Title PRIMJENA SEKVENCIRANJA CIJELOG EGZOMA U
ISTRAŽIVANJU GENETIČKE OSNOVE PARKINSONOVE
BOLESTI
Title (english) APPLICATION OF WHOLE-EXOME SEQUENCING IN GENETIC
RESEARCH OF PARKINSON’S DISEASE
Author Valentino Rački
Mentor Vladimira Vuletić (mentor)
Committee member David Bonifačić (predsjednik povjerenstva)
Committee member Marija Heffer (član povjerenstva)
Committee member Nina Pereza (član povjerenstva)
Granter University of Rijeka Faculty of Medicine Rijeka
Defense date and country 2024-01-22, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Neurology
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Basic Medical Sciences Human Genetics, Genomics and Proteomics
Universal decimal classification (UDC ) 61 - Medical sciences
Thesaurus (MESH - Medical Subject Headings )
Parkinson Disease
genetics
Abstract Ciljevi istraživanja: Parkinsonova bolest je česti neurodegenerativni poremećaj koji
zahvaća do 1% populacije iznad 65 godina, uz predviđanja postepenog porasta
prevalencije do 2% u idućih nekoliko desetljeća. Genetska osnova bolesti se može
pronaći kod 15% do 30% pacijenata, uz sve rastući broj zahvaljujući novim tehnologijama
sekvenciranja. U dosadašnjim istraživanjima nije bila zastupljena južnoslavenska
populacija, te je specifični cilj ovog istraživanja utvrditi učestalost poznatih genetičkih
varijanti kod hrvatskih pacijenata.
Materijali i metode: Uključni kriteriji za ispitivanje su potvrđena Parkinsonova bolest,
koristeći najrelevatnije kliničke dijagnostičke kriterije. Svi ispitanici su dali informirani
pristanak i ispunili genetski upitnik prije uzorkovanja krvi te su bili podijeljeni u tri grupe
ovisno o vrsti nastanka (rani, obiteljski i sporadični) Postupak sekvenciranja cijelog
egzoma se učinio po dosadašnjim primjerima dobre prakse.
Rezultati: 152 pacijenta su uključena u ispitivanje. Kod ukupne kohorte je otkriveno 14
uzročnih mutacija po kriterijima proglašenim kao patogene i vjerojatno patogene (GBA,
n=11; PRKN, n=2; ITM2B n=1). Nadalje, u cijeloj kohorti od 152 pacijenata, njih 41 je
imalo barem jednu varijantu nejasnog značaja (n=41, 26,97%). Patogene su bile prisutne
u svim grupama, uz razlike u učestalosti: rani nastup - 12,2%, obiteljski nastup - 12,5%,
sporadični nastup - 5,63%. Kod varijanti nejasnog značaja bila sljedeća učestalost unutar
grupa: rani nastup – 29,27%, obiteljski nastup - 15%, sporadični nastup – 32,39%
Zaključak: Sekvenciranje cijelog egzoma ima primjenu u istraživanju genetske osnove
Parkinsonove bolesti. Patogene varijante su pronađene u sve tri skupine ispitanika,
najčešće u GBA genu, što odgovara dosadašnjim spoznajama za europske populacije.
Uz to, otkriveno je nekoliko varijanti nejasnog značaja, koje zahtijevaju daljnju analizu.
Ovakav pristup ima i istraživačku i kliničku vrijednost, te se omogućuje individualno
predviđanje specifičnih faktora rizika.
Abstract (english) Research objectives: Parkinson's disease is a common neurodegenerative disorder that
affects up to 1% of the population over 65 years of age, with predictions of a gradual
increase in prevalence up to 2% in the next few decades. The genetic basis of the disease
can be found in 15% to 30% of patients, with the number increasing thanks to new
sequencing technologies. In previous research, the South Slavic population was not
represented, so the specific goal of this research is to determine the frequency of known
genetic variants in Croatian patients.
Materials and methods: Inclusion criteria for the trial were confirmed Parkinson's
disease, using the most relevant clinical diagnostic criteria. All subjects gave informed
consent and filled out a genetic questionnaire before blood sampling and were divided
into three groups depending on the type of origin (early, familial, and sporadic). The entire
exome sequencing procedure was done according to established methods.
Results: 152 patients were included in the study. In the total cohort, 14 causative
mutations were detected according to the criteria declared as pathogenic and probably
pathogenic (GBA, n=11; PRKN, n=2; ITM2B n=1). Furthermore, in the entire cohort of
152 patients, 41 of them had at least one variant of unclear significance (n=41, 26.97%).
Pathogens were present in all groups, with differences in frequency: early onset - 12.2%,
familial onset - 12.5%, sporadic onset - 5.63%. For variants of unclear significance, the
frequency within the groups was as follows: early onset - 29.27%, familial onset - 15%,
sporadic onset - 32.39%
Conclusion: Whole-exome sequencing has applications in research into the genetic
basis of Parkinson's disease. Pathogenic variants were found in all three groups of
subjects, most often in the GBA gene, which corresponds to current knowledge for
European populations. In addition, several interesting variants of unclear significance
were discovered, which require further analysis. This approach has both research and
clinical value since individual prediction of specific risk factors is possible.
Keywords
Parkinsonova bolest
sekvenciranje cijelog egzoma
genetika poremećaja pokreta.
Keywords (english)
Parkinson's disease
whole exome sequencing
genetics of movement disorder
Language croatian
URN:NBN urn:nbn:hr:184:837076
Promotion 2024
Project Number: IP-2019-04-7276 Title: Epidemiologija Parkinsonove bolesti u Hrvatskoj i utjecaj genetskih čimbenika i mikrobiote na progresiju bolesti i ishod liječenja Acronym: GiOPARK Leader: Vladimira Vuletić Jurisdiction: Croatia Funder: Hrvatska zaklada za znanost Funding stream: Research Projects
Project Number: uniri-biomed-18-198 Title: Genetska epidemiologija Parkinsonove bolesti u Hrvatskoj Title: Genetic epidemiology of Parkinson's disease in Croatia Leader: Vladimira Vuletić Jurisdiction: Croatia Funder: Sveučilište u Rijeci
Study programme Title: Biomedicine Postgraduate (doctoral) study programme Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Catalog URL https://libraries.uniri.hr/cgi-bin/lb02/unilib.cgi?form=610000000199990&id=0880489003
Type of resource Text
File origin Born digital
Access conditions Access restricted to students and staff of home institution
Terms of use
Created on 2024-05-03 07:12:49