dc.contributor.author |
Cáceres, Alejandro |
dc.contributor.author |
Esko, Tõnu |
dc.contributor.author |
Pappa, Irene |
dc.contributor.author |
Gutiérrez, Armand |
dc.contributor.author |
Lopez-Espinosa, Maria-Jose |
dc.contributor.author |
Llop, Sabrina |
dc.contributor.author |
Bustamante, Mariona |
dc.contributor.author |
Tiemeier, Henning |
dc.contributor.author |
Metspalu, Andres |
dc.contributor.author |
Joshi, Peter K. |
dc.contributor.author |
Wilsonx, James F. |
dc.contributor.author |
Reina-Castillón, Judith |
dc.contributor.author |
Shin, Jean |
dc.contributor.author |
Pausova, Zdenka |
dc.contributor.author |
Paus, Tomáš |
dc.contributor.author |
Sunyer, Jordi |
dc.contributor.author |
Pérez-Jurado, Luis Alberto |
dc.contributor.author |
González, Juan R. |
dc.date |
2016 |
dc.identifier |
https://ddd.uab.cat/record/254168 |
dc.identifier |
urn:10.1371/journal.pone.0157739 |
dc.identifier |
urn:oai:ddd.uab.cat:254168 |
dc.identifier |
urn:pmcid:PMC4927142 |
dc.identifier |
urn:pmc-uid:4927142 |
dc.identifier |
urn:pmid:27355585 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:4927142 |
dc.identifier |
urn:scopus_id:84978975193 |
dc.identifier |
urn:articleid:19326203v11n6e0157739 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Ministerio de Ciencia e Innovación MTM2011-26515 |
dc.relation |
Ministerio de Ciencia e Innovación MTM2010-09526-E |
dc.relation |
Instituto de Salud Carlos III PI1002512 |
dc.relation |
Instituto de Salud Carlos III PI13/02481 |
dc.relation |
Instituto de Salud Carlos III G03/176 |
dc.relation |
Instituto de Salud Carlos III PI041436 |
dc.relation |
Instituto de Salud Carlos III PI081151 |
dc.relation |
Instituto de Salud Carlos III PI041705 |
dc.relation |
Instituto de Salud Carlos III PS09/00432 |
dc.relation |
Instituto de Salud Carlos III PI03/1615 |
dc.relation |
Instituto de Salud Carlos III PI04/1509 |
dc.relation |
Instituto de Salud Carlos III PI04/1112 |
dc.relation |
Instituto de Salud Carlos III PI04/1931 |
dc.relation |
Instituto de Salud Carlos III PI05/1079 |
dc.relation |
Instituto de Salud Carlos III PI05/1052 |
dc.relation |
Instituto de Salud Carlos III PI06/1213 |
dc.relation |
Instituto de Salud Carlos III PI07/0314 |
dc.relation |
Instituto de Salud Carlos III PI09/02647 |
dc.relation |
Instituto de Salud Carlos III PI13/1944 |
dc.relation |
Instituto de Salud Carlos III PI14/0891 |
dc.relation |
Instituto de Salud Carlos III CP15/0025 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1468 |
dc.relation |
Ministerio de Ciencia e Innovación SAF2008-00357 |
dc.relation |
European Commission 201413 |
dc.relation |
European Commission 282957 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 1999/SGR-00241 |
dc.relation |
Instituto de Salud Carlos III FIS-PI1302481 |
dc.relation |
Ministerio de Economía y Competitividad MDM-2014-0370 |
dc.relation |
PloS one ; Vol. 11, Issue 6 (June 2016), art. e0157739 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
dc.title |
Ancient Haplotypes at the 15q24.2 Microdeletion Region Are Linked to Brain Expression of MAN2C1 and Children's Intelligence |
dc.type |
Article |
dc.description.abstract |
The chromosome bands 15q24.1-15q24.3 contain a complex region with numerous segmental duplications that predispose to regional microduplications and microdeletions, both of which have been linked to intellectual disability, speech delay and autistic features. The region may also harbour common inversion polymorphisms whose functional and phenotypic manifestations are unknown. Using single nucleotide polymorphism (SNP) data, we detected four large contiguous haplotype-genotypes at 15q24 with Mendelian inheritance in 2,562 trios, African origin, high population stratification and reduced recombination rates. Although the haplotype-genotypes have been most likely generated by decreased or absent recombination among them, we could not confirm that they were the product of inversion polymorphisms in the region. One of the blocks was composed of three haplotype-genotypes (N1a, N1b and N2), which significantly correlated with intelligence quotient (IQ) in 2,735 children of European ancestry from three independent population cohorts. Homozygosity for N2 was associated with lower verbal IQ (2.4-point loss, p-value = 0.01), while homozygosity for N1b was associated with 3.2-point loss in non-verbal IQ (p-value = 0.0006). The three alleles strongly correlated with expression levels of MAN2C1 and SNUPN in blood and brain. Homozygosity for N2 correlated with over-expression of MAN2C1 over many brain areas but the occipital cortex where N1b homozygous highly under-expressed. Our population-based analyses suggest that MAN2C1 may contribute to the verbal difficulties observed in microduplications and to the intellectual disability of microdeletion syndromes, whose characteristic dosage increment and removal may affect different brain areas. |