Deleterious Nonsynonymous SNP Found within <i>HLA-DRB1</i> Gene Involved in Allograft Rejection in Sudanese Family: Using DNA Sequencing and Bioinformatics Methods

Abstract

Renal transplantation provides the best long-term treatment for chronic renal failure. Singlenucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases. Also, the genetics of human phenotype variation could be understood by knowing the functions of these SNPs. It is still a major challenge to identify the functional SNPs in a disease-related gene. This work explored how SNPs mutations in HLA-DRB1 gene could affect renal transplantation rejection. This study was carried out in Ahmed Gasim Hospital, Renal Dialysis Center during the period, from September 2012 to November 2013. Blood samples from five Sudanese patients (different families) with known renal transplantation rejection were collected before hemodialysis, furthermore one blood sample for control. DNA sequences results and detected SNPs were analyzed using bioinformatics tools (BLAST, SIFT, nsSNP Analyzer, PolyPhen, I-mutant, BioEdit, CPH, Chimera, Box shade and Project Hope). In addition, international databases were used for datasets [NCBI, Uniprot]. Results showed that, three SNPs were detected; two of three SNPs were predicted as tolerant or benign (rs1059575, novel) and one was deleterious (rs17885437). This study concluded that the identification of pathological SNPs could be an answer to unknown causes for a lot of organ transplantation rejection cases. * Corresponding author. M. M. Hassan et al. 223

NeoCoV Is Closer to MERS-CoV than SARS-CoV

“…The second presents probability values for each secondary structure at each amino acid position. The program gives the predicted secondary structure with the highest probability compatible with a predicted helix segment of at least 4 residues and a predicted extended segment of at least 2 residues 29 as shown in Figures 16 to 21.…”

Detection of Nonsynonymous Single Variants in Human HLA-DRB1 Exon 2 Associated with Renal Transplant Rejection

“…According to the IPD-IMGT/HLA database, HLA-DRB1 is the most polymorphic in class II of this system, with 3298 alleles in September 2022 (https://www.ebi.ac.uk/ipd/imgt/hla/about/statistics/) (accessed on 25 September 2022). The HLA-DRB1 gene is located in GRCh38.p12 (Genome Reference Consortium Human Build 38.p12) coordinates 32,578,775 to 32,589,848, has five introns, and is encoded by six exons [22]. Exon one encodes the leader peptide, exons two and three encode the two extracellular domains, exon four encodes the transmembrane domain, and exon five encodes the cytoplasmic tail (https://www.ncbi.nlm.nih.gov/gene/3123) (accessed on 25 September 2022 [23].…”

“…The 1000 Genomes Project provides an in-depth analysis of common genetic variations (single nucleotide polymorphisms (SNPs) and Insertions–deletions (indels)) in humans and their association with diseases [ 34 ]. HLA variants are strongly linked to various diseases and organ transplantation [ 22 , 31 , 35 , 36 ]. SNPs are single nucleotide variants (SNVs) in DNA sequences with a population allele frequency of 1% or higher [ 37 , 38 ].…”