Abstract
BackgroundIntegration of genomic variation with phenotypic information is an effective approach for uncovering genotype-phenotype associations. This requires an accurate identification of the different types of variation in individual genomes.ResultsWe report the integration of the whole genome sequence of a single Holstein Friesian bull with data from single nucleotide polymorphism (SNP) and comparative genomic hybridization (CGH) array technologies to determine a comprehensive spectrum of genomic variation. The performance of resequencing SNP detection was assessed by combining SNPs that were identified to be either in identity by descent (IBD) or in copy number variation (CNV) with results from SNP array genotyping. Coding insertions and deletions (indels) were found to be enriched for size in multiples of 3 and were located near the N- and C-termini of proteins. For larger indels, a combination of split-read and read-pair approaches proved to be complementary in finding different signatures. CNVs were identified on the basis of the depth of sequenced reads, and by using SNP and CGH arrays.ConclusionsOur results provide high resolution mapping of diverse classes of genomic variation in an individual bovine genome and demonstrate that structural variation surpasses sequence variation as the main component of genomic variability. Better accuracy of SNP detection was achieved with little loss of sensitivity when algorithms that implemented mapping quality were used. IBD regions were found to be instrumental for calculating resequencing SNP accuracy, while SNP detection within CNVs tended to be less reliable. CNV discovery was affected dramatically by platform resolution and coverage biases. The combined data for this study showed that at a moderate level of sequencing coverage, an ensemble of platforms and tools can be applied together to maximize the accurate detection of sequence and structural variants.
Highlights
Integration of genomic variation with phenotypic information is an effective approach for uncovering genotype-phenotype associations
3% of the reads were not mapped to the reference assembly, possibly because of a combination of breed or individual uniqueness, sequencing errors and contamination
The single nucleotide polymorphism (SNP) detected in this study provided a means to survey large identity by descent (IBD) regions that were revealed as runs of homozygosity (ROH) in the sequenced animal
Summary
Integration of genomic variation with phenotypic information is an effective approach for uncovering genotype-phenotype associations. Whole genome sequencing of single individuals removes the polymorphism ascertainment bias, detects rare putative functional variants and retrieves structural variants [16], an important category of genomic variation that only recently has become fully appreciated [17,18,19,20,21,22,23,24] Despite their known functional importance in humans [21,23], so far only a few smallscale studies have probed the extent of structural variants, mainly copy number variation (CNV), in cattle [25,26,27,28,29,30]. To work out the links between DNA sequence and phenotype, efforts to sequence the genomes of more individuals are intensifying [48,49]
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