Association between genotype and clinical manifestation of the most spread monogenic hereditary disorders

Human genome mutation and rearrangement studies – the way to investigate monogenic and complex disease pathogenesis

“…Wide enough variation in phenotypical features of fragile X syndrome (Martin-Bell syndrome) including mental function peculiarities in both patients with expanded CGG-region of FMR1 gene (full mutation) and women-carriers of pre-mutation can be associated with somatic mosaicism (the presence of alleles with different number of CGG-repeats) which we have observed practically in all these individuals [14,15]. It is supposed that the presence in different tissues and primarily in brain neurons of alleles with various changes of gene sequence can stipulate large stage-specific and tissuespecific variation of the gene expression [13]. Negative correlation between age of HD manifestation and CAGrepeat number in expanded allele of ²Ò15 gene, and the presence of 3-nucleotied deletion in 58 th exon of the gene are established [6].…”

“…Majority of CF patients with delF508 in genotype have the highest levels of chlorides in sweat and the most severe form of disease (lung-gastric form with pancreal failure) [13].…”

“…Study on the genotype-phenotype association in patients with SMA revealed correlation between severity and the size of deletion in 5q13 region. In the worst case the deletion involves not only determinator gene SMN1 but also NAIP gene, which is a phenotype modifier for this pathology [13,17].…”