Studies on the Identification of Variants in Ribosomal RNA Genes in Maternal Diabetic Families: A Combined Approach Involving Nucleotide Sequence Analysis and Bioinformatics
Studies on the Identification of Variants in Ribosomal RNA Genes in Maternal Diabetic Families: A Combined Approach Involving Nucleotide Sequence Analysis and Bioinformatics
Sajid ul Ghafoor1*, Aziz-ud-Din1*, Khushi Muhammad1, Inamullah1 and Abid ul Ghafoor2
ABSTRACT
The MT-RNR2 gene plays a crucial role in encoding 16S ribosomal RNA, which is essential for the mitoribosomal larger subunit (mt-LSU). Variations in this gene have the potential to disrupt the secondary structure of 16S rRNA, affecting the assembly of mt-LSU necessary for protein synthesis. These alterations can compromise oxidative phosphorylation (OXPHOS) complexes, which have been implicated in the development of diabetes mellitus (DM). In this study, we analyzed four maternal diabetic families to investigate MT-RNR2 gene variation and its impact on 16S rRNA secondary structure. Next-generation sequencing (NGS) of the entire mitochondrial DNA (mtDNA) of sample “B3” revealed the presence of the m.1811A>G variation in the MT-RNR2 gene, classified into haplogroup “U”. Subsequent verification through Sanger sequencing identified the same m.1811A>G variation in fourteen members across the four families. The secondary structure of the entire 1559 bases 16S rRNA was constructed, incorporating the single variation “141A>G” corresponding to m.1811A>G. Analysis of maximum free energy (MFE ∆G) indicated -337.37 kcal/mol for the reference structure and -338.87 kcal/mol for the altered structure. Three-dimensional structure analysis of the entire reference and altered 16S rRNA showed a root mean square deviation (RMSD) of 85.390 Å. The presence of the m.1811A>G variation in fourteen members of the diabetic families, along with its verified impact on MFE and structures of mitochondrial 16S rRNA, suggests its potential association with DM within these families. Future investigations may further explore the functional consequences of identified variants through in vitro and in vivo experiments, providing deeper insights into the pathophysiological mechanisms underlying mitochondrial dysfunction in diabetes.
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