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 to 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.
For some prevalent pathologies in Talana such as essential hypertension
and nephrolithiasis we identified two main loci and one candidate gene.
These results were obtained through genome wide search of a negligible
number of initial samples (about twenty!) strategically placed on large
and deep rooted genealogical trees which connect all the people affected
by the same pathology in one village.
The gene associated to nephrolithiasis has already undergone mutational
analysis and we are studying the protein variants associated to this
pathology.
Research results on this model population have great potential for
molecular diagnostics, for the development of new pharmacological
treatments and for the pharmacogenomic field.
A patent has been deposited for this gene.
Population structure studies on mtDNA and on Y chromosome are being
conducted on other villages and they have revealed a much greater
antiquity than expected form historical sources and a high degree of
genetic drift among them.
Epidemiological research is enriching the number of affected by
pathologies under study and is providing other research leads
Financing has been obtained so far only by private contributors such as
Renato Soru, the Sardinian Bank, the Sardinian Financial agency
S.F.I.R.S., by a private clinic from Jerzu (NU), and the Consortium 21.
Another financing agency has been the Ogliastra Genetic Park, a consortium
that collects various Ogliastra villages which have invested in this
project in order to give job and training opportunities to their youths.
Vedi anche:
Immagini:
