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dc.contributor.authorCáceres, Alejandroen_US
dc.contributor.authorEsko, Tõnuen_US
dc.contributor.authorPappa, Ireneen_US
dc.contributor.authorGutiérrez, Armanden_US
dc.contributor.authorLopez-Espinosa, Maria-Joseen_US
dc.contributor.authorLlop, Sabrinaen_US
dc.contributor.authorBustamante, Marionaen_US
dc.contributor.authorTiemeier, Henningen_US
dc.contributor.authorMetspalu, Andresen_US
dc.contributor.authorJoshi, Peter K.en_US
dc.contributor.authorWilsonx, James F.en_US
dc.contributor.authorReina-Castillón, Judithen_US
dc.contributor.authorShin, Jeanen_US
dc.contributor.authorPausova, Zdenkaen_US
dc.contributor.authorPaus, Tomášen_US
dc.contributor.authorSunyer, Jordien_US
dc.contributor.authorPérez-Jurado, Luis A.en_US
dc.contributor.authorGonzález, Juan R.en_US
dc.date.accessioned2016-08-09T14:52:46Z
dc.date.issued2016en_US
dc.identifier.citationCáceres, A., T. Esko, I. Pappa, A. Gutiérrez, M. Lopez-Espinosa, S. Llop, M. Bustamante, et al. 2016. “Ancient Haplotypes at the 15q24.2 Microdeletion Region Are Linked to Brain Expression of MAN2C1 and Children's Intelligence.” PLoS ONE 11 (6): e0157739. doi:10.1371/journal.pone.0157739. http://dx.doi.org/10.1371/journal.pone.0157739.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:27822185
dc.description.abstractThe 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.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0157739en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927142/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectEvolutionary Biologyen
dc.subjectPopulation Geneticsen
dc.subjectHaplotypesen
dc.subjectGeneticsen
dc.subjectPopulation Biologyen
dc.subjectGene Expressionen
dc.subjectPsychologyen
dc.subjectDevelopmental Psychologyen
dc.subjectAutism Spectrum Disorderen
dc.subjectAutismen
dc.subjectSocial Sciencesen
dc.subjectNeuroscienceen
dc.subjectDevelopmental Neuroscienceen
dc.subjectNeurodevelopmental Disordersen
dc.subjectMedicine and Health Sciencesen
dc.subjectNeurologyen
dc.subjectPeople and Placesen
dc.subjectPopulation Groupingsen
dc.subjectAge Groupsen
dc.subjectChildrenen
dc.subjectFamiliesen
dc.subjectCognitive Scienceen
dc.subjectCognitive Neuroscienceen
dc.subjectCognitive Neurologyen
dc.subjectCognitive Impairmenten
dc.subjectComputational Biologyen
dc.subjectGenome Analysisen
dc.subjectGenomic Librariesen
dc.subjectGenomicsen
dc.subjectHeredityen
dc.subjectHomozygosityen
dc.subjectGeographical Locationsen
dc.subjectAfricaen
dc.subjectEthiopiaen
dc.titleAncient Haplotypes at the 15q24.2 Microdeletion Region Are Linked to Brain Expression of MAN2C1 and Children's Intelligenceen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorEsko, Tõnuen_US
dc.date.available2016-08-09T14:52:46Z
dc.identifier.doi10.1371/journal.pone.0157739*
dash.authorsorderedfalse
dash.contributor.affiliatedEsko, Tõnu
dc.identifier.orcid0000-0003-1982-6569


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