Possible relationships between single nucleotide polymorphisms and expression of human HBA1, HBA2, HBB and HBD genes

Functional assessment of single nucleotide polymorphisms (SNPs) is one of the effective approaches in evolutionary biology, mapping of genes and loci of monogenic and complex diseases, and determination of regulatory elements of genomes. In particular, in the case of beta-globin genes, SNPs can lead to thalassemia of varying severity. To date, more than 324 million SNPs and short (no longer than 50 bp) insertions/deletions identified in the human genome have been collected in dbSNP resources (https://www.ncbi.nlm.nih.gov/snp/). The article presents the results of studies on the influence of single nucleotide polymorphisms on gene expression in humans using two families (alpha and beta) of globin genes, HBA1 and HBA2, HBB and HBD. An analysis of 5454 (1245, 1181, 1777, and 1251) known SNPs and indels in these genes showed that 310 (24, 55, 221, and 10) mutations may be associated with known pathologies and 183 (28, 22, 132, and 1) mutations are "ineffective" mutations (i.e., without symptoms), and the remaining 4961 (~91%) variations are functionally and clinically insignificant. Among SNPs of pathological effect, 262, 25, and 23 variations are localized, respectively, in DNA coding sequences, 5'-untranslated regions (including promoters and potential transcription factor binding sites), and introns. These results are consistent with the known evidence that the genetic causes of some clinical complications are mutations in non-coding regions of genes