Strong association of de novo copy number mutations with autism

Jonathan Sebat, B. Lakshmi, Dheeraj Malhotra, Jennifer Troge, Christa Lese-Martin, Tom Walsh, Boris Yamrom, Seungtai Yoon, Alex Krasnitz, Jude Kendall, Anthony Leotta, Deepa Pai, Ray Zhang, Yoon Ha Lee, James Hicks, Sarah J. Spence, Annette T. Lee, Kaija Puura, Terho Lehtimäki, David Ledbetter & 12 others Peter K. Gregersen, Joel Bregman, James S. Sutcliffe, Vaidehi Jobanputra, Wendy Chung, Dorothy Warburton, Mary Claire King, David Skuse, Daniel H. Geschwind, T. Conrad Gilliam, Qian K. Ye, Michael Wigler

Research output: Contribution to journalArticle

1786 Citations (Scopus)

Abstract

We tested the hypothesis that de novo copy number variation (CNV) is associated with autism spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the genomic DNA of patients and unaffected subjects to detect copy number variants not present in their respective parents. Candidate genomic regions were validated by higher-resolution CGH, paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping. Confirmed de novo CNVs were significantly associated with autism (P = 0.0005). Such CNVs were identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (3%) of patients with an affected first-degree relative, and in 2 out of 196 (1%) of controls. Most de novo CNVs were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous and included mutations of single genes. These findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized.

Original languageEnglish (US)
Pages (from-to)445-449
Number of pages5
JournalScience
Volume316
Issue number5823
DOIs
StatePublished - Apr 20 2007

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Autistic Disorder
Comparative Genomic Hybridization
Mutation
Paternity
Germ-Line Mutation
Fluorescence In Situ Hybridization
Cytogenetics
Microsatellite Repeats
Parents
DNA
Genes
Autism Spectrum Disorder

ASJC Scopus subject areas

  • General

Cite this

Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., ... Wigler, M. (2007). Strong association of de novo copy number mutations with autism. Science, 316(5823), 445-449. https://doi.org/10.1126/science.1138659

Strong association of de novo copy number mutations with autism. / Sebat, Jonathan; Lakshmi, B.; Malhotra, Dheeraj; Troge, Jennifer; Lese-Martin, Christa; Walsh, Tom; Yamrom, Boris; Yoon, Seungtai; Krasnitz, Alex; Kendall, Jude; Leotta, Anthony; Pai, Deepa; Zhang, Ray; Lee, Yoon Ha; Hicks, James; Spence, Sarah J.; Lee, Annette T.; Puura, Kaija; Lehtimäki, Terho; Ledbetter, David; Gregersen, Peter K.; Bregman, Joel; Sutcliffe, James S.; Jobanputra, Vaidehi; Chung, Wendy; Warburton, Dorothy; King, Mary Claire; Skuse, David; Geschwind, Daniel H.; Gilliam, T. Conrad; Ye, Qian K.; Wigler, Michael.

In: Science, Vol. 316, No. 5823, 20.04.2007, p. 445-449.

Research output: Contribution to journalArticle

Sebat, J, Lakshmi, B, Malhotra, D, Troge, J, Lese-Martin, C, Walsh, T, Yamrom, B, Yoon, S, Krasnitz, A, Kendall, J, Leotta, A, Pai, D, Zhang, R, Lee, YH, Hicks, J, Spence, SJ, Lee, AT, Puura, K, Lehtimäki, T, Ledbetter, D, Gregersen, PK, Bregman, J, Sutcliffe, JS, Jobanputra, V, Chung, W, Warburton, D, King, MC, Skuse, D, Geschwind, DH, Gilliam, TC, Ye, QK & Wigler, M 2007, 'Strong association of de novo copy number mutations with autism', Science, vol. 316, no. 5823, pp. 445-449. https://doi.org/10.1126/science.1138659
Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T et al. Strong association of de novo copy number mutations with autism. Science. 2007 Apr 20;316(5823):445-449. https://doi.org/10.1126/science.1138659
Sebat, Jonathan ; Lakshmi, B. ; Malhotra, Dheeraj ; Troge, Jennifer ; Lese-Martin, Christa ; Walsh, Tom ; Yamrom, Boris ; Yoon, Seungtai ; Krasnitz, Alex ; Kendall, Jude ; Leotta, Anthony ; Pai, Deepa ; Zhang, Ray ; Lee, Yoon Ha ; Hicks, James ; Spence, Sarah J. ; Lee, Annette T. ; Puura, Kaija ; Lehtimäki, Terho ; Ledbetter, David ; Gregersen, Peter K. ; Bregman, Joel ; Sutcliffe, James S. ; Jobanputra, Vaidehi ; Chung, Wendy ; Warburton, Dorothy ; King, Mary Claire ; Skuse, David ; Geschwind, Daniel H. ; Gilliam, T. Conrad ; Ye, Qian K. ; Wigler, Michael. / Strong association of de novo copy number mutations with autism. In: Science. 2007 ; Vol. 316, No. 5823. pp. 445-449.
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AU - Yamrom, Boris

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AU - King, Mary Claire

AU - Skuse, David

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