Genetic variation, a fundamental concept in genetics, encompasses the intricate differences in DNA sequences among individuals within the same species. Delving into the depths of this subject reveals a mosaic of variations occurring at various levels, including single nucleotide variants (SNV), insertions and deletions (indel), copy number variants (CNV), and structural variants (SV). Of these, SNVs, arising from single nucleotide base alterations, stand as the predominant form of genetic variation. They can be inherited from parents or emerge spontaneously due to mutations, thus shaping the genetic landscape of individuals.
The paramount significance of comprehending genetic variation lies in its direct influence on individual phenotypic dissimilarities. These dissimilarities encompass a wide range of traits, including disease susceptibility, drug response patterns, and other distinctive characteristics. Notably, genetic variation plays a pivotal role in molding protein structure and function, governing gene regulation, and orchestrating the overall machinery of cellular processes. By scrutinizing and analyzing genetic variation, researchers gain valuable insights into the vast diversity and distinctive attributes of both individuals and populations.
Explore with our Variant Detection and Analysis Service for more information.
Fig. 1. Common Genetic Variations. (Cardoso J G R, et al, 2015)
The realm of bioinformatics emerges as a cornerstone in the analysis and interpretation of genetic variation data. As high-throughput sequencing technologies surge forth, the generation of large-scale genomic data becomes a rapid reality, necessitating sophisticated computational tools and algorithms for analysis. Several methods and processes have been developed to identify, annotate, and interpret genetic variants. Here, we explore two commonly employed methods:
Sanger Sequencing Analysis
Sanger sequencing, a time-honored method, assumes a significant role in DNA sequencing endeavors. Amplification and sequencing of individual DNA fragments, employing modified nucleotides that halt DNA synthesis at specific sites, constitute the essence of this technique. Capillary electrophoresis facilitates the separation of resulting DNA fragments by size, unraveling the elusive DNA sequence. Although Sanger sequencing stands as a reliable and accurate approach, its scalability and cost-effectiveness face limitations when scrutinizing extensive genomic regions or analyzing multiple samples simultaneously.
The advent of NGS technologies has ushered in a revolution in genetic variation analysis, harnessing the power of high-throughput sequencing. Illumina sequencing, Ion Torrent sequencing, and Pacific Biosciences sequencing, among others, rapidly generate millions to billions of short DNA sequence reads in parallel. By employing diverse sequencing chemistries and strategies, NGS platforms usher in a workflow encompassing DNA fragmentation, library preparation, sequencing, and bioinformatics analysis. This groundbreaking technology dramatically reduces sequencing costs while exponentially expanding the scale and speed of genetic variation analysis.
Bioinformatics analysis of NGS data revolves around comparing sequence reads with reference genomes, deploying variant calling algorithms to identify genetic variants, and annotating detected variants against databases and function prediction tools. The culmination of these analyses yields variant call format (VCF) files, which furnish vital information about genomic location, variant type, and quality of identified variants.
Genetic variant analysis serves as a versatile tool, yielding insights across diverse fields, including human health, population genetics, evolutionary biology, and personalized medicine. Highlighting a few notable applications:
Delving into the genetic variation associated with diseases unravels critical insights into disease mechanisms, aids in the identification of disease-causing mutations, and propels the development of targeted therapies. Genome-wide association studies (GWAS) stand as formidable endeavors, analyzing genetic variants in large populations to unravel associations between specific genetic variations and diseases. Through GWAS, significant strides have been made in comprehending complex diseases such as cancer, diabetes, and cardiovascular disorders.
Genetic variation assumes a central role in modulating an individual's response to drugs, influencing both efficacy and potential side effects. Pharmacogenomic studies delve into how genetic variation impacts drug metabolism, drug targets, and inter-individual variability in drug response. This wealth of knowledge underpins the realm of personalized medicine, empowering healthcare professionals to tailor treatment plans based on an individual's unique genetic makeup.
Genetic variation analysis assumes an indispensable position in forensic genetics, aiding in human identification and criminal investigations. DNA analysis techniques, such as short tandem repeat (STR) analysis and single nucleotide polymorphism (SNP) genotyping, exploit genetic variation to establish individual identities or relationships, thereby assisting in criminal investigations.
Analyzing genetic variation within and among populations unearths a treasure trove of insights into human migration patterns, ancestry, and evolutionary relationships. By comparing genetic maps, researchers can trace population histories, identify genetic markers associated with population-specific traits, and unravel the effects of natural selection on genetic variation.