Polysialic acid, a unique glycan that is developmentally regulated by two polysialyltransferases, PST and STX, in the central nervous system: From biosynthesis to function

Polysialic acid is a developmentally regulated carbohydrate composed of a linear homopolymer of a-2,a-linked sialic acid residues. This unique glycan is mainly attached to the neural cell adhesion molecule (N-CAM) and implicated in many morphogenic events of the neural cells by modulating the adhesive property of N-CAM. Recently, the cDNA that encodes polysialyltransferase, which is responsible for the polysialylation of N-CAM, was successfully cloned from three mammalian species. This review focuses on the molecular cloning of human polysialyltransferase, designated PST. it then describes the number of enzymes actually required for the polysialylation of N-CAM using an in vitro polysialyltransferase assay. Comparisons between PST and another polysialyltransferase, sialyltransferase X (STX), are made and it Is demonstrated that both enzymes can independently form polysiatic acid In vitro , but that during neural development they coordinately but distinctly synthesize polysialic acid on N-CAM. The role of polysialic acid in the central nervous system is also discussed. Finally, evidence that the two polysialyltransferases, PST and STX, apparently have distinct roles in the development of neural cells is provided by using a neurite outgrowth assay.     

A Gln/Arg polymorphism at codon 349 of the hBUBR1 gene

We found a glutamine/arginine polymorphism at codon 349 of the hBUBR1 gene, encoding a protein kinase required for spindle assembly checkpoint function. The observed heterozygosity was estimated to be 45% in the Japanese population. This polymorphism may be helpful for genetic studies of many cancer types in which chromosomal instability is observed. Received: October 19, 1998 / Accepted: October 24, 1998     

An Extension of the Regression of Offspring on Mid-Parent to Test for Association and Estimate Locus-Specific Heritability: The Revised ROMP Method

The Regression of Offspring on Mid-Parent (ROMP) method is a test of association between a quantitative trait and a candidate locus. ROMP estimates the trait heritability and the heritability attributable to a locus and requires genotyping the offspring only. In this study, the theory underlying ROMP was revised (ROMP_rev) and extended. Computer simulations were used to determine the type I error and power of the test of association, and the accuracy of the locus-specific heritability estimate. The ROMP_rev test had good power at the 5% significance level with properly controlled type I error. Locus-specific heritability estimates were, on average, close to simulated values. For non-zero locus-specific heritability, the proposed standard error was downwardly biased, yielding reduced coverage of 95% confidence intervals. A bootstrap approach with proper coverage is suggested as a second step for loci of interest.
ROMP_rev was applied to a study of cardiovascular-related traits to illustrate its use. An association between polymorphisms within the fibrinogen gene cluster and plasma fibrinogen was detected (p < 0.005) that accounted for 29% of the estimated fibrinogen heritability. The ROMP_rev method provides a computationally fast and simple way of testing for association and obtaining accurate estimates of locus-specific heritability while minimizing the genotyping required.     

应用微阵列初步分析髓母细胞瘤的基因表达谱

目的　应用微阵列技术研究髓母细胞瘤的分子发病机理。方法　收集新鲜髓母细胞瘤 4例及正常脑组织 1份的组织标本 ,提取总 RNA,逆转录成 32 P标记的 c DNA探针 ,与 Atlas人肿瘤芯片杂交 ,通过放射自显影获得基因谱 ,应用 Atlas Image TM1.0 1a分析。结果　与正常脑组织相比 ,髓母细胞瘤下调基因 6个 ,上调基因 35个 ;逆转录 -聚合酶链反应技术验证结果与芯片检测结果相符。除少数基因外 ,大部分基因的表达趋势与肿瘤生物学特性相符。结论　髓母细胞瘤是与星形细胞起源胶质瘤具有不同分子发病机理的多基因病变 ,不同基因之间可能存在复杂的相互作用和联系 ,值得进一步研究。     

Blepharophimosis sequence and de novo balanced autosomal translocation [46, XY,t(3;4)(q23;p15.2)]: Possible assignment of the trait to 3q23

We report on a boy with the blepharophimosis sequence and de novo, apparently balanced reciprocal translocation between 3q23 and 4p15.2 [46, XY,t(3;4)(q23;p15.2)de novo]. Possible assignment of this autosomal dominant disorder is discussed. A 3q23 band is a more preferable gene locus of the blepharophi mosis sequence, based on the comparison of clinical manifestations between 4p- and 3q-syndromes.     

Nine-bp repeat polymorphism in exon 1 of thehMSH3 gene

Summary We have identified a polymorphic 9-bp repeat sequence in exon 1 of thehMSH3 gene using polymerase chain reaction (PCR). Five alleles were observed in unrelated Japanese individuals with heterozygosity of 0.57.     

DNA microarray analysis reveals novel gene expression profiles in collagen-induced arthritis

Global gene expression was analyzed in early and late collagen-induced arthritis (CIA). Of 8734 cDNAs analyzed, 330 were induced and 55 downregulated greater than twofold in early or late disease. Hierarchical clustering of these 385 cDNAs demonstrated five distinct expression patterns differentiating early from late disease and correlating with histopathologic changes in the paw. Of the 385 cDNAs, 185 are known, characterized genes, the majority of which are not described as playing a role in arthritis. However, several of these genes are involved in pathological processes relating to arthritis, including apoptosis, inflammation, and cellular proliferation. One interesting gene, follistatin-like gene, is highly expressed along the margin of contact between inflammatory synovial pannus and eroding bone, suggesting a role in joint destruction. These results demonstrate that global gene expression profiles distinguish early and late CIA and reveal several genes novel to arthritis the further characterization of which will advance our understanding of arthritis.     

A mating deficient and temperature-sensitive lethal mutant of Schizosaccharomyces pombe defines a new fertility locus

Summary A recessive mutant allele, mef1-84, of a novel locus mapping on the left arm of chromosome I, between ade3 and ura1, 5 cM apart from lys5, confers temperature-sensitive growth and mating deficiency at the nonrestrictive temperatures for growth. Two other mutations suppress the phenotype conferred by mef1-84: sts1-1 suppresses the temperature-sensitive growth only, and smd1-35 suppresses both temperature-sensitive growth and mating deficiency.     

Reduced visuospatial performance in children with the D2 dopamine receptor A1 allele

Previous studies suggest a reduced dopaminergic function in subjects with the A1 (minor) allele of the D2 dopamine receptor (DRD2) gene. To explore influences on visuospatial ability as a function of the DRD2 gene, 182 alcohol- and other drug-naive sons (age 10–14) of active alcoholic, recovered alcoholic, and nonalcoholic fathers were administered a visuospatial task (Benton's Judgment of Line Orientation Test) which makes minimal motoric/verbal demands. Visuospatial scores were lower for boys with the A1 allele and for sons of active alcoholics. A1-allele boys made more errors than A2 boys on all 11 of the template lines, with the effect being largest for the rightmost presentations. In contrast, the effect of family history for alcoholism was strongest on both right and left midquadrant presentations. Moreover, separate analyses of the two types of errors produced allele but not family history of alcoholism effects when the two lines were misjudged as farther apart than they actually were and family history but not allele effects where the two lines were misjudged as closer together. These results suggest that polymorphism of the DRD2 gene and family history of alcoholism are dissociable determinants of visuospatial ability and that visuospatial defects previously observed in alcoholics may, in part, be antecedent to their drinking behavior.