Spider Lamb Syndrome
by Dawn Fox, Laurie Soliday, and Kyle Barnard
What is "Spider Lamb Syndrome"?
Spider Syndrome is a disorder related to abnormal transformation of cartilage to bone. (SID Update: Spider Syndrome 1991)
In a report given by OSU (Oklahoma Extension Service) spider syndrome is classified as "a simple, autosomal, recessive gene".
Where did this disorder come from?
It is said in the late 1960s, a genetic mutation within the Suffolk breed is the cause of Spider Lamb Syndrome.
In the 1980s reports began to grow rapidly and scientist were working diligently to determine the cause of this progressing gene. It was in 1986 the "Spider Syndrome" Symposium was held in Sedalia, Missouri.
Where are we today?
Today we see this disease in our outer black-faced breeds as well, possibly due to cross breeding programs involving the Suffolk breed.
Nobody talks about "spider lambs" today compared to the mid 1980s, but it does play a role in sheep production today. Today we use DNA testing, and watch breeding techniques in order to alleviate the outbreak or spider lamb syndrome.
"Spider Syndrome" Symposium
On June 27th, 1986 a meeting was held in Sedalia, Missouri involving teams of researchers and sheep breeders to discuss Spider Syndrome.
Goals: to hear what researchers have been discovering, and ideas for breeders to be alert and identify the problem.
In the meeting, research reports were given by five different universities. A question and answer session followed the reports, between university representatives and the livestock breeders.
They are born abnormal and will not be able to stand.
They appear normal at birth but develop into a spider at two to six weeks of age.
Flexed lateral radiographs of the right elbow in newborn.
Notice multiple islands of ossification (arrows).
Postmortem ventrodorsal radiograph (sternum).
Notice the irregular nonsymmetrical appearance to the sternebrae.
Spider Lamb Syndrome (SLS) is a genetic disease, inherited through a single recessive allele. The syndrome is strongly displayed in the homozygote recessive animal. Tests of the ovine FGFR3 gene seen in figure 1, showed a single-base mutation causing a non-conservative (non-polar to charged) amino acid substitution in the tyrosine kinase domain of the receptor (Beever et al, 1998). It is most likely that the mutation leads to loss of receptor function in homozygotes that results in poorly controlled chondrocyte differentiation. This lack of control of cartilage cells leads to the skeletal deformities.
However, although FGFR3 is clearly a candidate for SLS, scientists can not eliminate the possibly that linkage disequilibrium between the alleles they detect in ovine FGFR3 and another tightly linked mutation may exist. In fact, several other skeletal defects, for which FGFR3 has been excluded, are also mapped to the distal portion of ovine chromosome 6 (Cockett et al, 1999). As SLS appears to be the result of a relatively recent mutational event, linkage disequilibrium would be expected do to the effects of having a small population of animals with the SLS gene (Cockett et al, 1999).
figure 2 figure 1
The reason that SLS has been so difficult to get rid of in flocks is due to the fact that carriers of the disease appear phenotypically normal. When two carriers are mated to each other, however, their offspring have a one half chance of being homozygous recessive and displaying SLS.
In order to test an animal that is a suspected carrier, one can a do test cross mating. Traditionally, this would mean mating the suspect animal to a homozygous recessive, but as spider lambs are not usually viable, any matings would be impossible. Thus, to test a suspect carrier, one can mate the animal to a known carrier. If the suspect animal is a carrier, the offspring has a one fourth chance of displaying SLS. As soon as one lamb is born with SLS, one can be one hundred percent positive that the suspect animal is indeed a carrier. This animal can then be culled. However, what happens if a normal animal is born? Even though a normal offspring could be a sign that the suspect animal is genetically clean, the offspring could also be a carrier. A normal animal has a one half chance of being a carrier, and a one fourth chance of being homozygous dominant. Because both of these animals appear normal, one still has no proof if the suspect animal is a carrier. One thus needs to do multiple matings to be sure the animal is clean. This can get expensive, and one can never be one hundred percent sure the animal is normal if it never has an offspring with SLS.
Luckily, with the identification of the gene and mutation that causes SLS, a test can now be performed on the blood of the suspected carrier. Because the mutation that causes SLS changes the weight of the DNA of that section of the chromosome, DNA containing the FGFR3 gene can be separated out and run on an electrophoresis gel. The normal DNA is heavier than the mutated DNA, thus it does not run as far on a gel. Since every animal has two copies of the gene, if only one strand is mutated, the mutated strand will run farther than the normal strand, as seen from figure 2. If both strands are mutated, a dark band will appear on the gel where the mutated DNA runs. If both strands are normal, a dark band will appear where normal DNA runs to one the gel. So far, this test has proved highly accurate at determining the genotype of these animals.
Now, nomenclature has been developed which provides breeders with a way to label blood tested clean animals in their pedigree. Using the letters NNI or NNP in the animals name at the time of registration would allow breeders to accurately track blood tested clean animals or the parental lines. As figure 3 shows, NNI should be used only where that specific individual (I) was blood tested as clean (NN) prior to registration. NNP should b used when the registration entry has both parents or parental lines (P) supported by NN blood tests.
Beever, J. E. et al (1998). Identification of the causative mutation in ovine hereditary chondrodysplasia.
Plant & Animal Genome VI Conference.
Cockett, N.E. et al (1999). Localization of the locus causing spider lamb syndrome to the distal end of
Ovine Chromosome 6. Mammalian Genome. 10, 35-38
Fitch, Gerald Q. Spider Syndrome. OSU Current Report.
Rook, Joseph S. et al (1988). Diagnosis of hereditary chondrodysplasia (spider lamb syndrome) in sheep.
Journal of the American Veterinary Medical Association. Vol. 193, No. 6, 713-718
SID Update: Spider Syndrome (1991)
"Spider Syndrome" Symposium (June 27, 1986).