Related Experiment Video
Updated: Aug 13, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Hyperfunction variant rs708035 of interleukin 1 receptor-associated kinases 2 gene involved in the predisposition of
Saima Saleem1, Mutaher Zia2, Farhatulain Siddiqui1
1The Karachi Institute of Biotechnology and Genetic Engineering, University of Karachi. Karachi, Karachi, Pakistan.
Background:
Mycobacterium leprae (slow-growing bacteria) is the etiological agent for leprosy infection, which is a chronic granulomatous disease. Symptoms initiate with the loss of sensation in the affected areas, which can lead to severe injuries, cuts and burns. IRAK2 (interleukin-1 receptor-associated kinases 2) is reported to function in the regulation of the NFκB pathway. The frequency of the IRAK2 polymorphism (rs708035) was unknown in the Pakistani population. Therefore, the study was designed to identify the role of the rs708035 SNP (single nucleotide polymorphism) in susceptibility to leprosy.
Methodology:
The case-control study was designed, and participants were selected by Ridley-Jopling Classification. Blood samples from healthy individuals and patients were collected after ethical approval. Genomic DNA was extracted for the amplification of selected polymorphisms by tetra-primer amplification refractory mutation system polymerase chain reaction. The desired products were observed via agarose gel (2.5%) electrophoresis followed by data analysis using bioinformatics tools (SNP Stats and SHEsis) and statistical tests (odds ratio, OR, and chi square).
Results:
The study revealed that the mutant genotype (TT) was found to be frequent among cases (22.80%) in comparison with the controls (1.66%). The SNP rs708035 was significantly associated with the progression of leprosy (χ2 = 17.62, p < 0.0001). The targeted SNP significantly increases the risk of leprosy 2.3 times (OR = 2.3119, 95% CI 1.2729-4.1989, p < 0.01). The genetic model also confirms the significant association of the A/T genotype with leprosy in the over-dominant model (OR = 2.83, 95% CI 1.16-6.89, p < 0.001).
Conclusions:
The study revealed a significant association of the targeted SNP with leprosy and provided baseline data regarding the association of rs708035. The current research could be utilized for the preparation of biomarkers by considering a larger sample size.
Highlights:
The patients suffering from leprosy faced various comorbidities, including hypertension and diabetes. The study reports for the first time a significant association of interleukin 1 receptor associated kinases 2 (IRAK2) single nucleotide polymorphism (SNP) rs708035 among the Pakistani population (Karachi). The current study provides baseline data to develop diagnostic biomarkers for early detection of leprosy.
More Related Videos
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
02:32Exon Recombination
Exon shuffling follows “splice frame rules.” Each exon...
01:33Pleiotropy
01:03Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
03:18Non-LTR Retrotransposons