Unit:
Κατεύθυνση Ιατρική Γενετική: Κλινική και Εργαστηριακή ΚατεύθυνσηLibrary of the School of Health Sciences
Supervisors info:
Κέκου Κυριακή, Ε.ΔΙ.Π., Ιατρική Σχολή, ΕΚΠΑ
Pons Roser, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Σοφοκλέους Χρυσταλλένα, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Το φαινόμενο των ιδρυτικών γενετικών παραλλαγών (founder inheritance) σε πληθυσμούς: το παράδειγμα των Ελλήνων Ρομά
Translated title:
The phenomenon of founder genetic variants in the population: The example of the Greek Roma
Summary:
Background: In population genetics, the founder effect occurs when a small subpopulation is cut off from a larger population, resulting in different allele frequencies in the small population that from those of the originated population and a subsequent reduction in genetic diversity. In this project we study this phenomenon by investigating the prevalence of certain rare pathogenic variants in three genes carrying pathogenic founder variants linked to different neuromuscular rare diseases according to the available international literature for European Roma.
Purpose of the study: In view of the above, this thesis aims to explore the frequency of three pathogenic founder variants associated with neuromuscular diseases in the population of Greek Roma in CHRNE, SGCG and TMEM70 coming from all over Greece.
Methodology: Targeted Sanger sequencing was applied for the pathogenic variants c.1327del (exon 12), c.848G>A (exon 8) and c.317-2A>G (intron 2) in the CHRNE, SGCG and TMEM70 genes respectively. For the analysis of the variants in CHRNE and SGCG genes, established protocols for the diagnosis in the Laboratory of Medical Genetics, were applied, while for the diagnosis of the variant in the TMEM70 gene, a relevant protocol was standardized for the purpose of this study. The same variants were retrospectively mined from next generation sequencing (NGS) data stored in Laboratory of Medical Genetics databases. The analysis included the bioinformatic analysis of data on Varsome Clinical and Franklin platforms. In total 55 individuals from various regions of Greece were analyzed. In particular, the data of 39 Greek Roma individuals were derived from the retrospective analysis by WES method while the remaining patients were analyzed with the Sanger targeted sequencing method and specifically, 11 individuals were screened for the c.848G>A variant in SGCG, 11 individuals were screened for the c.1327del variant in the CHRNE gene and 16 individuals were screened for the c.317-2A>G variant in the TMEM70 gene. All subjects in the study were unrelated to each other and did not present symptoms for examined diseases.
Results: In the total number of individuals screened, 4 individuals were found to carry the pathogenic variant c.1327del of the CHRNE gene and 2 carried the pathogenic variant c.848G>A of the SCGC gene. The c.317-2A>G pathogenic variant of the TMEM70 gene was not detected in any of the subjects tested. The carrier frequency of the variants are calculated to be 8% and 4.08% respectively.
Conclusions: The results of the present study and their comparison with corresponding European studies on founder variants of the Roma population, show evidence that variants in the CHRNE and SGCG genes are possibly founder variants for the Greek Roma subpopulation following the European pattern. Regarding the pathogenic founder variant TMEM70 there was not strong enough evidence to classify it as a founder variant for the Greek Roma. Further larger scale genetic studies are necessary to confirm the rate of carriage in Greek Roma.
Main subject category:
Health Sciences
Keywords:
Founder effect, Greek Roma, Neuromuscular disease
