39
(4) It should be emphasised that aspirin is the drug of first choice, taking precedence over all other N.S.A.I.D.S, the very plethora of which points to their individual inadequacies. Department of Medicine (Immunology), Stanford University Medical Center, Stanford, California 94305, U.S.A.
ANDREI CALIN.
LOCALISATION OF HUMAN GENE FOR GALACTOSE-1-PHOSPHATE-URIDYLTRANSFERASE SIR,-One of us has reported evidence for the assignment of the human gene for galactose-1-phosphate-uridyltransferase (transferase) to chromosome 3.1 Mouse-human hybrid clones were used to demonstrate this syntenic relationship, and both electrophoretic and immunological criteria were used to distinguish mouse and human enzymes. This conflicts with the view of Sun et al.,2 who have assigned the human gene for transferase to chromosome 2, using hamster-human hybrids. One of us has described a patient with multiple congenital anomalies who carries one recombinant chromosome 3 inherited from his mother, who carries a pericentric inversion chromosome 3: inv (3) (p25q21).3 We report here preliminary evidence, based on quantitative redblood-cell (R.B.c.)-transferase assays on this patient and his parents, which supports the assignment of human R.B.C.
GALACTOSE-1-PHOSPHATE-URIDYLTRANSFERASE ACTIVITIES OF THE CHROMOSOME-3-VARIANT FAMILY
The ratios obtained on the patient’s parents (2-23 and are within the predicted normal range (1-40-2-24) calculated from the mean ±2 S.D. of a random sample of 1700 adults. The ratios presented for the patient represent four separate assays of the same blood-sample and suggest the expression of 2.51 to 3.19 normal alleles. The controls for the patient and his parents were transported and assayed under identical conditions, and R.B.c. galactokinase assays were all normal. Since the frequency of individuals with R.B.C. transferase activities consistently greater than 8-0 in a population survey of 1700 was 0’0059,4 we cannot rule out the possibility that the elevated activity in this patient is due to a variant of human transferase, such as the L.A. variant.5 However, we feel that the more likely explanation is that three normal transferase alleles are expressed, which confirms the previous assignment of this gene to chromosome 3 by a completely different approach and localises the gene to the segment 3q21→qter.
2-21)
This work was aided by a Basil O’Connor starter research grant from the National Foundation-March of Dimes.
Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada.
P. W. ALLERDICE.
College of Medicine, University of South Florida, Tampa, Florida, 33620, U.S.A.
T. A. TEDESCO.
HYPOPHOSPHATÆMIA IN REYE’S SYNDROME SIR,—The observations of Dr Cooperstock and his associates (June 7, p. 1272) confirm our own, reported in October, 1974,6describing hypophosphatæmia in Reye’s syndrome. In our patients, mean serum-inorganic-
. !J.mol substrate converted per hour per ml. R.B.C. t Individual transferase activity/mean transferase activity of obligate heterozygotes (parents of galactosmmics).
transferase to chromosome 3 and further localises the gene to the region q21-qter on the long arm. Quantitative assay of R.B.C. transferase activity easily distinguishes galactosaemic patients, their parents, and normal individuals who respectively express 0, 1, and 2 normal allele doses of enzyme activity. It follows that R.B.C. transferase activity from an individual trisomic for the portion of the chromosome that contains the transferase gene should produce transferase activity consistent with the expression of the 3 alleles. The table shows the results of the R.B.C. transferase assays on the patient (case 1, Allderdice et al.3), who is monosomic for the segment p25--pter and trisomic for the segment q21→qter of chromosome 3, and his parents, one of whom carries an inv (3) (p25q21). The ratio of individual transferase activity to the mean transferase activity of obligate heterozygotes presumably is a measure of the number of alleles producing normal enzyme.
0
24
36
48
60
HOURS
Serum-inorganic-phosphorus values in 2 non-survivors and 6 survivors. At no point were the differences statistically significant.
phosphorus (Pi) before the start of treatment was significantly less than that of age-matched controls and decreased further after the initiation of glucose infusion (see accompanying figure). In 4 of 8 children studied, levels below 1.0 mg. per 100 ml. were recorded. Erythrocyte 2,3 diphosphoglycerate and adenosine triphosphate values were
normal
at
that time.
Tedesco, T. A., Miller, K. L., Rawnsley, B. E., Memmutti, M. T., Spielman, R. S., Mellman, W. J. Unpublished. 5. Ng, W. G., Bergren, W. R., Donnell, G. N. Ann. hum. Genet. 1973, 37, 1. 6. Keating, J. P., Karl, I. E., DeVivo, D. C., Haymond, M. W. in Reye’s Syndrome (edited by J. D. Pollack). New York, 1975. 4.
Tedesco, T. A., Diamond, R., Orwiszewski, K. G., Boedecker, H. J., Croce, C. M. Proc. natn. Acad. Sci. U.S.A. 1974, 71, 3483. 2. Sun, N. C., Chang, C. C., Chu, E. H. Y. ibid. p. 404. 3. Allderdice, P. W., Browne, N., Murphy, D. P. Am. J. hum. Genet. (in the press). 1.
12
(4) It should be emphasised that aspirin is the drug of first choice, taking precedence over all other N.S.A.I.D.S, the very plethora of which points to their individual inadequacies. Department of Medicine (Immunology), Stanford University Medical Center, Stanford, California 94305, U.S.A.
ANDREI CALIN.
LOCALISATION OF HUMAN GENE FOR GALACTOSE-1-PHOSPHATE-URIDYLTRANSFERASE SIR,-One of us has reported evidence for the assignment of the human gene for galactose-1-phosphate-uridyltransferase (transferase) to chromosome 3.1 Mouse-human hybrid clones were used to demonstrate this syntenic relationship, and both electrophoretic and immunological criteria were used to distinguish mouse and human enzymes. This conflicts with the view of Sun et al.,2 who have assigned the human gene for transferase to chromosome 2, using hamster-human hybrids. One of us has described a patient with multiple congenital anomalies who carries one recombinant chromosome 3 inherited from his mother, who carries a pericentric inversion chromosome 3: inv (3) (p25q21).3 We report here preliminary evidence, based on quantitative redblood-cell (R.B.c.)-transferase assays on this patient and his parents, which supports the assignment of human R.B.C.
GALACTOSE-1-PHOSPHATE-URIDYLTRANSFERASE ACTIVITIES OF THE CHROMOSOME-3-VARIANT FAMILY
The ratios obtained on the patient’s parents (2-23 and are within the predicted normal range (1-40-2-24) calculated from the mean ±2 S.D. of a random sample of 1700 adults. The ratios presented for the patient represent four separate assays of the same blood-sample and suggest the expression of 2.51 to 3.19 normal alleles. The controls for the patient and his parents were transported and assayed under identical conditions, and R.B.c. galactokinase assays were all normal. Since the frequency of individuals with R.B.C. transferase activities consistently greater than 8-0 in a population survey of 1700 was 0’0059,4 we cannot rule out the possibility that the elevated activity in this patient is due to a variant of human transferase, such as the L.A. variant.5 However, we feel that the more likely explanation is that three normal transferase alleles are expressed, which confirms the previous assignment of this gene to chromosome 3 by a completely different approach and localises the gene to the segment 3q21→qter.
2-21)
This work was aided by a Basil O’Connor starter research grant from the National Foundation-March of Dimes.
Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada.
P. W. ALLERDICE.
College of Medicine, University of South Florida, Tampa, Florida, 33620, U.S.A.
T. A. TEDESCO.
HYPOPHOSPHATÆMIA IN REYE’S SYNDROME SIR,—The observations of Dr Cooperstock and his associates (June 7, p. 1272) confirm our own, reported in October, 1974,6describing hypophosphatæmia in Reye’s syndrome. In our patients, mean serum-inorganic-
. !J.mol substrate converted per hour per ml. R.B.C. t Individual transferase activity/mean transferase activity of obligate heterozygotes (parents of galactosmmics).
transferase to chromosome 3 and further localises the gene to the region q21-qter on the long arm. Quantitative assay of R.B.C. transferase activity easily distinguishes galactosaemic patients, their parents, and normal individuals who respectively express 0, 1, and 2 normal allele doses of enzyme activity. It follows that R.B.C. transferase activity from an individual trisomic for the portion of the chromosome that contains the transferase gene should produce transferase activity consistent with the expression of the 3 alleles. The table shows the results of the R.B.C. transferase assays on the patient (case 1, Allderdice et al.3), who is monosomic for the segment p25--pter and trisomic for the segment q21→qter of chromosome 3, and his parents, one of whom carries an inv (3) (p25q21). The ratio of individual transferase activity to the mean transferase activity of obligate heterozygotes presumably is a measure of the number of alleles producing normal enzyme.
0
24
36
48
60
HOURS
Serum-inorganic-phosphorus values in 2 non-survivors and 6 survivors. At no point were the differences statistically significant.
phosphorus (Pi) before the start of treatment was significantly less than that of age-matched controls and decreased further after the initiation of glucose infusion (see accompanying figure). In 4 of 8 children studied, levels below 1.0 mg. per 100 ml. were recorded. Erythrocyte 2,3 diphosphoglycerate and adenosine triphosphate values were
normal
at
that time.
Tedesco, T. A., Miller, K. L., Rawnsley, B. E., Memmutti, M. T., Spielman, R. S., Mellman, W. J. Unpublished. 5. Ng, W. G., Bergren, W. R., Donnell, G. N. Ann. hum. Genet. 1973, 37, 1. 6. Keating, J. P., Karl, I. E., DeVivo, D. C., Haymond, M. W. in Reye’s Syndrome (edited by J. D. Pollack). New York, 1975. 4.
Tedesco, T. A., Diamond, R., Orwiszewski, K. G., Boedecker, H. J., Croce, C. M. Proc. natn. Acad. Sci. U.S.A. 1974, 71, 3483. 2. Sun, N. C., Chang, C. C., Chu, E. H. Y. ibid. p. 404. 3. Allderdice, P. W., Browne, N., Murphy, D. P. Am. J. hum. Genet. (in the press). 1.
12
