Tracing the mutated HTT and haplotype of the African ancestor who spread Huntington disease into the Middle East.
Genet Med
; 22(11): 1903-1908, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32661355
ABSTRACT
PURPOSE:
We aimed to determine the origin and genetic characteristics of Huntington disease (HD) in the Middle East.METHODS:
We performed genetic and genealogical analyses to establish the ancestral origin of the HTT pathgenic variant from a large kindred from Oman (hereafter called the OM-HD-01 pedigree) by single-nucleotide polymorphism and dense haplotype analysis genotyping.RESULTS:
We traced the oldest ancestry of the largest, eight-generation, OM-HD-01 pedigree (n = 302 subjects, with 54 showing manifest HD) back to sub-Saharan Africa and identified a unique HD haplotype carried by all pedigree members, which consisted of portions of the C6 and C9 haplotypes and was carried by all affected members. Such a unique HD haplotype was of African origin and appeared to be associated with large CAG repeat expansions on average and high frequency of juvenile-onset HD. Three other families from the same area were also identified and found carrying a Caucasian HD haplotype A, also shared by most families of Arab ancestry.CONCLUSION:
Mutated HTT spread into Middle East with a unique haplotype of African origin, appeared to be associated with juvenile-onset, a HD condition frequently occurring in Black Africans, and may have a significant impact on further development of novel targeted genetic therapies.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Huntington
Tipo de estudo:
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Genet Med
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Itália