Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/100562
Title: Ancient Haplotypes at the 15q24.2 Microdeletion Region Are Linked to Brain Expression of MAN2C1 and Children's Intelligence
Author: Cáceres, Alejandro
Esko, Tonu
Pappa, Irene
Gutierrez, Armand
López-Espinosa, Maria-Jose.
Llop, Sabrina
Bustamante Pineda, Mariona
Tiemeier, Henning
Metspalu, Andres
Joshi, Peter K.
Wilsonx, James F.
Reina-Castillon, Judith
Shin, Jean
Pausova, Zdenka
Paus, Tomas
Sunyer Deu, Jordi
Pérez Jurado, Luis
González, Juan R.
Keywords: Expressió gènica
Infants
Autisme
Gene expression
Children
Autism
Issue Date: 29-Jun-2016
Publisher: Public Library of Science (PLoS)
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.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0157739
It is part of: PLoS One, 2016, vol. 11, num. 6, p. e0157739
Related resource: http://dx.doi.org/10.1371/journal.pone.0157739
URI: http://hdl.handle.net/2445/100562
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (ISGlobal)

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