creating a
healthier future



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.



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.

This image shows a C. elegans worm, an excellent model to study neurodegenerative diseases, expressing GFP at dopaminergic neurons. Our interests start with the clinical characterization of patients and families, using genetic epidemiological tools and the identification of mutations and disease mec


Selected Publications

Mendes Á., Paneque M., Sousa L., Clarke A., Sequeiros J.,
How communication of genetic information within the family is addressed in genetic counselling: A systematic review of research evidence. European Journal of Human Genetics24(3):315-325, 2016. [Journal: Article] [CI: 55] [IF: 4,3]
DOI: 10.1038/ejhg.2015.174 SCOPUS: 84958109101

Bras J., Alonso I., Barbot C., Costa M.M., Darwent L., Orme T., Sequeiros J., Hardy J., Coutinho P., Guerreiro R.,
Mutations in PNKP cause recessive ataxia with oculomotor apraxia type 4. American Journal of Human Genetics96(3):474-479, 2015. [Journal: Article] [CI: 101] [IF: 10,8]
DOI: 10.1016/j.ajhg.2015.01.005 SCOPUS: 84924246336

Ramos E.M., Gillis T., Mysore J.S., Lee J.M., Gögele M., D'Elia Y., Pichler I., Sequeiros J., Pramstaller P.P., Gusella J.F., Macdonald M.E., Alonso I.,
Haplotype analysis of the 4p16.3 region in Portuguese families with Huntington's disease. American Journal of Medical Genetics - Neuropsychiatric Genetics168(2):135-143, 2015. [Journal: Article] [CI: 3] [IF: 3,4]
DOI: 10.1002/ajmg.b.32289 SCOPUS: 84923108709

da Conceição Pereira M., Morais S., Sequeiros J., Alonso I.,
Large-scale functional RNAi Screen in C. elegans identifies TGF-ß and notch signaling pathways as modifiers of CACNAIA. ASN Neuro8(2):, 2016. [Journal: Article] [CI: 7] [IF: 3]
DOI: 10.1177/1759091416637025 SCOPUS: 84961625995

Alves-Ferreira M., Coelho T., Santos D., Sequeiros J., Alonso I., Sousa A., Lemos C.,
A Trans-acting Factor May Modify Age at Onset in Familial Amyloid Polyneuropathy ATTRV30M in Portugal. Molecular Neurobiology55(5):3676-3683, 2018. [Journal: Article] [CI: 19] [IF: 4,6]
DOI: 10.1007/s12035-017-0593-4 SCOPUS: 85019539928

Paneque M., Sequeiros J., Skirton H.,
Quality issues concerning genetic counselling for presymptomatic testing: A European Delphi study. European Journal of Human Genetics23(11):1468-1472, 2015. [Journal: Article] [CI: 9] [IF: 4,6]
DOI: 10.1038/ejhg.2015.23 SCOPUS: 84944353845

Raposo M., Ramos A., Bettencourt C., Lima M.,
Replicating studies of genetic modifiers in spinocerebellar ataxia type 3: Can homogeneous cohorts aid?. Brain138(12):e398, 2015. [Journal: Letter] [CI: 19] [IF: 10,1]
DOI: 10.1093/brain/awv206 SCOPUS: 84951098086

Lemos C., Coelho T., Alves-Ferreira M., Martins-Da-Silva A., Sequeiros J., Mendonça D., Sousa A.,
Overcoming artefact: Anticipation in 284 Portuguese kindreds with familial amyloid polyneuropathy (FAP) ATTRV30M. Journal of Neurology Neurosurgery and Psychiatry85(3):326-330, 2014. [Journal: Article] [CI: 58] [IF: 6,8]
DOI: 10.1136/jnnp-2013-305383 SCOPUS: 84896709791

Quintas M., Neto J.L., Pereira-Monteiro J., Barros J., Sequeiros J., Sousa A., Alonso I., Lemos C.,
Interaction between γ-Aminobutyric Acid A Receptor Genes: New Evidence in Migraine Susceptibility. PLoS ONE8(9):, 2013. [Journal: Article] [CI: 17] [IF: 3,5]
DOI: 10.1371/journal.pone.0074087 SCOPUS: 84883511876

Coutinho P., Ruano L., Loureiro J.L., Cruz V.T., Barros J., Tuna A., Barbot C., Guimarães J., Alonso I., Silveira I., Sequeiros J., Neves J.M., Serrano P., Silva M.C.,
Hereditary ataxia and spastic paraplegia in Portugal: A population-based prevalence study. JAMA Neurology70(6):746-755, 2013. [Journal: Article] [CI: 100] [IF: 7]
DOI: 10.1001/jamaneurol.2013.1707 SCOPUS: 84878770734

Ongoing Projects

The genetic maze of Familial Amyloid Polyneuropathy ATTRV30M: a genomic approach
Reference: 2022.01656.PTDC
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-MAR-23 to 28-FEB-26