MORECULAR GENETICAL INVESTIGATION AND DNA DIAGNOSTIC SYSTEM FOR BOVINE CHONDRODYSPLASTIC DWARFISM

本研究的目的是鉴定与牛软骨发育不良性侏儒症相关的基因，建立该疾病的DNA诊断体系。据报道，在日本褐牛的特定群体中存在遗传性软骨发育不良性侏儒症。受影响的动物显示四肢长骨软骨内骨化不足，无其他相关变化。本研究利用微卫星标记和一个从商业牛群中获得的患病动物父系半同胞家系（n=82），通过连锁分析，对该病的致病基因进行了定位。连锁分析表明，一个显着的连锁之间的基因座，称为bcd，和标记基因座上的牛6号染色体。bcd位点定位在微卫星标记BP7和BM 9257之间。牛和人类遗传图谱的比较表明，牛6号染色体的大部分与人类4号染色体4p16.3至4q25之间的区段同源。该片段涉及包括FGFR 3基因在内的多个候选基因，该基因是人类软骨发育不全的致病基因。为了确定牛6号染色体和人4号染色体之间的确切关系，我们使用牛仓鼠辐射杂交板进行辐射杂交作图。构建了包含33个功能基因和32个微卫星标记的牛6号染色体辐射杂种综合图谱。比较牛6号染色体和人4号染色体的辐射杂交图谱，发现人4号染色体的区域对应于牛6号染色体的区域，bcd位点位于该区域。

The aim of the present study is to identify the gene responsible for bovine chondrodysplatic dwarfism and establish the DNA diagnosis system for the disease. A hereditary chondrodysplastic dwarfism has been reported in the particular population of Japanese Brown cattle. Affected animal shows an insufficiency of endochondral ossification at long bones of the limbs and no other associated changes. An autosomal recessive trait of inheritance has been revealed by investigating pedigrees of the affected animals.In the present study, we mapped the locus responsible for the disease by linkage analysis using microsatellite markers and a single paternal half-sib family (n=82) of affected animals obtained from commercial herds. The linkage analysis revealed a significant linkage between the locus, referred as bcd, and marker loci on bovine Chromosome 6. The bcd locus was mapped between microsatellite markers BP7 and BM9257. A comparison of genetic maps between bovine and human indicates that the majority of bovine chromosome 6 is homologous to the segment of human chromosome 4 between 4p16.3 to 4q25. The segment involves several candidate genes including FGFR3 gene which is responsible for human achondroplasia. To determine exact relation between bovine chromosome 6 and human chromosome 4, we performed radiation hybrid mapping using the bovine hamster radiation hybrid panel. Consequently, a comprehensive radiation hybrid map of bovine chromosome 6 consisting with 33 functional genes and 32 microsatellite markers was constructed. A comparison between the radiation hybrid map of bovine chromosome 6 and human chromosome 4 revealed the region of human chromosome 4 corresponding to the region of bovine chromosome 6 in which the bcd locus is localized.