'Fawn Calf Syndrome' Gene Marker Development

Summary

This reports concludes the first two stages of research into the development of prototype test for Fawn Calf Syndrome (FCS) in Angus cattle. The project was jointly funded by Angus Australia, Te Mania Australia and MLA donor company. The research was conducted at the University of Sydney by Reprogen Animal Bioscience group.The research achieved its stated objectives of:
a)  Identification of genome regions carrying the FCS locus based on a full genome screen with high density marker panels (Stage I).
b) Identification of a marker panel for FCS for pre-commercial development (Stage II). 
The DNA test is an indirect test, which is based on closely linked markers to the FCS gene and its unknown causative mutation. The use of an indirect marker test poses technical challenges for use in a commercial setting since many haplotype (genetic variants of the marker panel) maybe observed. The technical and logistical considerations for use of such a test have been detailed in this report. A major recommendation is to introduce a beta test based on an extended panel of 29 markers in a diverse set of Angus families in which FCS has been reported. 
The stage III beta test phase will allow for assessment of accuracy in classifying animals as likely AFFECTED, CARRIER or NORMAL and UNKNOWN (affected/carrier) UNKNOWN (carrier/normal). Ongoing technical input as well as pedigree analysis is required to interpret the results and finalize a commercial test for routine use by industry. Recommendations on the development and conduct of the beta test has been provided.
The final commercial test is likely to be a combination of a reduced subset of SNP markers, and pedigree information. Based on background data a high degree of accuracy is likely in prediction of FCS state, however expectations need to be managed that DNA tests are never 100% accurate. The commercial test could be conducted in combination with other DNA testing services such as parentage verification, however additional technical input is required to interpret the complex haplotype analysis and likelihood of  carrying zero, one or two copies of the FCS locus.  Recommendations for the development and implementation of a commercial test have been made in the report.
Finally, recommendations for ongoing research have been made then. The primary objectives would be to re-analyze beta  test results and ongoing commercial results, for evidence of recombination between normal haplotypes and disease haplotypes. This is important in order to maintain accuracy of the FCS test. A major objective should be to identify the causative mutation for FCS. Recommendations on a  research strategy have been made which include the banking of DNA, hair or tissue from animals subjected to commercial FCS test, associated pedigree information, and records on FCS for future confirmation of a direct FCS test.
In conclusion sufficient evidence has been generated to manage FCS in pedigreed Australian Angus breeding programmes with the use of an indirect panel of SNP markers.  The utility of the FCS outside these settings remains uncertain and has to be validated before recommending as commercial routine test.