Uncovering the genetic and molecular features of huntington’s disease in northern Colombia
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Fecha
2024
Autores
Ahmad, Mostapha
Ríos Anillo, Margarita Rosa
Acosta-Lopez, Johan E.
Cervantes-Henríquez, Martha L.
Martinez-Banfi, Martha Luz
Pineda-Alhucema, Wilmar
Puentes-Rozo, Pedro
Sánchez Barros, Cristian Manuel
Pinzón, Andrés
Patel, Hardip
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MDPI
Facultad de Ciencias de la Salud
Facultad de Ciencias de la Salud
Resumen
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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Ahmad, M.; Ríos-Anillo, M.R.; Acosta-López, J.E.; Cervantes-Henríquez, M.L.; Martínez-Banfi, M.; Pineda-Alhucema,W.; Puentes-Rozo, P.; Sánchez-Barros, C.; Pinzón, A.; Patel, H.R.; et al. Uncovering the Genetic and Molecular Features of Huntington’s Disease in Northern Colombia. Int. J. Mol. Sci. 2023, 24, 16154. https://doi.org/10.3390/ijms242216154
