Showing papers by "Uta Francke published in 1981"
TL;DR: Analysis of mousexhuman hybrid cells containing only part of the long arm of chromosome 17 enabled us to localize the genes for growth hormone and chorionic somatomammotropin to region 17q21→17qter.
Abstract: We used a cloned cDNA probe for human growth hormone and Southern blotting techniques to analyze DNA from a series of rodent x human somatic cell hybrids for the presence of growth hormone-related sequences. Our results provide evidence for the assignment of the genes for growth hormone and chorionic somatomammotropin as well as a growth hormone-like gene to human chromosome 17. Analysis of mouse x human hybrid cells containing only part of the long arm of chromosome 17 enabled us to localize these genes to region 17q21 to 17qter.
123 citations
TL;DR: It is concluded that PFKL is located on chromosome 21 and that the previously noted elevation of erythrocyte PFK activity in individuals with trisomy 21 is due to a gene-dosage effect.
Abstract: Human 6-phosphofructokinase (PFK; ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) is under the control of structural loci that code for muscle (M), liver (L), and platelet (P) subunits, which are variably expressed in different tissues; human diploid fibroblasts and leukocytes express all three genes. Random tetramerization of these subunits produces various isozymes, which can be distinguished from one another by ion exchange chromatography or by subunit-specific monoclonal antibodies. We have examined 17 somatic cell hybrids established between Chinese hamster cells and human diploid fibroblasts or leukocytes for the expression of L-type subunits of human PFK. As electrophoresis does not distinguish between Chinese hamster PFKs and human PFKs, we used an anti-human L-subunit-specific monoclonal antibody, which does not react with chinese hamster PFKs. The expression of human L subunits in the hybrids was detected by the enzyme-immunoprecipitation technique using staphylococci bearing protein A as an immunoadsorbent. Twelve out of 17 hybrids expressed human L subunits and retained chromosome 21, as determined by chromosome and isozyme marker analysis, whereas 5 did not express human PFKL and lacked chromosome 21. The mean erythrocyte PFK of seven individuals with trisomy 21 was found to be elevated (147% of normal). A specific increase in L subunits in trisomic erythrocytes was evident chromatographically by a striking increase in L4 species (50%; normal 10%) and immunologically by decreased precipitation with anti-M monoclonal antibody (50%; normal 80%). We conclude from these data that PFKL is located on chromosome 21 and that the previously noted elevation of erythrocyte PFK activity in individuals with trisomy 21 is due to a gene-dosage effect.
67 citations
TL;DR: An unbalanced karyotype most likely consisting of a partial duplication of the short arm of chromosome 2 (p13 leads to pter) was found in a newborn infant with intrauterine growth retardation, facial, skeletal, and cardiac abnormalities.
Abstract: An unbalanced karyotype most likely consisting of a partial duplication of the short arm of chromosome 2 (p13 leads to pter) was found in a newborn infant with intrauterine growth retardation, facial, skeletal, and cardiac abnormalities. There was no evidence of a translocation in either parent. At autopsy, striking histopathologic abnormalities were detected in the central nervous system and ovaries.
26 citations
TL;DR: It appears that the mutation leading to campomelic dysplasia interferes with normal H-Y antigen expression, and the “sexreversal” (chromosomal male→phenotypic female) previously noted in patients with autosomal recessive campo-dysplasia thus may be mediated through lack of detectable H-y antigen on the cell surface.
Abstract: We have studied a stillborn infant who had the clinical and radiographic characteristics of campomelic dysplasia. External and internal genitalia were those of a normal female, except for slight enlargement of the clitoris. Microscopic examination of the ovaries revealed some areas resembling immature dysgenetic testicular tissue. Karyotypes from lymphocyte and fibroblast cultures were 46,XY with a structurally normal Y chromosome and no evidence of mosaicism. H-Y antigen was not detected on the fibroblasts in repeated assays using Raji cells as target cells after absorption. The “sexreversal” (chromosomal male→phenotypic female) previously noted in patients with autosomal recessive campomelic dysplasia thus may be mediated through lack of detectable H-Y antigen on the cell surface. It appears that the mutation leading to campomelic dysplasia interferes with normal H-Y antigen expression.
25 citations
TL;DR: A six-week-old female infant with multiple congenital anomalies including a hypoplastic left-heart malformation was found to have duplication of 12p, one of only two previously reported cases of dup.
Abstract: A six-week-old female infant with multiple congenital anomalies including a hypoplastic left-heart malformation was found to have duplication of 12p. Only two of 17 previously reported cases of dup (12p) had congenital heart disease, and both had hypoplastic left-heart abnormality.
19 citations
TL;DR: Evidence for another syntenic relationship that has been conserved is found by regional mapping of human DIA1 and ARSA using somatic cell hybrids segregating a human chromosome translocation t(15;22)(q14;q13.31).
Abstract: We have utilized a panel of Chinese hamster × mouse somatic cell hybrids segregating mouse chromosomes to assign a gene for arylsulfatase A (ARSA) to mouse chromosome 15. Considering our previous assi
17 citations
Journal Article•
TL;DR: 2-D gel electrophoretic analysis of extracts from somatic cell hybrids provides a general method for identifying polypeptides in crude cell extracts coded for by any specific chromosome and can be used to study primary gene products not previously amenable to genetic analysis.
Abstract: The technique of two-dimensional (2-D) gel electrophoresis was sued to identify five human X-linked gene products in crude cell extracts of mouse-human and Chinese hamster-human somatic cell hybrids. The human origin of these five polypeptides was demonstrated by their comigration with human fibroblast proteins and their failure to comigrate with polypeptides in extracts from the mouse or hamster parental cells. All five polypeptides were present in extracts of rodent-human hybrids that contained a human X chromosome, but were not found in extracts of cells that lacked a human X chromosome. Chromosome analysis of the hybrid clones revealed that the human X chromosome is both necessary and sufficient for the expression of the five polypeptides, designated pX-24, pX-27, pX-37, pX-40, and pX-56. pX-56 can be identified as the human X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD) (E.C.1.1.1.49), while polypeptides pX-24, pX-27, pX-37 and pX-40 have molecular properties unlike those of known human X-linked gene products. pX-24 appears to be a membrane-bound protein that maps to the distal portion of the long arm of the human X chromosome, while pX-27, pX-37, and pX-40 are soluble proteins that map to the proximal long arm or to the short arm of the human X chromosome. 2-D gel electrophoretic analysis of extracts from somatic cell hybrids provides a general method for identifying polypeptides in crude cell extracts coded for by any specific chromosome and can be used to study primary gene products not previously amenable to genetic analysis.
13 citations
TL;DR: A lymphoblastic leukemia cell line that is over 100,000-fold resistant to methotrexate (MTX) has been developed and the most striking consistent difference between the resistant and sensitive cells was the presence of a large, faintly banded region of intermediate staining intensity, termed a “homogeneously staining region” (HSR).
Abstract: A lymphoblastic leukemia cell line, L5178YR, that is over 100,000-fold resistant to methotrexate (MTX) has been developed. Previous work has demonstrated that the resistant line has dihydrofolate reductase (DHFR) levels 300-fold higher than the sensitive parental cells, L5178Y. Resistant cells grown in the absence of MTX (L5178YR–) showed a similar level of DHFR activity. The increase in DHFR could be entirely accounted for by a corresponding increase in DHFR-specific mRNA and gene copies. Studies were carried out to determine whether these changes in the resistant cells were accompanied by karyotypic alterations. A detailed karyotypic analysis of the sensitive parental line (L5178YS) and the two resistant cell lines (L5178YR+ and L5178YR-) was performed. Although certain abnormal marker chromosomes were present in all three cell lines, the most striking consistent difference between the resistant and sensitive cells was the presence of a large, faintly banded region of intermediate staining intensity, termed a “homogeneously staining region” (HSR), inserted within a reduplicated part of chromosome 2. It was present in approximately 90% of resistant cells, and no more than one HSR was ever present in a cell. Hybridization in situ was performed to determine the chromosomal locations of DHFR genes. Utilizing a purified complementary DNA probe made from messenger RNA of the L5178YR+ cells, the genes were shown to be localized exclusively to the HSR.
10 citations
TL;DR: This work uses the recombinant plasmid pAW101 as a probe to examine the presence of homologous sequences in the DNA extracted from 17 human x Chinese hamster somatic cell hybrid clones, and assigns the first highly polymorphic RFLP locus identified in man to region q21→qter of chromosome 14.
Abstract: 710 ASSIGNMENT OF THE FIRST HIGHLY POLYMORPHIC DNA MARKER LOCUS TO A HUMAN CHROMOSOME REGION
6 citations