Assignment of the bovine C10orf2 gene to bovine 26q13-->q21 by fluorescence in situ hybridization and confirmation by radiation hybrid mapping.

Mutations in coding regions of the C10orf2 (chromosome 10 open reading frame 2) gene encoding the mitochondrial protein twinkle were shown to co-segregate in man with autosomal dominant progressive external ophthalmoplegia (adPEO) in several pedigrees of various ethnic origin (Spelbrink et al., 2001). A specific feature of the disease is accumulation of multiple deletions of mtDNA in tissues, mostly in the brain, muscle and heart, which results in a lack of the respiratory chain proteins thus leading to defective energy production and muscle weakness, most severely in the ocular muscles (Soumalainen et al., 1995). The human C10orf2 gene is located on HSA10q24.31 (http://www.ensembl.org). The objective of this study was to map the C10orf2 gene by fluorescence in situ hybridization and radiation hybrid mapping in cattle. C10orf2 appears as an appropriate candidate gene for bilateral convergent strabismus with exophthalmus (BCSE) in cattle, because the phenotype of BCSE in cattle shows striking similarities to the heterogeneous dominant and recessive forms of PEO in man (Distl, 1993). BCSE is similarly to adPEO characterized by a progressive symmetrical insufficient function of the eye muscles recti laterals and retractores. Furthermore, in German Brown cattle a monogenic, autosomal dominant inheritance proved to be most probable using complex segregation analysis (Distl, 1993). Due to the wide dissemination of BCSE in many cattle breeds, the late onset in life not earlier than by an age of 1–2 years, and a high incidence of 0.9% of this inherited anomaly in German Brown cattle, the development of an effective genetic program based on molecular genetic tests is strongly warranted.