Recurrent 16p11.2 microdeletions in autism

Ravinesh A. Kumar, Samer Karamohamed, Jyotsna Sudi, Don Conrad, Camille Brune, Judith A. Badner, T. Conrad Gilliam, Norma J. Nowak, Edwin H. Cook, William B. Dobyns, Susan L. Christian

Research output: Contribution to journalArticle

456 Citations (Scopus)

Abstract

Autism is a childhood neurodevelopmental disorder with a strong genetic component, yet the identification of autism susceptibility loci remains elusive. We investigated 180 autism probands and 372 control subjects by array comparative genomic hybridization (aCGH) using a 19K whole-genome tiling path bacterial artificial chromosome microarray to identify submicroscopic chromosomal rearrangements specific to autism. We discovered a recurrent 16p11.2 microdeletion in two probands with autism and none in controls. The deletion spans ∼500-kb and is flanked by ∼147-kb segmental duplications (SDs) that are >99% identical, a common characteristic of genomic disorders. We assessed the frequency of this new autism genomic disorder by screening an additional 532 probands and 465 controls by quantitative PCR and identified two more patients but no controls with the microdeletion, indicating a combined frequency of 0.6% (4/712 autism versus 0/837 controls; Fisher exact test P = 0.044). We confirmed all 16p11.2 deletions using fluorescence in situ hybridization, microsatellite analyses and aCGH, and mapped the approximate deletion breakpoints to the edges of the flanking SDs using a custom-designed high-density oligonucleotide microarray. Bioinformatic analysis localized 12 of the 25 genes within the microdeletion to nodes in one interaction network. We performed phenotype analyses and found no striking features that distinguish patients with the 16p11.2 microdeletion as a distinct autism subtype. Our work reports the first frequency, breakpoint, bioinformatic and phenotypic analyses of a de novo 16p11.2 microdeletion that represents one of the most common recurrent genomic disorders associated with autism to date.

Original languageEnglish (US)
Pages (from-to)628-638
Number of pages11
JournalHuman Molecular Genetics
Volume17
Issue number4
DOIs
StatePublished - Feb 14 2008
Externally publishedYes

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Autistic Disorder
Genomic Segmental Duplications
Comparative Genomic Hybridization
Computational Biology
Bacterial Artificial Chromosomes
Oligonucleotide Array Sequence Analysis
Fluorescence In Situ Hybridization
Microsatellite Repeats
Genome
Phenotype
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Kumar, R. A., Karamohamed, S., Sudi, J., Conrad, D., Brune, C., Badner, J. A., ... Christian, S. L. (2008). Recurrent 16p11.2 microdeletions in autism. Human Molecular Genetics, 17(4), 628-638. https://doi.org/10.1093/hmg/ddm376

Recurrent 16p11.2 microdeletions in autism. / Kumar, Ravinesh A.; Karamohamed, Samer; Sudi, Jyotsna; Conrad, Don; Brune, Camille; Badner, Judith A.; Gilliam, T. Conrad; Nowak, Norma J.; Cook, Edwin H.; Dobyns, William B.; Christian, Susan L.

In: Human Molecular Genetics, Vol. 17, No. 4, 14.02.2008, p. 628-638.

Research output: Contribution to journalArticle

Kumar, RA, Karamohamed, S, Sudi, J, Conrad, D, Brune, C, Badner, JA, Gilliam, TC, Nowak, NJ, Cook, EH, Dobyns, WB & Christian, SL 2008, 'Recurrent 16p11.2 microdeletions in autism', Human Molecular Genetics, vol. 17, no. 4, pp. 628-638. https://doi.org/10.1093/hmg/ddm376
Kumar RA, Karamohamed S, Sudi J, Conrad D, Brune C, Badner JA et al. Recurrent 16p11.2 microdeletions in autism. Human Molecular Genetics. 2008 Feb 14;17(4):628-638. https://doi.org/10.1093/hmg/ddm376
Kumar, Ravinesh A. ; Karamohamed, Samer ; Sudi, Jyotsna ; Conrad, Don ; Brune, Camille ; Badner, Judith A. ; Gilliam, T. Conrad ; Nowak, Norma J. ; Cook, Edwin H. ; Dobyns, William B. ; Christian, Susan L. / Recurrent 16p11.2 microdeletions in autism. In: Human Molecular Genetics. 2008 ; Vol. 17, No. 4. pp. 628-638.
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