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Identifier

000419742

Title

Tracing disease variants in healthy populations

Alternative Title

Ανίχνευση πολυμορφισμών που σχετίζονται με ασθενείς σε υγιείς πληθυσμούς

Author

Μαθιουδάκη, Άννα Α.

Thesis advisor

Παυλίδης, Παύλος

Thesis advisor

Σπηλιανάκης, Χαράλαμπος
Νικολάου, Χριστόφορος

Abstract

The study of the genetic background of complex traits and diseases is of great interest due to its contribution to the understanding of the underlying related biological mechanisms. Here, we traced disease variants from the ClinVar database in 2,504 healthy individuals of the 1000 Genomes Projects. Interestingly, we identified 1.690 variants to be present. Our goal was to investigate their presence in healthy individuals; to trace their origin and course among populations and unravel their impact in the genotype. Thus, we implemented Population Genetics methodologies on haplotypes carrying the disease allele, clarifying the genetic variation within those haplotypes and detecting negative selection and demographic model for those haplotypes. We noticed that none of those are located in sex chromosomes. We could not identify any general pattern of population stratification since some patterns imply isolated populations and some mixed, with varying measurements of genotypic differentiation. Moreover, we identified 111 genomic regions in the neighborhood of pathogenic alleles indicating to be under positive selection. Though, there was no correlation between frequency within the healthy individuals and those selection events. Our study identifies specific population patterns of the variants’ haplotypes and supports the aspect of misclassification of variants in ClinVar database.

Language

English

Subject

Genetic diseases

Genetic variation

Population genetics

Γενετικές ασθένειες

Γενετική ποικιλομορφία

Πληθυσμιακή γενετική

Issue date

2018-11-23

Collection