During the last 10 years genes responsible for rare genetic disorders have been identified through the selection of clinically well characterized large families, linkage analysis, candidate gene identification and search for mutations in candidate genes. One of the main thrusts of the genetics of the next years will be to develop the tools to identify the genes responsible for common disorders, to clarify their inheritance pattern and to provide new diagnosis and appropriate therapies. Two such groups of disorders, non-syndromic Mental Retardation (MR) and Premature Ovarian Failure (POF), are studied for different historical reasons in our laboratory. Both are very common and highly heterogeneous. Both may have genetic and environmental causes that may be difficult to distinguish from the clinical point of view. The laboratory has identified a number of genes and candidate genes involved in the two disorders, that are now studied to obtain clues on the etiology of the diseases and identify new candidate genes and interacting molecules. Large scale genetic analysis of sporadic patients and familial cases and the use of animal models are the tools used.
A new project was recently started, the study of an entire population in the Appennine. The Val Borbera study is aimed at the clinical, genetic and genealogical characterization of a population of about 2000 people that for geographical reasons have been isolated from the surrounding area for centuries: the endogamy and the common environmental conditions have produced a more homogeneous genetic set up that should result very important for identification of genes involved in complex disorders.