Genetic Variation Between Human Individuals
Humans differ from one another at approximately 0.1% of nucleotide positions, which accounts for most heritable phenotypic variation.
Overview of Human Genetic Variation
The human genome contains substantial genetic diversity, with each individual harboring millions of variants that distinguish them from other members of our species. According to the most recent and comprehensive evidence:
- The ExAC consortium demonstrated that the human exome contains an average of 1 coding variant every 8 base pairs 1
- The 1000 Genomes Project characterized over 88 million variants across 2,504 individuals from 26 populations, including:
- 84.7 million single nucleotide polymorphisms (SNPs)
- 3.6 million short insertions/deletions (indels)
- 60,000 structural variants 2
Quantifying Genetic Variation Between Individuals
The genetic variation between humans is remarkably small when considering the entire genome:
- Humans differ from one another at only approximately 0.1% of nucleotide positions 3
- This small percentage of variation accounts for most heritable phenotypic differences between individuals 3
Composition of Genetic Variation Within Genes
The average human gene contains significant genetic diversity:
- 126 biallelic polymorphisms per gene
- 46 of these polymorphisms are common (≥5% minor allele frequency)
- Only 5 polymorphisms are typically found in coding regions 4
Distribution of Genetic Variants
The distribution of variants across the genome is not uniform:
- More than half of the 9 million variants uncovered in large sequencing projects were extremely rare, observed only once as a heterozygote in a single individual 1
- Over 99% of SNP variants with a frequency >1% have been characterized across various ancestries 2
Clinical Relevance of Genetic Variation
Understanding which variants impact health is a major challenge:
- Recent research using primate comparative genomics identified 4.3 million protein-altering variants that are likely benign in humans 5
- This approach classified only about 6% of all possible human protein-altering variants as likely benign, suggesting that the remaining 94% may have some functional impact 5
Regulatory Variation
Much of the phenotypic variation between individuals and species appears to be driven by differences in gene regulation rather than protein-coding changes:
- Differential gene regulation contributes significantly to variation both within and between species 6
- Regulatory sequences may evolve at different rates compared to coding sequences 6
Implications for Medicine and Research
The small percentage of genetic variation between humans has profound implications:
- Rare variants may contribute significantly to phenotypic diversity and genetic disorders 3
- High-throughput methods for detecting rare nucleotide differences are increasingly important for understanding human disease 3
- Population-specific genetic databases are essential for interpreting genetic variation in clinical contexts 1
Understanding this 0.1% variation is crucial for advancing personalized medicine and our knowledge of human evolution and diversity.