Search PubMed⌕ Search

Biomedical subjects

M A Morris

Publications and source records attributed to M A Morris.

At least 73 records · Page 4Linked to original sources
PubMed1995

Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11.

We report the results of two studies examining the genetic overlap between schizophrenia and velocardiofacial syndrome. In study A, we characterize two interstitial deletions identified on chromosome 22q11 in a sample of schizophrenic patients. The size of the deletions was estimated to be between 1.5 and 2 megabases. In study B, we examine whether variations in deletion size are associated with the schizophrenic phenotype in velocardiofacial syndrome patients. Our results show that a region of the genome that has been previously implicated by genetic linkage analysis can harbor genetic lesions that increase the susceptibility to schizophrenia. Our findings should facilitate identification and cloning of the schizophrenia susceptibility gene(s) in this region and identification of more homogeneous subgroups of patients.

Abnormalities, Multiple↗
PubMed1995

Cloning of the cDNA for the human ATP synthase OSCP subunit (ATP5O) by exon trapping and mapping to chromosome 21q22.1-q22.2.

Exon trapping was used to clone portions of potential genes from human chromosome 21. One trapped sequence showed striking homology with the bovine and rat ATP synthase OSCP (oligomycin sensitivity conferring protein) subunit. We subsequently cloned the full-length human ATP synthase OSCP cDNA (GDB/HGMW approved name ATP50) from infant brain and muscle libraries and determined its nucleotide and deduced amino acid sequence (EMBL/GenBank Accession No. X83218). The encoded polypeptide contains 213 amino acids, with more than 80% identity to bovine and murine ATPase OSCP subunits and over 35% identity to Saccharomyces cerevisiae and sweet potato sequences. The human ATP5O gene is located at 21q22.1-q22.2, just proximal to D21S17, in YACs 860G11 and 838C7 of the Chumakov et al. (Nature 359:380, 1992) YAC contig. The gene is expressed in all human tissues examined, most strongly in muscle and heart. This ATP5O subunit is a key structural component of the stalk of the mitochondrial respiratory chain F1F0-ATP synthase and as such may contribute in a gene dosage-dependent manner to the phenotype of Down syndrome (trisomy 21).

Adenosine Triphosphatases↗
PubMed1995

Mapping of the human transcription factor GABPA (E4TF1-60) gene to chromosome 21.

Exon trapping/amplification was used to clone portions of genes from human chromosome 21. One trapped sequence showed complete homology with nucleotide sequence D13318 of GenBank, which corresponds to the gene for human transcription factor E4TF1-60 (HGMW-approved nomenclature GABPA). We mapped this gene to human chromosome 21 by FISH, somatic cell hybrids, and hybridization to chromosome 21-specific YACs. The GABPA gene localizes to YACs 816B7 and 848G1 of the Chumakov et al. (Nature 359: 380, 1992) YAC contig, near the APP gene in 21q21-q22.1. This transcription factor, which is an ETS-related DNA-binding protein and forms heterodimers with other polypeptides, may contribute in a gene dosage-dependent manner to the phenotype of Down syndrome.

Base Sequence↗
PubMed1995

Trisomy 3 mosaicism on CVS: case report with literature review and propositions for investigation and counseling.

Chorionic villus sampling performed for advanced maternal age revealed trisomy 3 in 20% of mitoses studied after a semi-direct chromosomal harvest. Amniocytes and cord blood showed a non-mosaic 46,XY karyotype. The birthweight of the normal newborn was at the tenth percentile. Analysis of term placenta by cytogenetics and by fluorescent in situ hybridization (FISH) confirmed the presence of the trisomy 3 in 20% and 12%, respectively, of cells from two peripheral placental biopsies. Placental histology was heterogeneous, some portions showing immature, edematous and undervascularized villi. DNA analysis confirmed the biparental origin of the chromosomes 3 in the child, whose development is normal at 36 months.

Adult↗
PubMed1995

A new dinucleotide repeat polymorphism at the telomere of chromosome 21q reveals a significant difference between male and female rates of recombination.

We have used a half-YAC containing the human chromosome 21 long-arm telomere to clone, map, and characterize a new dinucleotide repeat polymorphism (D21S1575) close to 21qter. This marker is < 120 kb from the telomeric (TTAGGG)n sequences and is the most distal highly polymorphic marker on chromosome 21q. This marker has a heterozygosity of 71% because of a variable (TA)n repeat embedded within a long interspersed element (LINE) element. Genotyping of the CEPH families and linkage analysis provided a more accurate determination of the full length of the chromosome 21 genetic map. A highly significant difference was detected between male and female recombination rates in the telomeric region: in the most telomeric 2.3 Mb of chromosome 21q, recombination was only observed in male meioses.

Base Sequence↗
PubMed1995

Characterization and chromosomal localization of a human P2X receptor from the urinary bladder.

A cDNA encoding an ion channel (hP2X), gated by extracellular ATP, was isolated from the human urinary bladder. It encodes a 399 amino acid protein, composed of a cysteine-rich central domain, flanked by two hydrophobic regions. A comparison of the sequence with those of the corresponding rat and mouse proteins shows predominantly conservative substitutions of hydrophilic residues. Northern blot analysis demonstrated the presence of the mRNA in several human tissues and established that the distal untranslated portion of the mRNA includes an 'expressed sequence tag' for the differentiation of the hemopoetic cell line, HL60. By fluorescent in situ hybridization the hP2X gene was mapped to the short arm of human chromosome 17. Expressed in Xenopus oocytes, the receptor was sensitive to the purinergic agonists ATP and alpha,beta-methylene ATP.

Amino Acid Sequence↗
PubMed1994

Angelman syndrome due to paternal uniparental disomy of chromosome 15: a milder phenotype?

The Angelman syndrome (AS) is a neurological disorder characterized by severe mental retardation, absent speech, seizures, gait disturbances, and a typical age-dependent facial phenotype. Most cases are due to an interstitial deletion on the maternally inherited chromosome 15, in the critical region q11-q13. Rare cases also result from paternal uniparental disomy of chromosome 15. In a group of 14 patients with sporadic AS diagnosed in Switzerland, we found 2 unrelated females with paternal isodisomy for the entire chromosome 15. Their phenotypes were milder than usually seen in this syndrome: one girl did not show the typical AS facial changes; both patients had late-onset mild seizures; as they grew older, they had largely undisturbed gross motor functions, in particular no severe ataxia. Both girls were born to older fathers (45 and 43 years old, respectively). The apparent association of a relatively milder phenotype in AS with paternal uniparental disomy will have to be confirmed by detailed clinical descriptions of further patients.

Adult↗
PubMed1994

Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells.

The factor VIII gene, which is defective in hemophilia A, is located in the last megabase of the long arm of the X chromosome. Inversions due to intrachromosomal homologous recombination between mispaired copies of gene A located within intron 22 of the gene and about 500 kb telomeric to it account for nearly half of all cases of severe hemophilia A. We hypothesized that pairing of Xq with its homolog inhibits the inversion process, and that, therefore, the event originates predominantly in male germ cells. In all 20 informative cases in which the inversion originated in a maternal grandparent, DNA polymorphism analysis determined that it occurred in the male germline. In addition, all but one of 50 mothers of sporadic cases due to an inversion were carriers. Thus, these data support the hypothesis and indicate that factor VIII gene inversions leading to severe hemophilia A occur almost exclusively in male germ cells.

Blotting, Southern↗
PubMed1993

Scaphotrapezio-trapezoidal dislocation. A case report.

A complex hand injury with scaphotrapezial dislocation and dislocation of the trapezoid, third, fourth, and fifth carpometacarpal joints occurred when a motorcyclist was involved in a road accident. The extent of the injury was initially overlooked. Combined injuries of the carpus and carpometacarpal joints can easily be missed at radiographic examination. The true lateral radiograph of the wrist is necessary in the diagnosis of complex wrist injuries.

Accidents, Traffic↗
PubMed1993

Nondisjunction of chromosome 15: origin and recombination.

Thirty-two cases of uniparental disomy (UPD), ascertained from Prader-Willi syndrome patients (N = 27) and Angelman syndrome patients (N = 5), are used to investigate the pattern of recombination associated with nondisjunction of chromosome 15. In addition, the meiotic stage of nondisjunction is inferred by using markers mapping near the centromere. Two basic approaches to the analysis of recombination are utilized. Standard methods of centromere mapping are employed to determine the level of recombination in specific pairwise intervals along the chromosome. This method shows a significant reduction in recombination for two of five intervals examined. Second, the observed frequency of each recombinant class (i.e., zero, one, two, three, or more observable crossovers) is compared with expected values. This is useful for testing whether the reduction in recombination can be attributed solely to a proportion of cases with no recombination at all (because of asynapsis), with the remaining groups showing normal recombination (or even excess recombination), or whether recombination is uniformly reduced. Analysis of maternal UPD(15) data shows a slight reduction in the multiple-recombinant classes, with a corresponding increase in both the zero- and one-recombinant classes over expected values. The majority, more than 82%, of the extra chromosomes in maternal UPD(15) cases are due to meiotic I nondisjunction events. In contrast, most paternal UPD(15) cases so far examined appear to have a postzygotic origin of the extra paternal chromosome.

Aneuploidy↗