Haplotype tests
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GENOMIC4 (12-18)

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) ~ john.cole@ars.usda.gov ~ https://aipl.arsusda.gov/

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.

Breed Haplotype OMIA
9913 ID1
gene name
frequency (%)
Chromosome ARS-UCD region (bp) Reference
Ayrshire AH1 001934 PIRM/UBE3B 11.16 17 63,668,380 Cooper et al. (2014), Venhoranta et al. (2014)
AH2 002134 RPAP2 10.50 3 51,086,099 – 51,119,146 Null et al. (2017)
Brown Swiss2 BH2 001939 TUBD1 6.65 19 10,833,921 Schwarzenbacher et al. (2016)
BHD 001247 SDM/SPAST 1.31 11 13,246,972 – 14,736,876 Hafner et al. (1993), Thomsen et al. (2010)
BHM 000939 SMA/KDSR(FVT1) 3.24 24 61,620,374 El-Hamidi et al. (1989), Krebs et al., 2007
BHP 000483 Polledness/POLLED 1.22 1 2,578,598 Medugorac et al. (2012), Rothammer et al. (2014)
BHW 000827 Weaver/PNPLA8 0.58 4 49,339,002 – 49,461,342 McClure et al. (2013), Kunz et al., 2016
Holstein HBR 001199 Black/red coat color/
0.75 18 14,705,501 Lawlor et al. (2014)
HCD 001965 Cholesterol deficiency/APOB 2.28 11 77,872,709 Kipp et al. (2015), Charlier (2016), Menzi et al. (2016), Schütz et al. (2016)
HDR 001529 Dominant red coat color 0.03 3 9,361,962 Capitan et al. (2014), Lawlor et al. (2014), Dorshorst et al., 2015
HH0 000151 Brachyspina/FANCI 1.65 21 20,775,563 Agerholm et al. (2006), Charlier et al. (2012)
HH1 000001 APAF1 1.28 5 62,810,245 Adams et al. (2012)
HH2 001823 1.21 1 93,501,204 – 95,581,556 VanRaden et al. (2011), McClure et al. (2014)
HH3 001824 SMC2 2.64 8 93,753,358 Daetwyler et al. (2014), McClure et al. (2014)
HH4 001826 GART 0.23 1 1,997,582 Fritz et al. (2013)
HH5 001941 TFB1M 2.39 9 91,847,117 – 91,937,003 Cooper et al. (2013), Schütz et al. (2016)
HH6 002149 SDE2 0.44 16 29,015,336 – 29,059,673 Fritz et al. (2018)
HHB 000595 BLAD/ITGB2 0.21 1 144,770,078 Shuster et al. (1992)
HHC 001340 CVM/SLC35A3 1.10 3 43,261,946 Agerholm et al. (2001)
HHD 000262 DUMPS/UMPS 0.01 1 69,151,931 Shanks et al. (1984)
HHM 000963 Mulefoot/LRP4 0.05 15 76,807,960 Eldridge et al. (1951), Duchesne et al. (2006)
HHP 000483 Polledness/POLLED 0.88 1 2,578,598 Medugorac et al. (2012), Rothammer et al. (2014)
HHR 001199 Red coat color/
3.29 18 14,705,965 Joerg et al. (1996)
Jersey2 JH1 001697 CWC15 9.21 15 15,449,431 Sonstegard et al. (2013)
JHP 000483 Polledness/POLLED 2.04 1 2,578,598 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"). Generally 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).


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