New method for mapping genes in human chromosomes

Goss, S.J.; Harris, Henry

doi:10.1038/255680a0

Cited by 336 publications

(129 citation statements)

References 18 publications

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“…While an X-linked mode of transmission of human PRPP synthetase appears to be established by the fibroblast studies reported here, confirmation of this finding may be obtained by the demonstration of synteny with other X-linked biochemical and antigenic markers in appropriate interspecific somatic cell hybrids, such as those between human and hamster cells (28 …”

Section: Resultssupporting

confidence: 61%

Evidence for X-linkage of human phosphoribosylpyrophosphate synthetase

Yen¹,

Adams²,

Lazar³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

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The mode of genetic transmission of human phosphoribosylpyrophosphate synthetase (ribosephosphate pyrophosphokinase; ATP:D-ribose-5-phosphate pyrophosphotransferase; EC 2.7.6.1) was studied in fibroblasts cultured from members of a family with a structurally and electrophoretically altered phosphoribosylpyrophosphate synthetase that has increased activity per enzyme molecule. Enzyme activity in fibroblast lysates from the daughter of an affected male patient was intermediate to the activities in lysates from her father (and her affected paternal uncle) and from her mother and other normal individuals. Two bands of enzyme activity corresponding to normal and mutant phosphoribosylpyrophosphate synthetases were found in fibroblast lysates from the daughter after cellulose acetate strip electrophoresis. In contrast, only mutant enzyme was detectable in lysates derived from the male patients. Fibroblasts cloned from the daughter contained two phenotypically distinct (normal and mutant) populations of cells with respect to phosphoribosylpyrophosphate synthetase activity and electrophoretic mobility. These studies support assignment of the structural gene for human phosphoribosylpyrophosphate synthetase to the X-chromosome. No evidence for the presence of the normal enzyme was found in erythrocyte or lymphocyte lysates or in partially purified erythrocyte enzyme preparations from the heterozygous daughter, suggesting either nonrandom X-chromosome inactivation in precursors of these cells or selection against hematopoietic cells bearing the normal enzyme after random X-chromosome inactivation.5-Phosphoribosyl-l-pyrophosphate (PRPP) synthetase (ATP: D-ribose-5-phosphate pyrophosphotransferase; EC 2.7.6.1) catalyzes the reaction between ATP and ribose-5-P to form PRPP and AMP. PRPP is a rate-limiting substrate in purine synthesis de novo as well as an allosteric activator of amidophosphoribosyltransferase (EC 2.4.2.14) (1), the first committed enzyme in this pathway. In three families reported to date (2-4), affected male members with excessive PRPP synthetase activity due to apparently different structural alterations in the enzyme show increased intracellular PRPP synthesis, concomitant purine overproduction, and gout. Thus, increased PRPP synthetase activity is a prototype for the association of a hereditary disease state with a structurally aberrant protein of increased rather than decreased catalytic activity.The identification of an excessively active and electrophoretically distinct form of PRPP synthetase (5) provides an opportunity to study the mode of inheritance of the enzyme. Pedigree data from two of the families thus far reported (6, 7) are compatible with either autosomal dominant or X-linked transmission of the gene for PRPP synthetase. Father-to-son transmission of aberrant forms of the enzyme, a criterion essential for the exclusion of X-linkage, has not been observed. On the other hand, studies in erythrocytes from female memThe costs of publication of this article were defrayed in part by the p...

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Section: Resultssupporting

confidence: 61%

Evidence for X-linkage of human phosphoribosylpyrophosphate synthetase

Yen¹,

Adams²,

Lazar³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

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“…1) [13][14][15] . When X-rays are used to randomly cleave DNA, neighboring markers are rarely separated, allowing linkage to be evaluated.…”

mentioning

confidence: 99%

Fine mapping of regulatory loci for mammalian gene expression using radiation hybrids

et al. 2008

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We mapped regulatory loci for nearly all protein-coding genes in mammals using comparative genomic hybridization and expression array measurements from a panel of mouse-hamster radiation hybrid cell lines. The large number of breaks in the mouse chromosomes and the dense genotyping of the panel allowed extremely sharp mapping of loci. As the regulatory loci result from extra gene dosage, we call them copy number expression quantitative trait loci, or ceQTLs. The −2log 10 P support interval for the ceQTLs was <150 kb, containing an average of <2-3 genes. We identified 29,769 trans ceQTLs with −log 10 P > 4, including 13 hotspots each regulating >100 genes in trans. Further, this work identifies 2,761 trans ceQTLs harboring no known genes, and provides evidence for a mode of gene expression autoregulation specific to the X chromosome.

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“…It is likely that some of the marsupial X eutherian hybrid combinations in which one or a few marsupial chromosomes are retained will prove useful for assigning marsupial genetic markers to chromosomes. Other hybrids in which complete loss of marsupial chromosome occurs cannot be used for chromosome assignment in the same way, but it may be/possible to use these hybrids for determining the order of genes syntenic with the selective markers by comparing the frequencies of cotransfer of markers, in the same manner as described by Goss and Harris (1975). Such mapping studies have been initiated.…”

Section: Discussionmentioning

confidence: 99%

“…By using somatic cell genetic techniques it is possible to assign human genes to particular chromosomes (Ruddle and Creagan 1975), and to establish gene order (Ricciutti and Ruddle 1973;Goss and Harris 1975). The same technique can be applied to gene mapping in other mammals, e.g.…”

Section: Introductionmentioning

confidence: 99%