Identification of polymorphic SVA retrotransposons using a mobile element scanning method for SVA (ME-Scan-SVA)

Area of Science:

• Genomics
• Molecular Biology
• Human Genetics

Background:

• Mobile element insertions are a significant source of human genomic variation.
• SVA (SINE-R/VNTR/Alu) is the youngest human retrotransposon family, implicated in various diseases.
• Identifying polymorphic SVA insertions and their impact is challenging, limiting extensive study.

Purpose of the Study:

• To systematically identify SVA insertions at the population level.
• To assess the genomic impact of SVA insertions.
• To overcome the difficulties in identifying polymorphic SVA insertions.

Main Methods:

• Developed a novel protocol: ME-Scan-SVA (mobile element scanning for SVA).
• Utilized a nested SVA-specific PCR enrichment method to amplify SVA elements and flanking regions.
• Constructed and sequenced a ME-Scan-SVA library from 21 individuals, analyzed with a new computational pipeline.

Main Results:

• Achieved high SVA-specificity (>90% reads from SVA insertions) and sensitivity (>90% for fixed insertions).
• Identified 151 novel polymorphic SVA candidates under relaxed criteria and 29 under stringent criteria.
• Validated six polymorphic SVAs with high genotype accuracy (average 92%).

Conclusions:

• The ME-Scan-SVA approach enables novel SVA insertion identification via high-throughput sequencing.
• This cost-effective method is suitable for large-scale population studies.
• The approach can detect active SVA elements and somatic retrotransposition events.