Towards the molecular analysis of microphthalmia in Texel sheep
J. Tetens and C. Drögemüller
The aim of the current study was to map the disease gene locus responsible for monogenic autosomal ecessive inherited congenital microphthalmia in the Texel breed. A comparative candidate gene approach was applied based upon previously mapped disease loci in human and mouse. The family material was obtained by collecting blood samples in the field and from an experimentally derived resource family. Clinical and pathological investigations were performed on affected and unaffected animals from this family and the morphology was described coincidently with previous
studies. No other malformations in addition to the isolated microphthalmia were found in any of the animals and a recessive pattern of inheritance with a complete
penetrance and variable expressivity was shown. Focussed on the predicted candidate gene regions linkage analysis was performed and the disease causing gene could be mapped to ovine chromosome 23 within an interval spanning 12.4 cM. The exact chromosomal positions of the two candidates RAX and TGIF as well as the orthologous regions on human chromosome 18 were determined applying a comparative RH-mapping approach. It was found that RAX is clearly located outside of the critical interval. Furthermore, a candidate gene analysis was undertaken for TGIF and it thereby could also be excluded as a candidate. The work presented herein provides a valuable base for further work towards the identification of the molecular cause of congenital microphthalmia in the Texel breed. Furthermore, it was shown that a marker based indirect gene diagnosis is already possible within families with affected offspring.
Keywords/Stichworte:Sheep, Texel breed, microphthalmia, congenital anomaly, linkage analysis,
comparative genome mapping, marker based gene diagnosis
studies. No other malformations in addition to the isolated microphthalmia were found in any of the animals and a recessive pattern of inheritance with a complete
penetrance and variable expressivity was shown. Focussed on the predicted candidate gene regions linkage analysis was performed and the disease causing gene could be mapped to ovine chromosome 23 within an interval spanning 12.4 cM. The exact chromosomal positions of the two candidates RAX and TGIF as well as the orthologous regions on human chromosome 18 were determined applying a comparative RH-mapping approach. It was found that RAX is clearly located outside of the critical interval. Furthermore, a candidate gene analysis was undertaken for TGIF and it thereby could also be excluded as a candidate. The work presented herein provides a valuable base for further work towards the identification of the molecular cause of congenital microphthalmia in the Texel breed. Furthermore, it was shown that a marker based indirect gene diagnosis is already possible within families with affected offspring.