Insights Into Functional and Structural Impacts of nsSNPs in XPA-DNA Repairing Gene

Insights Into Functional and Structural Impacts of nsSNPs in XPA-DNA Repairing Gene

Nadeem Ahmad, Zubair Sharif, Sarah Bukhari, Omer Aziz
Copyright: © 2022 |Pages: 12
DOI: 10.4018/IJARB.2022010103
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Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation in people. SNPs are valuable resource for exploring the genetic basis of disease. The XPA gene provides a way to produce a protein used to repair damaged DNA. This study used the computational methods to classify SNPs and estimate their probability of being neutral or deleterious. The purpose of this analysis is to predict the effect of nsSNPs on the structure and function of XPA proteins. Data was collected from the NCBI hosted dbSNP. The authors examined the pathogenic effect of 194 nsSNPs in the XPA gene with computational tools. Four nsSNPs (C126S, C126W, R158S, and R227Q) those potentially effect on structure and function of the XPA protein were identified with combination of SIFT, PolyPhen, Provean, PHD-SNP, I-Mutant, ConSurf server and Project HOPE. This is the first comprehensive analysis in which XPA gene variants studied using in silico methods and this research able to gain further insight into XPA protein variants and function.
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Single nucleotide polymorphisms (SNPs) are most common type of genetic variation in humans(Ke, Taylor, & Cardon, 2008). SNPs are a useful resource for the study of the spread of the disease genetic base(E Capriotti, Calabrese, & Casadio, 2006). The variants may be used as markers in studies of genetic mapping and genome interaction. Some of those polymorphisms may prevent people from developing diseases such as diabetes, high blood pressure or cancer or effect the progression of diseases(Zhu & Zhao, 2007). Each SNPs is a variance in one Deoxyribonucleic acid (DNA) building block(E Capriotti et al., 2006). SNPs normally happen in DNA in an individual. They take place almost 1 in each one thousand DNA bases, meaning that in a person genome there are about 4 to 5 million SNPs. For many people around the world these differences are rare and more than 100 million SNPs are known by scientists. Variations are most often observed between DNA genes. They function as biological markers enabling scientists to classify disease associated genes. When SNPs occur in a regulatory area within or close the gene, by influencing gene function they can be more involved in the disease(What Are Single Nucleotide Polymorphisms (SNPs)? - Genetics Home Reference - NIH, n.d.).

Although SNPs cause variations in DNA but still most SNPs do not have any clinical impact. Nevertheless, some of these genetic differences in human health studies have proved to be very important. SNPs have been identified by researchers to help predict individual reactions to certain drugs, their susceptibility and ability to acquire various diseases to environmental factors such as toxins. In order to monitor gene transmission from diseases within families, SNPs might be used. Future investigations can often classify SNPs associated with chronic conditions, those include cardiac disease, diabetes, and cancer.(What Are Single Nucleotide Polymorphisms (SNPs)? - Genetics Home Reference - NIH, n.d.).

The gene xeroderma pigmentosum, complementation group A (XPA) codes a zinc-fiber protein, a specialized form of DNA repair, that plays vital role in the nucleotide excision repair (NER) repair (E Capriotti et al., 2006). NER is responsible for the regeneration of photoproducts and DNA adducts caused by ultra violet (UV) radiation from organic carcinogens and chemotherapeutic drugs. It interacts with DNA and other NER proteins and is used to build up the NER incision complex at sites which harm the DNA. Mutations produced in this gene, Sunlight hypersensitive autosomal recessive skin disorder and increased risk of skin cancer(XPA, DNA Damage Recognition and Repair Factor [Homo Sapiens (Human)] - Gene - NCBI, n.d.). xeroderma pigmentosum XPA gene provides instructions on how to make a protein to repair damaged DNA. Sun UV rays and toxic chemicals as well as emission and volatility of free radicals and can damage the DNA. Normally, common cells can repair DNA damage before it can cause problems. The NER is one of the most essential pathways used by cells to repair DNA. The XPA protein helps to track and protect DNA damage, as it is repaired in this repair process. XPA is linked to damaging DNA areas in which XPA interacts as part of with several other proteins. In this way removes abnormal unit and replaces the damaged area with correct DNA where the damage has happened (XPA Gene - Genetics Home Reference - NIH, n.d.).

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