docICAR-Parentage Recording + Genetic Analysis WGs_MS
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ICAR-Parentage Recording + Genetic Analysis WGs_MS
Matthew McClure October 18, 2013 Microsatellite Imputation Infer MS from SNP Haplotype Genotyped ONCE Initial Study 347 cattle -ISAG bovine MS parentage panel -Illumina HDSNP -Phased using BEAGLE Brown Swiss= 33 Guernsey= 16 Holstein= 250 Jersey= 48 SNP haplotype - MS allele Associations BM1824 Haplotype BABBAABBAAAABBBAABABABBBABBBAAAB BAABAABBAAAABBBAABABABBBABBBAAAB BBBBAABBAAAABBBAABABABBBABBBAAAB BABBAABBAAAABBBAABABABBBAABBBBAB BABBAABBAAAABBBAABABABBBABBBAABA BAABBAABBAAABBBAABABABABABBBAAAB BAABABABBAAABBAABAABABBBABAAAABA BAABABABBAAABBAABAABABBBABBBAAAB AABBAABBBAAABBAABAABABBBABBBAAAB AAAABAAABBABBAAABAABABABABAAAAAB AAAABAAABBABBAAABAABABABABAAAABA AAAABAAABBABBAAABAABABABABAAAAAA BAABBAABBBABBBAABBABABABABABAAAA AAAABAAABBABBAAABAABABABABABAAAA BABBAABBAABAABBBBBBABAAABABBBBAB BAAABABBAABAABBBBBBABAAABABBBBAB BAABAABBAABAABBBBBBABAAABABBBBAB AABBAABBAABAABBBBBBABAAABABBBBAB AAAABABBAABAABBBBBBABAAABABBBBAB Imputated Allele Brown Swiss Guernesy Holstein Jersey Overall 178 178 178 178 178 178 178 178 178 178 178 178 178 178 178 180 180 180 180 180 180 180 180 180 182 182 182 182 182 182 182 182 182 182 182 182 182 188 188 182 188 182_188 188 188 188 188 188 188_190 188_190 188_190 17% MS-SNP haplotypes identical across >2 breeds Beef Application • 8 beef breeds: 116 animals – Beagle phased – Vlookup for MS • • • • • • • • Belgian Blue Charolais Maine-Anjou Texas Longhorn Ankole-Watusi Angus Devon Dexter ~77% had imputed alleles ~86% Concordance Microsatellite Imputation Initial reference population: SNP + ISAG MS genotypes 7,076 Bos taurus 1,008 B. indicus 39 pure breeds B. taurus: 1,463 to 7,069 animals per MS Breed Abondance Angus Aubrac Ayshire Bazadaise Beefmaster Belmont Red Belgian Blue Blonde D'Aquitain Brahman Brangus Braunvieh Bretonne Pie Noire Brown Swiss Brune Des Alpes Charolais Chiangus Crossbred Devon Dexter Fresian Gasconne Gelbvieh Gir Guernsey Hereford Holstein Jersey Kerry Limousin Longhorn Maine Anjou Montbeliarde Murray Grey N'Dama Nelore Normande Parthenaise Pie Rouge Des Plaines Piedmontese Red Angus Red Pie (italial) Romagnola Rouge Flamande Salers Santa Gertrudis Sheko Shorthorn Simmental Swedish Red Tarentaise Tropical Composite Vosgienne Watusi TOTAL SNP 172 623 239 523 80 36 40 210 225 410 13 17 27 91 109 1449 19 506 16 15 163 142 44 209 110 853 2596 87 1 2171 13 38 257 22 24 2659 256 291 160 24 61 2 23 41 258 99 18 188 907 12 167 53 15 17138 SNP+MS 165 235 234 86 53 36 12 201 364 13 17 16 64 109 1109 0 3 16 15 35 142 0 101 18 243 678 131 0 1572 13 16 251 0 135 242 218 116 17 47 0 23 41 234 0 0 0 324 9 155 336 49 15 8259 Haplotype Selection: 1: Haplotypes centered on MS 2: >4 SNP-MS haplotype count 3: Haplotype is associated with 1 MS >90% 4: Maximize # animals selected A: Increase haplotype if >1% animals selected Per MS: ~780 haplotypes, ~70 SNP per haplotype (1,088 total) Microsatellite Imputation Initial reference population: SNP + ISAG MS genotypes 7,076 Bos taurus 1,008 B. indicus 39 pure breeds Initial validation population: SNP genotypes 8,622 Bos taurus & B. indicus animals 45 pure breeds, some crossbreds Breed Abondance Angus Aubrac Ayshire Bazadaise Beefmaster Belmont Red Belgian Blue Blonde D'Aquitain Brahman Brangus Braunvieh Bretonne Pie Noire Brown Swiss Brune Des Alpes Charolais Chiangus Crossbred Devon Dexter Fresian Gasconne Gelbvieh Gir Guernsey Hereford Holstein Jersey Kerry Limousin Longhorn Maine Anjou Montbeliarde Murray Grey N'Dama Nelore Normande Parthenaise Pie Rouge Des Plaines Piedmontese Red Angus Red Pie (italial) Romagnola Rouge Flamande Salers Santa Gertrudis Sheko Shorthorn Simmental Swedish Red Tarentaise Tropical Composite Vosgienne Watusi TOTAL SNP 172 623 239 523 80 36 40 210 225 410 13 17 27 91 109 1449 19 506 16 15 163 142 44 209 110 853 2596 87 1 2171 13 38 257 22 24 2659 256 291 160 24 61 2 23 41 258 99 18 188 907 12 167 53 15 17138 SNP+MS 165 235 234 86 53 36 12 201 364 13 17 16 64 109 1109 0 3 16 15 35 142 0 101 18 243 678 131 0 1572 13 16 251 0 135 242 218 116 17 47 0 23 41 234 0 0 0 324 9 155 336 49 15 8259 MS Accuracy: Parental Validation 1 MS conflict allowed Validation Population (N=1287) 90.55% Discovery Population (N=3470) 96.47% Microsatellite Imputation -Beagle used . Angus Ayshire BelgianBlue Charolais Guernsey Hereford Holstein Jersey Limousin RedAngus Shorthorn Simmental 266 266 266 266 266 BBBBBAAAABBAABABBBBAABAABAABAAABABBABAABABBAAAAABBAAAABABBBAAAAAAABBAAAABBABAAAA . AABBBABBAAABBABAAABAABAABAABAAABABBABAABABBAAAAABBAAAABAABBAAAAAAABABBBBBBBABBBB . 270 BBBBBAAAABBAABABBBBAABAABAABBAAAABBABAABBABAAAAABBAAAABAABBAAAAABBABAAAABBABAAAA . 262 AABBABAAABBAABABBBBBAABBAABABABAAABBAABABABBBBBBAABBBBABAABBBABBBBAAAAAAAAABABAB . 280 280 AABBBABBABABBABAAABBAAABAAABBAAAABBABAAABAABBBBBAABBBBABBBBAAAABAABAABAAAABAABBB . AABBBABBABABBABAAABBAABBAAABBAAAABBABAAABAABBBBBAABBBBABAAABBBBBBBAAAAAAABBAABBA . 268 AABBABBAABBAABABBBBBAABBAABABABAABBBBAAABABBBBBBAAABBBABAABBBBBBBAAAAAAABBBABBAB . 262 AABBABBAABBAABABBBBBBABBAABBAABAABBBAAAABABBBBBBAAABBBABAABBBBBBBAAAAAAABBBAABAB . BBBBBAAAABBAABABBBBBAABBBAABBAABABBABBABABABBBBBAABBBBABBBBAAAAAAABABBBBBBBABAAA . 272 272 AABBABBAABBAABABBBBBAABBAAABBAAAABBABAAABAABBBBBAABBBBABAAABBBBBBBAAAAAAABBABBBB . 260 AABBBABBABABBABAAABBABAABAABBAAAABBABAAABAABAABBAABBBAABBABABBBBBBBAAAAAABBABBBB . 260 AAABABBAABBAABABBBBBAABBAAABBAAAABBABAAABAABBBBBAABBBBABAAABBBBBBBAAAAAAABBAABBA . 268 268 268 AAABBABBABABBABAAAAAABAABAABABBAAAABAAAABAABBBBBAABBBBABABBBBBBBBBABAAAABBABAAAA . 262 262 262 AABBABBAABBAABABBBBBAABBAAABBAAAABBABAAABAABBBBBAABBBBABAAABBBBBBBAAAAAAABBABBBB . 258 258 258 258 AAABABAAABBAABABBBBBAABBAAABBAAAABBABAAABAABBBBBAABBBBABABBBBBBBBBABAAAABBABAAAA . 266 266 266 266 AAABABBAABBAABABBBBBAABBAAABBAAAABBABAAABAABBBBBAABBBBABAAABBBBBBBAAAAAAABBAABBA . 268 268 268 AAABABBAABBAABABBBABABAABAABABBAAAABAAAABAABBBBBAABBBBABBBBAAAAAAABABBBBBBBABAAA . 262 AABBBABBAAABBABAAABAABBABAABBAABABBABAABABBAAAAABBAAAAABBBBAAAABAABBAAAABBABAAAA . 266 266 266 AABBBABBABABBABAAAABAABBAABABAABABBABBABABBAAAAABBAAAABABAABBBBBBBAAAAAAABBABBBB . 266 266 Haplotype AAABABBAABBAABABBBBBAABBAAABBAAAABBABAAABAABBBBBAABBBBABABBBBBBBBBABAAAABBABAAAA . 266 266 266 + PHASE Overall 266 262 270 262 280 286 268 262 268 272 260 260 268 262 258 266 268 262 266 266 BM1818 262/258 Irish Parent Verification Process Herdbook Certificate Issued Rules Applied Verified 2000 SNP shared: 3K, LD, 50K, HD, IDB Failed Verified ICBF Database Hair Roots ISAG 120 SNP Weatherbys Irish Parent Verification Process Herdbook Certificate Issued Rules Applied Failed 1088 SNP Verified + BEAGLE + Failed Verified 7,699 reference Imputed MS ICBF Database Hair Roots Weatherbys Irish Parent Verification Process Report Generated Herdbook Certificate Issued Wrong Sire Rules Applied Failed Verified Verified Verify Result Verified Failed Verified Imputed MS ICBF Database Hair Roots Weatherbys No Sire MS Genotyping –Irish status for 2013 • ~16,680 Animals genotyped – ~5,600 Beef Animals – ~750 failed genotyped: Call Rate <0.90 • Sire Verification within breed – By SNP: 48% to 10% – By Microsatellite: 60% to 20% – Remaining are ‘Typed’ Imputation Accuracy for Parentage Verification TGLA53= ~20% TGLA53= ~16% Applied: ICBF imputed MS genotypes. Reference: McClure et al. 2013’s imputed MS genotype. Validation: McClure et al. 2013’s traditional MS genotype Passed: no marker conflicts. Passed -1 off: 1 marker conflict occurred. Fail: >2 marker conflicts exist. Impact of Microsatellite Imputation • 4,952 Irish animals have had microsatellite genotypes imputed (October, 2013) as: • SNP parentage failed (small #) • Embryo transfer animal • No SNP genotype on sire (most of them) • >96% accuracy with imputed microsatellites – Accuracy will increase for new runs – >97% accuracy without TGLA53 • Microsatellite imputation has saved Irish cattle farmers ~€95,000, as cost of MS genotyping is ~€20/animal. Thank you <1990’s Present Future
TRI VILLEFRANCHE SAONE VALL