Cell complementation using Genebridge 4 human:rodent hybrids for physical mapping of novel mitochondrial respiratory chain deficiency genes

摘要: The mapping and identification of respiratory chain deficiency genes is particularly tedious owing to the large number encoding catalytic subunits involved in (RC) assembly maintenance. We have developed a functional complementation approach by: (i) growing patient's fibroblasts highly selective medium; (ii) transferring human chromosome fragments into RC-deficient by microcell-mediated transfer. In absence carbohydrates culture medium, deficient cells rapidly disappeared unless they were rescued fragment carrying disease gene. Microcells prepared from human:rodent Genebridge 4 panel whole genome radiation hybrids fused with fibroblast strains two patients complex II or I + IV allowed map disease-causing small intervals (4 12 Mb) on chromosomes 12p13 7p21, respectively. These are similar that obtained genetic linkage analyses informative families. recovery normal RC enzyme activity skin supported relevance transferred disease. This makes physical feasible some sporadic cases deficiency.