ABOUT

UnIGENe was created in 1992, stemming from and following the research efforts of Corino Andrade and Paula Coutinho on hereditary transthyretin amyloidosis (ATTRv) and Machado-Joseph disease (also called spinocerebellar ataxia type 3, MJD/SCA3). We focus mainly on mechanisms of neurodegeneration, using hereditary cerebellar ataxias (including MJD), spastic paraplegias, ATTRv and other neurological diseases as models.

Our research has been centred mainly on discovery of new genes and variants in families, functional studies and genetic modifiers for several neurological disorders.

We resorted animal models (natural mutant or transgenic mice and C. elegans) for Friedreich ataxia (FRDA), MJD, SCA6 and Parkinson disease (PD), to look into disease mechanisms and function of normal and mutant proteins; as well as cell models, including patient-derived fibroblasts and CRISPR-Cas9-edited cell lines, to characterize several genes and proteins and assess the role of protein processing and degradation systems in neurodegenerative diseases.

We are also involved in identifying genetic modifiers and the role of epigenetic alterations in Huntington Disease (HD), MJD, ATTRv and migraine.

Other research interests are founder effects, mutational origins and ancestral haplotypes in MJD, but also SCA2, SCA10, DRPLA and ATTRv.

We are also engaged studying some complex diseases, as migraine and common PD. We studied familial aggregation and ascertained susceptibility genes for common migraine (closely linked and with overlapping features and mechanisms with familial hemiplegic migraine, episodic ataxia and SCA6). Channelopathies are also research path of interest for neurodegeneration.

RESEARCH

Our major accomplishments include: (1) a national systematic population-based survey on hereditary ataxias and spastic paraplegias; (2) the best documented European cohort of MJD patients (in the Azores); (3) identification of global transcriptional dysregulation in peripheral blood in MJD and its potential as biomarker; (4) identification and functional characterization of new genes and variants for hereditary ataxias and spastic paraplegias; (5) genomic mechanisms resulting in large gene rearrangements; (6) identification of genetic and epigenetic modifiers in MJD; (7) population stratification has an impact on finding genetic modifiers for HD; (8) genetic components identified in common migraine; (9) evidence for genetic anticipation in ATTRv; (10) a worldwide study of mutational origins of MJD showing two major ancestral haplotypes - Joseph and Machado lineages, dating about 7,000 and 1,500 years ago - the Joseph haplotype having an Asian origin and being present also in Australian aborigines; (11) the (ATTCT)n expansion in ATXN10 has probable Amerindian origin; (12) large normal alleles at HTT are present in 6% of the general population (what lead to a change in the international recommendations for genetic counselling and testing in HD).

Clinical and psychosocial research is being developed in collaboration with CGPP (Centre for Predictive and Preventive Genetics, IBMC).

We published over 300 publications in peer-reviewed journals; over 30 PhD students successfully completed their theses.