Barton P J, Cullen M E, Townsend P J, Brand N J, Mullen A J, Norman D A, Bhavsar P K, Yacoub M H
Imperial College School of Medicine, National Heart and Lung Institute, Dovehouse Street, London, SW3 6LY, United Kingdom.
Genomics. 1999 Apr 1;57(1):102-9. doi: 10.1006/geno.1998.5702.
Based on chromosomal mapping data, we recently revealed an unexpected linkage of troponin genes in the human genome: the six genes encoding striated muscle troponin I and troponin T isoforms are located at three chromosomal sites, each of which carries a troponin I-troponin T gene pair. Here we have investigated the organization of these genes at the DNA level in isolated P1 and PAC genomic clones and demonstrate close physical linkage in two cases through the isolation of individual clones containing a complete troponin I-troponin T gene pair. As an initial step toward fully characterizing this pattern of linkage, we have determined the organization and complete sequence of the locus encoding cardiac troponin I and slow skeletal troponin T and thereby also provide the first determination of the structure and sequence of a slow skeletal troponin T gene. Our data show that the genes are organized head to tail and are separated by only 2.6 kb of intervening sequence. In contrast to other troponin genes, and despite their close proximity, the cardiac troponin I and slow skeletal troponin T genes show independent tissue-specific expression. Such close physical linkage has implications for the evolution of the troponin gene families, for their regulation, and for the analysis of mutations implicated in cardiomyopathy.
基于染色体定位数据，我们最近揭示了人类基因组中肌钙蛋白基因的一种意外连锁关系：编码横纹肌肌钙蛋白I和肌钙蛋白T同工型的六个基因位于三个染色体位点，每个位点都携带一个肌钙蛋白I - 肌钙蛋白T基因对。在此，我们在分离的P1和PAC基因组克隆中研究了这些基因在DNA水平上的组织情况，并通过分离包含完整肌钙蛋白I - 肌钙蛋白T基因对的单个克隆，在两个案例中证明了紧密的物理连锁关系。作为全面表征这种连锁模式的第一步，我们确定了编码心肌肌钙蛋白I和慢骨骼肌肌钙蛋白T的基因座的组织和完整序列，从而也首次确定了慢骨骼肌肌钙蛋白T基因的结构和序列。我们的数据表明，这些基因是头对头排列的，仅由2.6 kb的间隔序列隔开。与其他肌钙蛋白基因不同，尽管它们紧密相邻，但心肌肌钙蛋白I和慢骨骼肌肌钙蛋白T基因表现出独立的组织特异性表达。这种紧密的物理连锁关系对肌钙蛋白基因家族的进化、它们的调控以及对与心肌病相关的突变分析都有影响。
