Amino acids exchange in patients with CKD as obtained via exome sequencing differ radically from those of natural variants 1000 genome and genomAD databases

Abstract

Background: Nonsynonymous mutations in the coding regions of human genes are responsible for phenotypic differences between humans and for their susceptibility to genetic disease. Methods: We performed Exome sequencing on CKD patients’ genomic DNA and put the focus in understanding the role played by the amino-acid mutation spectrum (PAM) in human chronic kidney disease CKD patients. More specifically, using SIFT algorithm, we generated the amino acids substitution on proteins and compared the PAM matrix derived from CKD patients representing the amino-acid mutational spectrum to non-disease PAM matrices representing spectra of mutual amino-acid mutation frequencies derived from 1000 genome and genomAD database. Results: We found a strong and positive correlation in term of mutabilities of amino acids distribution in human proteome and the average distribution of amino acid mutability remains higher in genomAD dataset as compared CKD and 1000 genome. The results also show a strong correlation of mutability between the three datasets, the coefficient of correlation being: (rCKD vs 1kg = 0.9225, rCKD vs genomAD = 0.9431 and rgenomAD vs 1kg = 0.9486) as well probabilistic distribution of amino acids in human proteome between the three datasets. Conclusion: The amino acids mutability index in CKD dataset was statistically different as compared with those in 1000 genome and genomAD datasets. There is strong positive correlation in mutabilities of amino acids distribution in human proteome and the average distribution of mutability is higher in genomAD dataset as compared CKD and 1000 genome. In the CKD dataset, Arginine remains a common product of mutability from four amino acids like: Tryptophan, Histidine, Glycine and Lysine and the spike of Arginine in blood samples should be an element to trace in diagnostic profile of CKD. The data paved a way for clinical use for amino acids exchanges in chronic kidney disease using illumine platform.