Design and performance of a bovine 200 k SNP chip developed for endangered German Black Pied cattle (DSN)

Abstract

Background: German Black Pied cattle (DSN) are an endangered dual-purpose breed which was largely replaced by Holstein cattle due to their lower milk yield. DSN cattle are kept as a genetic reserve with a current herd size of around 2500 animals. The ability to track sequence variants specific to DSN could help to support the conservation of DSN's genetic diversity and to provide avenues for genetic improvement.

Results: Whole-genome sequencing data of 304 DSN cattle were used to design a customized DSN200k SNP chip harboring 182,154 variants (173,569 SNPs and 8585 indels) based on ten selection categories. We included variants of interest to DSN such as DSN unique variants and variants from previous association studies in DSN, but also variants of general interest such as variants with predicted consequences of high, moderate, or low impact on the transcripts and SNPs from the Illumina BovineSNP50 BeadChip. Further, the selection of variants based on haplotype blocks ensured that the whole-genome was uniformly covered with an average variant distance of 14.4 kb on autosomes. Using 300 DSN and 162 animals from other cattle breeds including Holstein, endangered local cattle populations, and also a Bos indicus breed, performance of the SNP chip was evaluated. Altogether, 171,978 (94.31%) of the variants were successfully called in at least one of the analyzed breeds. In DSN, the number of successfully called variants was 166,563 (91.44%) while 156,684 (86.02%) were segregating at a minor allele frequency > 1%. The concordance rate between technical replicates was 99.83 ± 0.19%.

Conclusion: The DSN200k SNP chip was proved useful for DSN and other Bos taurus as well as one Bos indicus breed. It is suitable for genetic diversity management and marker-assisted selection of DSN animals. Moreover, variants that were segregating in other breeds can be used for the design of breed-specific customized SNP chips. This will be of great value in the application of conservation programs for endangered local populations in the future.

Keywords: Axiom MyDesign; Breed-specific; Conservation; Custom SNP array; Genetic reserve; Holstein cattle.

Fig. 1

Comparison of variant effects between the DSN200k SNP chip and the Illumina BovineSNP50 BeadChip using the Ensembl Variant Effect Predictor (VEP). The color indicates the impact of each consequence from the least severe (blue) to the most severe (red)

Fig. 2

Distribution of the physical distances between adjacent variants tiled on the DSN200k SNP chip per chromosome. Boxplots are shown for all variants on the DSN200k SNP chip (light green) and successfully called variants in all 300 genotyped DSN animals (green). The red line indicates the maximum distance of 250 kb aimed for during chip design. Two gaps longer than 250 kb exist on chromosomes 10 and 12, and ten gaps on the Y chromosome that could not be filled with variants. New gaps longer than 250 kb but shorter than 500 kb appeared due to failing variants after genotyping

Fig. 3

Distribution of p-convert scores derived from in silico analysis for successfully called and failed variants tiled on the DSN200k SNP chip used for 462 animals from 10 different taurine breeds