Several web servers were used to distinguish deleterious nsSNPs from neutral ones. First, the missense nsSNPs obtained from the NCBI-SNP database were submitted to SIFT (Sorting Intolerant from Tolerant; http://sift.bii.a-star.edu.sg/) and PolyPhen v2 (Polymorphism Phenotyping v2; http: //genetics.bwh. harvard.edu/pph2/) tools. SIFT uses a query sequence and builds a multiple sequence alignment and based on position-specific information predicts tolerated and deleterious substitutions. A substitution in the protein sequence that is conserved in the alignment will be scored as intolerant to most changes and a poorly conserved substitution will be scored as tolerating. SIFT analyzes the occurrence of a new amino acid at a position and the normalized score ranges from 0 to 1. A score between 0 and 0.05 is determined to be deleterious and the value above the cutoff of 0.05 is considered tolerant. Polyphen v2 predicts the consequence of amino acid variants by doing multiple sequence alignments, phylogenetic predictions, and analyzing structural features. The result of the PolyPhen v2 is a numerical score varying from 0.0 (benign) to 1.0 (damaging) and a prediction showing the substitution as probably damaging, possibly damaging, or benign. SIFT and PolyPhen are able to predict 90% of deleterious SNPs and are the representatives of the empirical rules-based method which uses a set of empirical rules based on sequence homology, evolutionary conservation, and structural features characterizing a particular variant.
Author(s) Details:
Harini Venkata Subbiah
Human Genetics Research Centre, Sree Balaji Dental College and Hospital, Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, 600100, India.
Usha Subbiah
Human Genetics Research Centre, Sree Balaji Dental College and Hospital, Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, 600100, India.
Recent Global Research Developments in Single Nucleotide Polymorphisms in Humans: Analysis and Impact
Recent Progress in Single-Nucleotide Polymorphism Biosensors: This review discusses advancements in SNP biosensing methods, focusing on fluorescent and electrochemical techniques. It highlights the challenges and improvements in detecting SNPs, which are crucial for understanding gene function and health [1] .
Cataloging the Potential SNPs Associated with Quantitative Traits: This article reviews SNPs linked to traits like BMI, IQ, and blood pressure. It identifies common SNPs across global populations and discusses their role in predicting complex diseases [2] .
Single Nucleotide Polymorphisms: Human Variation and a Coming Age of Personalized Medicine: This book provides a comprehensive overview of SNPs, their classification, and their role in human diseases. It also explores how SNPs can affect therapeutic interventions and personalized medicine [3] .
Exploring the Impact of Single-Nucleotide Polymorphisms on Translation: This research examines how SNPs influence protein translation and folding, impacting human physiology and response to therapies. It leverages data from the Cancer Genome Atlas project [4] .
Genetic Variation and Recent Positive Selection in Worldwide Human Populations: This study uses genome-wide scans to identify new susceptibility variants to common diseases. It offers insights into the genetic structure and relationships of human populations [5] .
References
- Wu K, Kong F, Zhang J, Tang Y, Chen Y, Chao L, Nie L, Huang Z. Recent Progress in Single-Nucleotide Polymorphism Biosensors. Biosensors. 2023; 13(9):864. https://doi.org/10.3390/bios13090864
- Chauhan, W., Fatma, R., Wahab, A. et al. Cataloging the potential SNPs (single nucleotide polymorphisms) associated with quantitative traits, viz. BMI (body mass index), IQ (intelligence quotient) and BP (blood pressure): an updated review. Egypt J Med Hum Genet 23, 57 (2022). https://doi.org/10.1186/s43042-022-00266-0
- Single Nucleotide Polymorphisms
- https://link.springer.com/book/10.1007/978-3-031-05616-1
- Robert F and Pelletier J (2018) Exploring the Impact of Single-Nucleotide Polymorphisms on Translation. Front. Genet. 9:507. doi: 10.3389/fgene.2018.00507
- López Herráez D, Bauchet M, Tang K, Theunert C, Pugach I, Li J, et al. (2009) Genetic Variation and Recent Positive Selection in Worldwide Human Populations: Evidence from Nearly 1 Million SNPs. PLoS ONE 4(11): e7888. https://doi.org/10.1371/journal.pone.0007888
