1. ABSTRACT OF THE PhD THESIS
'USING DNA MARKERS IN GENETIC ANALYSIS OF FOCAL GLOMERULOSCLEROSIS
SEGMANTALE AND SUSCEPTIBILITY TO TB'
Author: Assist. univ. Dr. GEORGIANA DUŢĂ CORNESCU
In this paper, the importance of DNA markers in medical genetics is exemplified by analyzing
the autosomal dominant form of focal segmental glomerulosclerosis, (FSGS), on the one hand, and
body susceptibility to TB, on the other hand.
PhD thesis is divided into four chapters, plus general conclusions, list of references used in this
paper works and personal scientific paper list. The first two chapters of theory, includes an overview
of issues quantify genetic variation in human populations and, respectevly, DNA polymorphism
analysis of focal segmental glomerulosclerosis associated with susceptibility to TB and. Chapter III
contains a description of molecular genetic techniques and statistical analysis used to achieve
practical part of this work, and the last chapter presents in detail the results of research and
discussion that followed a number of issues related to the use of DNA markers to identify human
genetic variation associated with the first character, ie mendelian autosomal dominant form of FSGS,
respectively susceptibility to tuberculosis.
The first major objective of this research sought to identify a possible new locus involved in
genetic determinism of autosomal dominant FSGS, analyzing two Italian families affected by this
disease. For this, we selected four candidate genes that may determine autzomal dominant form of
FSGS (ACTN4, CD2AP, ZO1 and ITGA3) and STR markers most suitable for linkage analyzes. We
applied molecular genetic techniques (PCR, PAGE-silver staining, sequencing) to identify individual
allelic variants and specific software was used to identify a positive linkage between a particular
chromosomal region and form of FSGS affecting two families. Results obtained from experiments
performed have shown for the first time that the region 17q12 - q23.3, a region bounded by
STR markers D17S588 - D17S1853, is involved in genetic determination of autosomal
dominant FSGS. This region, as determined by the candidate genes, includes coding gene for a
podocytar protein, ITGA3, essential in mediating the adhesion to glomerular basement membrane to
extracellular matrix.
The second part of our research involves the analysis of Taq I and Apa I polymorphism of the
VDR gene in determining body susceptibility to developing TB, using DNA markers. This study is a
case control type in which two groups were analyzed, control group consisting of 110 healthy
individuals and group of patients, consisting of 68 persons infected with M. tuberculosis who
developed TB. This study reports for the first time possible correlation between genotype "aa"
in the water I polymorphism and resistance to TB (p = 0.006). Also, our case-control study, the
involvement of ApaI and TaqI polymorphism in the human body susceptibility determinism to
TB, is the first of its kind in the country, it can be extended to other SNP type gene
polymorphisms of VDR.
This studies, linkage analysis or case control type, have proven the efficiency of DNA markers
in medical genetics (to identify genetic factors of human disease or susceptibility to several infectious
diseases) and population genetics (to establish relationships gene between human populations).