Comprehensive genomic interrogation for both SNPs and CNVs together is an effective approach to elucidate the genetic causes of complex phenotypes and disease susceptibility in humans. This dual approach is necessary because each variant type contributes distinct information about gene expression and disease associations. [@stranger_relative_2007]
Definitions
- single nucleotide polymorphisms (SNPs)
- copy number variations (CNVs)
- complex phenotypes
- disease susceptibility
- gene expression
Synthesis
Multiple lines of evidence establish that single nucleotide polymorphisms and copy number variations contribute independently to gene expression architecture, with SNPs capturing approximately 84% of detectable genetic variation while CNVs account for a substantial but secondary 18%. Mechanistically, these two forms of genetic variation exhibit minimal overlap in their gene expression associations, suggesting they affect transcript abundance through distinct pathways and provide non-redundant information about regulatory mechanisms. Because complex phenotypes and disease susceptibility result from the combined effects of multiple genetic factors, comprehensive interrogation of both SNPs and CNVs is necessary to fully characterize the genetic basis of these traits. What remains unresolved is whether the asymmetry in contribution between SNPs and CNVs reflects fundamental differences in their regulatory mechanisms or merely differences in detection sensitivity and allele frequencies across populations.
Related
- SNP and CNV signals show minimal overlap in gene expression associations
- SNPs capture majority of genetic variation affecting gene expression
- Copy number variations account for substantial but secondary gene expression variation