The work carried out by INRA scientists1 had a dual objective: to develop a reliable test to detect healthy carriers of the condition for breeding professionals, and to understand the genetic and molecular mechanisms underlying syndactyly and thus contribute to a clearer comprehension of limb development in cattle.
Syndactyly is inherited as a simple autosomal recessive condition, i.e. affected animals possess two unfavourable alleles in the gene responsible and this gene is not situated on a sex chromosome. Animals with only one unfavourable allele are healthy carriers. The condition mainly results in fusion of the digits of one or more feet. The animals are also more susceptible to hyperthermia. All these symptoms render them more vulnerable. As their age advances, these animals find it difficult to move about normally, so that it is no longer possible to keep them with the rest of the herd and they often need to be isolated.
© INRA / A. Duc
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Photo A: animal with all four feet affected by syndactyly.
Photo B: X-ray showing fusion of the digits of an affected foot on the left and a healthy foot on the right.
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Identification of the gene mutation responsible for the condition
The region implicated in syndactyly was mapped on cattle chromosome 15 in 1996. The genotyping of around 250 animals for numerous additional markers in the region, and a functional genomics approach to affected animals bred in an experimental unit, made it possible to refine the region implicated in the condition.
It was the discovery of mice presenting with a form of syndactyly which put the INRA scientists on the path of the gene. Indeed, these studies in mice, performed by the Pasteur Institute, demonstrated a mutation in the LRP4 gene, so that the INRA researchers turned their attention to this gene in cattle. Studies of genetic and physiological aspects were pursued and enabled identification of the mutation responsible for syndactyly: it is present in a homozygous form in all affected animals, in a heterozygous form in all healthy carriers and never present in healthy animals.
The mutation affects the gene coding for the LRP4 protein. It generates a modification to two amino acids in this protein, thus modifying its function. It was known that this protein is involved in limb development in the mouse, so that results in that animal demonstrated that it was also probably implicated in the development of limbs in cattle also.
Identification of the mutation responsible for syndactyly in Holstein cattle is the result of ten years' research at an international level.
Towards the total eradication of syndactyly
This discovery will in the long term enable total eradication of this condition from Holstein cattle. Work is ongoing to determine whether the molecular origin of the condition is identical in other cattle breeds: the same gene or even the same mutation.
The genetic test for the causal mutation has been transferred to GIE LABOGENA for its application to cattle breeding.
1 This work was carried out in a context of a thesis funded jointly by INRA and GIE Labogena.
References:
Identification of a doublet missense substitution in the bovine LRP4 gene as a candidate causal mutation for syndactyly in Holstein cattle
Genomics, Volume 88, Issue 5, November 2006, Pages 610-621
A. Duchesnea, M. Gautiera, S. Chadia, C. Grohsa, S. Floriota, Y. Gallardb, G. Castec, A. Ducosd and A. Eggena,
a Laboratoire de Génétique Biochimique et de Cytogénétique, Département de Génétique Animale, INRA-CRJ, 78350 Jouy-en-Josas, France
b Domaine Expérimental du Pin-au-Haras INRA, Département de Génétique Animale, Domaine de Borculo, 61310 Le Pin-au-Haras, France
c Domaine Expérimental de la Verrerie INRA, Département de Génétique Animale, Domaine de la Verrerie, 81400 Blaye-les-Mines, France
d UMR INRA-ENVT 898, Cytogénétique des Populations Animales, 23 Chemin des Capelles, 31076 Toulouse Cedex 03, France
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