Repository logo
 
Publication

The role of rare compound heterozygous events in autism spectrum disorder

2020-06-22Journal article Open access
Simple item page
dc.contributor.authorLin, Bochao Danae
dc.contributor.authorColas, Fabrice
dc.contributor.authorNijman, Isaac J.
dc.contributor.authorMedic, Jelena
dc.contributor.authorBrands, William
dc.contributor.authorParr, Jeremy R.
dc.contributor.authorvan Eijk, Kristel R.
dc.contributor.authorKlauck, Sabine M.
dc.contributor.authorChiocchetti, Andreas G.
dc.contributor.authorFreitag, Christine M.
dc.contributor.authorMaestrini, Elena
dc.contributor.authorBacchelli, Elena
dc.contributor.authorCoon, Hilary
dc.contributor.authorVicente, Astrid
dc.contributor.authorOliveira, Guiomar
dc.contributor.authorPagnamenta, Alistair T.
dc.contributor.authorGallagher, Louise
dc.contributor.authorEnnis, Sean
dc.contributor.authorAnney, Richard
dc.contributor.authorBourgeron, Thomas
dc.contributor.authorLuykx, Jurjen J.
dc.contributor.authorVorstman, Jacob
dc.date.accessioned2021-03-05T16:18:32Z
dc.date.available2021-03-05T16:18:32Z
dc.date.issued2020-06-22
dc.description.abstractThe identification of genetic variants underlying autism spectrum disorders (ASDs) may contribute to a better understanding of their underlying biology. To examine the possible role of a specific type of compound heterozygosity in ASD, namely, the occurrence of a deletion together with a functional nucleotide variant on the remaining allele, we sequenced 550 genes in 149 individuals with ASD and their deletion-transmitting parents. This approach allowed us to identify additional sequence variants occurring in the remaining allele of the deletion. Our main goal was to compare the rate of sequence variants in remaining alleles of deleted regions between probands and the deletion-transmitting parents. We also examined the predicted functional effect of the identified variants using Combined Annotation-Dependent Depletion (CADD) scores. The single nucleotide variant-deletion co-occurrence was observed in 13.4% of probands, compared with 8.1% of parents. The cumulative burden of sequence variants (n = 68) in pooled proband sequences was higher than the burden in pooled sequences from the deletion-transmitting parents (n = 41, X2 = 6.69, p = 0.0097). After filtering for those variants predicted to be most deleterious, we observed 21 of such variants in probands versus 8 in their deletion-transmitting parents (X2 = 5.82, p = 0.016). Finally, cumulative CADD scores conferred by these variants were significantly higher in probands than in deletion-transmitting parents (burden test, β = 0.13; p = 1.0 × 10-5). Our findings suggest that the compound heterozygosity described in the current study may be one of several mechanisms explaining variable penetrance of CNVs with known pathogenicity for ASD.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationTransl Psychiatry. 2020 Jun 22;10(1):204. doi: 10.1038/s41398-020-00866-7.pt_PT
dc.identifier.doi10.1038/s41398-020-00866-7pt_PT
dc.identifier.eissn2158-3188
dc.identifier.urihttp://hdl.handle.net/10400.18/7339
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Publishing Grouppt_PT
dc.relation.publisherversionhttps://www.nature.com/articles/s41398-020-00866-7pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAutismpt_PT
dc.subjectAutism Spectrum Disorderspt_PT
dc.subjectASDpt_PT
dc.subjectPerturbações do Desenvolvimento Infantil e Saúde Mentalpt_PT
dc.titleThe role of rare compound heterozygous events in autism spectrum disorderpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue1pt_PT
oaire.citation.startPage204pt_PT
oaire.citation.titleTranslational Psychiatrypt_PT
oaire.citation.volume10pt_PT
rcaap.embargofctAcesso de acordo com página web do editor da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
The role of rare compound heterozygous events.pdf
Size:
831.09 KB
Format:
Adobe Portable Document Format
Download

Collections

DPSPDNT - Artigos em revistas internacionais