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

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.

doi:10.1038/nature09146

Μονάδα:

Ερευνητικό υλικό ΕΚΠΑ

Τίτλος:

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

Γλώσσες Τεκμηρίου:

Αγγλικά

Περίληψη:

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.

Έτος δημοσίευσης:

2010

Συγγραφείς:

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.

Περιοδικό:

Nature

Εκδότης:

Nature Publishing Group

Τόμος:

466

Αριθμός / τεύχος:

7304

Σελίδες:

368-372

Λέξεις-κλειδιά:

guanosine triphosphatase; Ras protein, abnormality; cognition; enzyme activity; genomics; genotype; heritability; mental health; motility; nervous system disorder, article; autism; cell motility; cell proliferation; cognitive development; controlled study; copy number variation; gene locus; genotype; human; intellectual impairment; interpersonal communication; major clinical study; priority journal; social interaction

Επίσημο URL (Εκδότης):

https://doi.org/10.1038/nature09146

DOI:

10.1038/nature09146

Μόνιμη διεύθυνση:

https://pergamos.lib.uoa.gr/uoa/dl/object/3057148

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

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