What is the most common type of genetic variant?

Single Nucleotide Polymorphisms (SNPs) Are the Most Common Type of Genetic Variant

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variant in the human genome, accounting for approximately 90% of all inter-individual genetic variation. 1, 2, 3

Understanding SNPs

SNPs represent a change in a single base pair (T, G, A, or C) in the DNA sequence. These simple changes occur throughout the genome at a frequency of about one in every 1,000 base pairs 1. They are characterized as follows:

• Definition: A SNP occurs when a single nucleotide in the genome differs between individuals or between paired chromosomes in an individual
• Frequency: To be classified as a polymorphism rather than a rare mutation, the variant must be present in at least 1% of the population 4
• Distribution: SNPs are found in both coding and non-coding regions of the genome

Types of SNPs

SNPs can be categorized based on their location and effect on protein function:

• Synonymous SNPs: Single base changes in exons that result in no change to the amino acid sequence; usually have no major clinical consequence but can occasionally affect splicing 4

• Non-synonymous (missense) SNPs: Lead to a change in one amino acid; may affect critical functional domains of proteins, though most do not 4

• Intronic SNPs: Occur in non-coding regions (introns); can rarely create or destroy splice sites 4

• Regulatory SNPs: Found in promoter or enhancer regions; can affect gene expression levels

Significance of SNPs

SNPs have important implications in multiple areas:

1. Population Genetics: Different ethnic groups have different frequencies of variants 4

2. Disease Association: SNPs may contribute to susceptibility to common complex diseases 1, 5

3. Pharmacogenomics: SNPs can influence individual drug responses, as seen with:

   • CYP2C9 variants affecting warfarin metabolism 6
   • CYP2C19 variants affecting clopidogrel activation 4

4. Normal Phenotypic Variation: SNPs contribute to common traits such as hair texture and other physical characteristics 1

Detection and Analysis of SNPs

The advancement of high-throughput technologies has facilitated SNP discovery and analysis:

• Genome-Wide Association Studies (GWAS): Used to identify SNPs associated with diseases 4, 2

• Candidate Gene Approaches: Focus on specific genes with potential relevance to diseases or traits 5

• Next-Generation Sequencing: Allows for comprehensive identification of SNPs across the genome 4

Clinical Implications

Understanding SNPs has important clinical applications:

• Disease Risk Assessment: Identification of SNPs associated with disease susceptibility can facilitate early diagnosis and prevention 5

• Personalized Medicine: Knowledge of an individual's SNP profile can guide treatment decisions, particularly in pharmacogenetics 4, 6

• Genetic Counseling: Information about disease-associated SNPs can inform family planning decisions

Challenges in SNP Interpretation

Despite their prevalence and importance, interpreting the significance of SNPs presents challenges:

• Functional Impact: Many SNPs have unknown functional consequences
• Complex Interactions: SNPs may interact with other genetic and environmental factors
• Population Differences: SNP frequencies and effects can vary across different ethnic groups 4

SNPs represent the foundation of human genetic variation and continue to be a focus of research aimed at understanding the genetic basis of disease and individual differences in drug response.