AIP RESEARCH REPORT 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	Functional/ gene name	Haplotype 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/ MC1R(MSHR)	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/ MC1R(MSHR)	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).

References

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