The Iberian legacy into a young genetic xeroderma pigmentosum cluster in central Brazil

The Iberian legacy into a young genetic xeroderma pigmentosum cluster in central Brazil

•Identifying a common genomic segment between Brazilian and Spanish XP patients.•The POLH intron 6 mutation in Brazil is originally from Europe.•The founder effect for XP families in Brazil is relatively recent: 200–300 years.•XP patients from Araras are genetically close to one specific family from...

Full description

Saved in:
Bibliographic Details
Published in:Mutation research Vol. 852; p. 503164
Main Authors: Castro, L.P., Sahbatou, M., Kehdy, F.S.G., Farias, A.A., Yurchenko, A.A., de Souza, T.A., Rosa, R.C.A., Mendes-Junior, C.T., Borda, V., Munford, V., Zanardo, É.A., Chehimi, S.N., Kulikowski, L.D., Aquino, M.M., Leal, T.P., Tarazona-Santos, E., Chaibub, S.C., Gener, B., Calmels, N., Laugel, V., Sarasin, A., Menck, C.F.M.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01-04-2020
Subjects:
Ancestry
Brazil - epidemiology
Consanguinity
DNA repair
DNA-Directed DNA Polymerase - genetics
Europe - epidemiology
Exons
Female
Founder mutations
Genetic cluster
Genetics, Population
Haplotypes
Heterozygote
Homozygote
Human Migration
Humans
Inheritance Patterns
Introns
Male
Mutation
Phenotype
POLH(XPV)
Reproductive Isolation
Xeroderma pigmentosum
Xeroderma Pigmentosum - epidemiology
Xeroderma Pigmentosum - genetics
Xeroderma Pigmentosum - pathology
Brazil
Europe
Xeroderma pigmentosum
Ancestry
POLH(XPV)
Founder mutations
Genetic cluster
DNA repair
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•Identifying a common genomic segment between Brazilian and Spanish XP patients.•The POLH intron 6 mutation in Brazil is originally from Europe.•The founder effect for XP families in Brazil is relatively recent: 200–300 years.•XP patients from Araras are genetically close to one specific family from Spain. 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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1383-5718
1879-3592
1873-135X
DOI:10.1016/j.mrgentox.2020.503164