G.R. Wiggans 1, T.S. Sonstegard 1, P.M. VanRaden 1, L.K. Matukumalli 1,2, R.D. Schnabel 3, J.F. Taylor 3, F.S. Schenkel 4, and C.P. Van Tassell 1 1 Agricultural.

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G.R. Wiggans 1, T.S. Sonstegard 1, P.M. VanRaden 1, L.K. Matukumalli 1,2, R.D. Schnabel 3, J.F. Taylor 3, F.S. Schenkel 4, and C.P. Van Tassell 1 1 Agricultural Research Service, United States Department of Agriculture, Beltsville, MD, USA 2 Bioinformatics and Computational Biology, George Mason University, Manassas, VA, USA 3 Division of Animal Sciences, University of Missouri, Columbia, MO, USA 4 University of Guelph, Guelph, ON, Canada 2008 ADSA-ASAS 2008 (1)G.R. Wiggans Selection of single nucleotide polymorphisms and genotype quality for genomic prediction of genetic merit in dairy cattle Abstr. #524

G.R. Wiggans 2008 ADSA-ASAS 2008 (2) Bovine SNP50 BeadChip Collaborators and users Bovine HapMap Consortium Existing SNP resources Bovine HapMap Consortium SNP discovery

G.R. Wiggans 2008 ADSA-ASAS 2008 (3) Laboratories & animals genotyped l Bovine Functional Genomics Laboratory, 8,236 ARS, USDA (Beltsville, MD) l GeneSeek (Lincoln, NE)2,288 l University of Alberta (Edmonton, AB) 1,325 l University of Missouri (Columbia, MO) 914 l Genetics & IVF Institute (Fairfax, VA)703 l Illumina (San Diego, CA) 116

G.R. Wiggans 2008 ADSA-ASAS 2008 (4) Genotypes by breed & sex BreedFemaleMaleAll Brown Swiss Holstein1,5679,04610,613 Jersey0589 All1,5709,98311,553

G.R. Wiggans 2008 ADSA-ASAS 2008 (5) SNP filtering & counts l SNP available 58,336 (including those not supported by Illumina) l Insufficient average number of beads1,389 l Unscorable 4,360 l Monomorphic in Holsteins 5,734 l Minor allele frequency (MAF) of <5% 6,145 l Percentage heterozygous different from282 expected or other scoring issues l Highly correlated 2,010 l Used for genomic prediction 38,416

G.R. Wiggans 2008 ADSA-ASAS 2008 (6) Bull distribution for unscorable SNP 4,389 Holstein bulls genotyped

G.R. Wiggans 2008 ADSA-ASAS 2008 (7) SNP distribution for bulls with unscorable SNP

G.R. Wiggans 2008 ADSA-ASAS 2008 (8) Identical twins & clones Missing SNP Changes l GLC Triton-ETN1910 GLC Triad-ETN GLC Trey-ETN145 l Comestar Laureat132 Comestar Loyalty165 l Bermath Monroe Bermath Morgan8376 l Granduc Blizzard1310 Granduc Spartan3633 l Granduc Performance84 Granduc Performer l U-of-Minn W Fatal Twyla2,2722,223 U-of-Minn W Fatal Tabina11665

G.R. Wiggans 2008 ADSA-ASAS 2008 (9) Genotyping for same bulls l 2 laboratories; 46 bulls; 38,416 SNP l SNP unscorable only once w Mean of 792 SNP w Range of 20 to 2,244 SNP l SNP conflict (<0.003%) w Mean of 0.9 SNP w Range of 0 to 7 SNP

G.R. Wiggans 2008 ADSA-ASAS 2008 (10) Highly correlated SNP l 4,286 bulls; 40,426 SNP l Compare each SNP with all others with MAF within 2% l Count all 9 combinations of 0, 1, and 2 for 2 SNP l Assumed highly correlated if only combinations with >21 SNP are 00, 11, and 22 or 20, 11, and 02

G.R. Wiggans 2008 ADSA-ASAS 2008 (11) Highly correlated SNP (cont.) l 2,444 pairs detected and categorized into 1,696 groups SNP in group Groups l Group sizes 21,450 for highly 3198 correlated 430 SNP

G.R. Wiggans 2008 ADSA-ASAS 2008 (12) Highly correlated SNP (cont.) l Distance between autosomal SNP w 65,531 mean base pairs between consecutive SNP w 19,826 base pairs between 1,199 consecutive highly correlated SNP w 423,033 base pairs between 469 SNP in group where  1 SNP in group is not consecutive

G.R. Wiggans 2008 ADSA-ASAS 2008 (13) Minor allele frequency distribution 38,416 SNP

G.R. Wiggans 2008 ADSA-ASAS 2008 (14) Heterozygosity differences l SNP different from expected heterozygosity by >7% Chromo -someSNP* MAF (%) Actual (%) Expected (%) 15 Hapmap39475-BTA ARS-BFGL-NGS ARS-BFGL-NGS ARS-BFGL-NGS X*X*ARS-BFGL-NGS BTB *SNP assigned based on bull homozygosity

G.R. Wiggans 2008 ADSA-ASAS 2008 (15) Sex determination l 605 SNP on X chromosome and not on Y (not in pseudo-autosomal region) l Bulls should not be heterozygous l Cows (n = 255) w Mean of heterozygous SNP w Range of 133 to 277 heterozygous SNP

G.R. Wiggans 2008 ADSA-ASAS 2008 (16) Parentage verification & discovery l Compare parent and progeny SNP if both homozygous l If >200 conflicts found, check every other genotype for one with <30 conflicts w May be parent, progeny, duplicate, clone, or identical twin

G.R. Wiggans 2008 ADSA-ASAS 2008 (17) Estimating missing SNP − imputing l Base population gene frequencies estimated with best linear unbiased prediction l Estimates provided for all genotyped animals and ancestors l If SNP genotype missing, estimate used if within 0.2 of 0, 1, or 2 l 6,268 genotyped animals w 0.9 % missing w 45% filled

G.R. Wiggans 2008 ADSA-ASAS 2008 (18) Summary l High-density Illumina BovineSNP50 BeadChip available l >38,000 SNP available for Holsteins l Genotypes consistent across laboratories l Few parent-progeny genotyping errors found l If parentage error found, correct parent often can be determined

G.R. Wiggans 2008 ADSA-ASAS 2008 (19) Summary (cont.) l SNP on X-chromosome support sex validation l Call rate is high and may be improved l Detection of highly correlated SNP revealed probable errors in map locations

G.R. Wiggans 2008 ADSA-ASAS 2008 (20) Financial support l National Research Initiative grants, USDA l Natl. Assoc. of Animal Breeders (NAAB, Columbia, MO) w ABS Global (DeForest, WI) w Accelerated Genetics (Baraboo, WI) w Alta (Balzac, AB) w Genex (Shawano, WI) w New Generation Genetics (Fort Atkinson, WI) w Select Sires (Plain City, OH) w Semex Alliance (Guelph, ON) w Taurus-Service (Mehoopany, PA) l Agricultural Research Service, USDA