Genética dos Açores

Interesse da Investigação

1. Genetics of human isolated populations (PI: Luisa Mota-Vieira)
1.1. Genetic structure of Azorean population
1.2. Effect of consanguinity on the incidence of genetic disorders.

Membros do Grupo

Projecto de Investigação

Genetic structure of the Azorean population – A surname study

To obtain a better understanding of the genetic structure of the Azorean population we conducted a survey based on surnames listed in the 2002 telephone book. First, we analyze the population living the 44 rural localities of São Miguel. In a total of 12,625 subscribers we found 812 different surnames. The highest value of surname diversity was found in Capelas (socio-economically more developed) and Rabo-de-Peixe (the most populated); and the lowest value was found in Lomba de S. Pedro (the least populated). Surname diversity was estimated by the coefficient of relationship between localities (Rij) and Nei's genetic distance. The analysis of rural population relationships reveals that Povoação and Nordeste are the two localities with highest value of Rij (0.217), whereas Capelas and Nordeste have the lowest value (0.0042). The rural locality displaying the greatest homogeneity is Salga (Fst=0.0145). The genetic similarity between localities was obtained by a dendogram based on Nei's distance matrix. We identified two main clusters, one includes Nordeste and Achada, both located in the most eastern part of S. Miguel, and the other includes the remaining 42 localities grouped in three major subclusters. The subcluster that stands out groups all the localities of the western part of the island. These data are consistent with the spatial distribution of surnames obtained by Principal Component (PC) analysis. In fact, the first two PC account for 59% of the total variance and shows a cluster at the upper left corner of the plot with 8 western localities. Second, we outline the structure of the Azorean population. We identified 2,455 different surnames in a total of 55,530 subscribers. In order to characterize the influence of geographic discontinuity on surname diversity, we performed a surname specificity analysis. Our results reveal that each island has surnames 50% more frequent than in the rest of the archipelago (specific surnames). This is particularly evident in the islands of S. Miguel, Santa Maria, Terceira and Corvo. To evaluate the genetic similarity between the islands's populations, we then analyzed surname distribution by spatial autocorrelation (Moran's I). In a total of 161 surnames, we identified 24 (15%) surnames with statistically significant patterns for 4 distance classes. These patterns were classified as: isolation by distance and depression (37.5%), cline (12.5%), intrusion (12.5%) and long-distance differentiation (8.3%). The remaining 29.2% had no defined pattern. The overall spatial correlogram plot of the 24 surname frequencies shows that the highest Moran's I coefficient (0.69) was present in the first distance class (105 Km). Moreover, autocorrelation change from positive to negative for distances greater than 105-250 Km, indicating that mobility is higher between islands of the same geographic group. In population genetic terms, the data show that geographic distance shapes surname diversity among Azores Islands.

Colaboradores

Dipartimento di Medicina Ambientale e Sanit Pubblica - sede di Igiene, Universit di Padova, Padova, Italy
GianUmberto Caravello and Miro Tasso

Projecto de Investigação

Y-chromosomal STR haplotypes in Sao Miguel's population (Azores)

This project aims to improve our understanding of the genetic structure of São Miguel's population, through the analyze of seven Y-chromosome STR loci (DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392 and DYS393) in 100 unrelated individuals. Father's birthplace was used to select the samples: Nordeste (n=4), Povoação (n=5), Vila Franca do Campo (n=8), Lagoa (n=11), Ribeira Grande (n=22) and Ponta Delgada (n=50), representing all the municipalities in Sao Miguel. The samples were typed by PCR with fluorescently labeled primers and products run in a CEQ8000 DNA Sequencer (Beckman Coulter). In a total of 100 complete seven-locus haplotypes, we observed 71 different haplotypes of which 54 appear only once. The mean heterozygosity per locus in the overall sample was 0.59, with the highest value in Nordeste (0.71) and the lowest in Ponta Delgada (0.56). On average the mean pairwise difference between two random haplotypes ranged from 4.49 in Ponta Delgada to 5.66 in Nordeste. The mean Fst value over all 7 loci was very low (-0.00758), denoting the absence of heterogeneity among the municipalities of the island. Pairwise genetic distances were computed for all six municipalities and no genetic heterogeneity was detected. AMOVA analysis shows that the percentage of variation attributable to differences within municipalities is extremely high compared to the differences between municipalities. These results provide evidence for reduced levels of Y-chromosome variability in the male lineages of Sao Miguel's population. We are currently analyzing 8 SNPs and 1 indel polymorphism, in order to characterize the frequency and distribution of Y-chromosome haplogroups in the population of São Miguel.

Projecto de Investigação

Establishment of a human DNA banking in São Miguel island (Azores)

This project aims to build a DNA bank of 1,000 healthy unrelated individuals (about 0.8% of the current population) living in the Azorean island of São Miguel (131,609 inhabitants). Resulting of a collaboration with the Hematology Department of the Hospital of Divino Espirito Santo, the only hospital located in S. Miguel island, the DNA bank follows the international ethical guidelines and has been approved by the Hospital's ethical committee. Blood samples (7.5 mL) were collected with appropriate Informed Consent, which includes (1) the distribution of free informative leaflet explaining the goals of proposed studies, the confidentiality of the personal data, and the methods of identification and storage of DNA samples; and (2) an interview with a health professional for additional information. All samples in the repository are anonymous and have self-reported data concerning sex, age, birth and current living places (locality and municipality in the island), and parental birthplaces. To date (Dec. 2002 through Oct. 2003), we collected 500 blood samples, of which 435 (87%) are male. The mean age of all participants is 36.3y (18-63y). All the six municipalities of the island are represented. The analysis of birthplaces shows that 427 (86%) of all participants have both parents born in S. Miguel island. Moreover, 256 (60%) of these participants have both parents born in the same locality. This data corroborates the high rate of marriages within the rural localities. Thus, the DNA bank of S. Miguel island represents a important resource for population and biomedical genetic research and provides opportunities for us to participate in international collaborative projects.

Colaboradores

Serviço de Hematologia do HDES, Ponta Delgada.
Pedro Mendonça, Maria .L. Almeida, Júlio Carvalho, Catarina. Matos, Marta Loura and Ana Luisa Araújo.

Projecto de Investigação

Genetic and consanguinity of congenital heart disease in Azores

Congenital heart defects (CHD) are the most common form of clinically significant birth defects. Based in the Azorean Registry of CHD, this project aims to study cardiac alterations in Azores, an archipelago with a population of 241,763 inhabitants, settled by Portuguese in the 15th century. Recently, we showed that this population is relatively homogeneous and has the highest value of consanguinity in Portugal. To date, 383 patients have been clinically evaluated and classified according to the predominant cardiac lesion. To investigate the epidemiology of CHD in São Miguel island, a retrospective 10-year (1993-2002) study was carried out.CHD shows a non-random geographic distribution in Azores, with the exception of Corvo, all islands present CHD cases. The highest frequency was found in São Miguel island where nine CHD clusters were detected. These clusters correspond to small localities with a number of inhabitants varying between 798 and 3,501. Now, we are interviewing CHD families in order to reconstruct extended multigenerational pedigrees. Special attention is been taken to detect consanguinity in families with CHD. Because of the genetic structure of Azorean population, the possibility of CHD families sharing a common ancestor is being investigated.

Funding

POCTI/ ESP/ 49236/ 2002
Genetic and consanguinity of congenital heart disease in Azores.

Colaboradores

Serviço de Pediatria –HDES, Ponta Delgada
Carlos P Duarte and Clara Macedo

Serviço de Cardiologia Pediátrica – Hospital de Santa Cruz, Lisboa
Rui Anjos

Publicações

Lima, M., Kay, T., Vasconcelos, J., Mota-Vieira, L., Gonzalez, C., Peixoto, A., Abade, A., MacLeod, P., Graça, R. and Santos, J. (2001). Disease knowledge and attitudes toward predictive testing and prenatal diagnosis in families with Machado-Joseph disease from the Azores islands (Portugal). Community Genet 4 :36-42

Leroux, A., Mota-Vieira, L. and Kahn, A. (2001). Transcriptional and translational mechanisms of cytochrome b5 reductase isoenzymes generation in humans. J. Biochem. 355 :529-535

Lavedan, C., Buchholtz, S., Auberger, G., Albin, R.L., Athanassiadou, A., Blancato, J., Burguera, J.A., Ferrel, R.E., Kostic, V., Leroy, E., Leube, B., Mota-Vieira, L., Papapetropoulous, T., Pericak-Vance, M.A., Pinkus, J., Scott, W.K., Ulm, G., Vasconcelos, J., Vilchez, J.J. and Nussbaum, R.L. (1998). Absence of mutational in the beta- and gamma-sinuclein genes in familial autosomal dominant Parkinson's disease. DNA Research 31 :401-402

Reguigne-Arnould, Faure, S., Chery, M., Mota-Vieira, L., Mollicone, R., Candelier, J.J., Oriol, R. and Couillin, P. (1996). Physical mapping of 49 microsatellite marquers on chromosome 19 and correlation with the genetic linkage map. Genomics 32 :458-461

Mota-Vieira, L., Kaplan, J-C., Kahn, A. and Leroux, A. (1995). Four new mutations in the NADH-cytochrome b5 reductase gene from patients with congenital methemoglobinemia type II. Blood 85 :2254-2262

Mota-Vieira, L., Kaplan, J-C., Kahn, A. and Leroux, A. (1994). Heterogeneity of the rat NADH-cytochrome b5 reductase transcripts resulting from multiple alternative first exons. Eur. J. Biochem. 220 :729-737