Showing papers by "Uta Francke published in 1977"

Assignment of the major histocompatibility complex to a region of the short arm of human chromosome 6

Abstract: Interspecific cell hybrids containing defined parts of human chromosome 6 were used for regional mapping of gene loci previously assigned to chromosome 6: the human leukocyte antigens (HLA) region, phosphoglucomutase-3 (PGM3; alpha-D-glucose-1,6-bisphosphate:alpha-D-glucose-1-phosphate phosphotransferase, EC 2751) and malic enzyme-1 [malic dehydrogenase(decarboxylating) (NADP+), L-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating), EC 11140] Human fibroblasts containing a balanced reciprocal translocation between the short arms of chromosome 1 and chromosome 6--designated t(1;6) (p3200;p2100)--were fused with an established line of Chinese hamster cells Hybrid clones with segregating human chromosomes were studied for the presence of the translocation chromosomes 1T and 6T and their normal homologues 1 and 6 Six clones that had retained 1T, three clones with 6T, and three clones with 6 and 6T as controls, were analyzed by a microabsorption test for expression of the allelic antigens HLA-A2 and HLA-A3, both of which were present on the human parental cells HLA-A2 segregated with the 1T translocation chromosome and HLA-A3 with the normal chromosome 6 Hybrid clones with 6T did not possess an HLA-A gene In contrast, human PGM3 and malic enzyme-1 expression segregated with the 6T translocation chromosome These results indicate the location of the major histocompatibility complex in region 6p2100 leads to 6pter of the short arm of chromosome 6 The genes for PGM2 and malic enzyme-1 map in region 6p2100 leads to 6qter The HLA:PGM3 genetic map distance is 15 centimorgans in males, as established by family studies This allows rather precise mapping of both loci because HLA is distal and PGM3 proximal to the translocation breakpoint in band 6p2100 The findings are consistent with earlier conclusions that HLA is proximal to 6p22 Quantitative correlation between the density of HLA antigens on the hybrid cell surface and the number of copies of the respective HLA gene-bearing chromosome suggests a gene dose effect for cell surface molecules, as it exists for intracellular gene products

Gene mapping in Mus musculus by interspecific cell hybridization: assignment of the genes for tripeptidase-1 to chromosome 10, dipeptidase-2 to chromosome 18, acid phosphatase-1 to chromosome 12, and adenylate kinase-1 to chromosome 2.

Abstract: Chinese hamster X mouse somatic cell hybrids segregating mouse chromosomes were examined for their mouse chromosome content using trypsin-Giemsa (GTG) banding and Hoechst 33258 staining techniques. Si

Inverted tandem (“mirror”) duplications in human chromosomes: Inv dup 8p, 4q, 22q

Abstract: We have studied 4 patients with inverted tandem duplications of parts of chromosomes, a hitherto rarely identified form of a structural rearrangement involving a single chromosome in man. In patients 1 and 2, the duplication involved parts of the short arm of chromosome 8 (regions 8p12 leads to 8p23 and 8p21 leads to 8p23, respectively). Both patients manifested certain characteristics of the mosaic trisomy 8 syndrome. Elevated levels of glutathione reductase (GSR) in their erythrocytes supported the interpretation of a partial duplication of chromosome 8 and indicated a regional localization for the GSR gene locus. In Partient 3, the distal half of the long arm of chromosome 4 was duplicated (region 4q23 leads to 4q35). Clinical evidence supported this interpretation, as Patient 3 resembled phenotypically the 13 reported cases with duplication of the distal 4q. The cytogenetic findings in Patient 4 suggested a possibly inverted duplication of 22q. The clinical correlation was less convincing due to the lack of a well-defined phenotype for trisomy 22. These chromosome aberrations had occurred de novo in all 4 cases. Although they involved different chromosomal regions, they might well have arisen by the same mechanism. Possible modes of origin that are discussed in detail include unequal exchange between homologous chromosomes, between chromatids of 1 chromosome or between strands of 1 DNA duplex.

Gene dose effect: intraband mapping of the LDH A locus using cells from four individuals with different interstitial deletions of 11p

Abstract: The quantitative expression of LDH A was studied in hemolysates from four patients with different but overlapping interstitial deletions of the short arm of chromosome 11. Deficiency of LDH A was demonstrated in one patient, and the LDH A locus has been assigned to that segment of lip for which this patient alone was deficient, i.e., to band llpl2 (region 11p1203→11p1208).

Regional mapping of human genes for hexosaminidase B and diphtheria toxin sensitivity on chromosome 5 using mouse × human hybrid cells

Abstract: Mouse 3T3 (TK−) cells were fused to human leukocytes containing a balanced translocation [ins(3;5) (q27;q13q15)] in which part of the long arm of a chromosome 5 has been inserted into the long arm of a chromosome 3. Two independent, primary hybrid clones (XVI-10C; XVI-18A) retained the deleted chromosome 5 [del(5) (q13q15)] translocation product and were informative for regional mapping on chromosome 5 of genes involved in expression of hexosaminidase B (HEX B ) and diphtheria toxin sensitivity (DTS). Both XVI-10C and XVI-18A clones were sensitive to diphtheria toxin. Toxin-resistant derivatives of these clones (XVI-10C DTR; XVI-18A DTR) were analyzed for chromosome content and expression of Hex B activity, as were XVI-10C and XVI-18A cells which had not been exposed to diphtheria toxin. The results of this study provide evidence for localization ofDTS to region 5q15→5qter on the long arm of chromosome 5, and localization ofHEX B to region 5pter→5q13.

Intrachromosomal gene mapping in man: The gene for tryptophanyl-tRNA synthetase maps in region q21→qter of chromosome 14

Abstract: A gene for tryptophanyl-tRNA synthetase (EC 6.1.1.2), the enzyme which attaches tryptophan to its tRNA, has previously been assigned to human chromosome 14 by analysis of man-mouse somatic cell hybrids. We report here a method for the electrophoretic separation of Chinese hamster and human tryptophanyl-tRNA synthetases and its application to a series of independently derived Chinese hamster-human hybrids in which part of the human chromosome 14 has been translocated to the human X chromosome. When this derivative der (X),t(X;14) (Xqter → Xp22::14q21 → 14qter) chromosome carrying the human gene for hypoxanthine-guanine phosphoribosyltransferase was selected for and against in cell hybrid lines by the appropriate selective conditions, the human tryptophanyl-tRNA synthetase activity was found to segregate concordantly. These results provide additional confirmation for the assignment of the tryptophanyl-tRNA synthetase gene to human chromosome 14 and define its intrachromosomal location in the region 14q21 → 14qter. Our findings indicate that the genes for tryptophanyl-tRNA synthetase and for ribosomal RNA are not closely linked on chromosome 14.

Experience with detection of heterozygous carriers and prenatal diagnosis of Lesch-Nyhan disease.

Abstract: For the purpose of genetic counselling, considerable efforts have been expended on the development of reliable methods necessary to identify the carriers of the Lesch-Nyhan syndrome, as well as to test in utero the sex of the fetus and its hypoxanthine phosphoribosyl transferase (HPRT, E.C. 2.4.2.8) activity.

The 2p Partial Trisomy Syndrome-Reply

Abstract: In Reply .—I would like to point out that phenotypic differences between unrelated individuals with apparently identical chromosomal duplications can be due to three mechanisms: (1) differences in the extent of the duplicated segment; (2) differences in the associated deletions in cases of inherited reciprocal translocations; and (3) different genetic backgrounds. Our patients with duplication of chromosome 2 (region 2p23→2pter) reported in theJournalpresumably also have a minute deletion from the 7q terminus, as we have described and discussed in the article. This deletion is hypothetical since it is not evident on banded metaphase chromosomes, and meiotic studies to prove the reciprocal nature of the translocation have not been possible. Therefore, we did not include the deletion in the title. We believe that the designation of "duplication/deficiency syndrome" should be reserved for those cases in which the deficiency is cytologically evident, such as in unbalanced off-spring of carriers of