Biogeographical origin and timing of the founder ichthyosis TGM1 c.1187G > A mutation in an isolated Ecuadorian population

An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabi. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in E...

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Detalles Bibliográficos
Autores: Esperón Moldes, Uxía Saraiva, Pardo Seco, Jacobo José, Montalván-Suárez, M., Fachal Vilar, Laura, Ginarte Val, Manuel Javier, Rodríguez Pazos, Laura, Gómez Carballa, Alberto, Moscoso, F., Ugalde-Noritz, N., Ordoñez Ugalde, Andrés, Tettamanti-Miranda, D., Ruiz, J. C., Salas Ellacuriaga, Antonio, Vega Gliemmo, Ana
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/15761
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509209/pdf/41598_2019_Article_43133.pdf
https://www.ncbi.nlm.nih.gov/pubmed/31073126
http://hdl.handle.net/20.500.11940/15761
Access Level:acceso abierto
Palabra clave:Humans
Transglutaminases
Ichthyosis
Haplotypes
Principal Component Analysis
Tandem Repeat Sequences
Genotype
transglutaminasas
genotipo
secuencias repetidas en tándem
análisis de componentes principales
humanos
haplotipos
ictiosis
FPGMX
CHUS
CHUVI
IDIS
Descripción
Sumario:An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabi. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in Ecuadorian patients and population matched controls, we were able to estimate the age of c.1187G > A and the time to their most recent common ancestor (TMRCA) of c.1187G > A Ecuadorian carriers. While the estimated mutation age is 41 generations ago (~1,025 years ago [ya]), the TMRCA of Ecuadorian c.1187G > A carrier haplotypes dates to just 17 generations (~425 ya). Probabilistic-based inferences of local ancestry allowed us to infer a most likely European origin of a few (16% to 30%) Ecuadorian haplotypes carrying this mutation. In addition, inferences on demographic historical changes based on c.1187G > A Ecuadorian carrier haplotypes estimated an exponential population growth starting ~20 generations, compatible with a recent founder effect occurring in Manabi. Two main hypotheses can be considered for the origin of c.1187G > A: (i) the mutation could have arisen in Spain >1,000 ya (being Galicia the possible homeland) and then carried to Ecuador by Spaniards in colonial times ~400 ya, and (ii) two independent mutational events originated this mutation in Ecuador and Galicia. The geographic and cultural characteristics of Manabi could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region.