Source: UNIVERSITY OF MISSOURI submitted to
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
Funding Source
Reporting Frequency
Accession No.
Grant No.
Project No.
Proposal No.
Multistate No.
Program Code
Project Start Date
Jan 1, 2008
Project End Date
Dec 31, 2009
Grant Year
Project Director
Taylor, J.
Recipient Organization
Performing Department
Non Technical Summary
In U.S. Hereford cattle, hypotrichosis is a non-lethal defect with a simple autosomal recessive mode of inheritance which is often referred to in the literature as viable hypotrichosis, congenital hypotrichosis, or semi-hairless. In afflicted Herefords, the hair coat can be very short, fine, kinky, curly, or appear frosted and the tail switch can be underdeveloped. Abnormal hair can appear over all or parts of the body, often on the poll, brisket, neck and legs. Affected animals can be born with abnormal hair that shortly falls out, or are born hairless and develop a short curly coat with age. The condition may vary in expression as the animal matures, thus becoming less noticeable with age. Congenital hair defects are detrimental to all segments of the livestock industry since affected animals are more vulnerable to environmental stress, skin infections, pests, sunburn, cold stress, and have a decreased economic value independently of where they are raised. A genetic diagnostic test is needed to effectively identify carrier animals and to allow the design of breeding programs to minimize the economic disadvantage caused by the disease. By analyzing a pedigree of Hereford cattle that segregates for hypotrichosis and genotyping 47 animals from the pedigree with the Illumina BovineSNP50 Whole Genome SNP Genotyping assay we shall identify the region of the genome that harbors the disease mutation by homozygosity mapping. We anticipate that this interval will be no larger than 1 Mb in size and that by either sequencing candidate genes within the region or by sequencing the entire region, if necessary, we shall be able to identify the mutation responsible for hypotrichosis. This will allow us to develop a commercial test for the mutation that beef producers can use to identify breeding stock that are carriers for hypotrichosis and develop breeding decisions with this knowledge.
Animal Health Component
Research Effort Categories

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
Goals / Objectives
The objective of this proposal is to identify the mutation that is responsible for hypotrichosis in Hereford cattle and to develop a molecular test to diagnose the genotypes of animals which may be at risk for the disease or for being carriers of the disease allele.
Project Methods
DNA will be provided for 47 Hereford animals in a pedigree segregating for hypotrichosis by Dr. Johnathan Beever from the University of Illinois Urbana-Champaign A high resolution genome scan will be performed at the University of Missouri-Columbia using the BovineSNP50 assay on hypotrichosis affected Hereford calves, their unaffected obligate carrier parents, and other close relatives. The BovineSNP50 kit allows the simultaneous assay of 51,386 single nucleotide polymorphisms (SNPs) that are approximately evenly spaced at intervals of 45 kb throughout the bovine genome. Missing genotypes will be estimated and corrected for any apparent genotyping errors using GENOPROB. Analysis of the data for concordance of SNP and inferred disease locus genotypes will identify the region of the bovine genome that harbors the hypotrichosis causing mutation. Because hypotrichosis is inherited as a fully penetrant autosomal recessive disease, we will look for a genomic region (GR) where all SNPs are homozygous for the same allele in the affected calves and are heterozygous in their obligate carrier relatives. This GR will harbor the causal mutation for hypotrichosis under the autosomal recessive model of inheritance. Since linkage disequilibrium extends up to 500 kb in cattle our use of the BovineSNP50 Kit should result in the identification of ~22 SNPs in a 1 Mb region centered on the Hereford hypotrichosis locus. SNPs towards the center of this interval should be completely concordant with the disease locus genotype (homozygous in the affected calves and heterozygous in the carrier parents) and the extent of concordance will decay for more distant SNPs. Thus, we expect to have sufficient SNPs in the BovineSNP50 assay to resolve the size of the GR to much less than 1 Mb. Next, the Btau4.0 sequence (from a Hereford cow) flanking the GR will be analyzed for candidate genes and also for repetitive elements and duplications by repeat masking and BLAST analysis against the NCBI bovine trace file archives to identify regions that might be problematic for PCR amplification. Based upon these analyses, primers will be designed for long PCR (~6 kb) within the 1 Mb region harboring the GR and any suitable candidate genes. This strategy allows the entire 1 Mb region for 4 affected and 4 obligate carrier animals to be amplified in two 96 well plates. Finally, 1 Mb region of genomic DNA that harbors the GR will be sequenced from 4 affected calves and 4 unaffected parents using an Illumina 1G Genome Analyzer to identify the causal mutation. The gene content in the vicinity of the GR will also be analyzed to identify candidate genes that should first be sequenced. For example, LIPH, EDA, DSG4, HR, and ED1 have been shown to have mutations causal for human or mouse forms of hypotrichosis. Consequently, if one of these genes is located in or close to the GR, we will focus our sequencing on the region that contains the GR and the candidate gene.

Progress 01/01/08 to 12/31/09

OUTPUTS: An autosomal recessive form of hairlessness or hypotrichosis has been known to exist within the polled Hereford breed of cattle for more than 30 years. Calves affected with hypotrichosis are born with partial or complete absence of hair. As affected calves mature they exhibit a hair coat that is curly or fuzzy in texture. Adult animals may periodically display a "patchy" hair coat where hair has been lost and is slow to regrow. In this study affected and known normal animals were genotyped using the Illumina BovineSNP50 BeadChip followed by whole genome association and homozygosity analyses. Based upon these analyses, we identified the mutation responsible for hypotrichosis in Hereford cattle and developed a DNA test for use by breeders which will allow elimination of the disease from the breed. These results have been reported to the American Hereford Breeders Association and to the scientific community at the Plant & Animal Genomes XVIII Conference January 9-13, 2010 in San Diego. PARTICIPANTS: This project involved a collaboration between the Taylor laboratory at the University of Missouri at Columbia and the Beever laboratory at the University of Illinois at Champaign-Urbana. TARGET AUDIENCES: The target audience for this project includes breeders of Hereford cattle and geneticists interested in the hereditary forms of hypotrichosis in humans. PROJECT MODIFICATIONS: Not relevant to this project.

The disease locus was mapped to a position of approximately 30 Mb on BTA5. Sequencing of six candidate genes within the region revealed an eight base pair deletion mutation in exon one of the keratin 71 (KRT71) gene. A DNA based diagnostic was developed which confirmed that the mutation segregated in concordance with putative genotypic status of animals within the pedigree. The deletion mutation results in a frameshift and an early truncation of the K71 protein. The K71 protein is a hair follicle specific protein that is thought to participate in the formation of structurally important keratin intermediate filaments within the inner root sheath of the hair follicle. These filaments are integral to support and shape the growing hair shaft. The DNA based diagnostic will permit animals to be screened for the mutation and thus allow producers to make informed breeding decisions and eliminate hypotrichosis from the Hereford breed.


  • Markey AD, JF Taylor, RD Schnabel, SD McKay, MC McClure and JE Beever. 2010. A Deletion Mutation In KRT71 Is Associated With Congenital Hypotrichosis In Hereford Cattle. Poster P552 at Plant & Animal Genomes XVIII Conference, January 9-13, San Diego, CA.