Rare de novo and transmitted copy-number variation in autistic spectrum disorders.

By D. Levy, M. Ronemus, B. Yamrom, Yoon-ha Lee, A. Leotta, J. Kendall, S. Marks, B. Lakshmi, D. Pai, Kenny Q. Ye and 7 more. Neuron, 2011

750 citations recorded by the source corpus.

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.

Subfields: Genetics, Pediatrics, Perinatology and Child Health

View Paper: https://www.semanticscholar.org/paper/38501686e8e20e81f59731ee2bf1f0b6d355629c

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In Genetics

In Pediatrics, Perinatology and Child Health

Citations in the corpus

De Novo Gene Disruptions in Children on the Autistic Spectrum (2012, background): “The lack of signal is not attributable to the type of population we study, as we observe de novo copy number imbalance of the expected magnitude in this very same population (Levy et al., 2011; Sanders et al., 2011).”
Advancing the understanding of autism disease mechanisms through genetics (2016, neutral): “Furthermore, estimates of the influence of de novo mutation on risk for ASD have been derived mostly from a sample of simplex families ( Box 1 ), which may inflate the contribution of de novo mutations 40,44,45,47,49 .”
Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. (2011, methodology): “1M arrays from among a total of 1340 overlapping subjects (probands or siblings), as described by Levy and colleagues in this issue (Levy et al., 2011).”
Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci (2015, methodology): “Including additional dnCNV data (Levy et al., 2011; Pinto et al., 2014) identifies an additional two loci: deletions at NRXN1 and deletions and duplications at 22q11.”
Sex/Gender Differences and Autism: Setting the Scene for Future Research (2015, background): “…females with autism have a greater etiological/genetic load (re ﬂ ecting a female-protective effect), data from the SSC show a trend toward more gene-rich de novo copy number variations (CNVs) in females than in males with autism, 22 particularly microduplications, 25 and in functional hub genes.”