C. (Rebecca C.), Povey, S. (Sue), Quail, M.A. (Michael A.), Quaye, L. (Lydia), Raymond, L. (Lucy), Rehnström, K. (Karola), Ridout, C.K. (Cheryl K.), Ring, S.M. (Susan), Ritchie, G.R.S. (Graham R.S.), Roberts, N. (Nicola), Robinson, R.L. (Rachel L.), Savage, D.B. (David), Scambler, P.J. (Peter), Schiffels, S. (Stephan), Schmidts, M. (Miriam), Schoenmakers, N. (Nadia), Scott, R.H. (Richard H.), Scott, R.A. (Robert), Semple, R.K. (Robert K.), Serra, E. (Eva), Sharp, S.I. (Sally I.), Shaw, A.C. (Adam C.), Shihab, H.A. (Hashem A.), Shin, S.-Y. (So-Youn), Skuse, D. (David), Small, K.S. (Kerrin), Smee, C. (Carol), Smith, A.V. (Davey), Southam, L. (Lorraine), Spasic-Boskovic, O. (Olivera), Spector, T.D. (Timothy), St. Clair, D. (David), St Pourcain, B. (Beate), Stalker, J. (Jim), Stevens, E. (Elizabeth), Sun, J. (Jianping), Surdulescu, G. (Gabriela), Suvisaari, J. (Jaana), Syrris, P. (Petros), Tachmazidou, I. (Ioanna), Taylor, R. (Rohan), Tian, J. (Jing), Tobin, M.D. (Martin), Toniolo, D. (Daniela), Traglia, M. (Michela), Tybjaerg-Hansen, A. (Anne), Valdes, A.M., Vandersteen, A.M. (Anthony M.), Varbo, A. (Anette), Vijayarangakannan, P. (Parthiban), Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, J.T. (James), Wang, G. (Guangbiao), Wang, J. (Jun), Wang, Y. (Yu), Ward, K. (Kirsten), Wheeler, E. (Eleanor), Whincup, P.H. (Peter), Whyte, T. (Tamieka), Williams, H.J. (Hywel J.), Williamson, K.A. (Kathleen), Wilson, C. (Crispian), Wilson, S.G. (Scott), Wong, K. (Kim), Xu, C. (Changjiang), Yang, J. (Jian), Zaza, G. (Gianluigi), Zeggini, E. (Eleftheria), Zhang, F. (Feng), Zhang, P. (Pingbo), and Zhang, W. (Weihua)

Abstract

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this

Published
2015
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38. The Human Variome Project: ensuring the quality of DNA variant databases in inherited renal disease

Author

Savige, J, Dalgleish, R, Cotton, RGH, den Dunnen, JT, Macrae, F, Povey, S, Savige, J, Dalgleish, R, Cotton, RGH, den Dunnen, JT, Macrae, F, and Povey, S

Abstract

A recent review identified 60 common inherited renal diseases caused by DNA variants in 132 different genes. These diseases can be diagnosed with DNA sequencing, but each gene probably also has a thousand normal variants. Many more normal variants have been characterised by individual laboratories than are reported in the literature or found in publicly accessible collections. At present, testing laboratories must assess each novel change they identify for pathogenicity, even when this has been done elsewhere previously, and the distinction between normal and disease-associated variants is particularly an issue with the recent surge in exomic sequencing and gene discovery projects. The Human Variome Project recommends the establishment of gene-specific DNA variant databases to facilitate the sharing of DNA variants and decisions about likely disease causation. Databases improve diagnostic accuracy and testing efficiency, and reduce costs. They also help with genotype-phenotype correlations and predictive algorithms. The Human Variome Project advocates databases that use standardised descriptions, are up-to-date, include clinical information and are freely available. Currently, the genes affected in the most common inherited renal diseases correspond to 350 different variant databases, many of which are incomplete or have insufficient clinical details for genotype-phenotype correlations. Assistance is needed from nephrologists to maximise the usefulness of these databases for the diagnosis and management of inherited renal disease.

Published
2015

39. The UK10K project identifies rare variants in health and disease

Author

Walter, K, Min, JL, Huang, J, Crooks, L, Memari, Y, McCarthy, S, Perry, JRB, Xu, C, Futema, M, Lawson, D, Iotchkova, V, Schiffels, S, Hendricks, AE, Danecek, P, Li, R, Floyd, J, Wain, LV, Barroso, I, Humphries, SE, Hurles, ME, Zeggini, E, Barrett, JC, Plagnol, V, Richards, JB, Greenwood, CMT, Timpson, NJ, Durbin, R, Soranzo, N, Bala, S, Clapham, P, Coates, G, Cox, T, Daly, A, Du, Y, Edkins, S, Ellis, P, Flicek, P, Guo, X, Huang, L, Jackson, DK, Joyce, C, Keane, T, Kolb-Kokocinski, A, Langford, C, Li, Y, Liang, J, Lin, H, Liu, R, Maslen, J, Muddyman, D, Quail, MA, Stalker, J, Sun, J, Tian, J, Wang, G, Wang, J, Wang, Y, Wong, K, Zhang, P, Birney, E, Boustred, C, Chen, L, Clement, G, Cocca, M, Smith, GD, Day, INM, Day-Williams, A, Down, T, Dunham, I, Evans, DM, Gaunt, TR, Geihs, M, Hart, D, Howie, B, Hubbard, T, Hysi, P, Jamshidi, Y, Karczewski, KJ, Kemp, JP, Lachance, G, Lek, M, Lopes, M, MacArthur, DG, Marchini, J, Mangino, M, Mathieson, I, Metrustry, S, Moayyeri, A, Northstone, K, Panoutsopoulou, K, Paternoster, L, Quaye, L, Ring, S, Ritchie, GRS, Shihab, HA, Shin, S-Y, Small, KS, Artigas, MS, Southam, L, Spector, TD, St Pourcain, B, Surdulescu, G, Tachmazidou, I, Tobin, MD, Valdes, AM, Visscher, PM, Ward, K, Wilson, SG, Yang, J, Zhang, F, Zheng, H-F, Anney, R, Ayub, M, Blackwood, D, Bolton, PF, Breen, G, Collier, DA, Craddock, N, Curran, S, Curtis, D, Gallagher, L, Geschwind, D, Gurling, H, Holmans, P, Lee, I, Lonnqvist, J, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Morris, J, O'Donovan, MC, Owen, MJ, Palotie, A, Parr, JR, Paunio, T, Pietilainen, O, Rehnstrom, K, Sharp, SI, Skuse, D, St Clair, D, Suvisaari, J, Walters, JTR, Williams, HJ, Bochukova, E, Bounds, R, Dominiczak, A, Farooqi, IS, Keogh, J, Marenne, GL, Morris, A, O'Rahilly, S, Porteous, DJ, Smith, BH, Wheeler, E, Al Turki, S, Anderson, CA, Antony, D, Beales, P, Bentham, J, Bhattacharya, S, Calissano, M, Carss, K, Chatterjee, K, Cirak, S, Cosgrove, C, Fitzpatrick, DR, Foley, AR, Franklin, CS, Grozeva, D, Mitchison, HM, Muntoni, F, Onoufriadis, A, Parker, V, Payne, F, Raymond, FL, Roberts, N, Savage, DB, Scambler, P, Schmidts, M, Schoenmakers, N, Semple, RK, Serra, E, Spasic-Boskovic, O, Stevens, E, van Kogelenberg, M, Vijayarangakannan, P, Williamson, KA, Wilson, C, Whyte, T, Ciampi, A, Oualkacha, K, Bobrow, M, Griffin, H, Kaye, J, Kennedy, K, Kent, A, Smee, C, Charlton, R, Ekong, R, Khawaja, F, Lopes, LR, Migone, N, Payne, SJ, Pollitt, RC, Povey, S, Ridout, CK, Robinson, RL, Scott, RH, Shaw, A, Syrris, P, Taylor, R, Vandersteen, AM, Amuzu, A, Casas, JP, Chambers, JC, Dedoussis, G, Gambaro, G, Gasparini, P, Isaacs, A, Johnson, J, Kleber, ME, Kooner, JS, Langenberg, C, Luan, J, Malerba, G, Maerz, W, Matchan, A, Morris, R, Nordestgaard, BG, Benn, M, Scott, RA, Toniolo, D, Traglia, M, Tybjaerg-Hansen, A, van Duijn, CM, van Leeuwen, EM, Varbo, A, Whincup, P, Zaza, G, Zhang, W, Walter, K, Min, JL, Huang, J, Crooks, L, Memari, Y, McCarthy, S, Perry, JRB, Xu, C, Futema, M, Lawson, D, Iotchkova, V, Schiffels, S, Hendricks, AE, Danecek, P, Li, R, Floyd, J, Wain, LV, Barroso, I, Humphries, SE, Hurles, ME, Zeggini, E, Barrett, JC, Plagnol, V, Richards, JB, Greenwood, CMT, Timpson, NJ, Durbin, R, Soranzo, N, Bala, S, Clapham, P, Coates, G, Cox, T, Daly, A, Du, Y, Edkins, S, Ellis, P, Flicek, P, Guo, X, Huang, L, Jackson, DK, Joyce, C, Keane, T, Kolb-Kokocinski, A, Langford, C, Li, Y, Liang, J, Lin, H, Liu, R, Maslen, J, Muddyman, D, Quail, MA, Stalker, J, Sun, J, Tian, J, Wang, G, Wang, J, Wang, Y, Wong, K, Zhang, P, Birney, E, Boustred, C, Chen, L, Clement, G, Cocca, M, Smith, GD, Day, INM, Day-Williams, A, Down, T, Dunham, I, Evans, DM, Gaunt, TR, Geihs, M, Hart, D, Howie, B, Hubbard, T, Hysi, P, Jamshidi, Y, Karczewski, KJ, Kemp, JP, Lachance, G, Lek, M, Lopes, M, MacArthur, DG, Marchini, J, Mangino, M, Mathieson, I, Metrustry, S, Moayyeri, A, Northstone, K, Panoutsopoulou, K, Paternoster, L, Quaye, L, Ring, S, Ritchie, GRS, Shihab, HA, Shin, S-Y, Small, KS, Artigas, MS, Southam, L, Spector, TD, St Pourcain, B, Surdulescu, G, Tachmazidou, I, Tobin, MD, Valdes, AM, Visscher, PM, Ward, K, Wilson, SG, Yang, J, Zhang, F, Zheng, H-F, Anney, R, Ayub, M, Blackwood, D, Bolton, PF, Breen, G, Collier, DA, Craddock, N, Curran, S, Curtis, D, Gallagher, L, Geschwind, D, Gurling, H, Holmans, P, Lee, I, Lonnqvist, J, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Morris, J, O'Donovan, MC, Owen, MJ, Palotie, A, Parr, JR, Paunio, T, Pietilainen, O, Rehnstrom, K, Sharp, SI, Skuse, D, St Clair, D, Suvisaari, J, Walters, JTR, Williams, HJ, Bochukova, E, Bounds, R, Dominiczak, A, Farooqi, IS, Keogh, J, Marenne, GL, Morris, A, O'Rahilly, S, Porteous, DJ, Smith, BH, Wheeler, E, Al Turki, S, Anderson, CA, Antony, D, Beales, P, Bentham, J, Bhattacharya, S, Calissano, M, Carss, K, Chatterjee, K, Cirak, S, Cosgrove, C, Fitzpatrick, DR, Foley, AR, Franklin, CS, Grozeva, D, Mitchison, HM, Muntoni, F, Onoufriadis, A, Parker, V, Payne, F, Raymond, FL, Roberts, N, Savage, DB, Scambler, P, Schmidts, M, Schoenmakers, N, Semple, RK, Serra, E, Spasic-Boskovic, O, Stevens, E, van Kogelenberg, M, Vijayarangakannan, P, Williamson, KA, Wilson, C, Whyte, T, Ciampi, A, Oualkacha, K, Bobrow, M, Griffin, H, Kaye, J, Kennedy, K, Kent, A, Smee, C, Charlton, R, Ekong, R, Khawaja, F, Lopes, LR, Migone, N, Payne, SJ, Pollitt, RC, Povey, S, Ridout, CK, Robinson, RL, Scott, RH, Shaw, A, Syrris, P, Taylor, R, Vandersteen, AM, Amuzu, A, Casas, JP, Chambers, JC, Dedoussis, G, Gambaro, G, Gasparini, P, Isaacs, A, Johnson, J, Kleber, ME, Kooner, JS, Langenberg, C, Luan, J, Malerba, G, Maerz, W, Matchan, A, Morris, R, Nordestgaard, BG, Benn, M, Scott, RA, Toniolo, D, Traglia, M, Tybjaerg-Hansen, A, van Duijn, CM, van Leeuwen, EM, Varbo, A, Whincup, P, Zaza, G, and Zhang, W

Abstract

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.

Published
2015

47. How to catch all those mutations--the report of the third Human Variome Project Meeting, UNESCO Paris, May 2010

Author

Kohonen-Corish, M.R.J., Al-Aama, J.Y., Auerbach, A.D., Axton, M., Barash, C.I., Bernstein, I., Beroud, C., Burn, J., Cunningham, F., Cutting, G.R., Dunnen, J.T. den, Greenblatt, M.S., Kaput, J., Katz, M., Lindblom, A., Macrae, F., Maglott, D., Moslein, G., Povey, S., Ramesar, R., Richards, S., Seminara, D., Sobrido, M.J., Tavtigian, S., Taylor, G., Vihinen, M., Winship, I., Cotton, R.G.H., Contributors Human Variome Project, HNPCC-register, Hvidovre Hospital, University of Copenhagen = Københavns Universitet (KU), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (JHU), Metabolic Unit, Dept Clinical Chemistry, University of Vermont College of Medicine, University of Vermont [Burlington], University of Massachusetts [Amherst] (UMass Amherst), University of Massachusetts System (UMASS), Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, National Center for Biotechnology Information (NCBI), Dept of Genetics, Evolution and Environment [London] (UCL-GEE), University College of London [London] (UCL), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Fundacion Publica Galega de Medicina Xenomica, Fundación Pública Galega de Medicina Xenómica, Department of Oncological Sciences, University of Utah-Huntsman Cancer Institute, Imperial College London, Department of Experimental Medical Science, Lund University [Lund], University of Copenhagen = Københavns Universitet (UCPH), IFR3, and Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
education, Human Variome Project, Library science, Human genetic variation, Biology, computer.software_genre, Article, 03 medical and health sciences, 0302 clinical medicine, Health care, Genetics, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Data collection, business.industry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 3. Good health, Variome, Incentive, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, Sustainability, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, computer, Data integration
Abstract

International audience; The third Human Variome Project (HVP) Meeting "Integration and Implementation" was held under UNESCO Patronage in Paris, France, at the UNESCO Headquarters May 10-14, 2010. The major aims of the HVP are the collection, curation, and distribution of all human genetic variation affecting health. The HVP has drawn together disparate groups, by country, gene of interest, and expertise, who are working for the common good with the shared goal of pushing the boundaries of the human variome and collaborating to avoid unnecessary duplication. The meeting addressed the 12 key areas that form the current framework of HVP activities: Ethics; Nomenclature and Standards; Publication, Credit and Incentives; Data Collection from Clinics; Overall Data Integration and Access-Peripheral Systems/Software; Data Collection from Laboratories; Assessment of Pathogenicity; Country Specific Collection; Translation to Healthcare and Personalized Medicine; Data Transfer, Databasing, and Curation; Overall Data Integration and Access-Central Systems; and Funding Mechanisms and Sustainability. In addition, three societies that support the goals and the mission of HVP also held their own Workshops with the view to advance disease-specific variation data collection and utilization: the International Society for Gastrointestinal Hereditary Tumours, the Micronutrient Genomics Project, and the Neurogenetics Consortium.

Published
2010

48. Novel intragenic polymorphisms in the tuberous sclerosis 2 (TSC2) gene. Mutations in brief no. 184. Online

Author

Aristotelis Astrinidis, Kouvatsi A, Nahmias J, Povey S, Pandeliadis C, Danzaki A, Schneider M, and Triantaphyllidis C

Subjects
Repressor Proteins, Polymorphism, Genetic, Tumor Suppressor Proteins, Tuberous Sclerosis Complex 2 Protein, Humans, Introns, Polymorphism, Restriction Fragment Length, Polymorphism, Single-Stranded Conformational
Abstract

Twenty-three unrelated patients with tuberous sclerosis have been screened for the presence of mutations in six regions of the TSC2 gene. Eight novel intragenic polymorphisms have been found, one in intron 36 and seven in intron 4, with the use of SSCP analysis. Four of these polymorphisms alter the recognition sequence of specific restriction enzymes and can be detected as RFLPs. Study in a random sample of unrelated individuals from Northern Greece, showed that these polymorphisms have mean observed and expected heterozygosity values of 0.2996 and 0.3349, respectively and could be useful for linkage analysis. It is most likely that the wild type alleles from two pairs of these polymorphisms are strongly associated. A 667 bp segment of intron 4 (954 bp) and an additional 75 bp of intron 36 (352bp) were sequenced, thus completing the sequence of both introns.

Published
2000

49. Practical Guidelines Addressing Ethical Issues Pertaining to the Curation of Human Locus-Specific Variation Databases (LSDBs)

Author

Povey, S, Al Aqeel, AI, Cambon-Thomsen, A, Dalgleish, R, den Dunnen, JT, Firth, HV, Greenblatt, MS, Barash, CI, Parker, M, Patrinos, GP, Savige, J, Sobrido, M-J, Winship, I, Cotton, RGH, Povey, S, Al Aqeel, AI, Cambon-Thomsen, A, Dalgleish, R, den Dunnen, JT, Firth, HV, Greenblatt, MS, Barash, CI, Parker, M, Patrinos, GP, Savige, J, Sobrido, M-J, Winship, I, and Cotton, RGH

Abstract

More than 1,000 Web-based locus-specific variation databases (LSDBs) are listed on the Website of the Human Genetic Variation Society (HGVS). These individual efforts, which often relate phenotype to genotype, are a valuable source of information for clinicians, patients, and their families, as well as for basic research. The initiators of the Human Variome Project recently recognized that having access to some of the immense resources of unpublished information already present in diagnostic laboratories would provide critical data to help manage genetic disorders. However, there are significant ethical issues involved in sharing these data worldwide. An international working group presents second-generation guidelines addressing ethical issues relating to the curation of human LSDBs that provide information via a Web-based interface. It is intended that these should help current and future curators and may also inform the future decisions of ethics committees and legislators. These guidelines have been reviewed by the Ethics Committee of the Human Genome Organization (HUGO).

Published
2010

50. Planning the human variome project: the Spain report.

Author

Kaput, J., Cotton, R.G., Hardman, L., Watson, M., Aqeel, A.I. Al, Al-Aama, J.Y., Al-Mulla, F., Alonso, S., Aretz, S., Auerbach, A.D., Bapat, B., Bernstein, I.T., Bhak, J., Bleoo, S.L., Blocker, H., Brenner, S.E., Burn, J., Bustamante, M., Calzone, R., Cambon-Thomsen, A., Cargill, M., Carrera, P., Cavedon, L., Cho, Y.S., Chung, Y.J., Claustres, M., Cutting, G., Dalgleish, R., Dunnen, J.T. den, Diaz, C., Dobrowolski, S., Santos, M.R. dos, Ekong, R., Flanagan, S.B., Flicek, P., Furukawa, Y., Genuardi, M., Ghang, H., Golubenko, M.V., Greenblatt, M.S., Hamosh, A., Hancock, J.M., Hardison, R., Harrison, T.M., Hoffmann, R., Horaitis, R., Howard, H.J., Barash, C.I., Izagirre, N., Jung, J., Kojima, T., Laradi, S., Lee, Y.S., Lee, J.Y., Gil-da-Silva-Lopes, V.L., Macrae, F.A., Maglott, D., Marafie, M.J., Marsh, S.G., Matsubara, Y., Messiaen, L.M., Moslein, G., Netea, M.G., Norton, M.L., Oefner, P.J., Oetting, W.S., O'Leary, J.C., Ramirez, A.M. de, Paalman, M.H., Parboosingh, J., Patrinos, G.P., Perozzi, G., Phillips, I.R., Povey, S., Prasad, S., Qi, M., Quin, D.J., Ramesar, R.S., Richards, C.S., Savige, J., Scheible, D.G., Scott, R.J., Seminara, D., Shephard, E.A., Sijmons, R.H., Smith, T.D., Sobrido, M.J., Tanaka, T., Tavtigian, S.V., Taylor, G.R., Teague, J., Topel, T., Ullman-Cullere, M., Utsunomiya, J., Kranen, H.J. van, Vihinen, M., Webb, E., Weber, T.K., Yeager, M., Kaput, J., Cotton, R.G., Hardman, L., Watson, M., Aqeel, A.I. Al, Al-Aama, J.Y., Al-Mulla, F., Alonso, S., Aretz, S., Auerbach, A.D., Bapat, B., Bernstein, I.T., Bhak, J., Bleoo, S.L., Blocker, H., Brenner, S.E., Burn, J., Bustamante, M., Calzone, R., Cambon-Thomsen, A., Cargill, M., Carrera, P., Cavedon, L., Cho, Y.S., Chung, Y.J., Claustres, M., Cutting, G., Dalgleish, R., Dunnen, J.T. den, Diaz, C., Dobrowolski, S., Santos, M.R. dos, Ekong, R., Flanagan, S.B., Flicek, P., Furukawa, Y., Genuardi, M., Ghang, H., Golubenko, M.V., Greenblatt, M.S., Hamosh, A., Hancock, J.M., Hardison, R., Harrison, T.M., Hoffmann, R., Horaitis, R., Howard, H.J., Barash, C.I., Izagirre, N., Jung, J., Kojima, T., Laradi, S., Lee, Y.S., Lee, J.Y., Gil-da-Silva-Lopes, V.L., Macrae, F.A., Maglott, D., Marafie, M.J., Marsh, S.G., Matsubara, Y., Messiaen, L.M., Moslein, G., Netea, M.G., Norton, M.L., Oefner, P.J., Oetting, W.S., O'Leary, J.C., Ramirez, A.M. de, Paalman, M.H., Parboosingh, J., Patrinos, G.P., Perozzi, G., Phillips, I.R., Povey, S., Prasad, S., Qi, M., Quin, D.J., Ramesar, R.S., Richards, C.S., Savige, J., Scheible, D.G., Scott, R.J., Seminara, D., Shephard, E.A., Sijmons, R.H., Smith, T.D., Sobrido, M.J., Tanaka, T., Tavtigian, S.V., Taylor, G.R., Teague, J., Topel, T., Ullman-Cullere, M., Utsunomiya, J., Kranen, H.J. van, Vihinen, M., Webb, E., Weber, T.K., and Yeager, M.

Abstract

Contains fulltext : 81952.pdf (publisher's version ) (Closed access), The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Because variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008.

Published
2009

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