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31 results on '"Bolton P.F."'

1. Molecular and Cytogenetic Investigations of the Fragile X Region Including the Frax A and Frax E CGG Trinucleotide Repeat Sequences in Families Multiplex for Autism and Related Phenotypes

Author: Gurling, H.M.D., Bolton, P.F., Vincent, J., Melmer, G., and Rutter, M.
Published: 1997

2. FOXP2 is not a major susceptibility gene for autism or specific language impairment. (Report)

Author: Newbury, D.F., Bonora, E., Lamb, J.A., Fisher, S.E., Lai, C.S.L., Baird, G., Jannoun, L., Slonims, V., Stott, C.M., Merricks, M.J., Bolton, P.F., Bailey, A.J., and Monaco, A.P.
Subjects: Autism -- Genetic aspects, Language disorders -- Genetic aspects, Biological sciences
Published: 2002

3. Neuroanatomical Correlates of Memory Deficits in Tuberous Sclerosis Complex

Author: Ridler, K., Suckling, J., Higgins, N.J., de Vries, P.J., Stephenson, C.M.E., Bolton, P.F., and Bullmore, E.T.
Published: 2007

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

Author: Haworth, S., Shapland, C.Y., Hayward, C., Prins, B.P., Felix, J.F., Medina-Gomez, C., Rivadeneira, F., Wang, C., Ahluwalia, T.S., Vrijheid, M., Guxens, M., Sunyer, J., Tachmazidou, I., Walter, K., Iotchkova, V., Jackson, A., Cleal, L., Huffmann, J., Min, J.L., Sass, L., Timmers, P.R.H.J., Turki, S.A., Anderson, C.A., Anney, R., Antony, D., Artigas, M.S., Ayub, M., Bala, S., Barrett, J.C., Barroso, I., Beales, P., Bentham, J., Bhattacharya, S., Birney, E., Blackwood, D., Bobrow, M., Bochukova, E., Bolton, P.F., 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, D.A., Cosgrove, C., Cox, T., Craddock, N., Crooks, Lucy, 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., Evans, D.M., Farooqi, I.S., 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., Gurling, H., Hart, D., Hendricks, A.E., Holmans, P., Howie, B., Huang, J., Huang, L., Hubbard, T., Humphries, S.E., Hurles, M.E., Hysi, P., and Jackson, D.K.
Abstract: © 2019, The Author(s). 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

5. Homozygous microdeletion of exon 5 in znf277 in a girl with specific language impairment

Author: Ceroni, F., Simpson, N.H., Francks, C., Baird, G., Conti-Ramsden, G., Clark, A., Bolton, P.F., Hennessy, E.R., Donnelly, P, Bentley, D.R., Martin, H., Parr, J., Pagnamenta, A.T., Maestrini, E., Bacchelli, E., Fisher, S.E., Newbury, D.F., Imgsac, ., Consortium, S.L.I., and Consortium, W.G.S.
Subjects: Neuroinformatics
Abstract: Contains fulltext : 133117.pdf (Publisher’s version ) (Open Access)
Published: 2014
Full Text: View/download PDF

6. 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

7. 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. L and 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. L
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

8. Reply to pembrey et al: 'Znf277 microdeletions, specific language impairment and the meiotic mismatch methylation (3m) hypothesis'

Author: Ceroni, F., Simpson, N.H., Francks, C., Baird, G., Conti-Ramsden, G., Clark, A., Bolton, P.F., Hennessy, E.R., Donnelly, P, Bentley, D.R., Martin, H., Parr, J., Pagnamenta, A.T., Maestrini, E., Bacchelli, E., Fisher, S.E., Newbury, D.F., Imgsac, ., Consrtium, S.L.I., Consortium, W.G.S., Ceroni, Fabiola, Simpson, Nuala H., Francks, Clyde, Baird, Gillian, Conti-Ramsden, Gina, Clark, Ann, Bolton, Patrick F., Hennessy, Elizabeth R., Donnelly, Peter, Bentley, David R., Martin, Hilary, Parr, Jeremy, Pagnamenta, Alistair T., Maestrini, Elena, Bacchelli, Elena, Fisher, Simon E., and Newbury, Dianne F.
Subjects: Proband, Male, Neuroinformatics, medicine.medical_specialty, Letter, DNA-Binding Protein, Exon, Biology, Specific language impairment, behavioral disciplines and activities, Language Development Disorder, 03 medical and health sciences, Genetic linkage, parasitic diseases, medicine, Genetics, Humans, Language Development Disorders, Risk factor, Allele frequency, Genetics (clinical), 030304 developmental biology, Sequence Deletion, 0303 health sciences, 030305 genetics & heredity, Exons, medicine.disease, Penetrance, DNA-Binding Proteins, Cohort, Medical genetics, lipids (amino acids, peptides, and proteins), Female, Human
Abstract: In a recent paper,1 we described a homozygous exonic microdeletion in ZNF277 in a girl with specific language impairment (SLI). This microdeletion was also identified in the heterozygous form in eight families of the SLI Consortium (SLIC) cohort and four families with ASD cases from the IMGSAC Cohort. We observed an increased allelic frequency of ZNF277 microdeletions in SLI probands (1.1%) compared with both ASD family members (0.3%) and unrelated controls (0.4%), suggesting that these microdeletions might be a risk factor for SLI. However, as the ZNF277 microdeletions showed incomplete segregation with the SLI phenotype, as they were also identified in unaffected family members and, in some cases, they were not inherited by the affected children (reverse discordance), we hypothesised that these CNVs might contribute to the SLI susceptibility in a complex manner, acting as a risk factor with a reduced penetrance.
Published: 2015

9. Genome-wide analysis identifies a role for common copy number variants in specific language impairment

Author: Simpson, N.H., Ceroni, F., Reader, R.H., Covill, L.E., Knight, J.C., Hennessy, E.R., Bolton, P.F., Conti-Ramsden, G., O'Hare, A., Baird, G., Fisher, S.E., Newbury, D.F., and Consortium, S.L.I.
Subjects: Neuroinformatics
Abstract: An exploratory genome-wide copy number variant (CNV) study was performed in 127 independent cases with specific language impairment (SLI), their first-degree relatives (385 individuals) and 269 population controls. Language-impaired cases showed an increased CNV burden in terms of the average number of events (11.28 vs 10.01, empirical P=0.003), the total length of CNVs (717 vs 513 Kb, empirical P=0.0001), the average CNV size (63.75 vs 51.6 Kb, empirical P=0.0005) and the number of genes spanned (14.29 vs 10.34, empirical P=0.0007) when compared with population controls, suggesting that CNVs may contribute to SLI risk. A similar trend was observed in first-degree relatives regardless of affection status. The increased burden found in our study was not driven by large or de novo events, which have been described as causative in other neurodevelopmental disorders. Nevertheless, de novo CNVs might be important on a case-by-case basis, as indicated by identification of events affecting relevant genes, such as ACTR2 and CSNK1A1, and small events within known micro-deletion/-duplication syndrome regions, such as chr8p23.1. Pathway analysis of the genes present within the CNVs of the independent cases identified significant overrepresentation of acetylcholine binding, cyclic-nucleotide phosphodiesterase activity and MHC proteins as compared with controls. Taken together, our data suggest that the majority of the risk conferred by CNVs in SLI is via common, inherited events within a ‘common disorder–common variant’ model. Therefore the risk conferred by CNVs will depend upon the combination of events inherited (both CNVs and SNPs), the genetic background of the individual and the environmental factors.
Published: 2015

10. The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism

Author: Hadley, D., Wu, Z.L., Kao, C., Kini, A., Mohamed-Hadley, A., Thomas, K., Vazquez, L., Qiu, H., Mentch, F., Pellegrino, R., Kim, C., Connolly, J., Glessner, J., Hakonarson, H., Pinto, D., Merikangas, A., Klei, L., Vorstman, J.A., Thompson, A., Regan, R., Pagnamenta, A.T., Oliveira, B., Magalhaes, T.R., Gilbert, J., Duketis, E., De Jonge, M.V., Cuccaro, M., Correia, C.T., Conroy, J., Conceição, I.C., Chiocchetti, A.G., Casey, J.P., Bolshakova, N., Bacchelli, E., Anney, R., Zwaigenbaum, L., Wittemeyer, K., Wallace, S., Engeland, Hv, Soorya, L., Rogé, B., Roberts, W., Poustka, F., Mouga, S., Minshew, N., McGrew, S.G., Lord, C., Leboyer, M., Le Couteur, A.S., Kolevzon, A., Jacob, S., Guter, S., Green, J., Green, A., Gillberg, C., Fernandez, B.A., Duque, F., Delorme, R., Dawson, G., Café, C., Brennan, S., Bourgeron, T., Bolton, P.F., Bölte, S., Bernier, R., Baird, G., Bailey, A.J., Anagnostou, E., Almeida, J., Wijsman, E.M., Vieland, V.J., Vicente, A.M., Schellenberg, G.D., Pericak-Vance, M., Paterson, A.D., Parr, J.R., Oliveira, G., Correia, C., Nurnberger, J.I., Monaco, A.P., Maestrini, E., Klauck, S.M., Haines, J.L., Geschwind, D.H., Freitag, C.M., Folstein, S.E., Ennis, S., Coon, H., Battaglia, A., Szatmari, P., Sutcliffe, J.S., Hallmayer, J., Gill, M., Cook, E.H., Buxbaum, J.D., Devlin, B., Gallagher, L., Betancur, C., and Scherer, S.W.
Subjects: Autism, Perturbações do Desenvolvimento Infantil e Saúde Mental
Abstract: Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions.
Published: 2014

11. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders

Author: Pinto, D., Delaby, E., Merico, D., Barbosa, M., Merikangas, A., Klei, L, Thiruvahindrapuram, B., Xu, X., Ziman, R., Wang, Z., Vorstman, J.A., Thompson, A., Regan, R., Pilorge, M., Pellecchia, G., Pagnamenta, A.T., Oliveira, B., Marshall, C.R., Magalhães, T.R., Lowe, J.K., Howe, J.L., Griswold, A.J., Gilbert, J., Duketis, E., Dombroski, B.A., De Jonge, M.V., Cuccaro, M., Crawford, E.L., Correia, C.T., Conroy, J., Conceição, I.C, Chiocchetti, A.G., Casey, J.P., Cai, G., Cabrol, C., Bolshakova, N., Bacchelli, E., Anney, R., Gallinger, S., Cotterchio, M., Casey, G., Zwaigenbaum, L., Wittemeyer, K., Wing, K., Wallace, S., van Engeland, H., Tryfon, A., Thomson, S., Soorya, L., Rogé, B., Roberts, W., Poustka, F., Mouga, S., Minshew, N., McInnes, L.A., McGrew, S.G., Lord, C., Leboyer, M., Le Couteur, A.S., Kolevzon, A., Jiménez González, P., Jacob, S., Holt, R., Guter, S., Green, J., Green, A., Gillberg, C., Fernandez, B.A., Duque, F., Delorme, R., Dawson, G., Chaste, P., Café, C., Brennan, S., Bourgeron, T., Bolton, P.F., Bölte, S., Bernier, R., Baird, G., Bailey, A.J., Anagnostou, E., Almeida, J., Wijsman, E.M., Vieland, V.J., Vicente, A.M., Schellenberg, G.D., Pericak-Vance, M., Paterson, A.D., Parr, J.R., Oliveira, G., Nurnberger, J.I., Monaco, A.P., Maestrini, E., Klauck, S.M., Hakonarson, H., Haines, J.L., Geschwind, D.H., Freitag, C.M., Folstein, S.E., Ennis, S., Coon, H., Battaglia, A., Szatmari, P., Sutcliffe, J.S., Hallmayer, J., Gill, M., Cook, E.H., Buxbaum, J.D., Devlin, B., Gallagher, L., and Betancur, C.
Subjects: Autism Spectrum Disorders, Rare copy-number variation, Autism, mental disorders, Perturbações do Desenvolvimento Infantil e Saúde Mental
Abstract: Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
Published: 2014

12. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Author: Casey, J.P. Magalhaes, T. Conroy, J.M. Regan, R. Shah, N. Anney, R. Shields, D.C. Abrahams, B.S. Almeida, J. Bacchelli, E. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Bolshakova, N. Bolton, P.F. Bourgeron, T. Brennan, S. Cali, P. Correia, C. Corsello, C. Coutanche, M. Dawson, G. De Jonge, M. Delorme, R. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B.A. Folstein, S.E. Foley, S. Fombonne, E. Freitag, C.M. Gilbert, J. Gillberg, C. Glessner, J.T. Green, J. Guter, S.J. Hakonarson, H. Holt, R. Hughes, G. Hus, V. Igliozzi, R. Kim, C. Klauck, S.M. Kolevzon, A. Lamb, J.A. Leboyer, M. Couteur, A.L. Leventhal, B.L. Lord, C. Lund, S.C. Maestrini, E. Mantoulan, C. Marshall, C.R. McConachie, H. McDougle, C.J. McGrath, J. McMahon, W.M. Merikangas, A. Miller, J. Minopoli, F. Mirza, G.K. Munson, J. Nelson, S.F. Nygren, G. Oliveira, G. Pagnamenta, A.T. Papanikolaou, K. Parr, J.R. Parrini, B. Pickles, A. Pinto, D. Piven, J. Posey, D.J. Poustka, A. Poustka, F. Ragoussis, J. Roge, B. Rutter, M.L. Sequeira, A.F. Soorya, L. Sousa, I. Sykes, N. Stoppioni, V. Tancredi, R. Tauber, M. Thompson, A.P. Thomson, S. Tsiantis, J. Van Engeland, H. Vincent, J.B. Volkmar, F. Vorstman, J.A.S. Wallace, S. Wang, K. Wassink, T.H. White, K. Wing, K. Wittemeyer, K. Yaspan, B.L. Zwaigenbaum, L. Betancur, C. Buxbaum, J.D. Cantor, R.M. Cook, E.H. Coon, H. Cuccaro, M.L. Geschwind, D.H. Haines, J.L. Hallmayer, J. Monaco, A.P. Nurnberger Jr., J.I. Pericak-Vance, M.A. Schellenberg, G.D. Scherer, S.W. Sutcliffe, J.S. Szatmari, P. Vieland, V.J. Wijsman, E.M. Green, A. Gill, M. Gallagher, L. Vicente, A. Ennis, S.
Subjects: mental disorders
Abstract: Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data. © The Author(s) 2011.
Published: 2012

13. Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders

Author: Anney, R.J., Kenny, E.M., O'Dushlaine, C., Parkhomenka, E., Buxbaum, J.D., Sutcliffe, J., Gill, M., Gallagher, L., Bailey, A.J., Fernandez, B.A., Szatmari, P., Nurnberger Jr, J.I., McDougle, C.J., Posey, D.J., Lord, C., Corsello, C., Hus, V., Kolevzon, A., Soorya, L., Parkhomenko, E., Scherer, S.W., Leventhal, B.L., Dawson, G., Vieland, V.J., Hakonarson, H., Glessner, J.T., Kim, C., Wang, K., Schellenberg, G.D., Devlin, B., Klei, L., Patterson, A., Minshew, N., Sutcliffe, J.S., Haines, J.L., Lund, S.C., Thomson, S., Yaspan, B.L., Coon, H., Miller, J., McMahon, W.M., Munson, J., Marshall, C.R., Estes, A., Wijsman, EM., The Autism Genome Project, Pinto, D., Vincent, J.B., Fombonne, E., Betancur, C., Delorme, R., Leboyer, M., Bourgeron, T., Mantoulan, C., Roge, B., Tauber, M., Freitag, C.M., Poustka, F., Duketis, E., Klauck, S.M., Poustka, A., Papanikolaou, K., Tsiantis, J., Anney, R., Bolshakova, N., Brennan, S., Hughes, G., McGrath, J., Merikangas, A., Ennis, S., Green, A., Casey, J.P., Conroy, J.M., Regan, R., Shah, N., Maestrini, E., Bacchelli, E., Minopoli, F., Stoppioni, V., Battaglia, A., Igliozzi, R., Parrini, B., Tancredi, R., Oliveira, G., Almeida, J., Duque, F., Vicente, A.M., Correia, C., Magalhaes, T.R., Gillberg, C., Nygren, G., Jonge, M.D., Van Engeland, H., Vorstman, J.A., Wittemeyer, K., Baird, G., Bolton, P.F, Rutter, M.L., Green, J., Lamb, J.A., Pickles, A., Parr, J.R., Couteur, A.L., Berney, T., McConachie, H., Wallace, S., Coutanche, M., Foley, S., White, K., Monaco, A.P., Holt, R., Farrar, P., Pagnamenta, A.T., Mirza, G.K., Ragoussis, J., Sousa, I., Sykes, N., Wing, K., Hallmayer, J., Cantor, R.M., Nelson, S.F., Geschwind, D.H., Abrahams, B.S., Volkmar, F., Pericak-Vance, M.A., Cuccaro, M.L., Gilbert, J., Cook, E.H., Guter, S.J., and Jacob, S.
Subjects: Pathway analysis, Autism, Perturbações do Desenvolvimento Infantil e Saúde Mental, Gene ontology, Genome-wide association analysis, Family-based association test
Abstract: Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP). Using a two-stage design we examine association enrichment in 5955 unique gene-ontology classifications across four groupings based on two phenotypic and two ancestral classifications. Based on estimates from simulation we identify excess of association enrichment across all analyses. We observe enrichment in association for sets of genes involved in diverse biological processes, including pyruvate metabolism, transcription factor activation, cell-signalling and cell-cycle regulation. Both genes and processes that show enrichment have previously been examined in autistic disorders and offer biologically plausibility to these findings.
Published: 2011

14. Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders

Author: Anney, R.J.L. Kenny, E.M. O'Dushlaine, C. Yaspan, B.L. Parkhomenka, E. Buxbaum, J.D. Sutcliffe, J. Gill, M. Gallagher, L. Bailey, A.J. Fernandez, B.A. Szatmari, P. Scherer, S.W. Patterson, A. Marshall, C.R. Pinto, D. Vincent, J.B. Fombonne, E. Betancur, C. Delorme, R. Leboyer, M. Bourgeron, T. Mantoulan, C. Roge, B. Tauber, M. Freitag, C.M. Poustka, F. Duketis, E. Klauck, S.M. Poustka, A. Papanikolaou, K. Tsiantis, J. Bolshakova, N. Brennan, S. Hughes, G. McGrath, J. Merikangas, A. Ennis, S. Green, A. Casey, J.P. Conroy, J.M. Regan, R. Shah, N. Maestrini, E. Bacchelli, E. Minopoli, F. Stoppioni, V. Battaglia, A. Igliozzi, R. Parrini, B. Tancredi, R. Oliveira, G. Almeida, J. Duque, F. Vicente, A. Correia, C. Magalhaes, T.R. Gillberg, C. Nygren, G. De Jonge, M. Van Engeland, H. Vorstman, J.A.S. Wittemeyer, K. Baird, G. Bolton, P.F. Rutter, M.L. Green, J. Lamb, J.A. Pickles, A. Parr, J.R. Le Couteur, A. Berney, T. McConachie, H. Wallace, S. Coutanche, M. Foley, S. White, K. Monaco, A.P. Holt, R. Farrar, P. Pagnamenta, A.T. Mirza, G.K. Ragoussis, J. Sousa, I. Sykes, N. Wing, K. Hallmayer, J. Cantor, R.M. Nelson, S.F. Geschwind, D.H. Abrahams, B.S. Volkmar, F. Pericak-Vance, M.A. Cuccaro, M.L. Gilbert, J. Cook, E.H. Guter, S.J. Jacob, S. Nurnberger, J.I., Jr. McDougle, C.J. Posey, D.J. Lord, C. Corsello, C. Hus, V. Kolevzon, A. Soorya, L. Parkhomenko, E. Leventhal, B.L. Dawson, G. Vieland, V.J. Hakonarson, H. Glessner, J.T. Kim, C. Wang, K. Schellenberg, G.D. Devlin, B. Klei, L. Minshew, N. Sutcliffe, J.S. Haines, J.L. Lund, S.C. Thomson, S. Coon, H. Miller, J. McMahon, W.M. Munson, J. Estes, A. Wijsman, E.M. Autism Genome Project
Abstract: Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP). Using a two-stage design we examine association enrichment in 5955 unique gene-ontology classifications across four groupings based on two phenotypic and two ancestral classifications. Based on estimates from simulation we identify excess of association enrichment across all analyses. We observe enrichment in association for sets of genes involved in diverse biological processes, including pyruvate metabolism, transcription factor activation, cell-signalling and cell-cycle regulation. Both genes and processes that show enrichment have previously been examined in autistic disorders and offer biologically plausibility to these findings. © 2011 Macmillan Publishers Limited All rights reserved.
Published: 2011

15. Exome Sequencing in an Admixed Isolated Population Indicates NFXL1 Variants Confer a Risk for Specific Language Impairment

Author: Villanueva, P., Nudel, R., Hoischen, A., Fernandez, M.A., Simpson, N.H., Gilissen, C., Reader, R.H., Jara, L., Echeverry, M.M., Francks, C., Baird, G., Conti-Ramsden, G., O'Hare, A., Bolton, P.F., Hennessy, E.R., Palomino, H., Carvajal-Carmona, L., Veltman, J.A., Cazier, J.B., Barbieri, Z. De, Fisher, S.E., Newbury, D.F., Villanueva, P., Nudel, R., Hoischen, A., Fernandez, M.A., Simpson, N.H., Gilissen, C., Reader, R.H., Jara, L., Echeverry, M.M., Francks, C., Baird, G., Conti-Ramsden, G., O'Hare, A., Bolton, P.F., Hennessy, E.R., Palomino, H., Carvajal-Carmona, L., Veltman, J.A., Cazier, J.B., Barbieri, Z. De, Fisher, S.E., and Newbury, D.F.
Abstract: Contains fulltext : 144496.pdf (publisher's version ) (Open Access), Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 x 10-4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model.
Published: 2015

16. 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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17. Functional impact of global rare copy number variation in autism spectrum disorders

Author: Pinto, D. Pagnamenta, A.T. Klei, L. Anney, R. Merico, D. Regan, R. Conroy, J. Magalhaes, T.R. Correia, C. Abrahams, B.S. Almeida, J. Bacchelli, E. Bader, G.D. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Bolshakova, N. Bölte, S. Bolton, P.F. Bourgeron, T. Brennan, S. Brian, J. Bryson, S.E. Carson, A.R. Casallo, G. Casey, J. Chung, B.H.Y. Cochrane, L. Corsello, C. Crawford, E.L. Crossett, A. Cytrynbaum, C. Dawson, G. De Jonge, M. Delorme, R. Drmic, I. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B.A. Folstein, S.E. Fombonne, E. Freitag, C.M. Gilbert, J. Gillberg, C. Glessner, J.T. Goldberg, J. Green, A. Green, J. Guter, S.J. Hakonarson, H. Heron, E.A. Hill, M. Holt, R. Howe, J.L. Hughes, G. Hus, V. Igliozzi, R. Kim, C. Klauck, S.M. Kolevzon, A. Korvatska, O. Kustanovich, V. Lajonchere, C.M. Lamb, J.A. Laskawiec, M. Leboyer, M. Le Couteur, A. Leventhal, B.L. Lionel, A.C. Liu, X.-Q. Lord, C. Lotspeich, L. Lund, S.C. Maestrini, E. Mahoney, W. Mantoulan, C. Marshall, C.R. McConachie, H. McDougle, C.J. McGrath, J. McMahon, W.M. Merikangas, A. Migita, O. Minshew, N.J. Mirza, G.K. Munson, J. Nelson, S.F. Noakes, C. Noor, A. Nygren, G. Oliveira, G. Papanikolaou, K. Parr, J.R. Parrini, B. Paton, T. Pickles, A. Pilorge, M. Piven, J. Ponting, C.P. Posey, D.J. Poustka, A. Poustka, F. Prasad, A. Ragoussis, J. Renshaw, K. Rickaby, J. Roberts, W. Roeder, K. Roge, B. Rutter, M.L. Bierut, L.J. Rice, J.P. Salt, J. Sansom, K. Sato, D. Segurado, R. Sequeira, A.F. Senman, L. Shah, N. Sheffield, V.C. Soorya, L. Sousa, I. Stein, O. Sykes, N. Stoppioni, V. Strawbridge, C. Tancredi, R. Tansey, K. Thiruvahindrapduram, B. Thompson, A.P. Thomson, S. Tryfon, A. Tsiantis, J. Van Engeland, H. Vincent, J.B. Volkmar, F. Wallace, S. Wang, K. Wang, Z. Wassink, T.H. Webber, C. Weksberg, R. Wing, K. Wittemeyer, K. Wood, S. Wu, J. Yaspan, B.L. Zurawiecki, D. Zwaigenbaum, L. Buxbaum, J.D. Cantor, R.M. Cook, E.H. Coon, H. Cuccaro, M.L. Devlin, B. Ennis, S. Gallagher, L. Geschwind, D.H. Gill, M. Haines, J.L. Hallmayer, J. Miller, J. Monaco, A.P. Nurnberger Jr, J.I. Paterson, A.D. Pericak-Vance, M.A. Schellenberg, G.D. Szatmari, P. Vicente, A.M. Vieland, V.J. Wijsman, E.M. Scherer, S.W. Sutcliffe, J.S. Betancur, C.
Subjects: mental disorders
Abstract: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours 1. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability2. Although ASDs are known to be highly heritable ( ∼90%)3, the underlying genetic determinants are still largely unknown.Hereweanalysed the genome-wide characteristics of rare (
Published: 2010

18. A genome-wide scan for common alleles affecting risk for autism

Author: Anney, R. Klei, L. Pinto, D. Regan, R. Conroy, J. Magalhaes, T.R. Correia, C. Abrahams, B.S. Sykes, N. Pagnamenta, A.T. Almeida, J. Bacchelli, E. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Bolshakova, N. Bölte, S. Bolton, P.F. Bourgeron, T. Brennan, S. Brian, J. Carson, A.R. Casallo, G. Casey, J. Chu, S.H. Cochrane, L. Corsello, C. Crawford, E.L. Crossett, A. Dawson, G. de Jonge, M. Delorme, R. Drmic, I. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B.A. Folstein, S.E. Fombonne, E. Freitag, C.M. Gilbert, J. Gillberg, C. Glessner, J.T. Goldberg, J. Green, J. Guter, S.J. Hakonarson, H. Heron, E.A. Hill, M. Holt, R. Howe, J.L. Hughes, G. Hus, V. Igliozzi, R. Kim, C. Klauck, S.M. Kolevzon, A. Korvatska, O. Kustanovich, V. Lajonchere, C.M. Lamb, J.A. Laskawiec, M. Leboyer, M. Le Couteur, A. Leventhal, B.L. Lionel, A.C. Liu, X.-Q. Lord, C. Lotspeich, L. Lund, S.C. Maestrini, E. Mahoney, W. Mantoulan, C. Marshall, C.R. McConachie, H. McDougle, C.J. McGrath, J. McMahon, W.M. Melhem, N.M. Merikangas, A. Migita, O. Minshew, N.J. Mirza, G.K. Munson, J. Nelson, S.F. Noakes, C. Noor, A. Nygren, G. Oliveira, G. Papanikolaou, K. Parr, J.R. Parrini, B. Paton, T. Pickles, A. Piven, J. Posey, D.J. Poustka, A. Poustka, F. Prasad, A. Ragoussis, J. Renshaw, K. Rickaby, J. Roberts, W. Roeder, K. Roge, B. Rutter, M.L. Bierut, L.J. Rice, J.P. Salt, J. Sansom, K. Sato, D. Segurado, R. Senman, L. Shah, N. Sheffield, V.C. Soorya, L. Sousa, I. Stoppioni, V. Strawbridge, C. Tancredi, R. Tansey, K. Thiruvahindrapduram, B. Thompson, A.P. Thomson, S. Tryfon, A. Tsiantis, J. van Engeland, H. Vincent, J.B. Volkmar, F. Wallace, S. Wang, K. Wang, Z. Wassink, T.H. Wing, K. Wittemeyer, K. Wood, S. Yaspan, B.L. Zurawiecki, D. Zwaigenbaum, L. Betancur, C. Buxbaum, J.D. Cantor, R.M. Cook, E.H. Coon, H. Cuccaro, M.L. Gallagher, L. Geschwind, D.H. Gill, M. Haines, J.L. Miller, J. Monaco, A.P. Nurnberger Jr., J.I. Paterson, A.D. Pericak-Vance, M.A. Schellenberg, G.D. Scherer, S.W. Sutcliffe, J.S. Szatmari, P. Vicente, A.M. Vieland, V.J. Wijsman, E.M. Devlin, B. Ennis, S. Hallmayer, J.
Abstract: Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 3 10-28. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10-28 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. © The Author 2010. Published by Oxford University Press. All rights reserved.
Published: 2010

19. A genome-wide linkage and association scan reveals novel loci for autism

Author: Weiss, L.A. Arking, D.E. Daly, M.J. Chakravarti, A. Brune, C.W. West, K. O'Connor, A. Hilton, G. Tomlinson, R.L. West, A.B. Cook Jr., E.H. Green, T. Chang, S.-C. Gabriel, S. Gates, C. Hanson, E.M. Kirby, A. Korn, J. Kuruvilla, F. McCarroll, S. Morrow, E.M. Neale, B. Purcell, S. Sasanfar, R. Sougnez, C. Stevens, C. Altshuler, D. Gusella, J. Santangelo, S.L. Sklar, P. Tanzi, R. Anney, R. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Betancur, C. Bölte, S. Bolton, P.F. Brian, J. Bryson, S.E. Buxbaum, J.D. Cabrito, I. Cai, G. Cantor, R.M. Coon, H. Conroy, J. Correia, C. Corsello, C. Crawford, E.L. Cuccaro, M.L. Dawson, G. De Jonge, M. Devlin, B. Duketis, E. Ennis, S. Estes, A. Farrar, P. Fombonne, E. Freitag, C.M. Gallagher, L. Geschwind, D.H. Gilbert, J. Gill, M. Gillberg, C. Goldberg, J. Green, A. Green, J. Guter, S.J. Haines, J.L. Hallmayer, J.F. Hus, V. Klauck, S.M. Korvatska, O. Lamb, J.A. Laskawiec, M. Leboyer, M. Le Couteur, A. Leventha, B.L. Liu, X.-Q. Lord, C. Lotspeich, L.J. Maestrini, E. Magalhaes, T. Mahoney, W. Mantoulan, C. McConachie, H. McDougle, C.J. McMahon, W.M. Marshall, C.R. Miller, J. Minshew, N.J. Monaco, A.P. Munson, J. Nurnberger Jr., J.I. Oliveira, G. Pagnamenta, A. Papanikolaou, K. Parr, J.R. Paterson, A.D. Pericak-Vance, M.A. Pickles, A. Pinto, D. Piven, J. Posey, D.J. Poustka, A. Poustka, F. Regan, R. Reichert, J. Renshaw, K. Roberts, W. Roge, B. Rutter, M.L. Salt, J. Schellenberg, G.D. Scherer, S.W. Sheffield, V. Sutcliffe, J.S. Szatmari, P. Tansey, K. Thompson, A.P. Tsiantis, J. Van Engeland, H. Vicente, A.M. Vieland, V.J. Volkmar, F. Wallace, S. Wassink, T.H. Wijsman, E.M. Wing, K. Wittemeyer, K. Yaspan, B.L. Zwaigenbaum, L. Yoo, S.-Y. Hill, R.S. Mukaddes, N.M. Balkhy, S. Gascon, G. Al-Saad, S. Hashmi, A. Ware, J. Joseph, R.M. LeClair, E. Partlow, J.N. Barry, B. Walsh, C.A. Pauls, D. Moilanen, I. Ebeling, H. Mattila, M.-L. Kuusikko, S. Jussila, K. Ignatius, J. Tolouei, A. Ghadami, M. Rostami, M. Hosseinipour, A. Valujerdi, M. Andresen, K. Winkloski, B. Haddad, S. Kunkel, L. Kohane, Z. Tran, T. Won Kong, S. O'Neil, S.B. Hundley, R. Holm, I. Peters, H. Baroni, E. Cangialose, A. Jackson, L. Albers, L. Becker, R. Bridgemohan, C. Friedman, S. Munir, K. Nazir, R. Palfrey, J. Schonwald, A. Simmons, E. Rappaport, L.A. Gauthier, J. Mottron, L. Joober, R. Rouleau, G. Rehnstrom, K. Von Wendt, L. Peltonen, L.
Abstract: Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 × 10-7). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.
Published: 2009

20. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Author: Szatmari, P. Paterson, A.D. Zwaigenbaum, L. Roberts, W. Brian, J. Liu, X.-Q. Vincent, J.B. Skaug, J.L. Thompson, A.P. Senman, L. Feuk, L. Qian, C. Bryson, S.E. Jones, M.B. Marshall, C.R. Scherer, S.W. Vieland, V.J. Bartlett, C. Mangin, L.V. Goedken, R. Segre, A. Pericak-Vance, M.A. Cuccaro, M.L. Gilbert, J.R. Wright, H.H. Abramson, R.K. Betancur, C. Bourgeron, T. Gillberg, C. Leboyer, M. Buxbaum, J.D. Davis, K.L. Hollander, E. Silverman, J.M. Hallmayer, J. Lotspeich, L. Sutcliffe, J.S. Haines, J.L. Folstein, S.E. Piven, J. Wassink, T.H. Sheffield, V. Geschwind, D.H. Bucan, M. Brown, W.T. Cantor, R.M. Constantino, J.N. Gilliam, T.C. Herbert, M. LaJonchere, C. Ledbetter, D.H. Lese-Martin, C. Miller, J. Nelson, S. Samango-Sprouse, C.A. Spence, S. State, M. Tanzi, R.E. Coon, H. Dawson, G. Devlin, B. Estes, A. Flodman, P. Klei, L. McMahon, W.M. Minshew, N. Munson, J. Korvatska, E. Rodier, P.M. Schellenberg, G.D. Smith, M. Spence, M.A. Stodgell, C. Tepper, P.G. Wijsman, E.M. Yu, C.-E. Rogé, B. Mantoulan, C. Wittemeyer, K. Poustka, A. Felder, B. Klauck, S.M. Schuster, C. Poustka, F. Bölte, S. Feineis-Matthews, S. Herbrecht, E. Schmötzer, G. Tsiantis, J. Papanikolaou, K. Maestrini, E. Bacchelli, E. Blasi, F. Carone, S. Toma, C. Van Engeland, H. De Jonge, M. Kemner, C. Koop, F. Langemeijer, M. Hijimans, C. Staal, W.G. Baird, G. Bolton, P.F. Rutter, M.L. Weisblatt, E. Green, J. Aldred, C. Wilkinson, J.-A. Pickles, A. Le Couteur, A. Berney, T. McConachie, H. Bailey, A.J. Francis, K. Honeyman, G. Hutchinson, A. Parr, J.R. Wallace, S. Monaco, A.P. Barnby, G. Kobayashi, K. Lamb, J.A. Sousa, I. Sykes, N. Cook, E.H. Guter, S.J. Leventhal, B.L. Salt, J. Lord, C. Corsello, C. Hus, V. Weeks, D.E. Volkmar, F. Tauber, M. Fombonne, E. Shih, A.
Subjects: mental disorders
Abstract: Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs. © 2007 Nature Publishing Group.
Published: 2007

21. A genome-wide scan for common alleles affecting risk for autism

Author: Anney, R. Klei, L. Pinto, D. Regan, R. Conroy, J. Magalhaes, T.R. Correia, C. Abrahams, B.S. Sykes, N. Pagnamenta, A.T. Almeida, J. Bacchelli, E. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Bolshakova, N. Bölte, S. Bolton, P.F. Bourgeron, T. Brennan, S. Brian, J. Carson, A.R. Casallo, G. Casey, J. Chu, S.H. Cochrane, L. Corsello, C. Crawford, E.L. Crossett, A. Dawson, G. de Jonge, M. Delorme, R. Drmic, I. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B.A. Folstein, S.E. Fombonne, E. Freitag, C.M. Gilbert, J. Gillberg, C. Glessner, J.T. Goldberg, J. Green, J. Guter, S.J. Hakonarson, H. Heron, E.A. Hill, M. Holt, R. Howe, J.L. Hughes, G. Hus, V. Igliozzi, R. Kim, C. Klauck, S.M. Kolevzon, A. Korvatska, O. Kustanovich, V. Lajonchere, C.M. Lamb, J.A. Laskawiec, M. Leboyer, M. Le Couteur, A. Leventhal, B.L. Lionel, A.C. Liu, X.-Q. Lord, C. Lotspeich, L. Lund, S.C. Maestrini, E. Mahoney, W. Mantoulan, C. Marshall, C.R. McConachie, H. McDougle, C.J. McGrath, J. McMahon, W.M. Melhem, N.M. Merikangas, A. Migita, O. Minshew, N.J. Mirza, G.K. Munson, J. Nelson, S.F. Noakes, C. Noor, A. Nygren, G. Oliveira, G. Papanikolaou, K. Parr, J.R. Parrini, B. Paton, T. Pickles, A. Piven, J. Posey, D.J. Poustka, A. Poustka, F. Prasad, A. Ragoussis, J. Renshaw, K. Rickaby, J. Roberts, W. Roeder, K. Roge, B. Rutter, M.L. Bierut, L.J. Rice, J.P. Salt, J. Sansom, K. Sato, D. Segurado, R. Senman, L. Shah, N. Sheffield, V.C. Soorya, L. Sousa, I. Stoppioni, V. Strawbridge, C. Tancredi, R. Tansey, K. Thiruvahindrapduram, B. Thompson, A.P. Thomson, S. Tryfon, A. Tsiantis, J. van Engeland, H. Vincent, J.B. Volkmar, F. Wallace, S. Wang, K. Wang, Z. Wassink, T.H. Wing, K. Wittemeyer, K. Wood, S. Yaspan, B.L. Zurawiecki, D. Zwaigenbaum, L. Betancur, C. Buxbaum, J.D. Cantor, R.M. Cook, E.H. Coon, H. Cuccaro, M.L. Gallagher, L. Geschwind, D.H. Gill, M. Haines, J.L. Miller, J. Monaco, A.P. Nurnberger Jr., J.I. Paterson, A.D. Pericak-Vance, M.A. Schellenberg, G.D. Scherer, S.W. Sutcliffe, J.S. and Anney, R. Klei, L. Pinto, D. Regan, R. Conroy, J. Magalhaes, T.R. Correia, C. Abrahams, B.S. Sykes, N. Pagnamenta, A.T. Almeida, J. Bacchelli, E. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Bolshakova, N. Bölte, S. Bolton, P.F. Bourgeron, T. Brennan, S. Brian, J. Carson, A.R. Casallo, G. Casey, J. Chu, S.H. Cochrane, L. Corsello, C. Crawford, E.L. Crossett, A. Dawson, G. de Jonge, M. Delorme, R. Drmic, I. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B.A. Folstein, S.E. Fombonne, E. Freitag, C.M. Gilbert, J. Gillberg, C. Glessner, J.T. Goldberg, J. Green, J. Guter, S.J. Hakonarson, H. Heron, E.A. Hill, M. Holt, R. Howe, J.L. Hughes, G. Hus, V. Igliozzi, R. Kim, C. Klauck, S.M. Kolevzon, A. Korvatska, O. Kustanovich, V. Lajonchere, C.M. Lamb, J.A. Laskawiec, M. Leboyer, M. Le Couteur, A. Leventhal, B.L. Lionel, A.C. Liu, X.-Q. Lord, C. Lotspeich, L. Lund, S.C. Maestrini, E. Mahoney, W. Mantoulan, C. Marshall, C.R. McConachie, H. McDougle, C.J. McGrath, J. McMahon, W.M. Melhem, N.M. Merikangas, A. Migita, O. Minshew, N.J. Mirza, G.K. Munson, J. Nelson, S.F. Noakes, C. Noor, A. Nygren, G. Oliveira, G. Papanikolaou, K. Parr, J.R. Parrini, B. Paton, T. Pickles, A. Piven, J. Posey, D.J. Poustka, A. Poustka, F. Prasad, A. Ragoussis, J. Renshaw, K. Rickaby, J. Roberts, W. Roeder, K. Roge, B. Rutter, M.L. Bierut, L.J. Rice, J.P. Salt, J. Sansom, K. Sato, D. Segurado, R. Senman, L. Shah, N. Sheffield, V.C. Soorya, L. Sousa, I. Stoppioni, V. Strawbridge, C. Tancredi, R. Tansey, K. Thiruvahindrapduram, B. Thompson, A.P. Thomson, S. Tryfon, A. Tsiantis, J. van Engeland, H. Vincent, J.B. Volkmar, F. Wallace, S. Wang, K. Wang, Z. Wassink, T.H. Wing, K. Wittemeyer, K. Wood, S. Yaspan, B.L. Zurawiecki, D. Zwaigenbaum, L. Betancur, C. Buxbaum, J.D. Cantor, R.M. Cook, E.H. Coon, H. Cuccaro, M.L. Gallagher, L. Geschwind, D.H. Gill, M. Haines, J.L. Miller, J. Monaco, A.P. Nurnberger Jr., J.I. Paterson, A.D. Pericak-Vance, M.A. Schellenberg, G.D. Scherer, S.W. Sutcliffe, J.S.
Abstract: Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 3 10-28. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10-28 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. © The Author 2010. Published by Oxford University Press. All rights reserved.
Published: 2010

22. Functional impact of global rare copy number variation in autism spectrum disorders

Author: Pinto, D. Pagnamenta, A.T. Klei, L. Anney, R. Merico, D. Regan, R. Conroy, J. Magalhaes, T.R. Correia, C. Abrahams, B.S. Almeida, J. Bacchelli, E. Bader, G.D. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Bolshakova, N. Bölte, S. Bolton, P.F. Bourgeron, T. Brennan, S. Brian, J. Bryson, S.E. Carson, A.R. Casallo, G. Casey, J. Chung, B.H.Y. Cochrane, L. Corsello, C. Crawford, E.L. Crossett, A. Cytrynbaum, C. Dawson, G. De Jonge, M. Delorme, R. Drmic, I. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B.A. Folstein, S.E. Fombonne, E. Freitag, C.M. Gilbert, J. Gillberg, C. Glessner, J.T. Goldberg, J. Green, A. Green, J. Guter, S.J. Hakonarson, H. Heron, E.A. Hill, M. Holt, R. Howe, J.L. Hughes, G. Hus, V. Igliozzi, R. Kim, C. Klauck, S.M. Kolevzon, A. Korvatska, O. Kustanovich, V. Lajonchere, C.M. Lamb, J.A. Laskawiec, M. Leboyer, M. Le Couteur, A. Leventhal, B.L. Lionel, A.C. Liu, X.-Q. Lord, C. Lotspeich, L. Lund, S.C. Maestrini, E. Mahoney, W. Mantoulan, C. Marshall, C.R. McConachie, H. McDougle, C.J. McGrath, J. McMahon, W.M. Merikangas, A. Migita, O. Minshew, N.J. Mirza, G.K. Munson, J. Nelson, S.F. Noakes, C. Noor, A. Nygren, G. Oliveira, G. Papanikolaou, K. Parr, J.R. Parrini, B. Paton, T. Pickles, A. Pilorge, M. Piven, J. Ponting, C.P. Posey, D.J. Poustka, A. Poustka, F. Prasad, A. Ragoussis, J. Renshaw, K. Rickaby, J. Roberts, W. Roeder, K. Roge, B. Rutter, M.L. Bierut, L.J. Rice, J.P. Salt, J. Sansom, K. Sato, D. Segurado, R. Sequeira, A.F. Senman, L. Shah, N. Sheffield, V.C. Soorya, L. Sousa, I. Stein, O. Sykes, N. Stoppioni, V. Strawbridge, C. Tancredi, R. Tansey, K. Thiruvahindrapduram, B. Thompson, A.P. Thomson, S. Tryfon, A. Tsiantis, J. Van Engeland, H. Vincent, J.B. Volkmar, F. Wallace, S. Wang, K. Wang, Z. Wassink, T.H. Webber, C. Weksberg, R. Wing, K. Wittemeyer, K. Wood, S. Wu, J. Yaspan, B.L. Zurawiecki, D. Zwaigenbaum, L. Buxbaum, J.D. Cantor, R.M. Cook, E.H. Coon, H. Cuccaro, M.L. Devlin, B. Ennis, S. Gallagher, L. Geschwind, D.H. Gill, M. and Pinto, D. Pagnamenta, A.T. Klei, L. Anney, R. Merico, D. Regan, R. Conroy, J. Magalhaes, T.R. Correia, C. Abrahams, B.S. Almeida, J. Bacchelli, E. Bader, G.D. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Bolshakova, N. Bölte, S. Bolton, P.F. Bourgeron, T. Brennan, S. Brian, J. Bryson, S.E. Carson, A.R. Casallo, G. Casey, J. Chung, B.H.Y. Cochrane, L. Corsello, C. Crawford, E.L. Crossett, A. Cytrynbaum, C. Dawson, G. De Jonge, M. Delorme, R. Drmic, I. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B.A. Folstein, S.E. Fombonne, E. Freitag, C.M. Gilbert, J. Gillberg, C. Glessner, J.T. Goldberg, J. Green, A. Green, J. Guter, S.J. Hakonarson, H. Heron, E.A. Hill, M. Holt, R. Howe, J.L. Hughes, G. Hus, V. Igliozzi, R. Kim, C. Klauck, S.M. Kolevzon, A. Korvatska, O. Kustanovich, V. Lajonchere, C.M. Lamb, J.A. Laskawiec, M. Leboyer, M. Le Couteur, A. Leventhal, B.L. Lionel, A.C. Liu, X.-Q. Lord, C. Lotspeich, L. Lund, S.C. Maestrini, E. Mahoney, W. Mantoulan, C. Marshall, C.R. McConachie, H. McDougle, C.J. McGrath, J. McMahon, W.M. Merikangas, A. Migita, O. Minshew, N.J. Mirza, G.K. Munson, J. Nelson, S.F. Noakes, C. Noor, A. Nygren, G. Oliveira, G. Papanikolaou, K. Parr, J.R. Parrini, B. Paton, T. Pickles, A. Pilorge, M. Piven, J. Ponting, C.P. Posey, D.J. Poustka, A. Poustka, F. Prasad, A. Ragoussis, J. Renshaw, K. Rickaby, J. Roberts, W. Roeder, K. Roge, B. Rutter, M.L. Bierut, L.J. Rice, J.P. Salt, J. Sansom, K. Sato, D. Segurado, R. Sequeira, A.F. Senman, L. Shah, N. Sheffield, V.C. Soorya, L. Sousa, I. Stein, O. Sykes, N. Stoppioni, V. Strawbridge, C. Tancredi, R. Tansey, K. Thiruvahindrapduram, B. Thompson, A.P. Thomson, S. Tryfon, A. Tsiantis, J. Van Engeland, H. Vincent, J.B. Volkmar, F. Wallace, S. Wang, K. Wang, Z. Wassink, T.H. Webber, C. Weksberg, R. Wing, K. Wittemeyer, K. Wood, S. Wu, J. Yaspan, B.L. Zurawiecki, D. Zwaigenbaum, L. Buxbaum, J.D. Cantor, R.M. Cook, E.H. Coon, H. Cuccaro, M.L. Devlin, B. Ennis, S. Gallagher, L. Geschwind, D.H. Gill, M.
Abstract: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours 1. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability2. Although ASDs are known to be highly heritable ( ∼90%)3, the underlying genetic determinants are still largely unknown.Hereweanalysed the genome-wide characteristics of rare (<1%frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P=0.012), especially so for loci previously implicated in either ASDand/or intellectual disability (1.69 fold, P=3.4×310-4). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways. © 2010 Macmillan Publishers Limited. All rights reserved.
Published: 2010

23. A genome-wide linkage and association scan reveals novel loci for autism

Author: Weiss, L.A. Arking, D.E. Daly, M.J. Chakravarti, A. Brune, C.W. West, K. O'Connor, A. Hilton, G. Tomlinson, R.L. West, A.B. Cook Jr., E.H. Green, T. Chang, S.-C. Gabriel, S. Gates, C. Hanson, E.M. Kirby, A. Korn, J. Kuruvilla, F. McCarroll, S. Morrow, E.M. Neale, B. Purcell, S. Sasanfar, R. Sougnez, C. Stevens, C. Altshuler, D. Gusella, J. Santangelo, S.L. Sklar, P. Tanzi, R. Anney, R. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Betancur, C. Bölte, S. Bolton, P.F. Brian, J. Bryson, S.E. Buxbaum, J.D. Cabrito, I. Cai, G. Cantor, R.M. Coon, H. Conroy, J. Correia, C. Corsello, C. Crawford, E.L. Cuccaro, M.L. Dawson, G. De Jonge, M. Devlin, B. Duketis, E. Ennis, S. Estes, A. Farrar, P. Fombonne, E. Freitag, C.M. Gallagher, L. Geschwind, D.H. Gilbert, J. Gill, M. Gillberg, C. Goldberg, J. Green, A. Green, J. Guter, S.J. Haines, J.L. Hallmayer, J.F. Hus, V. Klauck, S.M. Korvatska, O. Lamb, J.A. Laskawiec, M. Leboyer, M. Le Couteur, A. Leventha, B.L. Liu, X.-Q. Lord, C. Lotspeich, L.J. Maestrini, E. Magalhaes, T. Mahoney, W. Mantoulan, C. McConachie, H. McDougle, C.J. McMahon, W.M. Marshall, C.R. Miller, J. Minshew, N.J. Monaco, A.P. Munson, J. Nurnberger Jr., J.I. Oliveira, G. Pagnamenta, A. Papanikolaou, K. Parr, J.R. Paterson, A.D. Pericak-Vance, M.A. Pickles, A. Pinto, D. Piven, J. Posey, D.J. Poustka, A. Poustka, F. Regan, R. Reichert, J. Renshaw, K. Roberts, W. Roge, B. Rutter, M.L. Salt, J. Schellenberg, G.D. Scherer, S.W. Sheffield, V. Sutcliffe, J.S. Szatmari, P. Tansey, K. Thompson, A.P. Tsiantis, J. Van Engeland, H. Vicente, A.M. Vieland, V.J. Volkmar, F. Wallace, S. Wassink, T.H. Wijsman, E.M. Wing, K. Wittemeyer, K. Yaspan, B.L. Zwaigenbaum, L. Yoo, S.-Y. Hill, R.S. Mukaddes, N.M. Balkhy, S. Gascon, G. Al-Saad, S. Hashmi, A. Ware, J. Joseph, R.M. LeClair, E. Partlow, J.N. Barry, B. Walsh, C.A. Pauls, D. Moilanen, I. Ebeling, H. Mattila, M.-L. Kuusikko, S. Jussila, K. Ignatius, J. Tolouei, A. Ghadami, M. Rostami, M. Hosseinipour, A. Valujerdi, M. Andre and Weiss, L.A. Arking, D.E. Daly, M.J. Chakravarti, A. Brune, C.W. West, K. O'Connor, A. Hilton, G. Tomlinson, R.L. West, A.B. Cook Jr., E.H. Green, T. Chang, S.-C. Gabriel, S. Gates, C. Hanson, E.M. Kirby, A. Korn, J. Kuruvilla, F. McCarroll, S. Morrow, E.M. Neale, B. Purcell, S. Sasanfar, R. Sougnez, C. Stevens, C. Altshuler, D. Gusella, J. Santangelo, S.L. Sklar, P. Tanzi, R. Anney, R. Bailey, A.J. Baird, G. Battaglia, A. Berney, T. Betancur, C. Bölte, S. Bolton, P.F. Brian, J. Bryson, S.E. Buxbaum, J.D. Cabrito, I. Cai, G. Cantor, R.M. Coon, H. Conroy, J. Correia, C. Corsello, C. Crawford, E.L. Cuccaro, M.L. Dawson, G. De Jonge, M. Devlin, B. Duketis, E. Ennis, S. Estes, A. Farrar, P. Fombonne, E. Freitag, C.M. Gallagher, L. Geschwind, D.H. Gilbert, J. Gill, M. Gillberg, C. Goldberg, J. Green, A. Green, J. Guter, S.J. Haines, J.L. Hallmayer, J.F. Hus, V. Klauck, S.M. Korvatska, O. Lamb, J.A. Laskawiec, M. Leboyer, M. Le Couteur, A. Leventha, B.L. Liu, X.-Q. Lord, C. Lotspeich, L.J. Maestrini, E. Magalhaes, T. Mahoney, W. Mantoulan, C. McConachie, H. McDougle, C.J. McMahon, W.M. Marshall, C.R. Miller, J. Minshew, N.J. Monaco, A.P. Munson, J. Nurnberger Jr., J.I. Oliveira, G. Pagnamenta, A. Papanikolaou, K. Parr, J.R. Paterson, A.D. Pericak-Vance, M.A. Pickles, A. Pinto, D. Piven, J. Posey, D.J. Poustka, A. Poustka, F. Regan, R. Reichert, J. Renshaw, K. Roberts, W. Roge, B. Rutter, M.L. Salt, J. Schellenberg, G.D. Scherer, S.W. Sheffield, V. Sutcliffe, J.S. Szatmari, P. Tansey, K. Thompson, A.P. Tsiantis, J. Van Engeland, H. Vicente, A.M. Vieland, V.J. Volkmar, F. Wallace, S. Wassink, T.H. Wijsman, E.M. Wing, K. Wittemeyer, K. Yaspan, B.L. Zwaigenbaum, L. Yoo, S.-Y. Hill, R.S. Mukaddes, N.M. Balkhy, S. Gascon, G. Al-Saad, S. Hashmi, A. Ware, J. Joseph, R.M. LeClair, E. Partlow, J.N. Barry, B. Walsh, C.A. Pauls, D. Moilanen, I. Ebeling, H. Mattila, M.-L. Kuusikko, S. Jussila, K. Ignatius, J. Tolouei, A. Ghadami, M. Rostami, M. Hosseinipour, A. Valujerdi, M. Andre
Abstract: Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 × 10-7). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.
Published: 2009

24. Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11‐q13

Author: Dennis, N.R., primary, Veltman, M.W.M., additional, Thompson, R., additional, Craig, E., additional, Bolton, P.F., additional, and Thomas, N.S., additional
Published: 2006
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25. Widespread anatomical abnormalities of grey and white matter structure in tuberous sclerosis

Author: Ridler, K., primary, Bullmore, E.T., additional, de Vries, P.J., additional, Suckling, J., additional, Barker, G.J., additional, Meara, S.J.P., additional, Williams, S.C.R., additional, and Bolton, P.F., additional
Published: 2001
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26. Molecular and Cytogenetic Investigations of the Fragile X Region Including the Frax A and Frax E CGG Trinucleotide Repeat Sequences in Families Multiplex for Autism and Related Phenotypes

Author: Gliding, H.M.D., primary, Bolton, P.F., additional, Vincent, J., additional, Melmer, G., additional, and Rutter, M., additional
Published: 1997
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27. MISINTERPRETING ROLE CHANGES AS CHANGES OF PERSON.

Author: Bolton, P.F.
Subjects: LETTERS to the editor, COGNITION disorders
Abstract: A letter to the editor is presented in response to an article about a syndrome of misinterpreting role changes as changes of person in the June 1984 issue.
Published: 1984
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28. Tuberous Sclerosis 2000 Study.

Author: MacLean, Cathy, Yates, J.R.W., and Bolton, P.F.
Subjects: TUBEROUS sclerosis, GENETIC research, PRECANCEROUS conditions
Abstract: The Tuberous Sclerosis 2000 study aims to recruit all children aged 0 16 years newly diagnosed with TS in the UK during the period 2001 2005, carry out detailed baseline assessments and then continue with follow up assessments until December 2010. The aims of the study are to obtain high quality data on disease natural history and determine how this is affected by age, gender, mode of presentation and genotype and in the case of intellectual, cognitive, behavioural and neurological impairments to determine their relationship to the number and distribution of TS lesions in the brain and the type and course of seizures and response to treatment. The TS 2000 National Coordinating Committee are responsible for the planning and monitoring of the study which is being funded by the Tuberous Sclerosis Association. Children enrolled in the study are seen at a network of TS clinics around the UK. The detailed developmental and behavioural assessments are carried out by designated clinical psychologists. To date, 52 children have been ascertained for the study (30 males and 22 females, aged 8 months to 15 years). The majority of children have presented with seizures. In 3 cases the diagnosis was suspected antenatally when cardiac rhabdomyomas were seen on ultrasound scan. 86% of oases have seizures and at least 41% have learning disability (minimum estimate because detailed assessments are not yet completed). Recruitment is ongoing and we would be pleased to hear about new cases. [ABSTRACT FROM AUTHOR]
Published: 2003

29. Genotype-phenotype correlations in tuberous sclerosis

Author: Vries, P.J. de and Bolton, P.F.
Published: 2000

30. Genome-wide analysis identifies a role for common copy number variants in specific language impairment

Author: Simpson N. H., Ceroni F., Reader R. H., Covill L. E., Knight J. C., Hennessy E. R., Bolton P. F., Conti-Ramsden G., O'Hare A., Baird G., Fisher S. E., Newbury D. F., Nudel R., Monaco A. P., Simonoff E., Pickles A., Slonims V., Dworzynski K., Everitt A., Clark A., Watson J., Seckl J., Cowie H., Cohen W., Nasir J., Bishop D. V. M., Simkin Z., Simpson N.H., Ceroni F., Reader R.H., Covill L.E., Knight J.C., Nudel R., Monaco A.P., Simonoff E., Pickles A., Slonims V., Dworzynski K., Everitt A., Clark A., Watson J., Seckl J., Cowie H., Cohen W., Nasir J., Bishop D.V.M., Simkin Z, Hennessy E.R., Bolton P.F., Conti-Ramsden G., O'Hare A., Baird G., Fisher S.E., and Newbury D.F.
Subjects: Male, Language Disorders, Genome, DNA Copy Number Variations, Specific Language Impairment, Polymorphism, Single Nucleotide, Article, Copy Number Variations, Case-Control Studies, Humans, Female, Genetic Predisposition to Disease, Aged, Genome-Wide Association Study, Language
Abstract: An exploratory genome-wide copy number variant (CNV) study was performed in 127 independent cases with specific language impairment (SLI), their first-degree relatives (385 individuals) and 269 population controls. Language-impaired cases showed an increased CNV burden in terms of the average number of events (11.28 vs 10.01, empirical P=0.003), the total length of CNVs (717 vs 513 Kb, empirical P=0.0001), the average CNV size (63.75 vs 51.6 Kb, empirical P=0.0005) and the number of genes spanned (14.29 vs 10.34, empirical P=0.0007) when compared with population controls, suggesting that CNVs may contribute to SLI risk. A similar trend was observed in first-degree relatives regardless of affection status. The increased burden found in our study was not driven by large or de novo events, which have been described as causative in other neurodevelopmental disorders. Nevertheless, de novo CNVs might be important on a case-by-case basis, as indicated by identification of events affecting relevant genes, such as ACTR2 and CSNK1A1, and small events within known micro-deletion/-duplication syndrome regions, such as chr8p23.1. Pathway analysis of the genes present within the CNVs of the independent cases identified significant overrepresentation of acetylcholine binding, cyclic-nucleotide phosphodiesterase activity and MHC proteins as compared with controls. Taken together, our data suggest that the majority of the risk conferred by CNVs in SLI is via common, inherited events within a 'common disorder-common variant' model. Therefore the risk conferred by CNVs will depend upon the combination of events inherited (both CNVs and SNPs), the genetic background of the individual and the environmental factors.
Published: 2014

31. Mutation screening and association analysis of six candidate genes for autism on chromosome 7q

Author: BONORA, ELENA, Lamb J. A., Barnby G., Sykes N., Moberly T., Beyer K. S., Klauck S. M., Poustka F., Battaglia A., Haracopos D., Pedersen L., Isager T., Eriksen G., Viskum B., Sorensen E. U., Brondum Nielsen K., Cotterill R., Engeland H., Jonge M., Kemner C., Steggehuis K., Scherpenisse M., Rutter M., Bolton P. F., Parr J. R., Poustka A., Bailey A. J., Monaco A. P., International Molecular Genetic Study of Austism Consortium, BACCHELLI, ELENA, BLASI, FRANCESCA, MAESTRINI, ELENA, Bonora E., Lamb J.A., Barnby G., Sykes N., Moberly T., Beyer K.S., Klauck S.M., Poustka F., Bacchelli E., Blasi F., Maestrini E., Battaglia A., Haracopos D., Pedersen L., Isager T., Eriksen G., Viskum B., Sorensen E.U., Brondum-Nielsen K., Cotterill R., Engeland H., Jonge M., Kemner C., Steggehuis K., Scherpenisse M., Rutter M., Bolton P.F., Parr J.R., Poustka A., Bailey A.J., Monaco A.P., and International Molecular Genetic Study of Austism Consortium.
Abstract: Genetic studies have provided evidence for an autism susceptibility locus (AUTS1) on chromosome 7q. Screening for mutations in six genes mapping to 7q, CUTL1, SRPK2, SYPL, LAMB1, NRCAM and PTPRZ1 in 48 unrelated individuals with autism led to the identification of several new coding variants in the genes CUTL1, LAMB1 and PTPRZ1. Analysis of genetic variants provided evidence for association with autism for one of the new missense changes identified in LAMB1; this effect was stronger in a subgroup of affected male sibling pair families, implying a possible specific sex-related effect for this variant. Association was also detected for several polymorphisms in the promoter and untranslated region of NRCAM, suggesting that alterations in expression of this gene may be linked to autism susceptibility.
Published: 2005

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31 results on '"Bolton P.F."'

1. Molecular and Cytogenetic Investigations of the Fragile X Region Including the Frax A and Frax E CGG Trinucleotide Repeat Sequences in Families Multiplex for Autism and Related Phenotypes

2. FOXP2 is not a major susceptibility gene for autism or specific language impairment. (Report)

3. Neuroanatomical Correlates of Memory Deficits in Tuberous Sclerosis Complex

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

5. Homozygous microdeletion of exon 5 in znf277 in a girl with specific language impairment

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

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

8. Reply to pembrey et al: 'Znf277 microdeletions, specific language impairment and the meiotic mismatch methylation (3m) hypothesis'

9. Genome-wide analysis identifies a role for common copy number variants in specific language impairment

10. The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism

11. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders

12. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

13. Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders

14. Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders

15. Exome Sequencing in an Admixed Isolated Population Indicates NFXL1 Variants Confer a Risk for Specific Language Impairment

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

17. Functional impact of global rare copy number variation in autism spectrum disorders

18. A genome-wide scan for common alleles affecting risk for autism

19. A genome-wide linkage and association scan reveals novel loci for autism

20. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

21. A genome-wide scan for common alleles affecting risk for autism

22. Functional impact of global rare copy number variation in autism spectrum disorders

23. A genome-wide linkage and association scan reveals novel loci for autism

24. Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11‐q13

25. Widespread anatomical abnormalities of grey and white matter structure in tuberous sclerosis

26. Molecular and Cytogenetic Investigations of the Fragile X Region Including the Frax A and Frax E CGG Trinucleotide Repeat Sequences in Families Multiplex for Autism and Related Phenotypes

27. MISINTERPRETING ROLE CHANGES AS CHANGES OF PERSON.

28. Tuberous Sclerosis 2000 Study.

29. Genotype-phenotype correlations in tuberous sclerosis

30. Genome-wide analysis identifies a role for common copy number variants in specific language impairment

31. Mutation screening and association analysis of six candidate genes for autism on chromosome 7q

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31 results on '"Bolton P.F."'

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