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M Leppert

Publications and source records attributed to M Leppert.

304 records · Page 17Linked to original sources
PubMed1986

Tetraploid partial hydatidiform moles: two cases with a triple paternal contribution and a 92,XXXY karyotype.

In the course of a systematic study of cytogenetics, morphology, and clinical follow-up of hydatidiform moles we encountered two unusual cases of partial hydatidiform moles each with a 92,XXXY karyotype. Previously reported cases of tetraploidy, of 92,XXXX or 92,XXYY karyotype, resulted from a failure of the first mitotic division of a normal zygote. This is to our knowledge the first report of tetraploidy with XXXY sex chromosomes. Study of chromosomal heteromorphisms, isozymes, and restriction fragment length polymorphisms reveal that both present cases resulted from a combination of a haploid ovum with three haploid sets of paternal chromosomes either by the mechanism of trispermy (involving three separate haploid spermatozoa) or through dispermy (involving one haploid and one diploid sperm). Both cases resembled closely partial moles in their morphology; one gave a highly typical clinical picture while the other was recognized at an early voluntary abortion. Partial moles are ordinarily triploids of nearly always diandric constitution that evince focal villous swelling with cistern formation and focal trophoblastic hyperplasia. The findings here presented point to an association of molar phenotype with an excess of paternal over maternal haploid sets.

Adolescent↗
PubMed1986

Further linkage data on cystic fibrosis: the Utah Study.

We reported earlier complete linkage between cystic fibrosis and an RFLP of the met proto-oncogene revealed by the probe pmetH. Another clone, pmetD, detects another polymorphism with the TaqI restriction enzyme. Further linkage studies, now involving 22 families, have confirmed the tight linkage of cystic fibrosis to the MET and D7S8 loci. Significant allelic association was found between CF and allelic series defined by the pmetH probe.

Alleles↗
PubMed1986

A primary genetic map of chromosome 13q.

We have constructed a primary genetic map spanning most of human chromosome 13. A total of 14 polymorphic DNA sequences and one protein polymorphism provided, after construction of haplotypes, seven markers for the long arm of this chromosome. A panel of cell lines from 30 three-generation families with large sibship size served as the sample set. Pairwise cross analysis of the inheritance patterns of the marker loci established that six of the seven loci constituted a single linkage group; the seventh was localized by physical means. Significantly higher recombination rates were found in female than in male meioses in several intervals. The six closely linked loci were arranged, based on the two-point data, in three clusters, and a number of alternate gene orders were excluded by three-point linkage tests. The order and spacing of the individual loci were refined by linkage analyses that considered five loci jointly.

Chromosome Banding↗
PubMed1985

Determination of the parental origin of sex-chromosome monosomy using restriction fragment length polymorphisms.

The parental origin of the single X chromosome in sex-chromosome monosomy was evaluated by comparing restriction fragment length polymorphisms (RFLPs) of 10 spontaneous aborted 45,X conceptions with those of their parents. Seven X-linked marker loci were used, and we were able to specify the origin of the X in nine cases, with six being maternally and three paternally derived. These results demonstrate the efficiency of the technique and show that the single X chromosome in 45,X spontaneous abortions can be derived from either parent.

Abortion, Spontaneous↗
PubMed1981

Interaction of VSV leader RNA and nucleocapsid protein may control VSV genome replication.

The discovery of plus- and minus-strand leader RNAs (short RNAs that are the complement of the exact 3' ends of the viral minus-strand genome and plus-strand antigenome) in VSV-infected cells has led to a model of genome replication in which the viral nucleocapsid protein acts as a modulator of genome transcription and replication. In this model, the VSV leader RNAs are the result of chain termination at an attenuation signal located approximately 50 nucleotides in from the 3' ends of the genome templates. The viral N protein is thought to modulate transcription and replication by its ability to bind to the nascent leader RNA and simultaneously promote read-through of the termination signal and initiate nucleocapsid assembly on the nascent RNA chain. Two predictions of this model, namely, that the requirement of continuous protein synthesis for genome replication is not at the level of the initiation of the genome chains but at the level of the suppression of the leader RNA termination signal, and that the site for the initiation of nucleocapsid assembly is located within the leader RNA sequence, have been tested experimentally and the results found to be consistent with the above model.

Capsid↗
PubMed1980

Effect of defective interfering particles on plus- and minus- strand leader RNAs in vesicular stomatitis virus-infected cells.

Vesicular stomatitis virus-infected cells contain short RNA transcripts, called leader RNAs, which are coded by the exact 3' end of both the minus-strand and plus-strand nucleocapsid templates. The molar amounts of both the plus-strand leader RNA (which is templated from the minus-strand genome) and the minus-strand leader RNA (which is templated from the plus-strand antigenome) were determined both in standard-virus- and mixed-virus-infected cells by using end-labeled genome probes. The results demonstrate that the presence of defective interfering particles in the infecting virus stock decreases the amount of plus-strand leader RNA but increases the amount of minus-strand leader RNA found in the infected cells. In addition, considerably more minus-strand leader RNA per mole of nucleocapsid template is synthesized in mixed-virus-infected cells than plus-strand leader RNA per mole of nucleocapsid template in both standard-virus- and mixed-virus-infected cells.

Animals↗
PubMed1979

Plus and minus strand leader RNAs in negative strand virus-infected cells.

Sendai virus and VSV minus strand genome RNAs, labeled specifically at their 3' ends with RNA ligase, were used as probes to detect leader RNA--that is, short transcripts (approximately 50 nucleotides) complementary to the exact 3' end of the minus strand genome. These probes have allowed the detection of plus strand leader RNAs in both Sendai virus and VSV-infected cells as well as in the virion transcriptase reactions. The use of a similar probe, prepared from the self-complementary ends of DI genome RNA and containing the 3' end of the plus strand antigenome RNA, has allowed the detection of a minus strand leader RNA of identical size in VSV-infected cells. Since the presence of DI genomes could not be detected by analytical sucrose gradient centrifugation in these VSV-infected cells, this minus strand leader RNA is apparently synthesized on the template formed by the exact 3' end of the antigenome RNA.

Animals↗
PubMed1977

Further characterization of Sendai virus DI-RNAs: a model for their generation.

Sendai virus DI-RNAs which contain complementary ends have been characterized as follows. First, the complementary ends of three DI-RNAs, although somewhat different in size (110-150 base pairs), contain sequences that are both identical to each other and to the 5' end of the nondefective (ND) genome. Second, almost all the sequences contained sequences that are both identical to each other and to the 5' end of the nondefective (ND) genome. Second, almost all the sequences contained in the DI-RNAs derive from sequences that are contiguous to the 5' end of the ND genome. The ND genome, on the other hand, does not contain any sequences that are complementary to its 5' end. A genetic map and a model for the generation of the Sendai DI-RNAs are presented.

Base Sequence↗
PubMedDate not supplied

A closely linked genetic marker for cystic fibrosis.

Cystic fibrosis is a recessive genetic disorder, characterized clinically by chronic obstructive lung disease, pancreatic insufficiency and elevated sweat electrolytes; affected individuals rarely live past their early twenties. Cystic fibrosis is also one of the most common genetic diseases in the northern European population. The frequency of carriers of mutant alleles in some populations is estimated to be as high as 1 in 20, carrying a concomitant burden of about one affected child in 1,500 births. Because little is known of the essential biochemical defect caused by the mutant gene, a genetic linkage approach based on arbitrary genetic markers and family studies is indicated to determine the chromosomal location of the cystic fibrosis (CF) gene. We have now obtained evidence for tight linkage between the CF locus and a DNA sequence polymorphism at the met oncogene locus. This evidence, combined with the physical localization data for the met locus presented in the accompanying paper, places the CF locus in the middle third of the long arm of chromosome 7, probably between bands q21 and q31.

Chromosome Mapping↗
PubMedDate not supplied

Genetic mapping of X-linked loci involved in skewing of X chromosome inactivation in the human.

We have analyzed X-chromosome inactivation patterns in lymphocytes of 264 females from 38 families not known to have any genetic disease. Quantitative measures of X-inactivation showed strong sister-sister correlation in the degree of departure from equal numbers of cells having each X chromosome active, suggesting heritability of this phenotype. Strong sister-sister correlation was also observed for the fraction of cells having the same parent's X chromosome active, consistent with the possibility that this trait might be controlled by a cis-acting, X-linked gene. We used a sib-pair approach to determine whether X-inactivation phenotype was linked to loci in any region of the X chromosome. Both quantitative and discrete measures of X-inactivation phenotype showed evidence of linkage to markers in the region of the X inactivation center (XIC). The quantitative measure of X-inactivation phenotype used in our study also showed linkage to loci at Xq25-q26. This study provides the first evidence for X-linked inheritance of X chromosome inactivation phenotype derived from linkage analysis in phenotypically normal human families.

Base Sequence↗
PubMedDate not supplied

Linkage analysis of schizophrenia: the D1 dopamine receptor gene and several flanking DNA markers.

Alterations in dopaminergic activity may play an important role in the pathogenesis of schizophrenia. The central effects of dopamine are mediated by at least five G protein-coupled receptors, D1, D2, D3, D4 and D5. The D1 receptor maps to 5q35.1 and it identifies an Eco RI as well as a Taq I RFLP. In the present study we undertook a linkage analysis between the D1 receptor RFLPs and schizophrenia in 9 multigenerational families in which segregation of disease was consistent with autosomal dominant inheritance and reduced penetrance. Several flanking DNA markers were also analyzed as the D1 receptor RFLPs were relatively uninformative in our families. Pairwise analyses of schizophrenia and several flanking markers indicate that inheritability of this region is unlikely to be involved in the pathogenesis of schizophrenia in the 9 families studied.

Chromosome Mapping↗