248 (418 )
R uddle, M cM orris
Assignment of MPI
Assignment of mannose phosphate isomerase to human chromosome 7: a retraction F.H. R uddle 1 and F.A. M cM orris 2
In 1973, we presented data supporting the assignment of the gene for mannose phosphate isomerase (MPI) to chromosome 7 in man.1 In that report, a perfect concordant relationship between MPI and 7 was observed in six different mouse X human somatic cell hybridization experiments, involving a total of 19 independently derived hybrid clones in which the mouse genome was IS (MPI/7: 7 + / + ; 0 + / —; 0 —/ + ; 12 —/ —). We also pointed out that the mouse human hybrids which possessed a 2S mouse genome failed to support a MPI to 7 assignment, stating “five clones of this make-up contained C-7 chromosomes, but did not express human M PI.” 1 At that time, we believed that the 2S murine input might in certain hybrids suppress otherwise constitutive human phenotypes. A similar situation had been observed in the WA (WI-38 X A9) series for GOT, which has been assigned to chromosome 10.2 Here a 2S hybrid clonal line possessed chromosome 10 but did not express GOT. However, in subclonal derivatives of this clone, GOT was again expressed.2 Another basis for the “extinction” hypothesis was the murine kidney cell origin of RAG, which was the mouse parental input in the 2S RK clones (RAG X KOP),3 four of which possessed chromosome 7 but did not express MPI. Shows 4 has observed that hybrids with RAG sometimes do not express PK-3 even though MPI was expressed. We concluded our discussion of these possibilities with the following statement: “Linkage of MPI to C-7 is therefore indicated, but is not as firmly established as the linkage of GPI to F-19.” 1 In this conference van H eyningen et al. have advanced data which contradict our provisional assignment of MPI to chromosome 7 and support the assignment of MPI to chromosome 15.5 We have re-examined
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'Department of Biology, Yale University, New Haven, Conn., and *The Wistar Institute, Philadelphia. Pa.
R uddle, M cM orris
Assignment of MPI
249 ( 419 )
Downloaded by: UCL 144.82.238.225 - 5/14/2018 1:20:50 PM
our more recently analyzed independent mouse X human hybrids in order to support or deny their choice. Thirteen hybridization experiments, including the original six discussed above, have been analyzed for chromosomes and for numerous enzyme markers, including MPI. Only independently derived mouse-human hybrid clones are considered, and all clones which possessed chromo some 7 had them in greater than 2 0 % of the cells examined. The total number of hybrid cell lines examined in this set was 56. The results of this analysis are MPI/7: 14 + / + ; 7 + / —; 10 —/ + ; 25 These results show 3 3 % discordant clones. The number of discordancies is thus too large to support an assignment relationship between MPI and chromo some 7. Particularly significant in this respect are the 10 clones which lack MPI but which possess chromosome 7’s. Moreover, a number of these discrepant clones are IS. It should be emphasized that absence of a positive assignment relation ship between MPI and chromosome 7 does not affect the well-established syntenic relationship between MPI, Hex-A, and PK-33A-V However, now all three markers must be shifted to another chromosome. V an H eyningen et al. provide data for the assignment of MPI to chromosome 15.5 It is difficult for us to comment directly on this rela tionship since, as pointed out in a number of our recent assignment reports,2’10’11 we cannot reliably discriminate chromosome 15 from similar chromosomes in the mouse genome. It has been possible, however, to exclude the assignment of MPI to all human chromosomes save chromo some 15. Thus, in this regard our data are at least consistent with those advanced by the Oxford group. Our difficulty in identifying chromosome 15 was also compounded by the absence of a phenotype in our repertoire of markers which was truly coded by chromosome 7. Such a circumstance would have permitted the use of the synteny test to confirm the assignment test. V an H eyningen et al. could capitalize on MDH-2, which appears to be assignable to chromosome 7 in this respect.5 If confirmed, Dr. van H eyningen’s findings are exceedingly helpful. A number of markers can now be placed on chromosome 15, and thus all D-group chromosomes can be detected by a phenotypic signature. Thus, good phenotypic markers can be associated with all of the autosomes except chromosome 22 and possibly chromosome 3.
250 (420 )
R uddle, M cM orris Assignment of MP1
References 1 M c M orris , F.A.; C hen , T.R.; Ricciun, R.; T ischfield , J.; C reagan, R. and R uddle , F.H.: Chromosome assignment in man of the genes for two hcxosephos-
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phate isomerases. Science 179: 1129-1131 (1973). 2 C reagan, R.; T ischfield , L; M c M orris , F.A.; C hen , S.; H irschi, M.; C hen , T.R.; Riccnm, F. and R uddle , F.H.: Assignment of the genes for human pepti dase A to chromosome 18 and cytoplasmic glutamic oxaloacetate transaminase to chromosome 10 using somatic cell hybrids. Cytogenet. Cell Genet. 12: 187-198 (1973). 3 R icciuti, F. and R uddle , F.H.: Assignment of nucleoside phosphorylase to D-14 and localization of X-linked loci in man by somatic cell genetics. Nature new Biol. 241: 180 (1973). 4 Show s , T.B.: Control and linkage relationships of pyruvate kinase in somatic cell hybrids. J. Cell Biol. 59: 314a (1973). 5 H eyningen , V. van ; Bobrow , M. and B odmer , W.F.; P ovey , S.; G ardiner, S.E. and H opkinson , D.A.: Assignment of the genes for human mitochondrial malate dehydrogenase to chromosome 7, for mannose phosphate isomcrase and pyruvate kinase to chromosome 15, and, probably, for human esterase-D to chromosome 13 using man-mouse hybrids. This conference (1974). 6 K ucherlapati, R.S.; C reagan, R.P.; N ichols , E.A.; Borgaonkar, D.S. and R uddle , F.H.: Synteny relationships of four human genes: mannose phosphate isomerase to pyruvate kinase-3 and trióse phosphate isomerase to lactate dehydrogenase-B. This Conference (1974). 7 G ilbert , F.; K ucherlapati, R.; M urnane, M.J.; D arlington, G .J.; C reagan, R.; and R uddle , F.H.: Assignment of a locus involved in the expression of hexosaminidase A to chromosome 7 in man, pp. 96-99. In N ew H aven C onfer ence (1973): First international workshop on human gene mapping. Birth Defects: Original Article Series, Vol. 10, No. 3 (The National Foundation, New York 1974). 8 Show s , T.B.: Linkage of loci for human pyruvate kinase and mannosephosphate isomerase in somatic cell hybrids. Am. J. hum. Genet. 24: 13a (1972). 9 L alley, P.A.; R attazzi, M.C. and S how s , T.B.: Human /?-D-A-acetylhexosaminidases A and B: expression of linkage relationships in somatic cell hybrids. Proc. natn. Acad. Sci. USA 71: 1569-1573 (1974). 10 C reagan, R.P.; C arrit, B.; C hen , S.; K ucherlapati, R.; M cM orris , F.A.; R icau n , F.; T an, Y.H.; T ischfield , J.A. and R uddle , F.H.: Chromosome assignments of genes in man using mouse-human somatic cell hybrids: cytoplasmic isocitrate dehydrogenase and malate dehydrogenase to chromosome 2. Am. J. hum. Genet. (1974, in press). 11 T an, Y.H.; C reagan, R.P. and R uddle , F.H.: The somatic cell genetics of human interferon: assignment of human interferon loci to chromosomes 2 and 5. Proc. natn. Acad. Sci. USA 71: 2251-2255 (1974).
R uddle, M cM orris
Assignment of MPI
Assignment of mannose phosphate isomerase to human chromosome 7: a retraction F.H. R uddle 1 and F.A. M cM orris 2
In 1973, we presented data supporting the assignment of the gene for mannose phosphate isomerase (MPI) to chromosome 7 in man.1 In that report, a perfect concordant relationship between MPI and 7 was observed in six different mouse X human somatic cell hybridization experiments, involving a total of 19 independently derived hybrid clones in which the mouse genome was IS (MPI/7: 7 + / + ; 0 + / —; 0 —/ + ; 12 —/ —). We also pointed out that the mouse human hybrids which possessed a 2S mouse genome failed to support a MPI to 7 assignment, stating “five clones of this make-up contained C-7 chromosomes, but did not express human M PI.” 1 At that time, we believed that the 2S murine input might in certain hybrids suppress otherwise constitutive human phenotypes. A similar situation had been observed in the WA (WI-38 X A9) series for GOT, which has been assigned to chromosome 10.2 Here a 2S hybrid clonal line possessed chromosome 10 but did not express GOT. However, in subclonal derivatives of this clone, GOT was again expressed.2 Another basis for the “extinction” hypothesis was the murine kidney cell origin of RAG, which was the mouse parental input in the 2S RK clones (RAG X KOP),3 four of which possessed chromosome 7 but did not express MPI. Shows 4 has observed that hybrids with RAG sometimes do not express PK-3 even though MPI was expressed. We concluded our discussion of these possibilities with the following statement: “Linkage of MPI to C-7 is therefore indicated, but is not as firmly established as the linkage of GPI to F-19.” 1 In this conference van H eyningen et al. have advanced data which contradict our provisional assignment of MPI to chromosome 7 and support the assignment of MPI to chromosome 15.5 We have re-examined
Downloaded by: UCL 144.82.238.225 - 5/14/2018 1:20:50 PM
'Department of Biology, Yale University, New Haven, Conn., and *The Wistar Institute, Philadelphia. Pa.
R uddle, M cM orris
Assignment of MPI
249 ( 419 )
Downloaded by: UCL 144.82.238.225 - 5/14/2018 1:20:50 PM
our more recently analyzed independent mouse X human hybrids in order to support or deny their choice. Thirteen hybridization experiments, including the original six discussed above, have been analyzed for chromosomes and for numerous enzyme markers, including MPI. Only independently derived mouse-human hybrid clones are considered, and all clones which possessed chromo some 7 had them in greater than 2 0 % of the cells examined. The total number of hybrid cell lines examined in this set was 56. The results of this analysis are MPI/7: 14 + / + ; 7 + / —; 10 —/ + ; 25 These results show 3 3 % discordant clones. The number of discordancies is thus too large to support an assignment relationship between MPI and chromo some 7. Particularly significant in this respect are the 10 clones which lack MPI but which possess chromosome 7’s. Moreover, a number of these discrepant clones are IS. It should be emphasized that absence of a positive assignment relation ship between MPI and chromosome 7 does not affect the well-established syntenic relationship between MPI, Hex-A, and PK-33A-V However, now all three markers must be shifted to another chromosome. V an H eyningen et al. provide data for the assignment of MPI to chromosome 15.5 It is difficult for us to comment directly on this rela tionship since, as pointed out in a number of our recent assignment reports,2’10’11 we cannot reliably discriminate chromosome 15 from similar chromosomes in the mouse genome. It has been possible, however, to exclude the assignment of MPI to all human chromosomes save chromo some 15. Thus, in this regard our data are at least consistent with those advanced by the Oxford group. Our difficulty in identifying chromosome 15 was also compounded by the absence of a phenotype in our repertoire of markers which was truly coded by chromosome 7. Such a circumstance would have permitted the use of the synteny test to confirm the assignment test. V an H eyningen et al. could capitalize on MDH-2, which appears to be assignable to chromosome 7 in this respect.5 If confirmed, Dr. van H eyningen’s findings are exceedingly helpful. A number of markers can now be placed on chromosome 15, and thus all D-group chromosomes can be detected by a phenotypic signature. Thus, good phenotypic markers can be associated with all of the autosomes except chromosome 22 and possibly chromosome 3.
250 (420 )
R uddle, M cM orris Assignment of MP1
References 1 M c M orris , F.A.; C hen , T.R.; Ricciun, R.; T ischfield , J.; C reagan, R. and R uddle , F.H.: Chromosome assignment in man of the genes for two hcxosephos-
Downloaded by: UCL 144.82.238.225 - 5/14/2018 1:20:50 PM
phate isomerases. Science 179: 1129-1131 (1973). 2 C reagan, R.; T ischfield , L; M c M orris , F.A.; C hen , S.; H irschi, M.; C hen , T.R.; Riccnm, F. and R uddle , F.H.: Assignment of the genes for human pepti dase A to chromosome 18 and cytoplasmic glutamic oxaloacetate transaminase to chromosome 10 using somatic cell hybrids. Cytogenet. Cell Genet. 12: 187-198 (1973). 3 R icciuti, F. and R uddle , F.H.: Assignment of nucleoside phosphorylase to D-14 and localization of X-linked loci in man by somatic cell genetics. Nature new Biol. 241: 180 (1973). 4 Show s , T.B.: Control and linkage relationships of pyruvate kinase in somatic cell hybrids. J. Cell Biol. 59: 314a (1973). 5 H eyningen , V. van ; Bobrow , M. and B odmer , W.F.; P ovey , S.; G ardiner, S.E. and H opkinson , D.A.: Assignment of the genes for human mitochondrial malate dehydrogenase to chromosome 7, for mannose phosphate isomcrase and pyruvate kinase to chromosome 15, and, probably, for human esterase-D to chromosome 13 using man-mouse hybrids. This conference (1974). 6 K ucherlapati, R.S.; C reagan, R.P.; N ichols , E.A.; Borgaonkar, D.S. and R uddle , F.H.: Synteny relationships of four human genes: mannose phosphate isomerase to pyruvate kinase-3 and trióse phosphate isomerase to lactate dehydrogenase-B. This Conference (1974). 7 G ilbert , F.; K ucherlapati, R.; M urnane, M.J.; D arlington, G .J.; C reagan, R.; and R uddle , F.H.: Assignment of a locus involved in the expression of hexosaminidase A to chromosome 7 in man, pp. 96-99. In N ew H aven C onfer ence (1973): First international workshop on human gene mapping. Birth Defects: Original Article Series, Vol. 10, No. 3 (The National Foundation, New York 1974). 8 Show s , T.B.: Linkage of loci for human pyruvate kinase and mannosephosphate isomerase in somatic cell hybrids. Am. J. hum. Genet. 24: 13a (1972). 9 L alley, P.A.; R attazzi, M.C. and S how s , T.B.: Human /?-D-A-acetylhexosaminidases A and B: expression of linkage relationships in somatic cell hybrids. Proc. natn. Acad. Sci. USA 71: 1569-1573 (1974). 10 C reagan, R.P.; C arrit, B.; C hen , S.; K ucherlapati, R.; M cM orris , F.A.; R icau n , F.; T an, Y.H.; T ischfield , J.A. and R uddle , F.H.: Chromosome assignments of genes in man using mouse-human somatic cell hybrids: cytoplasmic isocitrate dehydrogenase and malate dehydrogenase to chromosome 2. Am. J. hum. Genet. (1974, in press). 11 T an, Y.H.; C reagan, R.P. and R uddle , F.H.: The somatic cell genetics of human interferon: assignment of human interferon loci to chromosomes 2 and 5. Proc. natn. Acad. Sci. USA 71: 2251-2255 (1974).
