Open Access Highly Accessed Research article

The genetic study of three population microisolates in South Tyrol (MICROS): study design and epidemiological perspectives

Cristian Pattaro1*, Fabio Marroni1, Alice Riegler1, Deborah Mascalzoni1, Irene Pichler1, Claudia B Volpato1, Umberta Dal Cero1, Alessandro De Grandi1, Clemens Egger1, Agatha Eisendle1, Christian Fuchsberger1, Martin Gögele1, Sara Pedrotti1, Gerd K Pinggera1, Stefan A Stefanov1, Florian D Vogl2, Christian J Wiedermann34, Thomas Meitinger56 and Peter P Pramstaller178

Author Affiliations

1 Institute of Genetic Medicine, European Academy, Bolzano, Italy

2 Department of Gynaecology, Hospital of Merano, Via Rossini 5, 39012 Merano-Meran, Italy

3 Laboratory of Medical Intensive Care, Division of General Internal Medicine, Department of Medicine, Medical University of Innsbruck, Innsbruck, Austria

4 Division of Internal Medicine II, Department of Medicine, Central Hospital of Bolzano, Bolzano/Bozen, Italy

5 Institute of Human Genetics, Technical University of Munich, Munich, Germany

6 GSF – National Research Center for Environment and Health, Institute of Human Genetics, München-Neuherberg, Germany

7 Department of Neurology, University of Lübeck, Lübeck, Germany

8 Department of Neurology, General Regional Hospital, Bolzano, Italy

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BMC Medical Genetics 2007, 8:29  doi:10.1186/1471-2350-8-29

Published: 5 June 2007

Abstract

Background

There is increasing evidence of the important role that small, isolated populations could play in finding genes involved in the etiology of diseases. For historical and political reasons, South Tyrol, the northern most Italian region, includes several villages of small dimensions which remained isolated over the centuries.

Methods

The MICROS study is a population-based survey on three small, isolated villages, characterized by: old settlement; small number of founders; high endogamy rates; slow/null population expansion. During the stage-1 (2002/03) genealogical data, screening questionnaires, clinical measurements, blood and urine samples, and DNA were collected for 1175 adult volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association studies, is ongoing. The selection of the traits is being driven by expert clinicians. Preliminary, descriptive statistics were obtained. Power simulations for finding linkage on a quantitative trait locus (QTL) were undertaken.

Results

Starting from participants, genealogies were reconstructed for 50,037 subjects, going back to the early 1600s. Within the last five generations, subjects were clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85 subjects each). A significant probability of familial clustering was assessed for many traits, especially among the cardiovascular, neurological and respiratory traits. Simulations showed that the MICROS pedigree has a substantial power to detect a LOD score ≥ 3 when the QTL specific heritability is ≥ 20%.

Conclusion

The MICROS study is an extensive, ongoing, two-stage survey aimed at characterizing the genetic epidemiology of Mendelian and complex diseases. Our approach, involving different scientific disciplines, is an advantageous strategy to define and to study population isolates. The isolation of the Alpine populations, together with the extensive data collected so far, make the MICROS study a powerful resource for the study of diseases in many fields of medicine. Recent successes and simulation studies give us confidence that our pedigrees can be valuable both in finding new candidates loci and to confirm existing candidate genes.