Name: Suellen Rosseto MendonçaType: MSc dissertationPublication date: 27/09/2018Advisor:

Name	Role
Daniela Amorim Melgaço Guimarães do Bem	Advisor *

Examining board:

Name	Role
Cristina Martins e Silva	Internal Examiner *
Daniela Amorim Melgaço Guimarães do Bem	Advisor *
Flavia Imbroisi Valle Errera	External Examiner *
MARCELO RAMOS MUNIZ	External Examiner *
Rita Gomes Wanderley Pires	Co advisor *

Summary: Huntington’s disease (HD) is a fatal neurodegenerative disease caused by an expansion of CAG nucleotide sequence in the huntingtin gene, characterized by motor dysfunction, cognitive deficits and psychiatric symptoms. A knock-in genetic mice model of HD showed alterations in several genes in striatum. Through microarray were selected the Dynein, axonemal, heavy chain 6 (DNAHC6), Dynein light chain Tctex, type 1 (DYNLT1), Sigma non-opioid intracellular receptor 1 (SIGMAR1), Leucine rich repeat and Ig domain containing 1 (Lingo1), Protocadherin 21 (Pcdh21) and Gamma-aminobutyric acid (GABA) A receptor (Gabra2) genes, which have a relation to neurodegeneration. The aim of this study was to test whether human HD carriers have these same molecular alterations, and if there are difference in expression of these genes at different stages of HD in humans and also in animal model for HD. A BACHD transgenic mice model was investigated in different stages of 4 and 12 months of age. We explored the genes expression in HD human blood and in BACHD mice brain tissue using qPCR analysis. SIGMAR1 gene is decreased in HD and in the striatum of (4 months) BACHD, suggests this gene could be a useful peripheral blood marker of HD in early stages of the disease. DYNLT1 gene expression in whole blood of HD patients is significant downregulated and this difference is increased in later stages of disease by monitoring patients in the time interval from 2015 to 2018. These studies confirm that these genes could usefully as peripheral markers and also targets for potential intervention in the future for HD and translational markers in HD mouse models, although continued studies are necessary.

Keywords: Huntington’s disease, gene expression, biomarker, DYNLT1, SIGMAR1, molecular diagnostics.Access to document