Imputation of microsatellite alleles from dense SNP genotypes for parentage verification across multiple Bos taurus and Bos indicus breeds

Matthew C. McClure, Tad S. Sonstegard, George R. Wiggans, Alison L. Van Eenennaam, Kristina L. Weber, Cecilia T. Penedo, Donagh P. Berry, John Flynn, Jose F. Garcia, Adriana S. Carmo, Luciana C. A. Regitano, Milla Albuquerque, Marcos V. G. B. Silva, Marco A. Machado, Mike Coffey, Kirsty Moore, Marie-Yvonne Boscher, Lucie Genestout, Raffaele Mazza, Jeremy F. Taylor, Robert D. Schnabel, Barry Simpson, Elisa Marques, John C. McEwan, Andrew Cromie, Luiz L. Coutinho, Larry A. Kuehn, John W. Keele, Emily K. Piper, Jim Cook, Robert Williams, Bovine HapMap Consortium, Curtis P. Van Tassell

To assist cattle producers transition from microsatellite (MS) to single nucleotide polymorphism (SNP) genotyping for parental verification we previously devised an effective and inexpensive method to impute MS alleles from SNP haplotypes. While the reported method was verified with only a limited data set (N = 479) from Brown Swiss, Guernsey, Holstein, and Jersey cattle, some of the MS-SNP haplotype associations were concordant across these phylogenetically diverse breeds. This implied that some haplotypes predate modern breed formation and remain in strong linkage disequilibrium. To expand the utility of MS allele imputation across breeds, MS and SNP data from more than 8000 animals representing 39 breeds (Bos taurus and B. indicus) were used to predict 9410 SNP haplotypes, incorporating an average of 73 SNPs per haplotype, for which alleles from 12 MS markers could be accurately be imputed. Approximately 25% of the MS-SNP haplotypes were present in multiple breeds (N = 2 to 36 breeds). These shared haplotypes allowed for MS imputation in breeds that were not represented in the reference population with only a small increase in Mendelian inheritance inconsistancies. Our reported reference haplotypes can be used for any cattle breed and the reported methods can be applied to any species to aid the transition from MS to SNP genetic markers. While ~91% of the animals with imputed alleles for 12 MS markers had ≤1 Mendelian inheritance conflicts with their parents' reported MS genotypes, this figure was 96% for our reference animals, indicating potential errors in the reported MS genotypes. The workflow we suggest autocorrects for genotyping errors and rare haplotypes, by MS genotyping animals whose imputed MS alleles fail parentage verification, and then incorporating those animals into the reference dataset.