Towards a comprehensive structural variation map of an individual human genome

Area of Science:

• Genomics
• Bioinformatics
• Human Genetics

Background:

• Millions of genetic variants (SNPs, indels) are annotated, but larger structural variants (SVs) are less understood.
• Previous analyses of personal genomes show varying results for copy number variations (CNVs) and inversions.
• The full extent of genomic differences from reference assemblies due to SVs is unclear.

Purpose of the Study:

• To comprehensively identify and characterize unreported structural variants in a personal genome.
• To quantify the impact of SVs on gene content and compare them to SNP-based variations.
• To assess the potential for imputation of SVs using SNP data.

Main Methods:

• Combined computational re-analysis of existing whole genome sequencing data.
• Novel microarray-based analysis for SV detection.
• Comparison with initial sequencing reports of the first personal genome.

Main Results:

• Detected 12,178 unreported structural variants (40.6 Mb) in a single personal genome.
• Estimated total non-SNP variation content at 48.8 Mb, with SVs (indels/CNVs, inversions) comprising ~1.2% difference from the reference.
• Identified that SVs impact 4,867 genes, with >24% not imputable by SNP-association.

Conclusions:

• A substantial number of structural variants remain unreported in personal genomes.
• The complexity and extent of SVs necessitate their active study in health-related genomic analyses.
• The generated catalogue of SVs serves as a vital resource for future comparative genomic studies.