Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism.
Although autism has a clear genetic component, the high genetic heterogeneity of the disorder has been a challenge for the identification of causative genes. We used homozygosity analysis to identify probands from nonconsanguineous families that showed evidence of distant shared ancestry, suggesting...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3325173?pdf=render |
| _version_ | 1819242397263986688 |
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| author | Maria H Chahrour Timothy W Yu Elaine T Lim Bulent Ataman Michael E Coulter R Sean Hill Christine R Stevens Christian R Schubert ARRA Autism Sequencing Collaboration Michael E Greenberg Stacey B Gabriel Christopher A Walsh |
| author_facet | Maria H Chahrour Timothy W Yu Elaine T Lim Bulent Ataman Michael E Coulter R Sean Hill Christine R Stevens Christian R Schubert ARRA Autism Sequencing Collaboration Michael E Greenberg Stacey B Gabriel Christopher A Walsh |
| author_sort | Maria H Chahrour |
| collection | DOAJ |
| description | Although autism has a clear genetic component, the high genetic heterogeneity of the disorder has been a challenge for the identification of causative genes. We used homozygosity analysis to identify probands from nonconsanguineous families that showed evidence of distant shared ancestry, suggesting potentially recessive mutations. Whole-exome sequencing of 16 probands revealed validated homozygous, potentially pathogenic recessive mutations that segregated perfectly with disease in 4/16 families. The candidate genes (UBE3B, CLTCL1, NCKAP5L, ZNF18) encode proteins involved in proteolysis, GTPase-mediated signaling, cytoskeletal organization, and other pathways. Furthermore, neuronal depolarization regulated the transcription of these genes, suggesting potential activity-dependent roles in neurons. We present a multidimensional strategy for filtering whole-exome sequence data to find candidate recessive mutations in autism, which may have broader applicability to other complex, heterogeneous disorders. |
| first_indexed | 2024-12-23T14:39:09Z |
| format | Article |
| id | doaj.art-2902585976fa4160a7a77dc60c4d5f5a |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-23T14:39:09Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-2902585976fa4160a7a77dc60c4d5f5a2022-12-21T17:43:15ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-0184e100263510.1371/journal.pgen.1002635Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism.Maria H ChahrourTimothy W YuElaine T LimBulent AtamanMichael E CoulterR Sean HillChristine R StevensChristian R SchubertARRA Autism Sequencing CollaborationMichael E GreenbergStacey B GabrielChristopher A WalshAlthough autism has a clear genetic component, the high genetic heterogeneity of the disorder has been a challenge for the identification of causative genes. We used homozygosity analysis to identify probands from nonconsanguineous families that showed evidence of distant shared ancestry, suggesting potentially recessive mutations. Whole-exome sequencing of 16 probands revealed validated homozygous, potentially pathogenic recessive mutations that segregated perfectly with disease in 4/16 families. The candidate genes (UBE3B, CLTCL1, NCKAP5L, ZNF18) encode proteins involved in proteolysis, GTPase-mediated signaling, cytoskeletal organization, and other pathways. Furthermore, neuronal depolarization regulated the transcription of these genes, suggesting potential activity-dependent roles in neurons. We present a multidimensional strategy for filtering whole-exome sequence data to find candidate recessive mutations in autism, which may have broader applicability to other complex, heterogeneous disorders.http://europepmc.org/articles/PMC3325173?pdf=render |
| spellingShingle | Maria H Chahrour Timothy W Yu Elaine T Lim Bulent Ataman Michael E Coulter R Sean Hill Christine R Stevens Christian R Schubert ARRA Autism Sequencing Collaboration Michael E Greenberg Stacey B Gabriel Christopher A Walsh Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. PLoS Genetics |
| title | Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. |
| title_full | Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. |
| title_fullStr | Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. |
| title_full_unstemmed | Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. |
| title_short | Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. |
| title_sort | whole exome sequencing and homozygosity analysis implicate depolarization regulated neuronal genes in autism |
| url | http://europepmc.org/articles/PMC3325173?pdf=render |
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