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A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects

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dc.contributor.author Acosta-Uribe, Juliana
dc.contributor.author Aguillón, David
dc.contributor.author Cochran, J. Nicholas
dc.contributor.author Giraldo, Margarita
dc.contributor.author Madrigal, Lucía
dc.contributor.author Killingsworth, Bradley W.
dc.contributor.author Singhal, Rijul
dc.contributor.author Labib, Sarah
dc.contributor.author Alzate, Diana
dc.contributor.author Velilla, Lina M.
dc.contributor.author Moreno, Sonia
dc.contributor.author García, Gloria P.
dc.contributor.author Saldarriaga, Amanda
dc.contributor.author Piedrahita, Francisco
dc.contributor.author Hincapié, Liliana
dc.contributor.author López, Hugo E.
dc.contributor.author Perumal, Nithesh
dc.contributor.author Surace, Ezequiel Ignacio
dc.contributor.author Itzcovich, Tatiana
dc.contributor.author Allegri, Ricardo Francisco
dc.date.accessioned 2022-12-28T13:49:50Z
dc.date.available 2022-12-28T13:49:50Z
dc.date.issued 2022-03-08
dc.identifier.citation Acosta-Uribe J, Aguillón D, Cochran JN, Giraldo M, Madrigal L, Killingsworth BW, Singhal R, Labib S, Alzate D, Velilla L, Moreno S, García GP, Saldarriaga A, Piedrahita F, Hincapié L, López HE, Perumal N, Morelo L, Vallejo D, Solano JM, Reiman EM, Surace EI, Itzcovich T, Allegri R, Sánchez-Valle R, Villegas-Lanau A, White CL 3rd, Matallana D, Myers RM, Browning SR, Lopera F, Kosik KS. A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects. Genome Med. 2022 Mar 8;14(1):27. doi: 10.1186/s13073-022-01035-9. es_ES
dc.identifier.uri https://doi.org/10.1186/s13073-022-01035-9
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/746
dc.description.abstract Background: The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries. Methods: We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer's disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes. Results: We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent. Conclusions: Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies. es_ES
dc.language.iso eng es_ES
dc.publisher BioMed Central es_ES
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/2.5/ar/
dc.subject Alzheimer Disease es_ES
dc.subject Enfermedad de Alzheimer es_ES
dc.subject Colombia es_ES
dc.title A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.type info:eu-repo/semantics/publishedVersion
dc.description.fil Fil: Surace, Ezequiel Ignacio. Fleni. Departamento de Neuropatología y Biología Molecular. Laboratorio de Biología Molecular; Argentina.
dc.description.fil Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría. Centro de Memoria y Envejecimiento; Argentina.
dc.description.fil Fil: Itzcovich, Tatiana. Fleni. Departamento de Neuropatología y Biología Molecular. Laboratorio de Enfermedades Neurodegenerativas; Argentina.
dc.description.fil Fil: Acosta-Uribe, Juliana. University of California. Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology; Estados Unidos. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia.
dc.description.fil Fil: Aguillón, David. University of California. Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology; Estados Unidos. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia.
dc.description.fil Fil: Madrigal, Lucía. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia.
dc.description.fil Fil: Cochran, J. Nicholas. HudsonAlpha Institute for Biotechnology; Estados Unidos.
dc.description.fil Fil: Giraldo, Margarita. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia. Instituto Neurológico de Colombia; Colombia.
dc.description.fil Fil: Killingsworth, Bradley W. University of California. Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology; Estados Unidos.
dc.description.fil Fil: Singhal, Rijul. University of California. Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology; Estados Unidos.
dc.description.fil Fil: Labib, Sarah. University of California. Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology; Estados Unidos.
dc.description.fil Fil: Alzate, Diana. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia.
dc.description.fil Fil: Velilla, Lina M. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia.
dc.description.fil Fil: Moreno, Sonia. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia.
dc.description.fil Fil: García, Gloria P. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia.
dc.description.fil Fil: Saldarriaga, Amanda. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia.
dc.description.fil Fil: Piedrahita, Francisco. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia.
dc.description.fil Fil: Hincapié, Liliana. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia.
dc.description.fil Fil: López, Hugo E. Universidad de Antioquia. School of Medicine. Grupo de Neurociencias de Antioquia; Colombia.
dc.description.fil Fil: Perumal, Nithesh. University of California. Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology; Estados Unidos.
dc.relation.ispartofVOLUME 14
dc.relation.ispartofNUMBER 1
dc.relation.ispartofPAGINATION 27.
dc.relation.ispartofCOUNTRY Inglaterra
dc.relation.ispartofCITY Londres
dc.relation.ispartofTITLE Genome medicine
dc.relation.ispartofISSN 1756-994X
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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