Detection and validation of structural variations in bovine whole-genome sequence data

Area of Science:

• Genomics
• Animal Genetics
• Population Genetics

Background:

• Structural variations (SV) impact cattle traits, but accurate identification from whole-genome sequencing (WGS) data is challenging due to high false positive rates.
• Previous methods for SV detection in cattle WGS data require improvement for precision and sensitivity.

Purpose of the Study:

• To develop a high-quality set of structural variation (SV) calls in cattle using whole-genome sequencing (WGS) data.
• To assess the overlap of SV between Holstein and Jersey cattle populations.
• To investigate the association of SV with conserved and recently expanded gene families in cattle.

Main Methods:

• Evaluated two SV detection programs (Breakdancer and Pindel) using simulated data to determine precision and sensitivity.
• Identified population SV from WGS data of 252 Holstein and 64 Jersey bulls based on overlapping calls from both programs.
• Validated identified SV sets using twice-sequenced individuals and sire-son transmissions, and analyzed gene set enrichment for SV.

Main Results:

• Identified 17,518 SV (27.36 Mb) in Holsteins and 4,285 SV (8.74 Mb) in Jerseys, with 4.62 Mb overlapping between breeds.
• Validated 11,534 candidate SV (5.64 Mb) in Holstein individuals and confirmed transmission in sire-son pairs.
• Found significant depletion of SV in core eukaryotic genes and enrichment in recently expanded gene families, with Long interspersed nuclear elements-1 enriched for deletions.

Conclusions:

• A substantial proportion of SV (53.5%) were shared between Holstein and Jersey populations.
• Validated SV through sire-son transmission demonstrated high concordance within and between breeds.
• The enrichment of SV in expanding gene families highlights their role as a source of genetic variation driving evolutionary adaptation in cattle.