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Biomedical subjects

Z Urban

Publications and source records attributed to Z Urban.

6 recordsLinked to original sources
PubMed2000

Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by calcification of elastic fibres in skin, arteries and retina that results in dermal lesions with associated laxity and loss of elasticity, arterial insufficiency and retinal haemorrhages leading to macular degeneration. PXE is usually found as a sporadic disorder, but examples of both autosomal recessive and autosomal dominant forms of PXE have been observed. Partial manifestations of the PXE phenotype have also been described in presumed carriers in PXE families. Linkage of both dominant and recessive forms of PXE to a 5-cM domain on chromosome 16p13.1 has been reported (refs 8,9). We have refined this locus to an 820-kb region containing 6 candidate genes. Here we report the exclusion of five of these genes and the identification of the first mutations responsible for the development of PXE in a gene encoding a protein associated with multidrug resistance (ABCC6).

ATP-Binding Cassette Transporters↗
PubMed2000

A quantitative evaluation of SAGE.

Serial Analysis of Gene Expression (SAGE) is an innovative technique that offers the potential of cataloging both the identity and relative frequencies of mRNA transcripts in a given poly(A(+)) RNA preparation. Although it is a very effective approach for determining the expression of mRNA populations, there are significant biases in the observed results that are inherent in the experimental process. These are caused by sampling error, sequencing error, nonuniqueness, and nonrandomness of tag sequences. The quantitative information desired from SAGE experiments consists of estimates of the number of genes and the frequency distribution of transcript copy numbers. Of additional concern is the extent to which a given tag sequence can be assumed to be unique to its gene. The present study takes these mathematical biases into account and presents a basis for maximum likelihood estimation of gene number and transcript copy frequencies given a set of experimental results. These estimates of the true state of genomic expression are markedly different from those based directly on the observations from the underlying experiments. It also is shown that while in many cases it is probable that a given tag sequence is unique within the genome, in larger genomes this cannot be safely assumed.

Computer Simulation↗
PubMed1999

Pseudoxanthoma elasticum maps to an 820-kb region of the p13.1 region of chromosome 16.

We have performed linkage analysis on 21 families with pseudoxanthoma elasticum (PXE) using 10 polymorphic markers located on chromosome 16p13.1. The gene responsible for the PXE phenotype was localized to an 8-cM region of 16p13.1 between markers D16S500 and D16S3041 with a maximum lod score of 8.1 at a recombination fraction of 0.04 for marker D16S3017. The lack of any locus heterogeneity suggests that the major predisposing allele for the PXE phenotype is located in this region. Haplotype studies of a total of 36 PXE families identified several recombinations that further confined the PXE gene to a region (< 1 cM) between markers D16S3060 and D16S79. This PXE locus was identified within a single YAC clone and several overlapping BAC recombinants. From sequence analysis of these BAC recombinants, it is clear that the distance between markers D16S3060 and D16S79 is about 820 kb and contains a total of nine genes including three pseudogenes. We predict that mutations in one of the expressed genes in the locus will be responsible for the PXE phenotype in these families.

Alleles↗
PubMed1999

Altered bladder function in transgenic mice expressing rat elastin.

The elasticity of tissues subjected to repeated deformation is provided by the presence of elastic fibers in the extracellular matrix (ECM). The most abundant component of elastic fibers is elastin, whose soluble precursor is tropoelastin. To establish the role elastin plays in the bladder, this study describes the biosynthetic, histologic, and physiologic consequences of expression of an isoform of rat tropoelastin in transgenic mouse bladder. The polymerase chain reaction (PCR) was used to determine expression of a rat tropoelastin minigene in transgenic mice. Histochemical methods were used to demonstrate changes in elastic fibers in frozen sections of bladder. Cystometric analysis was carried out in transgenic and non-transgenic mice, prior to and after 3 weeks of partial outlet obstruction. The PCR assay demonstrated that bladder tissue of transgenic mice expressed rat tropoelastin mRNA, whereas non-transgenes did not. Increased deposition of elastic fibers was demonstrated with the Verhoeff-van Gieson stain. Bladders of transgenic animals were more compliant than bladders of their non-transgenic littermates. Partial outlet obstruction resulted in increased bladder volume and more compliant bladders in non-transgenic mice. In contrast, the bladder volume and compliance in transgenes was almost unchanged by obstruction. This study demonstrates that normal elastic fiber assembly is prerequisite for the compliant properties of the bladder wall. Moreover, the response of the bladder to obstruction is critically influenced by elastin synthesis.

Animals↗