High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility

Janine Lamb; E. Maestrini; A. T. Pagnamenta; J. A. Lamb; E. Bacchelli; N. H. Sykes; I. Sousa; C. Toma; G. Barnby; H. Butler; L. Winchester; T. S. Scerri; F. Minopoli; J. Reichert; G. Cai; J. D. Buxbaum; O. Korvatska; G. D. Schellenberg; G. Dawson; A. D. Bildt; R. B. Minderaa; E. J. Mulder; A. P. Morris; A. J. Bailey; A. P. Monaco

doi:10.1038/mp.2009.34

High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility

Janine Lamb, E. Maestrini, A. T. Pagnamenta, J. A. Lamb, E. Bacchelli, N. H. Sykes, I. Sousa, C. Toma, G. Barnby, H. Butler, L. Winchester, T. S. Scerri, F. Minopoli, J. Reichert, G. Cai, J. D. Buxbaum, O. Korvatska, G. D. Schellenberg, G. Dawson, A. D. BildtR. B. Minderaa, E. J. Mulder, A. P. Morris, A. J. Bailey, A. P. Monaco

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Abstract

Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family. © 2010 Macmillan Publishers Limited All rights reserved.

Original language	English
Pages (from-to)	954-968
Number of pages	14
Journal	Molecular psychiatry
Volume	15
Issue number	9
DOIs	https://doi.org/10.1038/mp.2009.34
Publication status	Published - Sept 2010

Keywords

autistic disorder
chromosome 2
chromosome 7
disease susceptibility
linkage disequilibrium
single nucleotide polymorphisms

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Lamb, J., Maestrini, E., Pagnamenta, A. T., Lamb, J. A., Bacchelli, E., Sykes, N. H., Sousa, I., Toma, C., Barnby, G., Butler, H., Winchester, L., Scerri, T. S., Minopoli, F., Reichert, J., Cai, G., Buxbaum, J. D., Korvatska, O., Schellenberg, G. D., Dawson, G., ... Monaco, A. P. (2010). High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility. Molecular psychiatry, 15(9), 954-968. https://doi.org/10.1038/mp.2009.34

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title = "High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility",

abstract = "Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family. {\textcopyright} 2010 Macmillan Publishers Limited All rights reserved.",

keywords = "autistic disorder, chromosome 2, chromosome 7, disease susceptibility, linkage disequilibrium, single nucleotide polymorphisms",

author = "Janine Lamb and E. Maestrini and Pagnamenta, {A. T.} and Lamb, {J. A.} and E. Bacchelli and Sykes, {N. H.} and I. Sousa and C. Toma and G. Barnby and H. Butler and L. Winchester and Scerri, {T. S.} and F. Minopoli and J. Reichert and G. Cai and Buxbaum, {J. D.} and O. Korvatska and Schellenberg, {G. D.} and G. Dawson and Bildt, {A. D.} and Minderaa, {R. B.} and Mulder, {E. J.} and Morris, {A. P.} and Bailey, {A. J.} and Monaco, {A. P.}",

year = "2010",

month = sep,

doi = "10.1038/mp.2009.34",

language = "English",

volume = "15",

pages = "954--968",

journal = "Molecular psychiatry",

issn = "1359-4184",

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Lamb, J, Maestrini, E, Pagnamenta, AT, Lamb, JA, Bacchelli, E, Sykes, NH, Sousa, I, Toma, C, Barnby, G, Butler, H, Winchester, L, Scerri, TS, Minopoli, F, Reichert, J, Cai, G, Buxbaum, JD, Korvatska, O, Schellenberg, GD, Dawson, G, Bildt, AD, Minderaa, RB, Mulder, EJ, Morris, AP, Bailey, AJ & Monaco, AP 2010, 'High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility', Molecular psychiatry, vol. 15, no. 9, pp. 954-968. https://doi.org/10.1038/mp.2009.34

TY - JOUR

T1 - High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility

AU - Lamb, Janine

AU - Maestrini, E.

AU - Pagnamenta, A. T.

AU - Lamb, J. A.

AU - Bacchelli, E.

AU - Sykes, N. H.

AU - Sousa, I.

AU - Toma, C.

AU - Barnby, G.

AU - Butler, H.

AU - Winchester, L.

AU - Scerri, T. S.

AU - Minopoli, F.

AU - Reichert, J.

AU - Cai, G.

AU - Buxbaum, J. D.

AU - Korvatska, O.

AU - Schellenberg, G. D.

AU - Dawson, G.

AU - Bildt, A. D.

AU - Minderaa, R. B.

AU - Mulder, E. J.

AU - Morris, A. P.

AU - Bailey, A. J.

AU - Monaco, A. P.

PY - 2010/9

Y1 - 2010/9

N2 - Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family. © 2010 Macmillan Publishers Limited All rights reserved.

AB - Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family. © 2010 Macmillan Publishers Limited All rights reserved.

KW - autistic disorder

KW - chromosome 2

KW - chromosome 7

KW - disease susceptibility

KW - linkage disequilibrium

KW - single nucleotide polymorphisms

U2 - 10.1038/mp.2009.34

DO - 10.1038/mp.2009.34

M3 - Article

SN - 1359-4184

VL - 15

SP - 954

EP - 968

JO - Molecular psychiatry

JF - Molecular psychiatry

IS - 9

ER -

High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility

Abstract

Keywords

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