Brooks B A, McBride O W, Dolphin C T, Farrall M, Scambler P J, Gonzalez F J, Idle J R
Department of Biochemistry, St. Mary's Hospital Medical School, London, United Kingdom.
Am J Hum Genet. 1988 Sep;43(3):280-4.
CYP3, the gene which encodes the hepatic cytochrome P450pcn1, the isozyme responsible for the metabolic oxidation of the calcium channel-blocking drug nifedipine, has recently been mapped to human chromosome 7 using somatic cell hybrids. Using multilocus linkage analysis in CEPH families, we examined the linkage of a cDNA probe (hPCN1) for CYP3 to the oncogene MET, the pro-alpha 2(1) collagen gene COL1A2, and the T-cell receptor beta-chain gene TCRB, together with three arbitrary loci D7S8, D7S13, and D7S16, defined by the anonymous DNA probes pJ3.11, pB79a, and p7C22, respectively. From 70 CEPH parents screened with a StyI RFLP for hPCN1, four informative families were found each with both parental and maternal grandparents and 6-11 children per family. Tight linkage emerged between CYP3 and COL1A2, with a maximum combined lod score of 5.72 at theta = 0, suggesting the most likely subchromosomal localization of CYP3 is 7q21.3-q22.1.
CYP3基因编码肝脏细胞色素P450pcn1，该同工酶负责钙通道阻滞剂硝苯地平的代谢氧化，最近利用体细胞杂种技术将其定位到人类第7号染色体上。我们在CEPH家系中进行多位点连锁分析，检测了CYP3的cDNA探针（hPCN1）与癌基因MET、α2（1）前胶原基因COL1A2、T细胞受体β链基因TCRB的连锁关系，以及分别由匿名DNA探针pJ3.11、pB79a和p7C22定义的三个任意位点D7S8、D7S13和D7S16。在70名用hPCN1的StyI限制性片段长度多态性筛选的CEPH家系父母中，发现了4个信息丰富的家系，每个家系都有祖父母和外祖父母，每家有6至11个孩子。CYP3与COL1A2之间出现紧密连锁，在θ=0时最大合并对数记分达到5.72，这表明CYP3最可能的亚染色体定位是7q21.3 - q22.1。
