Neuron
Volume 70, Issue 5, 9 June 2011, Pages 886-897
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Article
Rare De Novo and Transmitted Copy-Number Variation in Autistic Spectrum Disorders

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Summary

To explore the genetic contribution to autistic spectrum disorders (ASDs), we have studied genomic copy-number variation in a large cohort of families with a single affected child and at least one unaffected sibling. We confirm a major contribution from de novo deletions and duplications but also find evidence of a role for inherited “ultrarare” duplications. Our results show that, relative to males, females have greater resistance to autism from genetic causes, which raises the question of the fate of female carriers. By analysis of the proportion and number of recurrent loci, we set a lower bound for distinct target loci at several hundred. We find many new candidate regions, adding substantially to the list of potential gene targets, and confirm several loci previously observed. The functions of the genes in the regions of de novo variation point to a great diversity of genetic causes but also suggest functional convergence.

Highlights

► Rare de novo CNVs and transmitted duplications contribute to ASDs ► More candidate regions are detailed at a finer scale than earlier CGH studies ► A lower bound on the total number of ASD target loci is at least several hundred ► The fate of undiagnosed female carriers of ASD-causing mutations is unclear

Cited by (0)

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Present address: Ontario Institute for Cancer Research, Toronto, Ontario, Canada M5G 0A3

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Present address: Mumbai, India

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Present address: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10026, USA