Molecular genetic analysis of Cytochrorne P4501B1 and allied genes

1)细胞色素P4501B1基因是一种先天性青光眼的致病基因，临床表现多样，在基因内表现出分散性。该基因也存在多态突变。考虑到与疾病易感性的遗传连锁，我们对成人型开角型青光眼患者进行了细胞色素P4501B1基因多态性的检测。根据移位纯合子/杂合子/正常纯合子的例数，每种基因的频率按POAG患者、正常对照组的顺序排列。R48G为8/11/76，R48G为3/18/93；A119S为12/52/31，20/53/47；A330V为2/3/83，A330V为1/11/125，S331R为0/7/83，0/6/82。2)在两个视网膜劈裂症家系(RS-1基因)和一个诺里氏病家系(ND基因)中发现了新的病理基因突变。3)为了研究人类学背景以及线粒体DNA单倍型与疾病表型的关系，对携带G11778A突变的日本Leber遗传性视神经病变(LHON)患者线粒体DNA置换环(D-loop)高变区的核苷酸序列进行了测定。对36例表现为双侧视神经疾病且存在mtDNA G11778A突变的无亲缘关系的日本LHON患者进行了mtDNA的遗传多态性检测。根据核苷酸比对数据集，评估了受检人群中mtDNA序列的系统发育和表型多样性。在37个不同的位点存在一个碱基多态性。在所研究的LHON人群中，D-loop序列没有任何确定的祖先单倍型。因此，在所研究的LHON人群中，存在一个碱基多态性GI1778A的突变事件似乎与D-loop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.