Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment.
Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techn...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-03-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1004925 |
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| author | Pía Villanueva Ron Nudel Alexander Hoischen María Angélica Fernández Nuala H Simpson Christian Gilissen Rose H Reader Lillian Jara María Magdalena Echeverry Clyde Francks Gillian Baird Gina Conti-Ramsden Anne O'Hare Patrick F Bolton Elizabeth R Hennessy SLI Consortium Hernán Palomino Luis Carvajal-Carmona Joris A Veltman Jean-Baptiste Cazier Zulema De Barbieri Simon E Fisher Dianne F Newbury |
| author_facet | Pía Villanueva Ron Nudel Alexander Hoischen María Angélica Fernández Nuala H Simpson Christian Gilissen Rose H Reader Lillian Jara María Magdalena Echeverry Clyde Francks Gillian Baird Gina Conti-Ramsden Anne O'Hare Patrick F Bolton Elizabeth R Hennessy SLI Consortium Hernán Palomino Luis Carvajal-Carmona Joris A Veltman Jean-Baptiste Cazier Zulema De Barbieri Simon E Fisher Dianne F Newbury |
| author_sort | Pía Villanueva |
| collection | DOAJ |
| description | Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10-4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model. |
| format | Article |
| id | doaj-art-66247ded0cac4a7f9d30a78d361fe1aa |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2015-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-66247ded0cac4a7f9d30a78d361fe1aa2025-08-20T02:34:09ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-03-01113e100492510.1371/journal.pgen.1004925Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment.Pía VillanuevaRon NudelAlexander HoischenMaría Angélica FernándezNuala H SimpsonChristian GilissenRose H ReaderLillian JaraMaría Magdalena EcheverryClyde FrancksGillian BairdGina Conti-RamsdenAnne O'HarePatrick F BoltonElizabeth R HennessySLI ConsortiumHernán PalominoLuis Carvajal-CarmonaJoris A VeltmanJean-Baptiste CazierZulema De BarbieriSimon E FisherDianne F NewburyChildren affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10-4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model.https://doi.org/10.1371/journal.pgen.1004925 |
| spellingShingle | Pía Villanueva Ron Nudel Alexander Hoischen María Angélica Fernández Nuala H Simpson Christian Gilissen Rose H Reader Lillian Jara María Magdalena Echeverry Clyde Francks Gillian Baird Gina Conti-Ramsden Anne O'Hare Patrick F Bolton Elizabeth R Hennessy SLI Consortium Hernán Palomino Luis Carvajal-Carmona Joris A Veltman Jean-Baptiste Cazier Zulema De Barbieri Simon E Fisher Dianne F Newbury Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment. PLoS Genetics |
| title | Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment. |
| title_full | Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment. |
| title_fullStr | Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment. |
| title_full_unstemmed | Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment. |
| title_short | Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment. |
| title_sort | exome sequencing in an admixed isolated population indicates nfxl1 variants confer a risk for specific language impairment |
| url | https://doi.org/10.1371/journal.pgen.1004925 |
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