2007 Paul VanRaden, Dan Null, Katie Olson, Jana Hutchison Animal Improvement Programs Lab, Beltsville, MD National Association of Animal Breeders, Columbia,

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2007 Paul VanRaden, Dan Null, Katie Olson, Jana Hutchison Animal Improvement Programs Lab, Beltsville, MD National Association of Animal Breeders, Columbia, MO 2011 Reporting of Haplotypes with Recessive Effects on Fertility

Interbull annual meeting, Norway, August 2011 (2) Paul VanRaden 2011 Introduction  Five haplotypes with recessive effects on fertility discovered Additive effects small and in EBVs All populations already carry these  At least 19 countries have ‘health’ laws excluding carriers of defects Only countries that test are banned? Import restrictions make little sense

Interbull annual meeting, Norway, August 2011 (3) Paul VanRaden 2011 Recessive Defect Discovery  Check for homozygous haplotypes 7 to 90 expected but none observed 5 of top 11 confirmed as lethal 936 to 52,449 carrier sire by carrier MGS fertility records 3.0% to 3.7% lower conception rates Some slightly higher stillbirth rates  Confirmed Brachyspina same way

Interbull annual meeting, Norway, August 2011 (4) Paul VanRaden 2011 Haplotypes Affecting Fertility Name Chrom- osome Loca- tion Carrier FreqEarliest Known Ancestors BTAMbase% HH Pawnee Farm Arlinda Chief HH Willowholme Mark Anthony HH Glendell Arlinda Chief, Gray View Skyliner JH Observer Chocolate Soldier BH West Lawn Stretch Improver

Interbull annual meeting, Norway, August 2011 (5) Paul VanRaden 2011 Hapl- Additive EffectSire x MGS Interaction otypeCRNR60NR100NR140CR280 CVM BY HH HH HH JH BH Additive and Nonadditive Effects on nonreturn rates or full gestation conception

Interbull annual meeting, Norway, August 2011 (6) Paul VanRaden 2011 Haplo-Conception Rates typeBullService SireHeiferCow BYRamosN / A HH1Lucius HH2Colby HH3O-Man JH1Country BH1Payoff Carrier Bulls with High Fertility

Interbull annual meeting, Norway, August 2011 (7) Paul VanRaden 2011 Using Crossovers to Fine Map Source Combined With Source Suspect Area Carrier Possible 75 marker haplotype (50K), about 5 Mbases

Interbull annual meeting, Norway, August 2011 (8) Paul VanRaden 2011 Crossover haplotypes Haplo- type That combined with source Within suspect area That contained suspect area SNPs in suspect area BY HH HH HH JH BH Crossovers used in Fine Mapping

Interbull annual meeting, Norway, August 2011 (9) Paul VanRaden 2011  3 methods to detect carriers: Use all genotypes and pedigrees One at a time (ignore pedigree) Find and test for causative mutation  Without vs. with haplotyping 2.5% false positive, 0.05% false neg Similar to Georges et al (2010) Brachyspina haplotype test Detection Without Haplotyping

Interbull annual meeting, Norway, August 2011 (10) Paul VanRaden 2011 Haplotype False positive (%) False negative (%) Error rate (%) BY HH HH HH JH Detection with 3K Genotypes 500 carriers, 500 noncarriers, with imputation

Interbull annual meeting, Norway, August 2011 (11) Paul VanRaden 2011 Conclusions  Recessive defects found in each breed (HH1, HH2, HH3, JH1, BH1) Officially reported in August Most embryo losses < 60 days  Breeders should select for fertility, not against individual defects, and mate carriers to noncarriers  Crossovers used for fine mapping