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M Gessler

Publications and source records attributed to M Gessler.

At least 55 records · Page 3Linked to original sources
PubMed1994

Confirmation of the localization of the human recombination activating gene 1 (RAG1) to chromosome 11p13.

The human recombination activating gene 1 (RAG1) has previously been mapped to chromosomes 14q and 11p. Here we confirm the chromosome 11 assignment by two independent approaches: autoradiographic and fluorescence in situ hybridization to metaphase spreads and analysis of human-hamster somatic cell hybrid DNA by the polymerase chain reaction (PCR) and Southern blotting. Our results unequivocally localize RAG1 to 11p13.

Animals↗
PubMed1993

Pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in a family.

The combined use of qualitative and quantitative analysis of 11p13 polymorphic markers together with chromosomal in situ suppression hybridization (CISS) with biotin labeled probes mapping to 11p allowed us to characterize a complex rearrangement segregating in a family. We detected a pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in the family: an insertion of brand 11p13-p14 carrying the genes for predisposition to Wilms' tumor, WT1, and for aniridia, AN2, into the long arm of chromosome 11 in 11q13-q14. Asymptomatic balanced carriers were observed over three generations. Classical cytogenetics had failed to detect this anomaly in the balanced carriers, who were first considered to be somatic mosaics for del(11)(p13). Two of these women gave birth to children carrying a deleted chromosome 11, most likely resulting from the loss of the 11p13 band inserted in 11q. Although in both cases the deletion encompassed exactly the same maternally inherited markers, there was a wide variation in clinical expression. One child, with the karyotype 46,XY, del(11)(p13p14), presented the full-blown WAGR syndrome with aniridia, mental retardation, Wilms' tumor, and pseudohermaphroditism, but also had proteinuria and glomerular sclerosis reminiscent of Drash syndrome. In contrast, the other one, a girl with the karyotype 46,XX,del(11)(p13), only had aniridia. Although a specific set of mutational sites has been observed in Drash patients, these findings suggest that the loss of one copy of the WT1 gene can result in similar genital and kidney abnormalities.

Child↗
PubMed1993

Homozygous inactivation of WT1 in a Wilms' tumor associated with the WAGR syndrome.

Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two-hit mechanism. A candidate 11p13 Wilms' tumor gene, WT1, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilm's tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome 11 allele encompassing the WT1 gene. Analysis of the remaining WT1 allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA-binding zinc finger domain that is essential for the function of the WT1 polypeptide as a transcriptional regulator.

Adolescent↗
PubMed1993

Sequence of the WT1 upstream region including the Wit-1 gene.

The Wilms tumor gene WT1 encodes a Cys2His2-type zinc finger protein that can bind DNA and function as a transcriptional regulator. The pathological spectrum of tumorigenesis and various developmental defects produced by different WT1 alterations suggests that WT1 controls a number of subsequent effector genes. To define the role of WT1 in these developmental processes it will be important to elucidate mechanisms that govern expression of WT1 itself. To facilitate mapping of the WT1 promoter region and 5' control elements we have determined the sequence upstream of the WT1 transcription unit. This includes the Wit-1 gene that is transcribed in the opposite direction.

Amino Acid Sequence↗
PubMed1993

Distinct molecular origins for Denys-Drash and Frasier syndromes.

The direct involvement of the Wilm's tumor suppressor gene (WT1) in Denys-Drash syndrome through mutations within exons 8 or 9 has recently been established. The absence of such alterations in three patients with Frasier syndrome provides a molecular basis for distinguishing these two syndromes that are associated with streak gonads, pseudohermaphroditism and renal failure.

Base Sequence↗
PubMed1993

Aspects of sandfly biology in southern Switzerland.

During three field surveys of phlebotomine sandflies in the region of Sessa, Minor Malcantone, southern Switzerland, annually 1987-89, Phlebotomus perniciosus and P. mascittii were caught regularly by means of light traps, but only when the traps were in close association with humans. The most productive catching sites were in the middle of Sessa village, in basements or partially closed shelters in the immediate vicinity of human dwellings. All catching sites outside the village were negative. The only other sandfly species caught was Sergentomyia minuta, four specimens only. P.perniciosus and P.mascittii always occurred together and were found to feed--at least occasionally--on human blood. Glucose and fructose were identified in wild-caught sandflies of both species. A breeding place of P. mascittii was identified in the basement of a house in the middle of Sessa. Analyses of soil samples revealed moderately loamy humus with a slightly acidic pH (5.6).

Animals↗
PubMed1992

The potassium channel gene HK1 maps to human chromosome 11p14.1, close to the FSHB gene.

Transiently activating (A-type) potassium (K) channels are important regulators of action potential and action potential firing frequencies. HK1 designates the first human cDNA that is highly homologous to the rat RCK4 cDNA that codes for an A-type K-channel. The HK1 channel is expressed in heart. By somatic cell hybrid analysis, the HK1 gene has been assigned to human chromosome 11p13-p14, the WAGR deletion region (Wilms tumor, aniridia, genito-urinary abnormalities and mental retardation). Subsequent pulsed field gel (PFG) analysis and comparison with the well-established PFG map of this region localized the gene to 11p14,200-600 kb telomeric to the FSHB gene.

Animals↗
PubMed1992

The genomic organization and expression of the WT1 gene.

The Wilms tumor gene WT1, a proposed tumor suppressor gene, has been identified based on its location within a homozygous deletion found in tumor tissue. The gene encodes a putative transcription factor containing a Cys/His zinc finger domain. The critical homozygous deletions, however, are rarely seen, suggesting that in many cases the gene may be inactivated by more subtle alterations. To facilitate the search for smaller deletions and point mutations we have established the genomic organization of the WT1 gene and have determined the sequence of all 10 exons and flanking intron DNA. The pattern of alternative splicing in two regions has been characterized in detail. These results will form the basis for future studies of mutant alleles at this locus.

Amino Acid Sequence↗
PubMed1992

Human CC10, the homologue of rabbit uteroglobin: genomic cloning, chromosomal localization and expression in endometrial cell lines.

Human and rat cDNAs to Clara Cell 10 kDa protein (CC10) have been previously isolated. Comparison of the amino acid sequences showed that CC10 is homologous to rabbit uteroglobin. Here we present further evidence that human CC10 is the human counterpart of rabbit uteroglobin. We have isolated the gene and have mapped its genomic localization to chromosome 11q11-qter. Sequence analysis of the 5'-flanking region reveals that the homology between the human and the rabbit gene starts at the first exon/intron boundary and extends up to -1.4 kb. A second region of 0.74 kb from -1.77 to -2.51 kb in the human 5'-flanking gene region is homologous to rabbit sequences that include four progesterone receptor binding sites which have been implicated in progesterone regulation of rabbit uteroglobin gene expression in endometrium. Sequence alignment of this region on the nucleotide level shows that only two weak progesterone receptor binding sites are partially conserved. In addition, close inspection of the human and rabbit promoters reveals that the estrogen responsive element and two recently identified cis elements of the rabbit promoter located between -177 and -258 bp are also absent in the human uteroglobin promoter. Despite these differences in the 5'-flanking regions of the genes, we report that the human uteroglobin mRNA is expressed in a human cell line of endometrial origin indicating that human uteroglobin is expressed in the uterus like its rabbit homologue. Thus, it appears that human uteroglobin is not only a marker for lung Clara cells but also an endometrial differentiation marker.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

[Parasitological and immunological progress control during and after chemotherapy of canine leishmaniasis].

Promastigote Leishmania-organisms were diagnostically cultivated in vitro from popliteal lymph node aspirates obtained from 32 of in total 36 dogs returning from endemic areas. Isoenzyme analysis (glucosephosphate-isomerase (GPI), phosphoglucomutase (PGM) and glutamate-oxaloacetate-transaminase (GOT) resulted in the identification of Leishmania infantum (syn. Leishmania (L.) infantum) for all 18 isolates investigated. Parasites were still able to be cultivated in vitro in 79% of 28 biopsies (from 15 dogs) even following chemotherapy by Glucantime, independent of the time of sampling and the course of disease after treatment. Dogs with a progressive form of disease (despite chemotherapy) showed only a minor or no reduction (between 0 and 4.8%) of the relative antibody concentration (determined by ELISA), whereas regressive forms of disease (without recurrences observed in the period of 10 to 37 months after therapy) demonstrated a marked reduction of the relative antibody concentration (between 6.7 and 16.2%) within the first 5 to 8 months; thereafter the decrease diminished and changed to a persistent low relative antibody concentration.

Animals↗
PubMed1991

GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families.

The Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder affecting limb and craniofacial development in humans. GCPS-affected individuals are characterized by postaxial polysyndactyly of hands, preaxial polysyndactyly of feet, macroephaly, a broad base of the nose with mild hypertelorism and a prominent forehead. The genetic locus has been pinpointed to chromosome 7p13 by three balanced translocations associated with GCPS in different families. This assignment is corroborated by the detection of two sporadic GCPS cases carrying overlapping deletions in 7p13 (ref. 7), as well as by tight linkage of GCPS to the epidermal growth factor receptor gene in 7p12-13 (ref. 8). Of the genes that map to this region, those encoding T cell receptor-gamma, interferon-beta 2, epidermal growth factor receptor, and Hox1.4, a potential candidate gene for GCPS, have been excluded from the region in which the deletions overlap. Here we show that two of the three translocations interup the GLI3 gene, a zinc-finger gene of the GLI-Krüppel family already localized to 7p13 (refs 5, 6). The breakpoints are within the first third of the coding sequence. In the third translocation, chromosome 7 is broken at about 10 kilobases downstream of the 3' end of GLI3. Our results indicate that mutations disturbing normal GLI3 expression may have a causative role in GCPS.

Chromosome Deletion↗
PubMed1991

A new photometric assay for testing trypanocidal activity in vitro.

A new in vitro test was developed to assess the trypanocidal activity of compounds against axenically grown Trypanosoma brucei bloodstream forms. Trypanosomes from continuous culture were exposed to series of drug dilutions in a microtiter plate. After an incubation time of 72 h at 37 degrees C, the pH indicator of the medium had changed its colour in non-inhibited cultures due to the production of pyruvate. Inhibited cultures showed less, if any, colour changes. Plates could be read by eye or using an enzyme-linked immunosorbent assay (ELISA) reader. Within the pH range of 7.0-7.5, the extinction values of phenol red at 560 nm showed a linear correlation with both the pH of the medium and the pyruvate concentration in the medium. By comparison of the decreases in extinction in test cultures with those in control cultures, IC50 values (drug concentrations causing 50% inhibition) could be determined. Minimal inhibitory concentrations (MICs) could be read by eye. The photometric test evaluation was compared with evaluation according to growth inhibition or to incorporation of radiolabelled hypoxanthine. The three methods of evaluation gave similar results.

Animals↗
PubMed1991

A somatic cell hybrid panel and DNA probes for physical mapping of human chromosome 7p.

To identify by reverse genetics genes on the short arm of human chromosome 7 expected to be involved in the regulation of human craniofacial and limb development, we have set up a human mouse somatic cell hybrid panel that divides 7p into 9 fragments. The breakpoints are defined by deletions or translocations involving one chromosome 7 in the cells of the human cell fusion partners. Particularly densely covered with these cytogenetic anchor points is the proximal area of 7p within and around 7p13. The number of cytogenetic mapping points within proximal 7p could be increased by four, using two diploid human cell lines with small interstitial deletions in this region for dosage studies. We used Southern blots of this panel to assign to 7q or subregions of 7p more than 300 arbitrary DNA probes or genes that provide reference points for physical mapping of 7p. Three reciprocal translocations with one of the breakpoints in 7p13 mark the location of a gene involved in Greig cephalopolysyndactyly syndrome. To define an area in which we could identify candidates for this developmental gene, we established a macrorestriction map using probes flanking the putative gene region. The Greig translocations were found to be located within a 630-kb NotI restriction fragment.

Animals↗
PubMed1990

Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping.

Cytogenetic analysis has identified chromosome 11p13 as the smallest overlap region for deletions found in individuals with WAGR syndrome, which includes Wilms tumour (a recessive childhood nephroblastoma), aniridia, genito-urinary abnormalities and mental retardation. The underlying loci have since been resolved into an aniridia (AN2) locus at a telomeric position, and a locus of closely spaced genes or a single pleiotropic gene involved in genito-urinary tract abnormalities and Wilms tumour at a more centromeric position. Pulsed-field gel analysis of the 11p13 region has revealed the presence of several putative CpG islands, structures which are frequently associated with the 5' ends of expressed sequences, mainly housekeeping genes and some tissue-specific genes. Starting from a CpG island, we have now isolated four neighbouring CpG islands, all within 650 kilobases (kb), by means of two consecutive bidirectional jumps in rare-cutting restriction-enzyme jumping libraries. In two instances, flanking sequences were conserved in other species and RNA transcripts were identified. A complementary DNA clone isolated for one of them derives from an RNA highly expressed in fetal kidney, and is predicted to encode a Krüppel-like zinc-finger protein that is probably a transcription factor. The entire cDNA region is included in two partially overlapping homozygous deletions found in Wilms tumour DNA samples. Cloning of the breakpoints in one tumour revealed a deletion size of 170 kb, one-third of which is covered by the cDNA. The expression pattern and sequence of this cDNA could point to an important role for its corresponding gene in the normal development of the renal system as well as in Wilms tumour.

Amino Acid Sequence↗
PubMed1990

The human MyoD1 (MYF3) gene maps on the short arm of chromosome 11 but is not associated with the WAGR locus or the region for the Beckwith-Wiedemann syndrome.

The human gene encoding the myogenic determination factor myf3 (mouse MyoD1) has been mapped to the short arm of chromosome 11. Analysis of several somatic cell hybrids containing various derivatives with deletions or translocations revealed that the human MyoD (MYF3) gene is not associated with the WAGR locus at chromosomal band 11p13 nor with the loss of the heterozygosity region at 11p15.5 related to the Beckwith-Wiedemann syndrome. Subregional mapping by in situ hybridization with an myf3 specific probe shows that the gene resides at the chromosomal band 11p14, possibly at 11p14.3.

Animals↗
PubMed1990

Role for the Wilms tumor gene in genital development?

Detailed molecular definition of the WAGR region at chromosome 11p13 has been achieved by chromosome breakpoint analysis and long-range restriction mapping. Here we describe the molecular detection of a cytogenetically invisible 1-megabase deletion in an individual with aniridia, cryptorchidism, and hypospadias but no Wilms tumor (WT). The region of overlap between this deletion and one associated with WT and similar genital anomalies but no aniridia covers a region of 350-400 kilobases, which is coincident with the extent of homozygous deletion detected in tumor tissue from a sporadic WT. A candidate WT gene located within this region has recently been isolated, suggesting nonpenetrance for tumor expression in the first individual. The inclusion within the overlap region of a gene for WT predisposition and a gene for the best-documented WT-associated genitourinary malformations leads us to suggest that both of these anomalies result from a loss-of-function mutation at the same locus. This in turn implies that the WT gene exerts pleiotropic effect on both kidney and genitourinary development, a possibility supported by the observed expression pattern of the WT candidate gene in developing kidney and gonads.

Aniridia↗