Polymorphism DNA sequence 12q24.1 linked to phenylalanine hydroxylase gene in population from Republic of Moldova
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StatusThe thesis was presented on the 23 September, 2004Approved by NCAA on the 23 December, 2004 Abstract – 0.38 Mb / in romanian |
Summary
We investigated the frequency and molecular basis of phenylketonuria in Moldova. On the
base of newborn-screening data, we found the frequency to be 1:9000. Was founded State Register
of patients with phenylketonuria (PKU) and DNA samples bank obtained from the families with
high risk for this pathology. We performed molecular-genetics analysis of the phenylalanine
hydroxylase gene of 59 patients with classical PKU and 68 individuals from controls with analysis
of alleles and genotypes of the polymorphic loci of PAH gene. Was calculated index of deviation of
empiric and theoretic heterozygosity by VNTR, Msp I(a), Pvu I(a) I and Bgl II polymorphic loci of
PAH gene in Moldavian population. Were determined significant differences of frequencies
distribution between normal and mutant chromosomes (p<0,01). Was calculated standard
coefficient of linkage disequilibrium of studied polymorphic loci with PAH gene mutations
(∆st=0,18-0,35). Was analyzed informativity of studied polymorph loci for PKU diagnosis in
Moldavian population (from 28% to 63,8%). Were investigated 8 of more frequent PAH gene
mutations which in overall shared 67,6% of defective alleles: R408W (49%), P281L (5,1%), R261Q
(3,4%), R252W (3,4%), IVS10nt546 (2,5%), R158Q (2,5%), IVS12nt1 (1,7%). As a result of study
of polymorph haplotypes and PAH gene mutations was developed scheme of molecular-genetic
diagnosis of phenylketonuria which allow determination of 97,7% of all cases of this pathology in
Moldavian population.
Oficial Reviewers
- Nicolae Barbacar
doctor habilitat, professor, Institute of Genetics, Physiology and Plant Protection of the ASM - Natalia Barbova
doctor, associate professor (docent)
Theses
