Haplotype tests
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GENOMIC3 (09-13)

Updated May 2, 2016

Haplotype tests for recessive disorders that affect fertility and other traits

J.B. Cole, P.M. VanRaden, D.J. Null, J.L. Hutchison, T.A. Cooper, and S.M. Hubbard
Animal Improvement Program, 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 ~ http://aipl.arsusda.gov/

Haplotype tests now are used routinely to identify new recessive disorders and to track the carrier status of genotyped animals. Changes in the reporting of recessive factors that affect fertility and stillbirth recently have been described in detail (VanRaden et al., 2013). Carrier status for Holstein haplotypes with mutations for 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) now are reported in the XML files distributed by the Council on Dairy Cattle Breeding. Brown Swiss haplotype tests for spinal dismyelination (SDM; haplotype BHD), spinal muscular atrophy (SMA; haplotype BHM), and Weaver Syndrome (haplotype BHW) also are provided, but those tests do not directly include the causative mutation as an additional single nucleotide polymorphism because too few bulls were previously tested; a haplotype for polledness (BHP) also is reported. An exact test of the loss-of-function (LOF) mutation within a haplotype that affects fertility in Jerseys (haplotype JH1) now is used to determine carrier status for genotyped Jerseys, and a new Jersey haplotype (JH2) that affects fertility has been discovered (Van Raden et al., 2014); a haplotype for polledness (JHP) also is reported. A haplotype that affects conception rate in Ayrshires (haplotype AH1) is now reported (Cooper et al., 2014).

The table below lists all of the recessive 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. 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 Region (bp) Reference
Ayrshire AH1 001934 PIRM/UBE3B 13.0 17 65,921,497 Cooper et al. (2014), Venhoranta et al. (2014)
Brown Swiss BH1 001825 6.67 7 42,811,272 – 47,002,161 VanRaden et al. (2011)
BH2 001939 TUBD1 7.78 19 11,063,520 Schwarzenbacher et al. (2016)
BHD 001247 SDM/SPAST 2.19 11 14,742,058 Hafner et al. (1993), Thomsen et al. (2010)
BHM 000939 SMA/KDSR(FVT1) 3.61 24 62,118,139 – 62,156,760 El-Hamidi et al. (1989), Krebs et al., 2007
BHP 000483 Polledness/POLLED 0.4 1 1,705,834 – 1,989,480 Medugorac et al. (2012), Rothammer et al. (2014)
BHW 000827 Weaver/PNPLA8 1.56 4 49,878,773 McClure et al. (2013), Kunz et al., 2016
Holstein HBR 001199 Black/red coat color/
0.8 18 14,757,332 – 14,759,082 Lawlor et al. (2014)
HCD 001965 Cholesterol deficiency/APOB 2.5 11 77,958,995 Kipp et al. (2015), Charlier (2016), Menzi et al. (2016), Schütz et al. (2016)
HDR 001529 Dominant red coat color 0.04 3 9,479,761 Capitan et al. (2014), Lawlor et al. (2014), Dorshorst et al., 2015
HH0 000151 Brachyspina/FANCI 2.76 21 21,184,869 – 21,188,198 Agerholm et al. (2006), Charlier et al. (2012)
HH1 000001 APAF1 1.92 5 63,150,400 Adams et al. (2012)
HH2 001823 1.66 1 94,860,836 – 96,553,339 VanRaden et al. (2011), McClure et al. (2014)
HH3 001824 SMC2 2.95 8 95,410,507 Daetwyler et al. (2014), McClure et al. (2014)
HH4 001826 GART 0.37 1 1,277,227 Fritz et al. (2013)
HH5 001941 TFB1M 2.22 9 93,223,651 – 93,370,998 Cooper et al. (2013), Schütz et al. (2016)
HHB 000595 BLAD/ITGB2 0.25 1 145,119,004 Shuster et al. (1992)
HHC 001340 CVM/SLC35A3 1.37 3 43,412,427 Agerholm et al. (2001)
HHD 000262 DUMPS/UMPS 0.01 1 69,757,801 Shanks et al. (1984)
HHM 000963 Mulefoot/LRP4 0.07 15 77,663,790 – 77,701,209 Eldridge et al. (1951), Duchesne et al. (2006)
HHP 000483 Polledness/POLLED 0.71 1 1,705,834– 1,989,480 Medugorac et al. (2012), Rothammer et al. (2014)
HHR 001199 Red coat color/
5.42 18 14,758,207 Joerg et al. (1996)
Jersey JH1 001697 CWC15 12.10 15 15,707,169 Sonstegard et al. (2013)
JH2 001942 1.3 26 8,812,759 – 9,414,082 VanRaden et al. (2014)
JHP 000483 Polledness/POLLED 2.2 1 1,705,834– 1,989,480 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).

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 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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