Interests and Focus
Our laboratory, established in 1982, studies the genetic basis of phenotypic variation, particularly in humans. The topics of our research are the following:
- Human genome variation
Individual genomes vary extensively from each other; individuality, evolutionary potential, and disease phenotypic risk, all heavily depend on this polymorphic variability. We study the phenotypic consequences at the cellular and organismic level of all classes of genomic variability.
- Functional analysis of the human genome
Understanding the functional role of each nucleotide, particularly those conserved in evolution is a prerequisite in order to unravel the causes of human genetic disorders. We are particularly interested in the functional characterization of the conserved fraction of the genome that is not protein-coding (conserved non-coding sequences). Our laboratory also participates in international collaborative projects for genome structure and function.
- Pathogenic variation leading to disorders, both monogenic and polygenic
The laboratory studies both monogenic disorders and polygenic complex phenotypes that map in selected regions of the human genome. Over the years we were able to contribute to the molecular understanding of the thalassemias, hemophilias, hereditary epilepsies, and autoimmune monogenic phenotypes. More recently we are investigating the genomic variation that confers risk to complex phenotypes with considerable heritability. The availability of high throughput sequencing now facilitates the discovery of pathogenic variants in mendelian disorders and neoplasias.
- Molecular pathogenesis of trisomy 21 and other aneuploidies
These quantitative genomic lesions are of particular importance in human nosology. Trisomy 21 is the model disease for aneuploidy, and our laboratory studies the effects of genome dosage imbalance. In particular we are focusing on the molecular basis of selected phenotypic characteristics of trisomy 21 such as the congenital heart defect, the cognitive impairment, and the acute megakaryocytic leukemia.