Molecular genetic analysis of Cytochrorne P4501B1 and allied genes

1)细胞色素P4501B1（CYPIBi）是先天性青光眼的致病基因，不同的临床表现表明该基因内存在弥散性。CYP1BI基因也存在多态替换。考虑与疾病易感性的遗传联系，我们在成人发病的原发性开角型青光眼患者中检测CYP lB I基因多态性。以置换纯合子/杂合子/正常纯合子的例数表示，POAG患者、正常对照中各基因型的出现频率依次为：R48G为76年8月11日，93年3月18日；A119S为12/52/31、20/53/47；A330V为2/3/83,1/11/125，S331R为0/7/83,0/6/82。虽然在统计学上证实了两组间基因型频率的差异，但没有具体的基因型差异。2) 2个视网膜裂家系（rs1基因）和1个诺里病家系（ND基因）发现新的病理基因突变。3)为探讨线粒体DNA（mtDNA）单倍型与该病表型的关系及人类学背景，测定了日本Leber遗传性视神经病变（LHON）患者G11778A突变mtDNA位移环（D-loop）区高变段核苷酸序列。对36例双侧视神经疾病且mtDNA G11778A突变的无亲缘关系的日本LHON患者进行mtDNA遗传多态性检测。从核苷酸比对的数据集，mtDNA序列的系统发育和表型多样性的研究群体进行了评估。37个位点存在单碱基多态性。在所调查的LHON群体中，D-loop序列没有任何确定的祖先单倍型。因此，GI 1778A的突变事件似乎与d环单倍型的进化过程无关。

1)Cytochrome P4501B1(CYPIBi)is a causative gene of congenital glaucoma, and dispersion has been shown within the gene by diverse clinical manifestations.There are also polymorphic substitutions in the CYP1BI gene.Considering genetic linkage with the disease susceptibility, CYP lB I genetic polymorphism was examined among patients with adult-onset primary open angle glaucoma.Frequency of each genotype was as follows in the order of the POAG patients, the normal controls, when it is shown by the number of examples of the displacement homozygote/heterozygote/normal homozygote.They were 8/11/76, 3/18/93 for R48G ; 12/52/31, 20/53/47 for A119S ; 2/3/83, 1/11/125 for A330V, and 0/7/83, 0/6/82 for S331R.Although statistical approval was given about' the genotype frequency between the groups, there was no specific genotype which recommended significant difference.2)Novel pathological gene mutations were found in two retinoschisis families(RS 1 gene)and a Norrie disease family(ND gene).3)To investigate the anthropological background and the association of mitochondrial DNA(mtDNA) haplotype with the disease phenotype, nucleotide sequence in the hypervariable segment of the displacement loop(D-loop)region of mtDNA was determined in Japanese patients with Leber's hereditary optic neuropathy(LHON)harboring G11778A mutation.Genetic polymorphism of mtDNA was examined in 36 unrelated Japanese LHON patients who presented with bilateral optic nerve disease and had mtDNA G11778A mutation.From the data set of nucleotide alignments, the phylogeny of mtDNA sequence and phenotypic diversity within the examined population were evaluated.One-base polymorphism was present at 37 different sites.There was not any definite ancestral haplotype of the D-loop sequence in the examined LHON population.Thus, the mutational event of GI 1778A appears to be independent of the evolutionary course in the D-loop haplotype.