NEWS RELEASE

February 16, 2001

COMPLEX VERTEBRAL MALFORMATION (CVM) UPDATE

In October 2000, Danish researchers reported a new genetic defect in the Holstein breed designated as Complex Vertebral Malformation (CVM). Typically CVM calves are stillborn with a noticeable shortening of the cervical and/or thoracic part of the spinal column; may have malformed or contracted rear legs and heart defects. Immediately following the announcement, NAAB and Holstein USA began working with Dr. David Steffen, Director Veterinary Diagnostic Center, University of Nebraska-Lincoln to clarify the diagnosis and evaluate genetic relationship of CVM. Because this defect had not previously been recognized nor reported in North America, the announcement was widely publicized to US veterinarians and diagnostic laboratories and placed in two dairy publications in an effort to increase surveillance.

To date, there have been no publications about the CVM defect in a peer reviewed scientific journal. Although the initial report implied that CVM is inherited as a simple recessive trait, no supporting data was included. An unpublished retrospective segregation study in Denmark, reportedly did not produce the expected number of CVM calves also creating uncertainty. We understand two papers are currently in review that describe the defect's phenotype and a mechanism by which recessive alleles could be responsible for the defect, but provide no definitive proof, as the sire lines implecated are widely used. Segregation data and molecular data the Danish workers allude to have not been released and are not in the manuscripts under review.

The US industry is treating CVM with serious concern. Since October, six CVM calves have been confirmed in the US. This low number would not seem consistent with the widespread use of Carlin-M Ivanhoe Bell the reputed founder animal in the Holstein population.

Questions that must be answered before recommending a specific course of actin and advising bredders are: 1) What is the mode of inheritance of CVM, 2) What is the specificity of the marker test and 3) What is the potential economic impact to the producer of the disease and intervention strategies?

NAAB and Holstein USA are supporting a research project to help clarify the mode of inheritance. The indicated simple recessive inheritance is questioned because supporting data are not available about the segregation analysis research or molecular research conducted in Denmark. Embryos will be produced using a carrier female and carrier male that have previously produced a CVM calf. Following transfer to recipients, the fetus will be examined morphologically at the earliest appropriate time to determine if the expected number of CVM affected calves are produced.

Concern over the genetic marker test for CVM is based on the sampling of more than 100 bulls from one AI center. The test results could not provide a definitive answer for more than 25% of the animals tested. This apparent lack of test specificity makes it difficult to know how to handle bulls with such inconclusive results. This is a linkage test which is less specific than the test for BLAD that many dairy producers are familiar with. Because the causative mutation for CVM has not yet been precisely pinpointed, the test is based on genetic markers which flank the putative gene defect. Another concern is the imposition of new health restrictions and required documentation that will likely prevent many samples from the US from entering Denmark for testing. In addition, because of the excessive cost and unacceptable provisions of a proposed licensing agreement, we do not expect the Danish test to be available in the US anytime soon. A laboratory in The Netherlands is offering the test.

Determining an economic impact at this time is impossible until the mode of inheritance and frequency in the Holstein population is proven and the specificity of the test is validated. The US industry will determine a specific course of action to manage the defect as soon as appropriate information is available.

We are reluctant to blindly accept results that have not been independently reviewed and validated. The US industry's history of handling defects like BLAD clearly demonstrates that we will take aggressive actions once all the facts are known. To our knowledge, the Danish research results have not been subjected to peer review or published in a referred journal before labeling bulls as carriers. In fact, data supporting a recessive mode of inheritance has not been released in any format. Open exchange of scientific information would make it much easier for the dairy industry to respond to CVM in a scientifically responsible manner.