The Population Genetics Institute carries on since 1995 a
multidisciplinary project for the identification of genes predisposing to
multifactorial diseases and to complex traits. This project is conducted
in the villages of the Ogliastra geographic isolate of central-eastern
Sardinia. These villages are examined under the epidemiological,
genealogical, genetic, molecular and statistical profile. The
identification of genes associated with pathological phenotypes in such
populations is important non only for a better comprehension of
etiopathogenesis of common diseases but also for the opportunity to create
better statistical models for the study of complex traits in population
isolates.
The project was initially conducted in one village (Talana) identified as
ideal model for these type of studies. His population indeed possess all
the desired characteristics: antiquity, slow demographic growth, isolation
and high degre of endogamy and consanguinity that render it particularly
apt for the proposed study. The proposed approach consists in the
identification of identical by descent haplotypes through a stepwise
genome-wide search.
Population studies on mitochondrial DNA and Y chromosome structure were extended from Talana to three other Ogliastra villages. The comparison of data revealed that all these geographical isolates are genetically different because of genetic drift and are all much more ancient than is revealed by historic data. Epidemiological investigations are increasing the number of individuals affected by the pathologies under investigation and are suggesting new research avenues.
For some of the pathologies under study in these villages we identified five loci associated with essential hypertension and one gene associated with renal stones. Moreover in the study of factors controlling the variation of lipid metabolism we found one QTL associated with total cholesterol and HDL cholesterol levels.
These results were reached through an initial genome-wide scan carried out on a very limited number of samples aptly selected on large and deep genealogical trees that included all the individuals affected by a single pathology in the village. The renal stones associated gene has already been examined for mutations and we are studying the protein variants associated with the pathology. We have applied for ...
The results obtained in this model population have great potential for the development of molecular diagnostic kits, of new drugs and for the development of a pharmacogenomic approach.
Financial support has so far come mostly from private sources such as Renato Soru, Banco di Sardegna, a Jerzu (NU) private clinic, the private Sardinian Bank SFIRS and the Consorzio 21.
The Parco Genos Consortium through its Ogliastra member villages, has greatly supported the research and has given the opportunity to many Ogliastra youths to work and learn in collaboration with our Institute.
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