In May 2011, I was asked by Angus Australia to begin investigating a phenotype that was being described as polymelia. The majority of calves exhibiting this trait are born with additional limbs, usually duplication of the front legs and originating from the neck or shoulder region.

With the exception of mortality associated with calving difficulty, these calves can often thrive, particularly if the extra limbs are surgically removed. Initially, we were presented with three DNA samples from affected calves as well as several of their parents. Even though pedigree analysis of the calves clearly showed evidence of line breeding, the molecular analysis revealed nothing that would have led us to believe the condition was genetic.

Throughout 2011 and 2012, Angus Australia continued to receive reports of polymelia calves and again in early 2013 was able to provide us with additional DNA samples for analysis (to read the article click here). The addition of these animals provided clear evidence of simple recessive inheritance.

Following this analysis, four calves displaying the same morphological features were reported here in the U.S. Samples from these calves were collected, and the analysis once again demonstrated that all of the affected calves, both Australian and American, shared a common region of homozygosity, thus confirming the presence of a recessive allele responsible for the phenotype.

Furthermore, we have since received additional Australian calves from both Angus Australia and Dr. Laurie Denholm that further substantiate our previous conclusions.

Most recently, we have completed sequencing of genes within the region shared by all affected calves. Recently, we identified a mutation that appeared to be consistent with the recessive pattern of inheritance in all affected calves and their parents.

In addition, functional analysis of the mutation suggests that the resulting change in the encoded protein would not be tolerated.

Subsequently, we initiated a population analysis to determine the frequency of the mutation within the breed. As was the case with genetic conditions such as AM, NH, CA and M1, the animals that best represent the genetics of the breed are the diverse population of A.I. sires that have been used over the past 20 years.

Examination of the genotyping data for these sires (which is currently being completed) reveals two important concerns.

First, the allele frequency among U.S. sires is moderately high at approximately 3 percent; this corresponds to a carrier frequency of approximately 6 percent.

Second, it shows that no homozygous individuals are present in the population. Of course, one would not expect a calf born with five or six legs to become an A.I. sire; however, given the moderate allele frequency, the rarity of affected calves, particularly as reported in the U.S., is somewhat puzzling.

Additionally, given the use of specific U.S. sires within Australia now known to be carriers, the frequency of reported calves is also unexpectedly low.

Thus, we believe these data indicate that calves presenting with polymelia at birth are rare events that survive embryonic death.

In support of this conclusion, we have also genotyped a case of conjoined twins that were submitted by Dr. Denholm as part of this project.

Indeed, these conjoined twins are also homozygous for the same mutation. We hypothesize that early developmental duplication events prevent many embryos from developing to term, resulting in embryonic death and the reduced frequency of live births being observed.

From a nomenclature standpoint, it has been decided to refer to this condition as Developmental Duplication (DD).