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Uncovering the Genetic and Molecular Features of Huntington’s Disease in Northern Colombia

Huntington’s disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world’s second-largest HD pedigree. Here, we include 291 descendants of this pedigree wit...

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Autores principales: Ahmad, Mostapha, Ríos-Anillo, Margarita R., Acosta-López, Johan E., Cervantes-Henríquez, Martha L., Martínez-Banfi, Martha, Pineda-Alhucema, Wilmar, Puentes-Rozo, Pedro, Sánchez-Barros, Cristian, Pinzón, Andrés, Patel, Hardip R., Vélez, Jorge I., Villarreal-Camacho, José Luis, Pineda, David A., Arcos-Burgos, Mauricio, Sánchez-Rojas, Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671691/
https://www.ncbi.nlm.nih.gov/pubmed/38003344
http://dx.doi.org/10.3390/ijms242216154
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author Ahmad, Mostapha
Ríos-Anillo, Margarita R.
Acosta-López, Johan E.
Cervantes-Henríquez, Martha L.
Martínez-Banfi, Martha
Pineda-Alhucema, Wilmar
Puentes-Rozo, Pedro
Sánchez-Barros, Cristian
Pinzón, Andrés
Patel, Hardip R.
Vélez, Jorge I.
Villarreal-Camacho, José Luis
Pineda, David A.
Arcos-Burgos, Mauricio
Sánchez-Rojas, Manuel
author_facet Ahmad, Mostapha
Ríos-Anillo, Margarita R.
Acosta-López, Johan E.
Cervantes-Henríquez, Martha L.
Martínez-Banfi, Martha
Pineda-Alhucema, Wilmar
Puentes-Rozo, Pedro
Sánchez-Barros, Cristian
Pinzón, Andrés
Patel, Hardip R.
Vélez, Jorge I.
Villarreal-Camacho, José Luis
Pineda, David A.
Arcos-Burgos, Mauricio
Sánchez-Rojas, Manuel
author_sort Ahmad, Mostapha
collection PubMed
description Huntington’s disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world’s second-largest HD pedigree. Here, we include 291 descendants of this pedigree with at least one family member with HD. Blood samples were collected, and genomic DNA was extracted. We quantified the HTT CAG expansion using an amplicon sequencing protocol. The genetic heterogeneity was measured as the ratio of the mosaicism allele’s read peak and the slippage ratio of the allele’s read peak from our sequence data. The statistical and bioinformatic analyses were performed with a significance threshold of p < 0.05. We found that the average HTT CAG repeat length in all participants was 21.91 (SD = 8.92). Of the 291 participants, 33 (11.3%, 18 females) had a positive molecular diagnosis for HD. Most affected individuals were adults, and the most common primary and secondary alleles were 17/7 (CAG/CCG) and 17/10 (CAG/CCG), respectively. The mosaicism increased with age in the participants with HD, while the slippage analyses revealed differences by the HD allele type only for the secondary allele. The slippage tended to increase with the HTT CAG repeat length in the participants with HD, but the increase was not statistically significant. This study analyzed the genetic and molecular features of 291 participants, including 33 with HD. We found that the mosaicism increased with age in the participants with HD, particularly for the secondary allele. The most common haplotype was 17/7_17/10. The slippage for the secondary allele varied by the HD allele type, but there was no significant difference in the slippage by sex. Our findings offer valuable insights into HD and could have implications for future research and clinical management.
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spelling pubmed-106716912023-11-10 Uncovering the Genetic and Molecular Features of Huntington’s Disease in Northern Colombia Ahmad, Mostapha Ríos-Anillo, Margarita R. Acosta-López, Johan E. Cervantes-Henríquez, Martha L. Martínez-Banfi, Martha Pineda-Alhucema, Wilmar Puentes-Rozo, Pedro Sánchez-Barros, Cristian Pinzón, Andrés Patel, Hardip R. Vélez, Jorge I. Villarreal-Camacho, José Luis Pineda, David A. Arcos-Burgos, Mauricio Sánchez-Rojas, Manuel Int J Mol Sci Article Huntington’s disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world’s second-largest HD pedigree. Here, we include 291 descendants of this pedigree with at least one family member with HD. Blood samples were collected, and genomic DNA was extracted. We quantified the HTT CAG expansion using an amplicon sequencing protocol. The genetic heterogeneity was measured as the ratio of the mosaicism allele’s read peak and the slippage ratio of the allele’s read peak from our sequence data. The statistical and bioinformatic analyses were performed with a significance threshold of p < 0.05. We found that the average HTT CAG repeat length in all participants was 21.91 (SD = 8.92). Of the 291 participants, 33 (11.3%, 18 females) had a positive molecular diagnosis for HD. Most affected individuals were adults, and the most common primary and secondary alleles were 17/7 (CAG/CCG) and 17/10 (CAG/CCG), respectively. The mosaicism increased with age in the participants with HD, while the slippage analyses revealed differences by the HD allele type only for the secondary allele. The slippage tended to increase with the HTT CAG repeat length in the participants with HD, but the increase was not statistically significant. This study analyzed the genetic and molecular features of 291 participants, including 33 with HD. We found that the mosaicism increased with age in the participants with HD, particularly for the secondary allele. The most common haplotype was 17/7_17/10. The slippage for the secondary allele varied by the HD allele type, but there was no significant difference in the slippage by sex. Our findings offer valuable insights into HD and could have implications for future research and clinical management. MDPI 2023-11-10 /pmc/articles/PMC10671691/ /pubmed/38003344 http://dx.doi.org/10.3390/ijms242216154 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ahmad, Mostapha
Ríos-Anillo, Margarita R.
Acosta-López, Johan E.
Cervantes-Henríquez, Martha L.
Martínez-Banfi, Martha
Pineda-Alhucema, Wilmar
Puentes-Rozo, Pedro
Sánchez-Barros, Cristian
Pinzón, Andrés
Patel, Hardip R.
Vélez, Jorge I.
Villarreal-Camacho, José Luis
Pineda, David A.
Arcos-Burgos, Mauricio
Sánchez-Rojas, Manuel
Uncovering the Genetic and Molecular Features of Huntington’s Disease in Northern Colombia
title Uncovering the Genetic and Molecular Features of Huntington’s Disease in Northern Colombia
title_full Uncovering the Genetic and Molecular Features of Huntington’s Disease in Northern Colombia
title_fullStr Uncovering the Genetic and Molecular Features of Huntington’s Disease in Northern Colombia
title_full_unstemmed Uncovering the Genetic and Molecular Features of Huntington’s Disease in Northern Colombia
title_short Uncovering the Genetic and Molecular Features of Huntington’s Disease in Northern Colombia
title_sort uncovering the genetic and molecular features of huntington’s disease in northern colombia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671691/
https://www.ncbi.nlm.nih.gov/pubmed/38003344
http://dx.doi.org/10.3390/ijms242216154
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