دورية أكاديمية
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Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia.

التفاصيل البيبلوغرافية
العنوان: Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia.
المؤلفون: Ahmad M; Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla 080002, Colombia.; Life Science Research Center, Universidad Simón Bolívar, Barranquilla 080002, Colombia., Ríos-Anillo MR; Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla 080002, Colombia.; Life Science Research Center, Universidad Simón Bolívar, Barranquilla 080002, Colombia.; Médica Residente de Neurología, Universidad Simón Bolívar, Barranquilla 080002, Colombia., Acosta-López JE; Life Science Research Center, Universidad Simón Bolívar, Barranquilla 080002, Colombia.; Facultad de Ciencias Jurídicas y Sociales, Universidad Simón Bolívar, Barranquilla 080002, Colombia., Cervantes-Henríquez ML; Life Science Research Center, Universidad Simón Bolívar, Barranquilla 080002, Colombia.; Facultad de Ciencias Jurídicas y Sociales, Universidad Simón Bolívar, Barranquilla 080002, Colombia., Martínez-Banfi M; Life Science Research Center, Universidad Simón Bolívar, Barranquilla 080002, Colombia.; Facultad de Ciencias Jurídicas y Sociales, Universidad Simón Bolívar, Barranquilla 080002, Colombia., Pineda-Alhucema W; Life Science Research Center, Universidad Simón Bolívar, Barranquilla 080002, Colombia.; Facultad de Ciencias Jurídicas y Sociales, Universidad Simón Bolívar, Barranquilla 080002, Colombia., Puentes-Rozo P; Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla 080002, Colombia.; Life Science Research Center, Universidad Simón Bolívar, Barranquilla 080002, Colombia.; Grupo de Neurociencias del Caribe, Universidad del Atlántico, Barranquilla 080001, Colombia., Sánchez-Barros C; Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla 080002, Colombia.; Life Science Research Center, Universidad Simón Bolívar, Barranquilla 080002, Colombia.; Departamento de Neurofisiología Clínica Palma de Mallorca, Hospital Juaneda Miramar, Islas Baleares, 07011 Palma, Spain., Pinzón A; Bioinformatics and Systems Biology Laboratory, Institute for Genetics, Universidad Nacional de Colombia, Bogota 111321, Colombia., Patel HR; National Centre for Indigenous Genomics, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia., Vélez JI; Department of Industrial Engineering, Universidad del Norte, Barranquilla 081007, Colombia., Villarreal-Camacho JL; Programa de Medicina, Facultad de Ciencias de la Salud, Universidad Libre Seccional Barranquilla, Barranquilla 081007, Colombia., Pineda DA; Grupo de Investigación en Neuropsicología y Conducta, Universidad de San Buenaventura, Medellin 050010, Colombia.; Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellin 050010, Colombia., Arcos-Burgos M; Grupo de Investigación en Psiquiatría (GIPSI), Departamento de Psiquiatría, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, Medellin 050010, Colombia., Sánchez-Rojas M; Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla 080002, Colombia.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2023 Nov 10; Vol. 24 (22). Date of Electronic Publication: 2023 Nov 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Huntington Disease*/genetics , Huntington Disease*/diagnosis, Adult ; Female ; Humans ; Colombia ; Alleles ; DNA ; Pedigree ; Huntingtin Protein/genetics ; Trinucleotide Repeat Expansion
مستخلص: 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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معلومات مُعتمدة: 777-2017 Miniciencias
فهرسة مساهمة: Keywords: CAG repeats; HTT; Huntington’s disease; mosaicism; slippage
المشرفين على المادة: 9007-49-2 (DNA)
0 (Huntingtin Protein)
تواريخ الأحداث: Date Created: 20231125 Date Completed: 20231127 Latest Revision: 20231127
رمز التحديث: 20231128
مُعرف محوري في PubMed: PMC10671691
DOI: 10.3390/ijms242216154
PMID: 38003344
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms242216154