The Iberian legacy into a young genetic xeroderma pigmentosum cluster in central Brazil.
Mutat Res Genet Toxicol Environ Mutagen
; 852: 503164, 2020 Apr.
Article
em En
| MEDLINE
| ID: mdl-32265042
ABSTRACT
In central Brazil, in the municipality of Faina (state of Goiás), the small and isolated village of Araras comprises a genetic cluster of xeroderma pigmentosum (XP) patients. The high level of consanguinity and the geographical isolation gave rise to a high frequency of XP patients. Recently, two founder events were identified affecting that community, with two independent mutations at the POLH gene, c.764 + 1 G > A (intron 6) and c.907 C > T; p.Arg303* (exon 8). These deleterious mutations lead to the xeroderma pigmentosum variant syndrome (XP-V). Previous reports identified both mutations in other countries the intron 6 mutation in six patients (four families) from Northern Spain (Basque Country and Cantabria) and the exon 8 mutation in two patients from different families in Europe, one of them from Kosovo. In order to investigate the ancestry of the XP patients and the age for these mutations at Araras, we generated genotyping information for 22 XP-V patients from Brazil (16), Spain (6) and Kosovo (1). The local genomic ancestry and the shared haplotype segments among the patients showed that the intron 6 mutation at Araras is associated with an Iberian genetic legacy. All patients from Goiás, homozygotes for intron 6 mutation, share with the Spanish patients identical-by-descent (IBD) genomic segments comprising the mutation. The entrance date for the Iberian haplotype at the village was calculated to be approximately 200 years old. This result is in agreement with the historical arrival of Iberian individuals at the Goiás state (BR). Patients from Goiás and the three families from Spain share 1.8 cM (family 14), 1.7 cM (family 15), and a more significant segment of 4.7 cM within family 13. On the other hand, the patients carrying the exon 8 mutation do not share any specific genetic segment, indicating an old genetic distance between them or even no common ancestry.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Xeroderma Pigmentoso
/
Haplótipos
/
Padrões de Herança
/
DNA Polimerase Dirigida por DNA
/
Isolamento Reprodutivo
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
País/Região como assunto:
America do sul
/
Brasil
/
Europa
Idioma:
En
Revista:
Mutat Res Genet Toxicol Environ Mutagen
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Brasil