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Biomedical subjects

M A Morris

Publications and source records attributed to M A Morris.

At least 55 records · Page 3Linked to original sources
PubMed1998

Gene structure and chromosomal localization of the human P2X7 receptor.

The genomic organization for the human P2X7 receptor gene was determined to comprise 13 exons. Alignment of the exon-intron junctions with those for the rat P2X2 gene demonstrated a precise conservation of the boundaries for the first 10 introns. The human P2X7 receptor gene was localized by in situ hybridization to chromosome 12q24. Radiation hybrid mapping indicated that this is within 130 kb of the gene for the homologous P2X4 receptor.

Animals↗
PubMed1997

Familial translocation t(Y;15)(q12;p11) and de novo deletion of the Prader-Willi syndrome (PWS) critical region on 15q11-q13.

We describe a 17-year-old girl with mild Prader-Willi syndrome (PWS) due to 15q11-q13 deletion. The deletion occurred on a paternal chromosome 15 already involved in a translocation, t(Y;15)(q12;p11), the latter being present in five other, phenotypically normal individuals in three generations. This appears to be the first case of PWS in which the causative 15q11-q13 deletion occurred on a chromosome involved in a familial translocation, but with breakpoints considerably distal to those of the familial rearrangement. The translocation could predispose to additional rearrangements occurring during meiosis and/or mitosis or, alternatively, the association of two cytogenetic anomalies on the same chromosome could be fortuitous.

Adolescent↗
PubMed1997

Dodecamer repeat expansion in cystatin B gene in progressive myoclonus epilepsy.

Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1; MIM 254800) is an autosomal recessive disorder with onset between 6 and 13 years followed by variable progression to mental deterioration and cerebellar ataxia. It is a rare disorder but more common in Finland (1 in 20,000) and the western Mediterranean. Two point mutations in the cysteine proteinase inhibitor gene cystatin B (CSTB), proved that this gene is responsible for EPM1 (ref. 3). An extensive search in the CSTB gene revealed mutations accounting only for 14% of the 58 unrelated EPM1 alleles studied. Here we report that the majority of EPM1 alleles contain expansions of a dodecamer (12-mer) repeat located about 70 nucleotides upstream of the transcription start site nearest to the 5' end of the CSTB gene. Normal alleles contain 2 or 3 copies of this repeat whereas mutant alleles contain more than 60 such repeats and have reduced levels of CSTB messenger RNA in blood but not in cell lines. 'Premutation' CSTB alleles with 12-17 repeats show marked instability when transmitted to offspring.

Alleles↗
PubMed1997

Mitochondrial anomalies in a Swiss family with autosomal dominant myoglobinuria.

We report on a Swiss family in which 10 individuals of both sexes in 4 successive generations suffered from myoglobinuria, precipitated by febrile illness. It is the second family described with autosomal dominant inheritance of myoglobinuria. Four individuals suffered acute renal failure, which in two was reversible only after dialysis. In a recent case, a mitochondrial disorder was suspected because of an abnormal increase in lactate levels during an exercise test and because of a subsarcolemmal accumulation of mitochondria in a muscle biopsy, associated with a lack of cytochrome C oxidase in some muscle fibers. No mutation in the mitochondrial DNA was identified. Along with the inheritance pattern, these findings suggest that the myoglobinuria in this family is caused by a nuclear-encoded mutation affecting the respiratory chain.

Adolescent↗
PubMed1997

Analysis of mutations and chromosomal localisation of the gene encoding RFX5, a novel transcription factor affected in major histocompatibility complex class II deficiency.

MHC class II deficiency is a severe primary immunodeficiency characterised by the absence of major histocompatibility complex class II (MHC-II) gene expression. It is genetically heterogeneous and can result from defects in at least four different trans-acting regulatory genes required for transcription of MHC-II genes. One of these genes has recently been shown to encode a novel DNA binding protein called RFX5, which is one subunit of a heteromeric protein complex (RFX) that binds to the promoters of MHC-II genes. We have characterised the mutations in all four patients known to harbour a defect in the RFX5 gene and have mapped this new human disease gene to chromosome 1 band q21, a region frequently exhibiting chromosomal aberrations in a variety of preneoplastic and neoplastic diseases.

Chromosome Mapping↗
PubMed1997

Adherence behavior among adolescents with type I insulin-dependent diabetes mellitus: the role of cognitive appraisal processes.

Guided by a transactional stress and coping model, this study examined the contribution of cognitive appraisal processes to diabetes adherence behavior among adolescents 12 to 18 years old (n = 40). Multiple hierarchical regression analyses indicated that esteem related to physical appearance accounted for a significant 16% of the variance in checking one's blood sugar. Perceived control when ill and attributional style for negative events each accounted for significant increments of variance as well (10 and 6%, respectively), yielding a total of 32% of the variance explained by appraisal processes. Results suggest that adolescents who (a) have a negative perception of their bodies, (b) perceive little internal control over health when ill, and (c) have an external attributional style for negative events were at greatest risk for poor compliance as indicated by less frequent checking of blood sugar.

Adaptation, Psychological↗
PubMed1997

Fortuitous detection of uniparental isodisomy of chromosome 6.

Uniparental isodisomy is defined as the inheritance of two copies of the same parental chromosome and can result in defects when it produces homozygosity for a recessive mutation or in the presence of imprinting. We describe the detection of a chromosome 6 uniparental isodisomy in a 9 year old girl, discovered during a search for an HLA identical sib. HLA typing, erythrocyte phenotyping, and genotypes of microsatellite polymorphisms were compatible with a paternal isodisomy of chromosome 6, with normal biparental origin of the other chromosomes. Paternal cells were not responsive to the patient's cells in mixed lymphocyte cultures. This fortuitous detection of a chromosome 6 isodisomy suggests that cases of chromosome 6 UPD may not be deleterious and may therefore go undetected.

Cells, Cultured↗
PubMed1997

Facilitation of parental-strain marrow engraftment by T cells of neonatally-tolerant mice.

T cells present in bone marrow cell (BMC) grafts promote engraftment in histoincompatible hosts, but they or other T cells may also initiate lethal graft-vs.-host disease (GVHD). The purpose of this study was to determine whether T cells from donors tolerant of host alloantigens were able to prevent natural killer (NK) cell-mediated rejection of BMC grafts without causing GVHD. Previous studies have shown that H2d C.B-17 SCID BMC grafts were rejected by (BALB/c x B6)F1 (CB6F1,H2d/b) host NK cells, and that this rejection was reversed by adding H2d T cells to the donor inoculum. T cells tolerant of H2d/b alloantigens were produced by irradiating (3 Gy) BALB/c newborn mice, and infusing CB6F1 BMCs. Tolerance was assessed by donor (H2b+) cell chimerism, acceptance of CB6F1 skin grafts, the inability of adoptively transferred lymphocytes to initiate GVHD in irradiated CB6F1 mice, and the inability of spleen or thymus cells to generate cytolytic T lymphocytes against H2b target cells in vitro. Whole or H2-Kb-depleted BMCs isolated from tolerant donors were able to proliferate in both BALB/c and H2b/d (C57BL/6 x DBA/2)F1 hosts as determined by incorporation of a radiolabelled DNA precursor in the spleen. Furthermore, thymocytes from tolerant donors were able to prevent rejection of H2d SCID BMCs. Because the percentage of donor F1 cells was so high in these chimeras, we generated BALB/c to CB6F1 SCID BMC chimeras; the percentage of BALB/c cells was approximately 100%, the BMCs grew well in irradiated CB6F1 hosts, and their lymph node cells failed to cause a graft-vs.-host (GVH) reaction in CB6F1 hosts. Thus, GVHD may be prevented without inhibiting the ability of donor T cells to promote engraftment. Perhaps separate T cells, or separate functions of a common T cell subset, induce GVHD and enhance engraftment of stem cells.

Animals↗
PubMed1996

Localization of a human homolog of the mouse pericentrin gene (PCNT) to chromosome 21qter.

Exon trapping was used to identify portions of genes from cosmid DNA of a human chromosome 21-specific library LL21NC02-Q. More than 650 potential exons have been cloned and characterized to date. Among these, 3 trapped "exons" showed strong homology to different regions of the cDNA for the mouse pericentrin (Pcnt) gene (Doxsey et al., Cell 76: 639-650, 1994), indicating that these 3 exons are portions of a human homolog of the mouse pericentrin gene. With PCR amplification, Southern blot analysis, and FISH, we have mapped this presumed human pericentrin gene (PCNT) to the long arm of chromosome 21 between marker PFKL and 21qter. Pericentrin is a conserved protein component of the filamentous matrix of the centrosome involved in the initial establishment of the organized microtubule array. No candidate hereditary disorder for pericentrin deficiency/abnormality has yet been mapped in the most distal region of 21q; in addition the role of triplication of the pericentrin gene in the pathophysiology or etiology of trisomy 21 is currently unknown.

Amino Acid Sequence↗
PubMed1996

The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3.

We used targeted exon trapping to clone portions of genes from human chromosome 21q22.3. One trapped sequence showed complete homology with the cDNA of human U2AF35 (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary factor. Using the U2AF1 cDNA as a probe, we mapped this gene to cosmid Q15D2, a P1, and YAC 350F7 of the Chumakov et al. (Nature 359: 380, 1992) contig, close to the cystathionine-beta-synthase gene (CBS) on 21q22.3. This localization was confirmed by PCR using oligonucleotides from the 3' UTR and by FISH. As U2AF1 associates with a number of different factors during mRNA splicing, overexpression in trisomy 21 individuals could contribute to some Down syndrome phenotypes by interfering with the splicing process. Furthermore, because this gene maps in the critical region for the progressive myoclonus epilepsy I locus (EPM1), mutation analysis will be carried out in patients to evaluate the potential role of U2AF1 as a candidate for EPM1.

Base Sequence↗
PubMed1996

Mapping of the gene for the p60 subunit of the human chromatin assembly factor (CAF1A) to the Down syndrome region of chromosome 21.

Exon trapping was used to clone portions of genes from the Down syndrome critical region (DSCR) of human chromosome 21. One trapped sequence showed complete homology with nucleotide sequence U20980 (GenBank), which corresponds to the gene for the p60 subunit of the human chromatin assembly factor-1 (CAF1A). We mapped this gene to human chromosome 21 by fluorescence in situ hybridization, by the use of somatic cell hybrids, and by hybridization to chromosome 21-specific YACs and cosmids. The CAF1A gene localizes to YACs 745H11 and 230E8 of the Chumakov et al. (1992, Nature 359: 380) YAC contig, within the DSCR on 21q22. This CAF1A, which belongs to the WD-motif family of genes and interacts with other polypeptide subunits to promote assembly of histones to replicating DNA, may contribute in a gene dosage-dependent manner to the phenotype of Down syndrome.

Animals↗
PubMed1996

Estradiol conjugated to BSA releases oxytocin from synaptosome-containing homogenates from the medial preoptic area-hypothalamus.

Estradiol conjugated to bovine serum albumin at position 6(E-6-BSA) released oxytocin (OT) from homogenates of the medial preoptic area and medial hypothalamus (MPOA-MH) within minutes of its superfusion. Using a superfusion system in which synaptosome-containing homogenates were layered onto acrodiscs maintained at 37 degrees C, we have found that E-6-BSA (100 ng/microliters) superfusions significantly elevated OT release within minutes. In contrast, superfusion of the same concentration of BSA or progesterone-3-BSA (P-3-BSA) had no effect on OT release. While superfusing homogenates with augmented levels of K+ had no effect on OT release itself, superfusing E-6-BSA with these concentrations of K+ consistently increased OT release. This is the first demonstration that E-6-BSA increases OT release in a nucleus-free medium.

Animals↗
PubMed1996

Cloning of 559 potential exons of genes of human chromosome 21 by exon trapping.

Chromosome 21 represents approximately 1% of the human genome, and its long arm has been estimated to contain 600-1000 genes. A dense linkage map and almost complete physical maps based on yeast artificial chromosomes (YACs) and cosmids have been developed. We have used exon trapping to identify portions of genes from randomly picked chromosome 21-specific cosmids, to contribute to the creation of the transcription (genic) map of this chromosome and the cloning of its genes. A total of 559 different sequences were identified after elimination of false-positive clones and repetitive elements. Among these, exons for 13 of the 30 known chromosome 21 genes have been "trapped." In addition, a considerable number of trapped sequences showed homologies to genes from other species and to human expressed sequence tags (ESTs). One hundred thirty-three trapped sequences were mapped, and every one mapped back to chromosome 21. We estimate that we have identified portions of up to approximately 40% of all genes on chromosome 21. The genic map of chromosome 21 provides a valuable tool for the elucidation of function of the genes and will enhance our understanding of the pathophysiology of Down syndrome and other disorders of chromosome 21 genes.

Chromosome Mapping↗