- Email: [email protected]
The human homolog of the mouse brown gene maps to the short arm of chromosome 9 and extends the known region of homology with mouse chromosome 4
GENOMICS
11,471-473
(19%)
SHORT COMMUNICATION The Human Homolog of the Mouse Brown Gene Maps to the Short Arm of Chromosome 9 and Extends the Known Region of Homology with Mouse Chromosome 4 CATHY ABBOTT, ** ’ IAN J. JAmsoN, t BEN CARRUT,*
AND SUE POVEY*
*Department of Genetics & Biometry, and SMRC Human Biochemical Genetics Unit, University College London, Wolfson House, 4 Stephenson Way, London NW7 ZHE, England; and tMRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 ZXU, Scotland Received
February
7, 1991;
The mouse brown locus encodes a tyrosinase-related protein TRP-1, a putative membrane-bound metalloenzyme (Jackson, 1988; Zdarsky et ai, 1990). TRP-1 shows 40% homology with tyrosinase at the amino acid level (Jackson, 1988). The b locus has a number of mutant alleles that can be either dominant or recessive to wild-type (Black). Recessive alleles (b, bH) give rise to the production of brown or dark brown eumelanin. Mutant brown melanocytes in culture that are infected by a retrovirus carrying a wildtype gene for TRP-1 convert to a dark brown or black color (Bennett et aZ., 1990). This phenotypic rescue helps to demonstrate that the b locus encodes TRP-1. Point mutations have been identified in mutant alleles (Zdarsky et al., 1990; and unpublished data). The brown, or Tyrp, locus maps to mouse chromosome 4 in a region of homology with human chromosome 9. However, the region appears to be somewhat scrambled in terms of gene order with respect to human chromosome 9, with the region of homology with 9p interrupted by a region of homology to 9q. A human correspondence
should
May
20, 1991
cDNA encoding TRP-1 was recently cloned by screening a cDNA library made from human melanoma cells with a mouse TRP-1 cDNA probe (Cohen et aZ., 1990). Human TRP-1 has recently been identified as gp 75, a melanosomal protein against which melanoma patients frequently develop autoantibodies (Vijayasaradhi et al, 1990). We synthesized PCR primers corresponding to sequences in the 3’ untranslated region of the human cDNA to map the human gene by species-specific PCR in human/rodent somatic cell hybrids (Abbott et aZ., 1989, 1990). The PCR was carried out on DNA from human and rodent parent cell lines and somatic cell hybrids using Taq polymerase from Promega under conditions recommended by the manufacturers. Thirty cycles of amplification were carried out; each cycle comprised 15 s at 94”C, 30 s at 55”C, and 60 s at 72°C on a Hybaid Thermal Reactor. A lo-p1 aliquot of the PCR product was removed, run on a 2% agarose gel, and visualized by ethidium bromide staining under uv light. The 25-mers used were 5’-GGATAGTGTGAAGATCTTTGGCATG-3’ and 5’-ACAGTGGCAAACACAGGCAATATCC-3’. PCR of human DNA with the TRPl primers gave a product of the expected size, 439 bp. No product was seen when mouse, rat, or hamster DNA was subjected to the PCR using the primers, demonstrating that the primers are specific for the human homolog of TRPl (Fig. 1). The results of the PCR analysis of DNA from a number of somatic cell hybrids are given in Table 1. The human chromosome complement of the hybrids was assessed by a mixture of isozyme, Southern blot, and PCR analysis, and in most cases also by karyotyping. Some of the hybrids have been regrown and recharacterized since they were first described. The
The mousebrown locusencodesa tyrosinase-related protein, TRP-1. The human homolog of TRP-1 was recently cloned from a melanomacDNA library and sequenced.We have made oligonucleotide primers corresponding to the human TRPl3’ untranslated region and usedthem to map the human TRPl gene by species-specificPCR in human/ rodent somatic cell hybrids. By this means, the human TRPl gene has been mapped to the short arm of chromo801118 9. 8 lS@l Academic praas. Inc.
1 To whom
revised
be addressed. 471
All
Copyright 0 1991 rights of reproduction
OS&l-7543/91$3.00 by Academic Press, Inc. in any form reserved.
472
SHORT
I
TRW1
HU
MO
FIG. 1. brid DNA.
results TRPl hybrids on 9p,
PCR PCR
Ha
IFNCX
I Ra
of TRP-1 of human
COMMUNICATION
1991). This ensured that the degree of sensitivity of detection of the presence of chromosome 9 in the hybrids was equivalent to that of the detection of the presence of the gene for TRP-1; i.e., there were no false results due to isozyme analysis being less sensitive than PCR analysis. The results from the final two hybrids in Table 1 establish that the human TRPl gene maps to the short arm of human chromosome 9. No amplification with TRPl primers is seen in the hybrid 640-63a12 that contains the whole of the long arm of chromosome 9. However, amplification of TRPl was seen in the hybrid 298-16 in which the only part of chromosome 9 present is 9pter+pl3. TRPl must therefore map to this region. The brown locus on mouse chromosome 4 is in a region of syntenic homology with human chromosome 9. However, the published map shows two sections of homology with human chromosome 4, interrupted by a section of homology with 9q. Recent results (J. Friedman, personal communication) now place Orm-1 1 CM distal to Lu. The mapping of TRPl to human chromosome 9p, in combination with the new map position for Orm, gives an uninterrupted
I
i
in human, rodent, and somatic cell hyIFN-ol is shown for the same hybrids.
clearly demonstrate that the human gene for is on chromosome 9. In all cases, DNA from was amplified with PCR primers for IFN-CY, and aldolase B, on 9q (Abbott and Povey,
TABLE Segregation
of TRP
1
in Human/Rodent
Hybrids
Chromosome Hybrid
Ref.
Ty~p
1
2
3
MOG 2C2 MOG 2E5 TWIN 19F9 RVL 13 C4all Taxi 2.6 Cl0 b2 TWINlSDlZ(14) FIR5 SIF4A31 MOG 34A4 CTP34B4 DUR 4.3 SIF15P5 DIS19 DISPO LLA5
(14) (14) (14) (5) (8) (8) (8)
+ + + + + + +
+ + + + p -
+ -
+ + + ++++++++-+++++++--+ + + + * * + + * - + + -
(8) (5)
-
f-++-+-+ + + + . + -
+ + + . + -
+ + . I
+ + * + + *
(8) (8) (9)
+ -
p -
-
. -
41632346 7 9 6
6
Taxi 3 298-16 640-63a12
(14) (14) (14) (14) (14) (1)
(8)
Concordant +/+ -/Discordant +I-/+ Note.
. . -
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
X
9p
9q
+
+
+
+
+
-
-
+
+
+
+
+
+
+
+
+ + -
+ + + + -
+ + + + +
* + + -
-
+ + + -
+ * -
+ + + + +
+ + + -
+ + * -
+ + + + -
+ * _
+ _
+ + + -
+ + * -
+ + + + * +
+ + + + _
+ + + + + + +
+ + + + + + +
+ + + + + +
p + + + .
+ .
-
+ + + + .
+ + + +
+ + + + + + +
+ + .
+ + + + + f + + -
+ p + . +
+ + + + + .
+ + + + + +
+ + + + + + .
+ -
+ + + + +
+ + + + +
+ + + + + .
p + + + p + +
_ -
-
. . -
+ . -
+ . -
+ -
p p
+ + -
+ -
+ -
. . -
+ -
. -
. + -
+ . -
. _
+ _
. _
. . _
. + _
. _
+ _
+
5
4
6
8
7524285563 11 6 8
4
8
4
7
5
5
5
24 10
7
4 6
6 5
4 5
352334320264302213 41534843054828357625555 p, part
of chromosome
present;
. , not tested.
63203
SHORT Mouse Chromosome
REFERENCES
Human Chromosome
4
473
COMMUNICATION
? ABBOTT, C., WEST, L., POVEY, S., JEREMIAH, S., MURAD, Z., DISCIPIO, R., AND FEY, G. (1989). The gene for human complement component C9 mapped to chromosome 5 by polymerase chain reaction. Gerwmics 4: 606-609.
2.
ABBO?T, C., PIAGGIO, G., AMMENDOLA, R., SOLOMON, E., PoVEY, S., GOUNARI, F., DE SIMONE, V., AND CORTESE, R. (1990). Mapping of the gene TCF2 coding for the transcription factor LFB3 to human chromosome 17 by polymerase chain reaction. Genomics 8: 165-167.
3.
ABBOTT, C., AND POVEY, S. (1991). Development of human chromosome-specific PCR primers for characterization of somatic cell hybrids. Genomics 9: 73-77.
4.
BENNETT, D. C., Husim, D., LAIPIS, P. J., JAENISX, R., AND JACKSON, I. J. (1990). Phenotypic rescue of mutant brown melanocytes by a retrovirus carrying a wild-type tyrosinaserelated protein gene. Deuelopment, in press.
5.
CARRITT, B., PARRINGTON, J., WELCH, H., AND POVEY, S. (1982). Diverse origins of multiple ovarian teratomas in a single individual. Proc. Natl. Ad. Sci. USA 79: 7400-7404.
6.
COHEN, T., MULLER, R., TOMITA, Y., AND SHIEIAHARA, S. (1990). Nucleotide sequence of the cDNA encoding human tyrosinase-related protein. Nucleic Acids Res. 18: 2807-2808.
I.
JACKSON, I. J. (1988). A cDNA encoding tyrosinase-related protein maps to the brown locus in mouse. Proc. Natl. Acad. Sci. USA 86: 4392-4396.
8.
JEREMIAH, S., WEST, L. F., DAVIS, M., POVEY, S., CA-, B., AND FEY, G. M. (1988). The assignment of the gene coding for complement C5 to chromosome 9q22-9q33. Ann. Hum. Genet. 52: 111-116.
9.
JONES, C., AND KAO, F. (1984). Regional polyglutamate synthetase gene (FPGS) genet. Cell Genet. 37: 499.
9p22-q32
Ace- I -
LVOrrr-l-
9q34 9q3 I -qte1
b
9pter-p I3
9~22
Ifa, Ifb
FIG. human
1.
2. Map of mouse chromosome homologues of genes flanking
4 showing the broum
map positions locus.
of
conserved synteny for 9q proximal to a conserved syntenic group for 9p. (Fig. 2). The only anomaly is the mapping of Rrm-2-ps-1 (a pseudogene of ribonucleotide reductase) in between Tyrp and Zfu/lfb, for which the human homolog is on chromosome lp. However, this is a pseudogene identified only by cross-hybridization with a human probe and the equivalence of the mouse and human pseudogenes is only speculative. We suggest, in fact, on the basis of our mapping, that the Rrm-2-ps-1 locus is not the mouse homolog for the human chromosome 1 pseudogene and that these pseudogenes were generated independently in mammalian evolution. There is a second conserved synteny of HSA 9p and MMU4 consisting of the genes Ace-1 and Gult, proximal to the 9q homology region. The only gene that appeared to interrupt this conserved synteny was Ahd-1, which was thought to be homologous to ALDHB on HSA19. However, these genes are now known not to be homologous (Searle et al., 1989). It will be of interest to map the human homologs of other mouse genes from this region of chromosome 4 to determine the full extent of the conserved syntenies and to establish whether conservation has occurred right across the centromere of human chromosome 9.
for the use of hybrid
640-63a12.
I.J.J.
folylCyto-
10.
NADEAU, J., BERGER, F., KELLEY, K., PITHA, P., SIDMAN, C., AND WARRALL, N. (1986). Rearrangement of genes located on homologous chromosomal segments in mouse and man: the location of genes for (Y- and &interferon, a, acid glycoprotein1 and -2, and aminolevulinate dehydratase on mouse chromosome 4. Genetics 104: 1239-1255.
11.
SEARLE, A., PETERS, J., LYON, M., HALL, J., EVANS, G., EDWARDS, J., AND BUCKLE, V. (1989). Chromosome maps of man and mouse IV. Ann. Hum. Genet. 63: 89-140.
12.
SOLOMON, E., SWALLOW, D., BURGESS, S., AND EVANS, L. (1979). Assignment of the human cu-glucosidase gene (oGLU) to chromosome 17 using somatic cell hybrids. Ann. Hum. Genet. 42: 273-281.
13.
VLJAYASARADHI, S., BOUCHAF~D, B., AND HOUGHTON, A. (1990). The melanoma antigen GP75 is the human homologue of the mouse b (Brown) locus gene product. J. Exp. Med. 171: 1375-1380.
14.
WONG, Z., WILSON, V., PATEL, I., POVEY, S., AND JEFFREYS, A. (1987). Characterization of a panel of highly variable minisatellites cloned from human DNA. Ann. Hum. Genet. 51: 290-298.
15.
ZDARSKY, E., FAVOR, J., AND JACKSON, I. J. (1990). The molecular basis of brown, an old mouse mutation, and of an induced revertant to wild type. Genetics 126: 443-449.
ACKNOWLEDGMENTS We thank Dr. Carol Jones is a Lister Institute Fellow.
mapping ofthe to 9 cen+q34.
11,471-473
(19%)
SHORT COMMUNICATION The Human Homolog of the Mouse Brown Gene Maps to the Short Arm of Chromosome 9 and Extends the Known Region of Homology with Mouse Chromosome 4 CATHY ABBOTT, ** ’ IAN J. JAmsoN, t BEN CARRUT,*
AND SUE POVEY*
*Department of Genetics & Biometry, and SMRC Human Biochemical Genetics Unit, University College London, Wolfson House, 4 Stephenson Way, London NW7 ZHE, England; and tMRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 ZXU, Scotland Received
February
7, 1991;
The mouse brown locus encodes a tyrosinase-related protein TRP-1, a putative membrane-bound metalloenzyme (Jackson, 1988; Zdarsky et ai, 1990). TRP-1 shows 40% homology with tyrosinase at the amino acid level (Jackson, 1988). The b locus has a number of mutant alleles that can be either dominant or recessive to wild-type (Black). Recessive alleles (b, bH) give rise to the production of brown or dark brown eumelanin. Mutant brown melanocytes in culture that are infected by a retrovirus carrying a wildtype gene for TRP-1 convert to a dark brown or black color (Bennett et aZ., 1990). This phenotypic rescue helps to demonstrate that the b locus encodes TRP-1. Point mutations have been identified in mutant alleles (Zdarsky et al., 1990; and unpublished data). The brown, or Tyrp, locus maps to mouse chromosome 4 in a region of homology with human chromosome 9. However, the region appears to be somewhat scrambled in terms of gene order with respect to human chromosome 9, with the region of homology with 9p interrupted by a region of homology to 9q. A human correspondence
should
May
20, 1991
cDNA encoding TRP-1 was recently cloned by screening a cDNA library made from human melanoma cells with a mouse TRP-1 cDNA probe (Cohen et aZ., 1990). Human TRP-1 has recently been identified as gp 75, a melanosomal protein against which melanoma patients frequently develop autoantibodies (Vijayasaradhi et al, 1990). We synthesized PCR primers corresponding to sequences in the 3’ untranslated region of the human cDNA to map the human gene by species-specific PCR in human/rodent somatic cell hybrids (Abbott et aZ., 1989, 1990). The PCR was carried out on DNA from human and rodent parent cell lines and somatic cell hybrids using Taq polymerase from Promega under conditions recommended by the manufacturers. Thirty cycles of amplification were carried out; each cycle comprised 15 s at 94”C, 30 s at 55”C, and 60 s at 72°C on a Hybaid Thermal Reactor. A lo-p1 aliquot of the PCR product was removed, run on a 2% agarose gel, and visualized by ethidium bromide staining under uv light. The 25-mers used were 5’-GGATAGTGTGAAGATCTTTGGCATG-3’ and 5’-ACAGTGGCAAACACAGGCAATATCC-3’. PCR of human DNA with the TRPl primers gave a product of the expected size, 439 bp. No product was seen when mouse, rat, or hamster DNA was subjected to the PCR using the primers, demonstrating that the primers are specific for the human homolog of TRPl (Fig. 1). The results of the PCR analysis of DNA from a number of somatic cell hybrids are given in Table 1. The human chromosome complement of the hybrids was assessed by a mixture of isozyme, Southern blot, and PCR analysis, and in most cases also by karyotyping. Some of the hybrids have been regrown and recharacterized since they were first described. The
The mousebrown locusencodesa tyrosinase-related protein, TRP-1. The human homolog of TRP-1 was recently cloned from a melanomacDNA library and sequenced.We have made oligonucleotide primers corresponding to the human TRPl3’ untranslated region and usedthem to map the human TRPl gene by species-specificPCR in human/ rodent somatic cell hybrids. By this means, the human TRPl gene has been mapped to the short arm of chromo801118 9. 8 lS@l Academic praas. Inc.
1 To whom
revised
be addressed. 471
All
Copyright 0 1991 rights of reproduction
OS&l-7543/91$3.00 by Academic Press, Inc. in any form reserved.
472
SHORT
I
TRW1
HU
MO
FIG. 1. brid DNA.
results TRPl hybrids on 9p,
PCR PCR
Ha
IFNCX
I Ra
of TRP-1 of human
COMMUNICATION
1991). This ensured that the degree of sensitivity of detection of the presence of chromosome 9 in the hybrids was equivalent to that of the detection of the presence of the gene for TRP-1; i.e., there were no false results due to isozyme analysis being less sensitive than PCR analysis. The results from the final two hybrids in Table 1 establish that the human TRPl gene maps to the short arm of human chromosome 9. No amplification with TRPl primers is seen in the hybrid 640-63a12 that contains the whole of the long arm of chromosome 9. However, amplification of TRPl was seen in the hybrid 298-16 in which the only part of chromosome 9 present is 9pter+pl3. TRPl must therefore map to this region. The brown locus on mouse chromosome 4 is in a region of syntenic homology with human chromosome 9. However, the published map shows two sections of homology with human chromosome 4, interrupted by a section of homology with 9q. Recent results (J. Friedman, personal communication) now place Orm-1 1 CM distal to Lu. The mapping of TRPl to human chromosome 9p, in combination with the new map position for Orm, gives an uninterrupted
I
i
in human, rodent, and somatic cell hyIFN-ol is shown for the same hybrids.
clearly demonstrate that the human gene for is on chromosome 9. In all cases, DNA from was amplified with PCR primers for IFN-CY, and aldolase B, on 9q (Abbott and Povey,
TABLE Segregation
of TRP
1
in Human/Rodent
Hybrids
Chromosome Hybrid
Ref.
Ty~p
1
2
3
MOG 2C2 MOG 2E5 TWIN 19F9 RVL 13 C4all Taxi 2.6 Cl0 b2 TWINlSDlZ(14) FIR5 SIF4A31 MOG 34A4 CTP34B4 DUR 4.3 SIF15P5 DIS19 DISPO LLA5
(14) (14) (14) (5) (8) (8) (8)
+ + + + + + +
+ + + + p -
+ -
+ + + ++++++++-+++++++--+ + + + * * + + * - + + -
(8) (5)
-
f-++-+-+ + + + . + -
+ + + . + -
+ + . I
+ + * + + *
(8) (8) (9)
+ -
p -
-
. -
41632346 7 9 6
6
Taxi 3 298-16 640-63a12
(14) (14) (14) (14) (14) (1)
(8)
Concordant +/+ -/Discordant +I-/+ Note.
. . -
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
X
9p
9q
+
+
+
+
+
-
-
+
+
+
+
+
+
+
+
+ + -
+ + + + -
+ + + + +
* + + -
-
+ + + -
+ * -
+ + + + +
+ + + -
+ + * -
+ + + + -
+ * _
+ _
+ + + -
+ + * -
+ + + + * +
+ + + + _
+ + + + + + +
+ + + + + + +
+ + + + + +
p + + + .
+ .
-
+ + + + .
+ + + +
+ + + + + + +
+ + .
+ + + + + f + + -
+ p + . +
+ + + + + .
+ + + + + +
+ + + + + + .
+ -
+ + + + +
+ + + + +
+ + + + + .
p + + + p + +
_ -
-
. . -
+ . -
+ . -
+ -
p p
+ + -
+ -
+ -
. . -
+ -
. -
. + -
+ . -
. _
+ _
. _
. . _
. + _
. _
+ _
+
5
4
6
8
7524285563 11 6 8
4
8
4
7
5
5
5
24 10
7
4 6
6 5
4 5
352334320264302213 41534843054828357625555 p, part
of chromosome
present;
. , not tested.
63203
SHORT Mouse Chromosome
REFERENCES
Human Chromosome
4
473
COMMUNICATION
? ABBOTT, C., WEST, L., POVEY, S., JEREMIAH, S., MURAD, Z., DISCIPIO, R., AND FEY, G. (1989). The gene for human complement component C9 mapped to chromosome 5 by polymerase chain reaction. Gerwmics 4: 606-609.
2.
ABBO?T, C., PIAGGIO, G., AMMENDOLA, R., SOLOMON, E., PoVEY, S., GOUNARI, F., DE SIMONE, V., AND CORTESE, R. (1990). Mapping of the gene TCF2 coding for the transcription factor LFB3 to human chromosome 17 by polymerase chain reaction. Genomics 8: 165-167.
3.
ABBOTT, C., AND POVEY, S. (1991). Development of human chromosome-specific PCR primers for characterization of somatic cell hybrids. Genomics 9: 73-77.
4.
BENNETT, D. C., Husim, D., LAIPIS, P. J., JAENISX, R., AND JACKSON, I. J. (1990). Phenotypic rescue of mutant brown melanocytes by a retrovirus carrying a wild-type tyrosinaserelated protein gene. Deuelopment, in press.
5.
CARRITT, B., PARRINGTON, J., WELCH, H., AND POVEY, S. (1982). Diverse origins of multiple ovarian teratomas in a single individual. Proc. Natl. Ad. Sci. USA 79: 7400-7404.
6.
COHEN, T., MULLER, R., TOMITA, Y., AND SHIEIAHARA, S. (1990). Nucleotide sequence of the cDNA encoding human tyrosinase-related protein. Nucleic Acids Res. 18: 2807-2808.
I.
JACKSON, I. J. (1988). A cDNA encoding tyrosinase-related protein maps to the brown locus in mouse. Proc. Natl. Acad. Sci. USA 86: 4392-4396.
8.
JEREMIAH, S., WEST, L. F., DAVIS, M., POVEY, S., CA-, B., AND FEY, G. M. (1988). The assignment of the gene coding for complement C5 to chromosome 9q22-9q33. Ann. Hum. Genet. 52: 111-116.
9.
JONES, C., AND KAO, F. (1984). Regional polyglutamate synthetase gene (FPGS) genet. Cell Genet. 37: 499.
9p22-q32
Ace- I -
LVOrrr-l-
9q34 9q3 I -qte1
b
9pter-p I3
9~22
Ifa, Ifb
FIG. human
1.
2. Map of mouse chromosome homologues of genes flanking
4 showing the broum
map positions locus.
of
conserved synteny for 9q proximal to a conserved syntenic group for 9p. (Fig. 2). The only anomaly is the mapping of Rrm-2-ps-1 (a pseudogene of ribonucleotide reductase) in between Tyrp and Zfu/lfb, for which the human homolog is on chromosome lp. However, this is a pseudogene identified only by cross-hybridization with a human probe and the equivalence of the mouse and human pseudogenes is only speculative. We suggest, in fact, on the basis of our mapping, that the Rrm-2-ps-1 locus is not the mouse homolog for the human chromosome 1 pseudogene and that these pseudogenes were generated independently in mammalian evolution. There is a second conserved synteny of HSA 9p and MMU4 consisting of the genes Ace-1 and Gult, proximal to the 9q homology region. The only gene that appeared to interrupt this conserved synteny was Ahd-1, which was thought to be homologous to ALDHB on HSA19. However, these genes are now known not to be homologous (Searle et al., 1989). It will be of interest to map the human homologs of other mouse genes from this region of chromosome 4 to determine the full extent of the conserved syntenies and to establish whether conservation has occurred right across the centromere of human chromosome 9.
for the use of hybrid
640-63a12.
I.J.J.
folylCyto-
10.
NADEAU, J., BERGER, F., KELLEY, K., PITHA, P., SIDMAN, C., AND WARRALL, N. (1986). Rearrangement of genes located on homologous chromosomal segments in mouse and man: the location of genes for (Y- and &interferon, a, acid glycoprotein1 and -2, and aminolevulinate dehydratase on mouse chromosome 4. Genetics 104: 1239-1255.
11.
SEARLE, A., PETERS, J., LYON, M., HALL, J., EVANS, G., EDWARDS, J., AND BUCKLE, V. (1989). Chromosome maps of man and mouse IV. Ann. Hum. Genet. 63: 89-140.
12.
SOLOMON, E., SWALLOW, D., BURGESS, S., AND EVANS, L. (1979). Assignment of the human cu-glucosidase gene (oGLU) to chromosome 17 using somatic cell hybrids. Ann. Hum. Genet. 42: 273-281.
13.
VLJAYASARADHI, S., BOUCHAF~D, B., AND HOUGHTON, A. (1990). The melanoma antigen GP75 is the human homologue of the mouse b (Brown) locus gene product. J. Exp. Med. 171: 1375-1380.
14.
WONG, Z., WILSON, V., PATEL, I., POVEY, S., AND JEFFREYS, A. (1987). Characterization of a panel of highly variable minisatellites cloned from human DNA. Ann. Hum. Genet. 51: 290-298.
15.
ZDARSKY, E., FAVOR, J., AND JACKSON, I. J. (1990). The molecular basis of brown, an old mouse mutation, and of an induced revertant to wild type. Genetics 126: 443-449.
ACKNOWLEDGMENTS We thank Dr. Carol Jones is a Lister Institute Fellow.
mapping ofthe to 9 cen+q34.