Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment

Research output: Contribution to journalArticle

Standard

Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment. / Villanueva, Pía; Nudel, Ron; Hoischen, Alexander; Fernández, María Angélica; Simpson, Nuala H; Gilissen, Christian; Reader, Rose H; Jara, Lillian; Echeverry, María Magdalena; Echeverry, Maria Magdalena; Francks, Clyde; Baird, Gillian; Conti-Ramsden, Gina; O'Hare, Anne; Bolton, Patrick F; Hennessy, Elizabeth R; Palomino, Hernán; Carvajal-Carmona, Luis; Veltman, Joris A; Cazier, Jean-Baptiste; De Barbieri, Zulema; Fisher, Simon E; Newbury, Dianne F; SLI Consortium.

In: PLoS Genetics, Vol. 11, No. 3, e1004925, 17.03.2015.

Research output: Contribution to journalArticle

Harvard

Villanueva, P, Nudel, R, Hoischen, A, Fernández, MA, Simpson, NH, Gilissen, C, Reader, RH, Jara, L, Echeverry, MM, Echeverry, MM, Francks, C, Baird, G, Conti-Ramsden, G, O'Hare, A, Bolton, PF, Hennessy, ER, Palomino, H, Carvajal-Carmona, L, Veltman, JA, Cazier, J-B, De Barbieri, Z, Fisher, SE, Newbury, DF & SLI Consortium 2015, 'Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment', PLoS Genetics, vol. 11, no. 3, e1004925. https://doi.org/10.1371/journal.pgen.1004925

APA

Villanueva, P., Nudel, R., Hoischen, A., Fernández, M. A., Simpson, N. H., Gilissen, C., Reader, R. H., Jara, L., Echeverry, M. M., Echeverry, M. M., Francks, C., Baird, G., Conti-Ramsden, G., O'Hare, A., Bolton, P. F., Hennessy, E. R., Palomino, H., Carvajal-Carmona, L., Veltman, J. A., ... SLI Consortium (2015). Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment. PLoS Genetics, 11(3), [e1004925]. https://doi.org/10.1371/journal.pgen.1004925

Vancouver

Author

Villanueva, Pía ; Nudel, Ron ; Hoischen, Alexander ; Fernández, María Angélica ; Simpson, Nuala H ; Gilissen, Christian ; Reader, Rose H ; Jara, Lillian ; Echeverry, María Magdalena ; Echeverry, Maria Magdalena ; Francks, Clyde ; Baird, Gillian ; Conti-Ramsden, Gina ; O'Hare, Anne ; Bolton, Patrick F ; Hennessy, Elizabeth R ; Palomino, Hernán ; Carvajal-Carmona, Luis ; Veltman, Joris A ; Cazier, Jean-Baptiste ; De Barbieri, Zulema ; Fisher, Simon E ; Newbury, Dianne F ; SLI Consortium. / Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment. In: PLoS Genetics. 2015 ; Vol. 11, No. 3.

Bibtex

@article{8e5939f1ca704b95b8600b65d92f91a8,
title = "Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment",
abstract = "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.",
author = "P{\'i}a Villanueva and Ron Nudel and Alexander Hoischen and Fern{\'a}ndez, {Mar{\'i}a Ang{\'e}lica} and Simpson, {Nuala H} and Christian Gilissen and Reader, {Rose H} and Lillian Jara and Echeverry, {Mar{\'i}a Magdalena} and Echeverry, {Maria Magdalena} and Clyde Francks and Gillian Baird and Gina Conti-Ramsden and Anne O'Hare and Bolton, {Patrick F} and Hennessy, {Elizabeth R} and Hern{\'a}n Palomino and Luis Carvajal-Carmona and Veltman, {Joris A} and Jean-Baptiste Cazier and {De Barbieri}, Zulema and Fisher, {Simon E} and Newbury, {Dianne F} and {SLI Consortium}",
year = "2015",
month = mar
day = "17",
doi = "10.1371/journal.pgen.1004925",
language = "English",
volume = "11",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science (PLOS)",
number = "3",

}

RIS

TY - JOUR

T1 - Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment

AU - Villanueva, Pía

AU - Nudel, Ron

AU - Hoischen, Alexander

AU - Fernández, María Angélica

AU - Simpson, Nuala H

AU - Gilissen, Christian

AU - Reader, Rose H

AU - Jara, Lillian

AU - Echeverry, María Magdalena

AU - Echeverry, Maria Magdalena

AU - Francks, Clyde

AU - Baird, Gillian

AU - Conti-Ramsden, Gina

AU - O'Hare, Anne

AU - Bolton, Patrick F

AU - Hennessy, Elizabeth R

AU - Palomino, Hernán

AU - Carvajal-Carmona, Luis

AU - Veltman, Joris A

AU - Cazier, Jean-Baptiste

AU - De Barbieri, Zulema

AU - Fisher, Simon E

AU - Newbury, Dianne F

AU - SLI Consortium

PY - 2015/3/17

Y1 - 2015/3/17

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pgen.1004925

DO - 10.1371/journal.pgen.1004925

M3 - Article

C2 - 25781923

VL - 11

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 3

M1 - e1004925

ER -