Spectra of Mutation Events in PAX6 Gene Locus Studied

Employees of the genetic epidemiology laboratory at RCMG under the supervision of Rena Zinchenko, Head of the laboratory, Holder of an Advanced Doctorate in Medical Sciences, corresponding member of RAS, published an article in the leading scientific journal “International Journal of Molecular Sciences”.

The article analyzes the spectra of mutation events in the locus of the PAX6 gene, obtained in separate studies, including the analysis of its own extensive sample of patients. The comparative analysis of these genes with other known genes responsible for the development of diseases with autosomal dominant type of inheritance (with full penetrance and haploinsufficiency of function as the main pathogenetic mechanism) was conducted. In addition, the laboratory compared the spectrum of mutation events in the PAX6 gene locus to the spectrum de novo mutations in the human genome.

The study found that in the Russian cohort of patients with congenital aniridium (199 people), as in the world population, a high relative frequency of chromosomal deletions and small indels was found, as well as a small percentage of missens in the PAX6 gene.

When compared to the mutational event spectra of 20 other genes responsible for the development of dominant diseases with full penetrance, it turned out that the locus of the PAX6 gene fits within the established interval, but in frequency of indels and large deletions in relation to substitutions is at the edge of the spectrum, resembling proportions for loci of genes VHL and APC.

The ratio between single-nucleotide substitutions, indels, and large chromosomal events differs significantly in the spectra obtained for loci of genes associated with dominant diseases, and in particular for PAX6 locus (1.5:0.8:1) and for de novo mutation events, occurring in the human genome (268.8:7.1:1).

The frequency of mutation events occurring at «hot spots» for the PAX6 gene locus was 24% (48/199), which is inconsistent with the previously assumed «minor contribution» of mutations in hot spots to the total pool de novo mutation events.

For more details follow the link of the published article: https://www.mdpi.com/1422-0067/23/12/6690