AIP RESEARCH REPORT
Haplotype tests for economically important traits of dairy cattle
J.B. Cole, P.M. VanRaden, D.J. Null, J.L. Hutchison, and S.M. Hubbard
Animal Genomics and Improvement Laboratory, Agricultural Research
Service, USDA, Beltsville, MD 20705-2350
301-504-8334 (voice) ~ 301-504-8092 (fax) ~ email@example.com
Haplotype tests are used routinely to identify animals with desirable traits of economic importance, discover new genetic disorders, and track carrier status of genotyped animals. Recessive haplotypes that affect fertility and stillbirth in dairy cattle (haplotypes BH1–BH2, HH1–HH5, and JH1–JH2 were described in detail by VanRaden et al. (2011, 2013, 2014). A recessive mutation that causes embryo death (haplotype HH6) was discovered by Fritz et al. (2018). Carrier status for Holstein haplotypes with mutations for brachyspina (haplotype HH0), bovine leucocyte adhesion deficiency (BLAD; haplotype HHB), complex vertebral malformation (CVM; haplotype HHC), deficiency of uridine monophosphate synthase (DUMPS; haplotype HHD), mulefoot (syndactyly; haploptype HHM), polledness (haplotype HHP), red coat color (haplotypes HBR, HDR, and HHR), and cholesterol deficiency (HCD) are reported by the Council on Dairy Cattle Breeding (Bowie, MD). Brown Swiss haplotype tests for spinal dismyelination (SDM; haplotype BHD), spinal muscular atrophy (SMA; haplotype BHM), and Weaver Syndrome (haplotype BHW) also are provided. Polledness haplotypes are reported for Brown Swiss (BHP) and Jerseys (JHP). A haplotype that affects conception rate in Ayrshires (AH1) was reported by Cooper et al. (2014), and an Ayrshire haplotype that affects fertility (AH2) was discovered by Null et al. (2017). Haplotypes BH1 and JH2 were discontinued in December 2018 (VanRaden and Null, 2018).
This report replaces AIP Research Report Genomic3, which gave locations based on the UMD3.1 assembly for the bovine genome. The table below lists all of the haplotypes currently tracked in the U.S. genomic evaluation system, the frequency of the minor (less common) haplotype, and the location in base pairs (bp) of the haplotype based on the 2018 ARS-UCD1.2 genome assembly (www.ncbi.nlm.nih.gov/assembly/GCF_002263795.1/reference; Rosen et al., 2018). Locations are exact (single bp) when the causative mutation is known and approximate (range of bp) when it is unknown, a duplication, a deletion, or multiple mutations. The frequency of carriers in the population is generally twice the haplotype frequency because carriers have 1 defective and 1 normal haplotype.
||ARS-UCD region (bp)
||Cooper et al. (2014), Venhoranta et al. (2014)
||51,086,099 – 51,119,146
||Null et al. (2017)
||Schwarzenbacher et al. (2016)
||13,246,972 – 14,736,876
||Hafner et al. (1993), Thomsen et al. (2010)
||El-Hamidi et al. (1989), Krebs et al., 2007
|| Medugorac et al. (2012), Rothammer et al. (2014)
||49,339,002 – 49,461,342
||McClure et al. (2013), Kunz et al., 2016
||Black/red coat color/
||Lawlor et al. (2014)|
||Kipp et al. (2015), Charlier (2016), Menzi et al. (2016), Schütz et al. (2016)|
||Dominant red coat color
|| Capitan et al. (2014), Lawlor et al. (2014), Dorshorst et al., 2015||HH0
||Agerholm et al. (2006), Charlier et al. (2012)
||Adams et al. (2012)
||93,501,204 – 95,581,556
||VanRaden et al. (2011), McClure et al. (2014)
||Daetwyler et al. (2014), McClure et al. (2014)
||Fritz et al. (2013)
||91,847,117 – 91,937,003
||Cooper et al. (2013), Schütz et al. (2016)
||29,015,336 – 29,059,673
||Fritz et al. (2018)
||Shuster et al. (1992)
||Agerholm et al. (2001)
||Shanks et al. (1984)
||Eldridge et al. (1951), Duchesne et al. (2006)
|| Medugorac et al. (2012), Rothammer et al. (2014)
||Red coat color/
||Joerg et al. (1996)
||Sonstegard et al. (2013)|
|| Medugorac et al. (2012), Rothammer et al. (2014)
|1Online Mendelian Inheritance in Animals (OMIA) identification number for Bos taurus (National Center for Biotechnology Information species code 9913).
2Discontinued haplotypes: BH1, JH2.
Recessives with very low frequencies (e.g., HH4)
can be identified because many Holsteins have been genotyped (current exact
counts of genotyped animals are shown in the Council
on Dairy Cattle Breeding's "Genotype
Counts by Chip Type, Breed Code, and Sex Code
recessives in breeds with fewer genotyped animals and smaller populations
will not be detected until they have a high frequency in the population.
Haplotype tests are less accurate than loss-of-function (LOF) mutation tests, and retesting
valuable animals that have been identified as carriers using a haplotype
test is recommended if an exact test is available. Further information
on combining LOF mutation tests with haplotype tests is available (VanRaden et al., 2012)
as is further detail on genetic defects (Nicholas and Hobbs, 2014
; OMIA - Online Mendelian Inheritance in Animals, 2014
Adams, H.A., T. Sonstegard, P.M. VanRaden, D.J. Null, C. Van Tassell,
and H. Lewin. 2012. Identification of a nonsense mutation in APAF1 that is causal for a decrease in reproductive efficiency in dairy cattle
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Cooper, T.A., G.R. Wiggans,
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Cooper, T.A., G.R. Wiggans, P.M. VanRaden, J.L. Hutchison, J.B. Cole, and
D.J. Null. 2013. Genomic evaluation of Ayrshire dairy cattle and new
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El-Hamidi, M., H.W. Leipold, J.G.E. Vestweber, and G. Saperstein. 1989. Spinal
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Eldridge, F.E., W.H. Smith, and W.M. McLeod. 1951. Syndactylism in Holstein-Friesian
cattle: Its inheritance, description and occurrence
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Fritz, S., A. Capitan, A. Djari, S. C. Rodriguez, A. Barbat, A. Baur, C. Grohs, B. Weiss, M. Boussaha, D. Esquerré, C. Klopp, D. Rocha, and D. Boichard. 2013.
Detection of haplotypes associated with prenatal death in dairy cattle and
identification of deleterious mutations in GART, SHBG and SLC37A2
Fritz, S., C. Hoze, E. Rebours, A. Barbat, M. Bizard, A. Chamberlain, C. Escouflaire, C. Vander Jagt, M. Boussaha, Baur, C. Grohs, A. Allais-Bonnet, M. Philippe, A. Vallée, Y. Amigues, B.J. Hayes, D. Boichard, and A. Capitan. 2018.
An initiator codon mutation in SDE2 causes recessive embryonic lethality in Holstein cattle
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Using haplotypes to unravel the inheritance of Holstein coat color
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mapping for Weaver Syndrome in Brown Swiss cattle and the identification
of 41 concordant mutations across NRCAM, PNPLA8 and CTTNBP2
McClure, M.C., D. Bickhart, D. Null, P. VanRaden, L. Xu, G. Wiggans, G. Liu, S. Schroeder, J. Glasscock, J. Armstrong, J.B. Cole, C.P. Van Tassell, and T.S. Sonstegard. 2014. Bovine exome sequence analysis and targeted SNP genotyping of recessive fertility defects BH1, HH2, and HH3 reveal causative mutation in SMC2 for HH3
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