Darby J K, Willems P J, Nakashima P, Johnsen J, Ferrell R E, Wijsman E M, Gerhard D S, Dracopoli N C, Housman D, Henke J
Department of Genetics, Stanford University School of Medicine, CA 94305.
Am J Hum Genet. 1988 Nov;43(5):749-55.
Human alpha-L-fucosidase is a lysosomal enzyme responsible for hydrolysis of alpha-L-fucoside linkages in fucoglycoconjugates. A single gene, FUCA 1, located on chromosome 1p34.1-1p36.1 encodes for alpha-L-fucosidase activity. To gain insight into the nature of the molecular defects leading to fucosidosis, we have characterized the genomic structure of FUCA 1. Restriction-endonuclease analysis suggests that at least seven exons dispersed over 22 kb are present in genomic FUCA 1. Two restriction-fragment-length polymorphisms (RFLPs) have been identified in the Caucasian population. The PvuII and BglI RFLPs each have two codominant alleles in Hardy-Weinberg equilibrium. Allele frequencies for the PvuII RFLP are .70/.30, and those for the BglI RFLP .63/.37. Both RFLPs are in strong linkage disequilibrium with each other, with a correlation coefficient of .94. The polymorphism information content (PIC) of the combined DNA markers is .38, high enough to be useful in the prenatal diagnosis of fucosidosis. The combined lod score for linkage between the fucosidosis mutation and FUCA 1 markers in two families was significant at a recombination fraction of 0. This suggests that the fucosidosis mutation resides in FUCA 1.
人α-L-岩藻糖苷酶是一种溶酶体酶，负责水解岩藻糖糖缀合物中的α-L-岩藻糖苷键。位于1号染色体1p34.1-1p36.1上的单个基因FUCA 1编码α-L-岩藻糖苷酶活性。为了深入了解导致岩藻糖苷贮积症的分子缺陷的本质，我们对FUCA 1的基因组结构进行了表征。限制性内切酶分析表明，基因组FUCA 1中存在至少7个分散在22 kb上的外显子。在白种人群中已鉴定出两种限制性片段长度多态性（RFLP）。PvuII和BglI RFLP在哈迪-温伯格平衡中各有两个共显性等位基因。PvuII RFLP的等位基因频率为0.70/0.30，BglI RFLP的等位基因频率为0.63/0.37。两种RFLP彼此处于强连锁不平衡状态，相关系数为0.94。组合DNA标记的多态性信息含量（PIC）为0.38，足以用于岩藻糖苷贮积症的产前诊断。两个家族中岩藻糖苷贮积症突变与FUCA 1标记之间连锁的组合lod分数在重组率为0时具有显著性。这表明岩藻糖苷贮积症突变位于FUCA 1中。
