An integrated analysis of rare CNV and exome variation in Autism Spectrum Disorder using the Infinium PsychArray
| Autor: | Cinzia Cameli, Elena Maestrini, Marta Viggiano, Roberta Igliozzi, Agatino Battaglia, Elena Bacchelli, Alice Mancini, Raffaella Tancredi |
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| Přispěvatelé: | Bacchelli, Elena, Cameli, Cinzia, Viggiano, Marta, Igliozzi, Roberta, Mancini, Alice, Tancredi, Raffaella, Battaglia, Agatino, Maestrini, Elena |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proband Male Parents Candidate gene CNTNAP2 Autism Spectrum Disorder Integrated analysi lcsh:Medicine Linkage Disequilibrium 0302 clinical medicine Gene Duplication Exome variant Exome Copy-number variation lcsh:Science Oligonucleotide Array Sequence Analysis Genetics Multidisciplinary Autism spectrum disorders Autism spectrum disorder (ASD) Pedigree Italy Autism spectrum disorder SFARI genes Female Risk Heterozygote DNA Copy Number Variations Genotype Copy number variants (CNVs) Genetic predisposition to disease Biology Polymorphism Single Nucleotide behavioral disciplines and activities Article 03 medical and health sciences mental disorders Infinium PsychArray medicine Genetic predisposition Humans Genetic Association Studies Family Health lcsh:R Rare variant medicine.disease 030104 developmental biology Autism lcsh:Q 030217 neurology & neurosurgery Gene Deletion |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) |
| Popis: | Autism spectrum disorder (ASD) is a neurodevelopmental condition with a complex and heterogeneous genetic etiology. While a proportion of ASD risk is attributable to common variants, rare copy-number variants (CNVs) and protein-disrupting single-nucleotide variants (SNVs) have been shown to significantly contribute to ASD etiology. We analyzed a homogeneous cohort of 127 ASD Italian families genotyped with the Illumina PsychArray, to perform an integrated analysis of CNVs and SNVs and to assess their contribution to ASD risk. We observed a higher burden of rare CNVs, especially deletions, in ASD individuals versus unaffected controls. Furthermore, we identified a significant enrichment of rare CNVs intersecting ASD candidate genes reported in the SFARI database. Family-based analysis of rare SNVs genotyped by the PsychArray also indicated an increased transmission of rare SNV variants from heterozygous parents to probands, supporting a multigenic model of ASD risk with significant contributions of both variant types. Moreover, our study reinforced the evidence for a significant role of VPS13B, WWOX, CNTNAP2, RBFOX1, MACROD2, APBA2, PARK2, GPHN, and RNF113A genes in ASD susceptibility. Finally, we showed that the PsychArray, besides providing useful genotyping data in psychiatric disorders, is a valuable and cost-efficient tool for genic CNV detection, down to 10 kb. |
| Databáze: | OpenAIRE |
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