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| Pàgina inicial > Articles > Articles publicats > Ancient Haplotypes at the 15q24.2 Microdeletion Region Are Linked to Brain Expression of MAN2C1 and Children's Intelligence |
(Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública) (Centre de Regulació Genòmica) (Erasmus Medical Center. Department of Psychiatry) (University of Tartu. Institute of Molecular and Cell Biology) (University of Edinburgh. Centre for Global Health Research) (University of Toronto. Hospital for Sick Children) (Institut Hospital del Mar d'Investigacions Mèdiques) (Universitat Autònoma de Barcelona. Departament de Matemàtiques)
| Data: | 2016 |
| Resum: | 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. |
| Ajuts: | Ministerio de Ciencia e Innovación MTM2011-26515 Ministerio de Ciencia e Innovación MTM2010-09526-E Instituto de Salud Carlos III PI1002512 Instituto de Salud Carlos III PI13/02481 Instituto de Salud Carlos III G03/176 Instituto de Salud Carlos III PI041436 Instituto de Salud Carlos III PI081151 Instituto de Salud Carlos III PI041705 Instituto de Salud Carlos III PS09/00432 Instituto de Salud Carlos III PI03/1615 Instituto de Salud Carlos III PI04/1509 Instituto de Salud Carlos III PI04/1112 Instituto de Salud Carlos III PI04/1931 Instituto de Salud Carlos III PI05/1079 Instituto de Salud Carlos III PI05/1052 Instituto de Salud Carlos III PI06/1213 Instituto de Salud Carlos III PI07/0314 Instituto de Salud Carlos III PI09/02647 Instituto de Salud Carlos III PI13/1944 Instituto de Salud Carlos III PI14/0891 Instituto de Salud Carlos III CP15/0025 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1468 Ministerio de Ciencia e Innovación SAF2008-00357 European Commission 201413 European Commission 282957 Agència de Gestió d'Ajuts Universitaris i de Recerca 1999/SGR-00241 Instituto de Salud Carlos III FIS-PI1302481 Ministerio de Economía y Competitividad MDM-2014-0370 |
| Drets: | 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.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Publicat a: | PloS one, Vol. 11, Issue 6 (June 2016) , art. e0157739, ISSN 1932-6203 |
