Candidate gene variant effects on language disorders in Robinson Crusoe Island
Background: Robinson Crusoe Island is a geographically and socially isolated settlement located over 600 km west of the Port of Valparíso, Chile. An unusually high incidence (30%) of the Chilean equivalent of developmental language disorder (in Spanish, trastorno especifico de lenguaje (TEL)), has b...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-02-01
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| Series: | Annals of Human Biology |
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| Online Access: | http://dx.doi.org/10.1080/03014460.2019.1622776 |
| _version_ | 1827818387740295168 |
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| author | Hayley S. Mountford Pía Villanueva María Angélica Fernández Zulema De Barbieri Jean-Baptiste Cazier Dianne F. Newbury |
| author_facet | Hayley S. Mountford Pía Villanueva María Angélica Fernández Zulema De Barbieri Jean-Baptiste Cazier Dianne F. Newbury |
| author_sort | Hayley S. Mountford |
| collection | DOAJ |
| description | Background: Robinson Crusoe Island is a geographically and socially isolated settlement located over 600 km west of the Port of Valparíso, Chile. An unusually high incidence (30%) of the Chilean equivalent of developmental language disorder (in Spanish, trastorno especifico de lenguaje (TEL)), has been reported in Islander children, with 90% of these affected children found to be direct descendants of a pair of original founder-brothers, therefore strongly suggesting a shared genetic basis. Aim: This study reports a comprehensive examination of 34 genes that have been previously directly implicated in language-related mechanisms. It utilises whole-genome sequencing to investigate potential underlying variants in seven TEL affected and 10 unaffected islanders. The aim was to identify the underlying genetic cause of the TEL phenotype under two inheritance model paradigms; Mendelian monogenic and complex susceptibility. Subjects and methods: A targeted candidate gene approach was used to look for rare, shared variants that may underlie the diagnosis of TEL in a Mendelian genetic model. This study tested whether an overall burden of rare variants is enriched in individuals affected by TEL or with Islanders related to the founder-brother lineage. It further examined if any variants segregate with affection status or with founder-brother-related status and, therefore, may increase risk of developing a language disorder as part of a complex model. Finally, gene-based tests were performed to evaluate relationships between combined variation across candidate genes and TEL affection status. Results: No single pathogenic rare variant segregated with either affection or founder-related status within the 34 candidate genes. Additionally, no evidence was found of an overall increased variant burden in TEL individuals compared to those with TLD. Gene-based analysis found no clear association between the combined effects of variants across the 34 genes and affection status or founder-brother-relatedness. Conclusion: The high prevalence of language disorders found on Robinson Crusoe Island is not caused by either a shared high-impact variant, or an increased burden of variants within candidate genes previously implicated in language disorders. We have comprehensively tested for ‘low hanging fruit’ in genes implicated in language disorders. Therefore, the underlying cause of TEL on Robinson Crusoe lies outside of these known language disorder genes, or within a complex susceptibility model. |
| first_indexed | 2024-03-12T00:47:02Z |
| format | Article |
| id | doaj.art-5f0fd0c36c864ba1bb378badd38d5733 |
| institution | Directory Open Access Journal |
| issn | 0301-4460 1464-5033 |
| language | English |
| last_indexed | 2024-03-12T00:47:02Z |
| publishDate | 2019-02-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Annals of Human Biology |
| spelling | doaj.art-5f0fd0c36c864ba1bb378badd38d57332023-09-14T15:36:10ZengTaylor & Francis GroupAnnals of Human Biology0301-44601464-50332019-02-0146210911910.1080/03014460.2019.16227761622776Candidate gene variant effects on language disorders in Robinson Crusoe IslandHayley S. Mountford0Pía Villanueva1María Angélica Fernández2Zulema De Barbieri3Jean-Baptiste Cazier4Dianne F. Newbury5Oxford Brookes UniversityUniversity of ChileUniversity of ChileUniversity of ChileUniversity of BirminghamOxford Brookes UniversityBackground: Robinson Crusoe Island is a geographically and socially isolated settlement located over 600 km west of the Port of Valparíso, Chile. An unusually high incidence (30%) of the Chilean equivalent of developmental language disorder (in Spanish, trastorno especifico de lenguaje (TEL)), has been reported in Islander children, with 90% of these affected children found to be direct descendants of a pair of original founder-brothers, therefore strongly suggesting a shared genetic basis. Aim: This study reports a comprehensive examination of 34 genes that have been previously directly implicated in language-related mechanisms. It utilises whole-genome sequencing to investigate potential underlying variants in seven TEL affected and 10 unaffected islanders. The aim was to identify the underlying genetic cause of the TEL phenotype under two inheritance model paradigms; Mendelian monogenic and complex susceptibility. Subjects and methods: A targeted candidate gene approach was used to look for rare, shared variants that may underlie the diagnosis of TEL in a Mendelian genetic model. This study tested whether an overall burden of rare variants is enriched in individuals affected by TEL or with Islanders related to the founder-brother lineage. It further examined if any variants segregate with affection status or with founder-brother-related status and, therefore, may increase risk of developing a language disorder as part of a complex model. Finally, gene-based tests were performed to evaluate relationships between combined variation across candidate genes and TEL affection status. Results: No single pathogenic rare variant segregated with either affection or founder-related status within the 34 candidate genes. Additionally, no evidence was found of an overall increased variant burden in TEL individuals compared to those with TLD. Gene-based analysis found no clear association between the combined effects of variants across the 34 genes and affection status or founder-brother-relatedness. Conclusion: The high prevalence of language disorders found on Robinson Crusoe Island is not caused by either a shared high-impact variant, or an increased burden of variants within candidate genes previously implicated in language disorders. We have comprehensively tested for ‘low hanging fruit’ in genes implicated in language disorders. Therefore, the underlying cause of TEL on Robinson Crusoe lies outside of these known language disorder genes, or within a complex susceptibility model.http://dx.doi.org/10.1080/03014460.2019.1622776developmental language disorder (dld)language geneticstrastorno especifico de lenguaje (tel)isolated populationlanguage development |
| spellingShingle | Hayley S. Mountford Pía Villanueva María Angélica Fernández Zulema De Barbieri Jean-Baptiste Cazier Dianne F. Newbury Candidate gene variant effects on language disorders in Robinson Crusoe Island Annals of Human Biology developmental language disorder (dld) language genetics trastorno especifico de lenguaje (tel) isolated population language development |
| title | Candidate gene variant effects on language disorders in Robinson Crusoe Island |
| title_full | Candidate gene variant effects on language disorders in Robinson Crusoe Island |
| title_fullStr | Candidate gene variant effects on language disorders in Robinson Crusoe Island |
| title_full_unstemmed | Candidate gene variant effects on language disorders in Robinson Crusoe Island |
| title_short | Candidate gene variant effects on language disorders in Robinson Crusoe Island |
| title_sort | candidate gene variant effects on language disorders in robinson crusoe island |
| topic | developmental language disorder (dld) language genetics trastorno especifico de lenguaje (tel) isolated population language development |
| url | http://dx.doi.org/10.1080/03014460.2019.1622776 |
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