Identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population.
Structural variation is thought to play a major etiological role in the development of autism spectrum disorders (ASDs), and numerous studies documenting the relevance of copy number variants (CNVs) in ASD have been published since 2006. To determine if large ASD families harbor high-impact CNVs tha...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/8f019b4696504a81b6489786168f61ab |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:8f019b4696504a81b6489786168f61ab |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:8f019b4696504a81b6489786168f61ab2021-11-18T08:01:42ZIdentification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population.1932-620310.1371/journal.pone.0052239https://doaj.org/article/8f019b4696504a81b6489786168f61ab2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23341896/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Structural variation is thought to play a major etiological role in the development of autism spectrum disorders (ASDs), and numerous studies documenting the relevance of copy number variants (CNVs) in ASD have been published since 2006. To determine if large ASD families harbor high-impact CNVs that may have broader impact in the general ASD population, we used the Affymetrix genome-wide human SNP array 6.0 to identify 153 putative autism-specific CNVs present in 55 individuals with ASD from 9 multiplex ASD pedigrees. To evaluate the actual prevalence of these CNVs as well as 185 CNVs reportedly associated with ASD from published studies many of which are insufficiently powered, we designed a custom Illumina array and used it to interrogate these CNVs in 3,000 ASD cases and 6,000 controls. Additional single nucleotide variants (SNVs) on the array identified 25 CNVs that we did not detect in our family studies at the standard SNP array resolution. After molecular validation, our results demonstrated that 15 CNVs identified in high-risk ASD families also were found in two or more ASD cases with odds ratios greater than 2.0, strengthening their support as ASD risk variants. In addition, of the 25 CNVs identified using SNV probes on our custom array, 9 also had odds ratios greater than 2.0, suggesting that these CNVs also are ASD risk variants. Eighteen of the validated CNVs have not been reported previously in individuals with ASD and three have only been observed once. Finally, we confirmed the association of 31 of 185 published ASD-associated CNVs in our dataset with odds ratios greater than 2.0, suggesting they may be of clinical relevance in the evaluation of children with ASDs. Taken together, these data provide strong support for the existence and application of high-impact CNVs in the clinical genetic evaluation of children with ASD.Nori MatsunamiDexter HadleyCharles H HenselG Bryce ChristensenCecilia KimEdward FrackeltonKelly ThomasRenata Pellegrino da SilvaJeff StevensLisa BairdBrith OtterudKaren HoTena VarvilTami LeppertChristophe G LambertMark LeppertHakon HakonarsonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e52239 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Nori Matsunami Dexter Hadley Charles H Hensel G Bryce Christensen Cecilia Kim Edward Frackelton Kelly Thomas Renata Pellegrino da Silva Jeff Stevens Lisa Baird Brith Otterud Karen Ho Tena Varvil Tami Leppert Christophe G Lambert Mark Leppert Hakon Hakonarson Identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population. |
| description |
Structural variation is thought to play a major etiological role in the development of autism spectrum disorders (ASDs), and numerous studies documenting the relevance of copy number variants (CNVs) in ASD have been published since 2006. To determine if large ASD families harbor high-impact CNVs that may have broader impact in the general ASD population, we used the Affymetrix genome-wide human SNP array 6.0 to identify 153 putative autism-specific CNVs present in 55 individuals with ASD from 9 multiplex ASD pedigrees. To evaluate the actual prevalence of these CNVs as well as 185 CNVs reportedly associated with ASD from published studies many of which are insufficiently powered, we designed a custom Illumina array and used it to interrogate these CNVs in 3,000 ASD cases and 6,000 controls. Additional single nucleotide variants (SNVs) on the array identified 25 CNVs that we did not detect in our family studies at the standard SNP array resolution. After molecular validation, our results demonstrated that 15 CNVs identified in high-risk ASD families also were found in two or more ASD cases with odds ratios greater than 2.0, strengthening their support as ASD risk variants. In addition, of the 25 CNVs identified using SNV probes on our custom array, 9 also had odds ratios greater than 2.0, suggesting that these CNVs also are ASD risk variants. Eighteen of the validated CNVs have not been reported previously in individuals with ASD and three have only been observed once. Finally, we confirmed the association of 31 of 185 published ASD-associated CNVs in our dataset with odds ratios greater than 2.0, suggesting they may be of clinical relevance in the evaluation of children with ASDs. Taken together, these data provide strong support for the existence and application of high-impact CNVs in the clinical genetic evaluation of children with ASD. |
| format |
article |
| author |
Nori Matsunami Dexter Hadley Charles H Hensel G Bryce Christensen Cecilia Kim Edward Frackelton Kelly Thomas Renata Pellegrino da Silva Jeff Stevens Lisa Baird Brith Otterud Karen Ho Tena Varvil Tami Leppert Christophe G Lambert Mark Leppert Hakon Hakonarson |
| author_facet |
Nori Matsunami Dexter Hadley Charles H Hensel G Bryce Christensen Cecilia Kim Edward Frackelton Kelly Thomas Renata Pellegrino da Silva Jeff Stevens Lisa Baird Brith Otterud Karen Ho Tena Varvil Tami Leppert Christophe G Lambert Mark Leppert Hakon Hakonarson |
| author_sort |
Nori Matsunami |
| title |
Identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population. |
| title_short |
Identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population. |
| title_full |
Identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population. |
| title_fullStr |
Identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population. |
| title_full_unstemmed |
Identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population. |
| title_sort |
identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large asd population. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/8f019b4696504a81b6489786168f61ab |
| work_keys_str_mv |
AT norimatsunami identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT dexterhadley identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT charleshhensel identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT gbrycechristensen identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT ceciliakim identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT edwardfrackelton identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT kellythomas identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT renatapellegrinodasilva identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT jeffstevens identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT lisabaird identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT brithotterud identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT karenho identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT tenavarvil identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT tamileppert identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT christopheglambert identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT markleppert identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation AT hakonhakonarson identificationofrarerecurrentcopynumbervariantsinhighriskautismfamiliesandtheirprevalenceinalargeasdpopulation |
| _version_ |
1718422616684888064 |