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Biomedical subjects

J E Parrish

Publications and source records attributed to J E Parrish.

17 recordsLinked to original sources
PubMed1998

MSG1 (melanocyte-specific gene 1): mapping to chromosome Xq13.1, genomic organization, and promoter analysis.

MSG1 (melanocyte-specific gene 1) is a recently isolated gene predominantly expressed in cultured normal melanocytes and pigmented melanoma cells. MSG1 encodes a 27-kDa nuclear protein that has strong intrinsic transcriptional transactivating activity. In this report, the human MSG1 gene was mapped to chromosome Xq13.1 using X chromosome-specific somatic cell hybrids, and the mouse Msg1 gene was mapped 1.9 +/- 1.3 cM proximal to Xist using an interspecific backcross panel. Both the human and the mouse MSG1 genes consist of three exons and two introns within 5 kb of genomic DNA, and their genomic structures are highly conserved. Southern blot analysis suggests the existence of MSG1 homologues in chicken, zebrafish, and Drosophila. A 2.0-kb fragment of the 5'-flanking region of the mouse Msg1 gene contains a TATA box and potential binding sites for several transcription factors including USF, Brn-3, Brn-2, TFE3, Oct-1, AP-2, and Spl. This promoter fragment activates transcription of a reporter gene in pigmented melanoma cells, but not in amelanotic melanoma cells or nonmelanocytic cells, indicating that Msg1 expression is at least partially regulated at the transcriptional level.

Animals↗
PubMed1997

Six novel mutations in the emerin gene causing X-linked Emery-Dreifuss muscular dystrophy.

Mutations in the emerin gene, also referred to as the STA- or EMD-gene, have been found to be the cause of X-linked Emery-Dreifuss muscular dystrophy (EMD). For the present study an optimized set of primers was designed to amplify and sequence each of the six emerin gene exons, including the intron/exon boundaries. All emerin gene exons of 30 unrelated EMD patients have been screened by heteroduplex analysis. Aberrant patterns of single exons were found in seven patients. Direct sequencing of the respective exons revealed six novel mutations distributed in the promotor region and exons 3-6 (delta nt -19 to -40; delta AG nt 620-621; ins A nt 895; delta AT nt 908-909; C-->A nt 1420; ins TA nt 1570). By this study, the first mutations in the promotor region and in exon 5 have been identified. Each of the 25 mutations that have been described so far, including those from the present study, abolishes the synthesis of functional emerin. The mutations were submitted to the EMD Mutation database (http://www.path.cam.ac.uk/emd).

Base Sequence↗
PubMed1996

Selection against mutant alleles in blood leukocytes is a consistent feature in Incontinentia Pigmenti type 2.

Incontinentia Pigmenti 2 (IP2) is an X-linked dominant disorder with male lethality. Affected females display a characteristic skin eruption that evolves through four classic stages, frequently accompanied by dental and retinal abnormalities. Non-random (skewed) X-inactivation in peripheral blood leukocytes and in fibroblasts has been observed in females with IP2; however, sample sizes have been small and methods of analysis varied. We have examined X-inactivation in a large group of multigenerational IP2 families, in smaller families, and in isolated cases. Ninety-eight percent of affected females in multigenerational IP2 pedigrees show completely skewed patterns of X-inactivation, while only approximately 10% of a normal control population is skewed. Results both in small families and in new mutation cases with subsequent segregation consistent with Xq28 linkage are similar. Isolated cases show a lower percentage (85%) of skewed affected individuals; this difference may be due to inaccurate clinical ascertainment. The parent of origin of new mutations could be determined in 15 families; paternal new mutations were twice as common as maternal. Fibroblast subclones from a biopsy at the boundary of a skin lesion in a newborn IP2 patient were isolated, and clones with either one or the other X active were identified, demonstrating that cells with the active disease-bearing X chromosome are still present in stage I skin lesions.

Adult↗
PubMed1995

The gene encoding the VP16-accessory protein HCF (HCFC1) resides in human Xq28 and is highly expressed in fetal tissues and the adult kidney.

After herpes simplex virus (HSV) infection, the viral regulatory protein VP16 activates transcription of the HSV immediate-early promoters by directing complex formation with two cellular proteins, the POU-homeodomain transcription factor Oct-1 and the host cell factor HCF. The function of HCF in uninfected cells is unknown. Here we show by fluorescence in situ hybridization and somatic cell hybrid analysis that the gene encoding human HCF, HCFC1, maps to the q28 region of the X chromosome. Yeast artificial chromosome and cosmid mapping localizes the HCFC1 gene within 100 kb distal of the renal vasopressin type-2 receptor (V2R) gene and adjacent to the renin-binding protein gene (RENBP). The HCFC1 gene is apparently unique. HCF transcripts and protein are most abundant in fetal and placental tissues and cell lines, suggesting a role in cell proliferation. In adults, HCF protein is abundant in the kidney, but not in the brain, a site of latent HSV infection and where HCF levels may influence progression of HSV infection.

Animals↗
PubMed1995

Refined mapping of caltractin in human Xq28 and in the homologous region of the mouse X chromosome places the gene within the bare patches (Bpa) and striated (Str) critical regions.

Caltractin belongs to a family of calcium-binding proteins and is a structural component of the centrosome. A human caltractin cDNA (CALT) has recently been mapped by fluorescence in situ hybridization (FISH) to Xq28. We report here refined mapping of the human CALT gene and its murine homolog between the loci DXS1104 (DXHXS1104) DXS52 (DXHXS52) by PCR and Southern analysis on YACs and somatic cell hybrids from the region in both species. These mapping studies place the gene within the critical region for the murine X-linked dominant, male lethal mutations bare batches and striated.

Animals↗
PubMed1995

Molecular dissection of a contiguous gene syndrome: localization of the genes involved in the Langer-Giedion syndrome.

The Langer-Giedion syndrome (tricho-rhino-phalangeal syndrome type II, TRPS II) is characterized by craniofacial dysmorphism and skeletal abnormalities. It combines the clinical features of TRPS I and multiple cartilaginous exostoses (EXT). We have used YAC cloning, Southern blotting, PCR analysis, and fluorescence in situ hybridization to study chromosome 8 deletions, translocations, an inversion, and an insertion in patients with TRPS I, TRPS II or EXT. Our results indicate that the TRPS gene maps more than 1,000 kb proximal to the EXT1 gene and that both genes are affected in TRPS II. We conclude that TRPS II is not due to pleiotropic effects of mutations in a single gene, but that it is a true contiguous gene syndrome.

Base Sequence↗
PubMed1995

A muscle-specific DNase I-like gene in human Xq28.

A novel cDNA which maps to human Xq28 has been isolated and characterized. Sequence similarity to DNase I is high at the DNA and peptide sequence levels. The transcript is present at highest levels in skeletal and cardiac muscle, with lower expression in other tissues. Mutation analysis has been performed using DNA samples from two unrelated patients with Barth syndrome, and from 11 unrelated patients with Emery-Dreifuss muscular dystrophy, two genetic disorders linked to Xq28. No disease-associated mutations were detected in the coding region of the gene; however, a novel 190 base pair insertion/deletion polymorphism was found in the 3' untranslated region. Translation of the long open reading frame found in the cDNA yields a putative 302 amino acid protein with 37.6% identity to human DNase I. The protein is predicted to contain a signal sequence at the amino terminus, a transmembrane domain near the carboxyl terminus, and a helix-loop-helix domain.

Amino Acid Sequence↗
PubMed1994

Alignment of physical and genetic maps of human 8q23-qter using somatic cell hybrid mapping panel.

We describe a mapping panel for the 8q23-qter region composed of human-hamster hybrid cell lines carrying deletion and translocation derivatives of human chromosome 8. The panel divides this region of the chromosome into nine intervals and has been used to map 40 loci by Southern blot hybridization and PCR. Use of this mapping panel has allowed us to align the terminal portions of two different genetic maps of chromosome 8 with each other and with the physical map of the chromosome.

Animals↗
PubMed1994

Isolation of a GCC repeat showing expansion in FRAXF, a fragile site distal to FRAXA and FRAXE.

Three folate-sensitive fragile sites, termed FRAXA, FRAXE and FRAXF, have been identified on the distal end of chromosome Xq. The first two contain expanded, hypermethylated and unstable CGG (or GCC) repeats within CpG islands. We now report the isolation of similar sequences responsible for the third fragile site, FRAXF. A 5-kilobase EcoRI fragment derived from a cosmid coincident with the cytogenetic anomaly detects expanded, methylated and unstable sequences in five individuals who exhibit fragile sites in distal Xq; these individuals have normal repeat lengths at both FRAXA and FRAXE. By sequence analysis, the expanded region contains a GCC repeat. PCR and sequence analysis of chromosomes from the general population indicates that the repeat is polymorphic (6 to 29 triplets), and is stable upon transmission.

Alleles↗
PubMed1993

Methods for finding genes. A major rate-limiting step in positional cloning.

Identification of transcribed sequences from within genomic regions has been a major rate-limiting step in the pursuit of genes involved in many human genetic diseases. Early efforts focused primarily on screening of cDNA libraries, identification of evolutionarily conserved sequences, and northern blot hybridization. In recent years, several innovative techniques for gene identification have been devised. These techniques expand the size of the genomic region capable of being scanned for genes, while also allowing detection of genes regardless of their expression patterns. This article reviews several new and older techniques and discusses the advantages and limitations of each.

Cloning, Molecular↗
PubMed1993

Regional assignment of 19 X-linked ESTs.

Subchromosomal localizations for 19 X-linked expressed sequence tags (ESTs) have been determined. Two ESTs are located in Xq28, adding two novel genes to this disease-rich region. The remaining ESTs are located primarily in the pericentromeric region, with most mapping to Xp11.1-p21.1. YAC and cosmid genomic clones have been isolated for several of these loci. Available cDNAs have been used to characterize the corresponding transcripts by Northern analysis in multiple human tissues.

Blotting, Northern↗
PubMed1991

Molecular analysis of overlapping chromosomal deletions in patients with Langer-Giedion syndrome.

We have obtained lymphoblastoid cell lines from three patients with Langer-Giedion syndrome who have overlapping deletions in 8q24.1. To isolate the deletion chromosomes from their normal homologs, patient cell lines were fused with hamster cells and hybrid cells were selected for retention of human chromosome 8. These hybrid cell lines were screened for the presence of chromosome 8 by fluorescence in situ hybridization and by Southern blot hybridization. We have hybridized 31 recombinant DNA clones derived from the 8q22-qter region to Southern blots of the hybrid cell lines; 8 were found to lie within the deletion of at least one patient. One clone identified sequences that were missing from one copy of chromosome 8 in all three patients. These clones help to further define the deletions in these patients and will serve as starting points for detailed characterization of the region.

Animals↗
PubMed1985

Evaluation of the effects of various anti-arthritic drugs on type II collagen-induced mouse arthritis model.

A battery of drugs which are commonly used as therapeutic agents for arthritis was tested for effects on the inflammatory and immunological responses of DBA/1J mice, after immunization with type II collagen. All the drugs were tested at more than one dosage. The mice were protected from the development of arthritis by treatment with paramethasone (0.25 mg/kg/day) or cyclophosphamide (5 mg/kg/day). The nonsteroidal anti-inflammatory drugs used in these studies, viz. aspirin (200 mg/kg/day), benoxaprofen (100 mg/kg/day) and naproxen (200 mg/kg/day), had no significant effect on the joint involvement, although naproxen and benoxaprofen at these high doses caused some reduction of immune responses of mice to collagen. Chloroquine (100 mg/kg/day), levamisol (50 mg/kg/day) and gold chlorophosphene (5 mg/kg/day) had no effect on the inflammatory or humoral response, while treatment with D-penicillamine (100 mg/kg/day) led to an early onset of arthritis in mice. These data suggest that the type II collagen-induced mouse arthritis model may not be highly suitable for detection of the traditional nonsteroidal anti-inflammatory class of drugs or the anti-rheumatic drugs, although the possibility remains that some new and novel immunosuppressive agents may be detected with this model.

Adjuvants, Immunologic↗
PubMed1984

Collagen-induced and adjuvant-induced arthritis in rats. Post-immunization treatment with collagen to suppress or abrogate the arthritic response.

Immunization of Lewis rats with native type II collagen results in an inflammatory arthritis and increased humoral and cellular immune responses to type II collagen. The exposure of rats to native type II collagen at day 7 or 10 after immunization suppressed the incidence of arthritis and anticollagen antibody levels, although the cellular response was not affected. The exposure to denatured type II collagen offered partial protection, while type I collagen had no significant effect. Rats immunized with Mycobacterium tuberculosis also showed reduced arthritic response when subsequently treated with type II collagen. The common modalities between the 2 models and the possible role of type II collagen in the interference with the inflammatory arthritic events are discussed.

Animals↗