Abstract

Exome Sequencing on Illumina Platform revealed Relation between Nucleic Acids Interconversion and the Ratio of Transition/Transversion in Chronic Kidney Disease (CKD) Patients

Aims: Renal Failure and Chronic Kidney Disease (CKD) represent major health problems that affect more than 10% of the general population worldwide amounting to more than 800 million individuals. CKD is a congruence of many diseases like Diabetes, Hypertension, hypercholesterolemia, and different cardiovascular diseases as well as epigenetic factors contributing to the development of this Disease. We undertook this work as a pilot study to establish a database of genetic variants for novel or existing genes involved in the development and progress of CKD in the Saudi population. Methods: Patients' blood samples of 12 donors suffering from CKD were used to perform the Whole Exome Sequencing (WES) on genomic DNA on the Illumina Platform. Bioinformatics algorithms were used to perform different callset to explore different mechanisms such as nucleic acids interconversion, INDELS search as well as Transition/Transversion (Ts/Tv) ratio determination. Results: Patterns of Transition and Transversion Ratio (Ts &Tv) in the Patient samples demonstrated the dominance of transition substitutions over transversion. Our data revealed the mean ratio metrics of (Ts/Tv) is roughly 2.75 which is consistent with former literature findings. Indels with less than 3 bp have a total count of more than 1e+05 whereas those with larger gap are present at the level of trace. Since there is an intrinsic relation between nucleotides interconversions and the transition and transversion mechanisms, and based on the higher rate of transition over transversion mechanisms, our study supports this assertion at the levels of the nucleotides, with the state nucleotides conversion being as (67% A→G, 64% G→A, 67% T→C, and 67% C→T) which mirrors the dominance of transition effects and lower representation of transversion effects as exemplified by lower state of interconversion of : (13% T→A), (12% A→T), (19% C→G), (17% C→G), (17% G→T) and (20% T→G). Conclusion: CKD is a widespread disease that overlaps the spectrum of many diseases’ spectrum in terms of gene variant expressions. The transition and Transversion ratio profile is around 2.75. Nucleotides interconversions rim with the concept of transition and transversion and INDELS counts and distribution favor the shorter length as compared with larger INDELS.

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