Mammalian Genome 3: $261-$265, 1992
enome 9 Springer-VerlagNew York Inc. 1992
Mouse Chromosome 18 Muriel T. Davisson* and Kenneth R. Johnson The Jackson Laboratory, Bar Harbor, Maine 04609, USA
Received February 25, 1992
This report includes two major changes in the Chromosome (Chr) 18 map since the 1991 report. First, a 13-locus multipoint linkage map, spanning most of the genetic length of the chromosome, has been completed and provides a framework for high-resolution genetic analysis of this chromosome (Johnson and Davisson 1992). Second, several simple sequence markers with PCR primers have been identified on Chr 18, including markers that detect the known loci Grl-1 (Dietrich et al. in press), Csfmr and Ii (Todd et al. 1991), and Mbp (Hearne et al. 1991; Dietrich et al. in press; Montagutelli et al. 1991). All the loci mapped to date on Chr 18 are listed in Table 1. The loci with PCR primers are indicated by P in the Type column in Table I. Note that not all neighboring genes have been mapped with respect to each other, and many genes are not securely positioned. The cM distances from the centromere given in Table 1 are approximate positions. On the basis of map position and frequency of use, we propose the anchor (or reference) loci designated in Table 1. Mbp is still the most solid anchor locus because virtually every multipoint cross uses it, and it marks the distal end of the chromosome. The order of loci and, in general, the genetic distances among the different multipoint crosses involving different genetic backgrounds do not differ from each other, and the data have been combined to generate the composite map of Chr 18 (Fig. 1). The only exception to date is increased recombination between the Csfmr cluster and Mbp in the cross between C57BL/Ks and M.m. molossinus (Sakai et al. 1991) compared with all the other crosses. In the case where a direct statistical comparison can be made, the re-
*Chair of Committee for Mouse Chromosome 18
combination of 39% for the Csfmr-Mbp interval in the C57BL/Ks x M.m. molossinus cross is significantly greater (• = 8.25, p ~ 0.025) than 25% for the same interval in the C57BL/6J x M. spretus cross of Johnson and Davisson (1992). The data are as yet insufficient, however, to determine the basis for this difference. The loci scored in multipoint crosses are summarized in Fig. 2. The crosses include (C57BL/6J x SPRET/Ei)F 1 females x SPRET/Ei (Johnson and Dav i s s o n 1992), (C57BL/6J x M. spretus)F 1 females x C57BL/6J (Cox et al. 1991), (C3H/HeJ-gld/gld x M. spretus)F 1 females x C3H/HeJ-gld/gld (Oakey et al. 1991), (NFS/N x M.m. musculus Skive)F1 females • Skive (Sikela et al. 1990), (C57BL/Ks-spm/ spm x MOL-MIT)F1 males x C57BL/Ks-spm/spm (ovaries) (Sakai et al 1991), (C57BL/6J x M.m. castaneus)F~ females x F l males (Dietrich et al. in press), (C.D2-r x CLA)F l x C.D2-cmo/cmo (Byrd et al. 1991), and backcrosses and intercrosses among laboratory strains or stocks. SPRET/Ei, MOL-MIT, and CLA are inbred strains of M. spretus, M.m. molossinus, and M.m. domesticus, respectively. C.D2 is a BALB/cAnPt.DBA/2J congenic. The centromeric end of Chr 18 was determined by use of a Robertsonian chromosome, Rb(2.18)6Rma (Lane et al. 1981). We estimated the distance between the centromere and loci on proximal 18 by combining data from crosses with Rb(2.18)6Rma, Rb(7.18)9Lub, or a pericentromeric heterochromatin duplication, Dp(Hcl8), in linkage analysis with the twirler (Tw) locus, taking into account that the Robertsonian chromosomes may inhibit recombination (Beechey and Searle 1979; Bechey et al. 1980; Lane et al. 1981; Lane and Eicher 1985). The five genes Csfmr, Cdx-1, Pdea, Pdgfrb, and Rpsl4 appear to be in a cluster because no recombination has been observed among them. Although this
M.T. D a v i s s o n a n d K . R . J o h n s o n : M o u s e C h r 18
$262 Table 1. Locus list for mouse Chr 18. New Locus Adrb-2 a.z
* *
* * * * * * * * * * * * * * * *
* *
*
bc Camk4 Cdl4 Cdx.l Cello Csfmr DlSLehl DlSt.~h2 DlSMitl DlSMit3 D18Mit4 D18Mit5 DlSMit6 DlSMit7 Dl8Mit8 D18Mit9 DlSMit10 D18Mit12 D18Mit14 D18Mit15 D18Mit16 DlSPasl Egr-I Emv.21 Fech Fgfa Fire-2 Fms Grl-1 li nbp Mtv.2 Mtv-38 P dea Pdgfrb Pep-]
# *
* *
*
* * *
Pray-20 Ptpt Rnrl8 Rp$14 shi spm sy Tpi-lO Tw Zfp-6 Z/p-35 Xmv-22 Xmv-23 Xmv-29
C,-enename adrenergic receptor, beta-2 ataxia bouncy calmodulin kinase IV CD14 antigen caudal type borneo box-1 chronic multifocal osteonayelitis colony stimulating factor 1 receptor (Fms, Fire-2) DNA segment, Chr 18, Lehrach- 1 DNA segment, Chr 18, Lehraeh-2 D N A segment, Chr 18, MIT-1 DNA segment, Chr 18, Mrr-3 D N A segment, Chr 18, MIT-4 DNA segment, Chr 18, MIT-5 DNA segment, Chr 18, MIT-6 DNA segment, Chr 18, Mrr-7 DNA segment, Chr 18, MIT-8 DNA segment, Chr 18, MIT-9 DNA segment, Chr 18, MIT-10 DNA segment, Chr 18, MIT- 12 DNA segment, Chr 18, MIT- 14 DNA segment, Chr 18, M/T-15 D N A segment, Chr 18, MIT- 16 DNA segment, Chr 18, Pasteur Institute- 1 early growth response- 1 endogenous ecotropic MuLV-21 * ferrochelatase fibroblast growth factor, acidic former symbol for Csfmr former symbol for Csfmr glueocorticoid receptor- 1 Ia associated invariam chain myelin basic protein
A M (cM) 2 33 10 25 19 synterdc 2 31 45 1 31 3 42 56 56 56 56 56 51 46 44 22 17 18 17 57 40 2 17 30 40 2 19
T D V V D
1 21 2 35 1 56
B,D,P L,S D,P Ie,S D,V,P I,L,S
mammary tumor virus loctas-2* mammary tumor virus locus-38 cGMP-phosphodiesterase alpha platelex-derived growth factor receptor, beta polypeptid 2 poptidase-1 (ex Dip-2) plucked polytropic murine leukemia vires-20 protein tyrosine phosphatase, T-cell rDNA, Chr 18 ribosomal protein S 14 shiverer, mutation at Mbp sphingomyelhaosis shaker- with-syndactyllsm triosephophate isoinerase related sequence- 10 twirler forr~aer symbol for Egr- 1 zinc finger protein-35 xenotropic murine leukemia virus-22 xenotropic routine leukemia vlrus-23 xeaotrol:ric routine leukemia virus-29
D
D V D,P D D D,P D,P D,P D,P D,P D,P D,P D,P D,P D,P D,P D,P D,P D D D V D
Method H. symbol H. location L,S ADRB2 5q31-q32 L L L,S CAMK4 5q21-q23 S CD14 5q31 L L I,L,P,S C S F I R 5q33 L L L L L,R L L L,R L,R R L,R L,R L,R L,R L L I,L EGRI 5q31 L L FECH 18q21.3 L FGFA 5q31-q33
Tw linked D 48 D 31 D 31 D synte~c B 23 V 48 or 54 D syntenic D 0 D 31 D 56 V 12 V 36 V 5 D 9 V
L L L,S L,S S L L S L L L L L L L
syntenic D 48 D 48 D 46 D
I R R L,R
GRL DHLAG MBP
PDEA PDGFRB PEPA
PTPT RPS14 MBP SMPD1
Reference 5,25,35,47 28,30,31,32 28,30 44 16 13,25 5 4,14,21,23,25,41,46,50,51 6 6 12 12 12 12 12 12 12 12 12 12 12 12 12 21 24,25 49 21 6,25
5q31-q32 5,6,12,17,25,35,41 5q31-q33 5,6,37,38,50,52 18q22-qter " 5,6,8,12,21,22,25,26, 27,34,35,36,41,44,45,46,50 33 45 5q31 -q34 8,25,44 5q33 4,14,25,35,47 I8q23 t8 29,49 19 18 40 48 5q31-q33 25 18q22-qter 1,26,43 11p15 41 28,29,30,43 25 2,3,28,29,30,31,32,33,43 7 I2 12 12
An asterisk in the '~New" column denotes a new locus added to last year's list. h " 1 " in the " A " column-denotes a primary anchor locus; a " 2 " denotes a secondary anchor. In the " M " column, estimated distances from the centromere are listed in cM. In the " T " column, D = DNA (any locus defined by a DNA sequence or clone); P = PCR primers; B = biochemical/protein/ immunological; and V = visible/other phenotype. In the " M e t h o d "
column, I = in situ hybridization; S = somatic cell genetics; R = RI strains; L = linkage analysis by backcross or intercross; C = cytogenetic analysis (translocations, visible deletions, etc.); D = deletion anaylsis (molecular); H = radiation hybrid analysis; and P - physical mapping (PFGE, YACs, etc.). Information on human genes was taken from the Human Genomic Database (GDB).
could be the result of recombination suppression by a small inversion difference between the spretus and laboratory mouse chromosomes, preliminary physical and comparative data suggest at least two of these loci are tightly linked in mouse and human chromosomes. In both species Csfrnr and Pdgfrb have been shown to
be physically linked by pulsed-field analysis (Eccles 1991; Roberts et al. 1988). Several important spontaneous mutations already have been localized to mouse Chr 18, including twirler (Tw), ataxia (ax), sphingomyelinosis (spm), plucked (pk), bouncy (bc), shaker-with-syndactylism (sy), and
M.T. Davisson and K.R. Johnson: Mouse Chr 18
$263 Loci Pgk-lrs5
DlCnrt8 1 - - Pgk-lrs5
A
- D18Lehl
-
Tw
Tpi-lO
2
spm
T50H
35 36
D18Mit12 D18Mitl4
2
B
~__HD18MitI2,D18Mit15 mgl 7-.9, E g r - l ~ -Dl8Mitl4 --Carnk4, Fgfa -'Grl.l -D18Mit10 -pk
25
33
spm
1
ax
Mtv-2(Tw)
30 31
D18Mit15 Camk4
bc
bc
Cdx-i
TSOH Emv-21(pk) 9~Tdx.l, Pdgfrb, Csfm~Pdea, R p s l 4 ~Adrb-2 -li
Csfr~ Pdea
m m
Pdgfrb 3
-sy
sy
iN
Adrb-2
-
Fech,D18Pasl
li
-
D18Leh2
Fech
- Dt8Mit9 D18Mit8, Xmv.29 - Mtv.38, Xrnv.22,X my-23
D18Leh2
51
- D18Mit7
D18Mit8
-Prav-20,(Xmv.29) D18Mitl,3,4,5,6, l]~J2~(=shl) -D18Mit16
Mbp
DtSPasl
- CnlO
-
Cdl4 Pep-I Ptpt Zf_o-35 [B3-CI
Fig. 1. Composite genetic and cytological maps of Chr 18. The G-band designations are based on Evans (1989). Human chromosomes to which homologs map are shown at the left in boxes; more precise human locations are given in Table 1. Translocation breakpoints for T I 8 H , T50H, and T12RI are indicated by arrows; the genetic breakpoint ot T12R1 is not published (Searle 1989). Bars to the left of the banded chromosome indicate in situ hybridization localization of underlined loci.
shiverer (shi) (Table 1). Two additional mutations, chronic multifocal osteomyelitis (cmo; Byrd et al. 1991) and multiple intestinal neoplasia (Min; Moser et al. 1990; A.P. Moser, personal communication) have recently been mapped to Chr I8. The precise location of Min has not yet been published. Resources available for fine structure mapping of Chr 18 are still limited. Few loci have been typed in recombinant inbred (RI) strains as compared with most other chromosomes. The strain distribution patterns for loci typed in RI strains are shown in Table 2.
---F--l
Rps14
cmo
Di8Mit7
[] ~]
i m
Grl-I pt
44 45 46 48
54 [~] 56 57
m
Fgfa
" ~ - TI8H
[ ] 40 42
mW
Tw
[ ] 12
23
rpi-lo
Egr-I
9 10
17 18 19 21
DlSLehl
1
D)8Mit6
i
m m mm mm mmm m mm mmm mmm m nm im~mnlm
References Fig. 2. A matrix of loci mapped in multipoint crosses. The loci are listed in order from centromere (top) to telomere (bottom) on the basis of the composite map in Fig. 1. Filled boxes in each column indicated the loci scored in the cross references at the bottom.
Cytologically and genetically mapped translocation breakpoints can be used to relate the cytological and genetic maps; three locations involving Chr 18 have been described (Searle 1989). Robertsonian chromosomes can be used to isolate individual chromosomes to make chromosome-specific libraries; six are available (Searle 1989). Pericentromeric heterochromatin variants and the nucleolus organizer region can be used as cytological markers for the centromere end of Chr 18 but are present in only a few strains (Davisson 1989). A restriction fragment length variant for the nucleolus organizer region, Rnr18, was reported at the Fourth Mouse Gene Mapping Workshop (Suzuki 1990), but no further information on this has been reported and, to our knowledge, it has not been used in any mapping crosses. Chromosome aberrations and variants known for Chr 18 are listed in Table 3 and illustrated on the maps in Fig. 1. They are described in
$264
M.T. Davisson and K.R. Johnson: Mouse Chr 18
Table 2. RI SDPs for Chr 18 loci. This information was provided by B.A.
Taylor. The BXD appear in Dietrich and co-workers (1992). The letters stand for C57BL/6 (B), DBA/2J (D), AKR/J (A, AK), C57/L (L), BALB/cBy (C), and C3H/HeJ (H).
Acknowledgments. We thank Dr. B.A. Taylor for providing the RI strain distribution patterns and Drs. J.H. Nadeau and D.P. Doolittle for critical review of the report.
BXD 0000000001111111111222222 1234567890123456789012345
References
2222333 6789012
D18Mitl5
D
BD BD DDDBDB BBDBDBBB BBB
D18Mit14
D
BD BD DDDDBB DBDBDBBB BBB
D18MitlO
D
DD DD DDBDDD DBDDDBBB BBB
D18Mit9
D
BD BD BDDDDD DBBBDDDB BBB
Xmv~9 D18MiN
BD D
D18Mit7
B
BD BD BDBBDD DBDBDBDB BBB
DISMiN
B
DD B
BD BD BDBBDD DBDBDDDB BBBBDD BD BD BDBBDD DBDBDDDB BBB
BDBBDD DBBBDBBB BDB
AKXD 0000000001 Illi 11111222222222 1234567890123456789012345678 DAA
AAADAADDADADA AADADADAA
Xmv-29
DDA
AAADADDADAA D DADDDDDDA
Xmv-22 Xmv~3
DAA DAA
DAADADDADAADD DADDDDDDA DAADADDADAADD DADDDDDDA
AKXL 0000011111111112222222222333333333 5678901234567890123456789012345678
Xmv~2
AALLL
LAA LL L L
LA
LL
LL
LALLL
LAL LA L L
LA
LL
AL
CXB 0000000 1234567 B
CBBCBBC
BXH 0000000001111111111 1234567890123456789 Xmv~9
BHH BBHBHBB B
H
detail in Searle (1989) and Davisson (1989) respectively. Probes and clones that detect markers on Chr 18 (Table I) are described in J.T. Eppig's probes and clones list. Somatic cell hybrid R44, held by F.H. Ruddie (Yale University), contains only Chrs 18, 17, and a small piece of 3, and can be used to make Chr 18enriched libraries. A cell line containing Chrs 17 and 3 but lacking Chr 18 can be used in combination with R44 to identify clones that contain Chr 18 DNA sequences. Table 3. Chromosome aberrations and variants for Chr 18.
Symbol Dp(Hel8)
Rb(4.18)3H
T7E2;18B2)50H
Hel8
Rb(6.18)2Dn
T(10B4;18C)181t
Rb(l.18)lORma
Rb(7.I8)7Mpl
T(10D;18D)12R1
Rb(2.18)6Rma
Rb(7.18)gLub
Abbreviations: Dp, duplication; Hc, pericentromeric heterochromatin; Rb, Robertsonian chromosome; and T, reciprocal translocation.
1. Akowitz, A.A., Barbarese, E., Scheld, K., and Carson, J.H.: Structure and expression of myelin basic protein gene sequences in the mid mutant mouse: reiteration and rearrangement of the MBP gene. Genetics 116: 447-464, 1987. 2. Beechey, C.V., Burtenshaw, M.D., Brown, B.B., Evans, E.P., and Searle, A.G.: Chr 18: distance of Tw from centromere. Mouse News Lett 63: 17, 1980. 3. Beechey, C.V. and Searle, A.G.: Centromeric end of Chr 18. Mouse News Lett 61: 40, 1979. 4. Buchberg, A.M., Brownell, E., Nagata, S., Jenkins, N.A., and Copeland, N.G.: A comprehensive genetic map of murine Chromosome 11 reveals extensive linkage conservation between mouse and human. Genetics 122: 153-161, 1989. 5. Byrd, L., Grossmann, M., Potter, M., and Shen-Ong, G.L.C.: Chronic multifocal osteomyelitis, a new recessive mutation on Chromosome 18 of the mouse. Genomics 11: 794-879, 1991. 6. Cox, R.D., Copeland, N.G., Jenkins, N,A., and Lehrach, H.: Interspersed repetitive element polymerase chain reaction product mapping using a mouse interspecific backcross. Genomics 10: 375-384, 1991. 7. Cunliffe, V., Williams, S., and Trowsdale, J.: Genomic analysis of a mouse zinc finger gene, Zfp-35, that is up-regulated during spermatogenesis. Genomics 8: 331-339, 1990. 8. Danciger, M., Kozak, C.A., Li, T., Applebury, M.L., and Farbet, D.B.: Genetic mapping demonstrates that the alpha-subunit of retinal cGMP-phosphodiesterase is not the site of the rd mutation. Exp Eye Res 51: 185-189, 1990. 9. Davisson, M.T.: Centromeric heterochromatin variants. In M.F. Lyon and A.G. Searle (eds.); Genetic Variants and Strains o f the Laboratory Mouse, 2nd edition, pp. 617--618, Oxford University Press, New York, 1989. 10. Davisson, M.T.: Nucleolus organizer regions. In M.F. Lyon and A.G. Searle (eds.); Genetic Variants and Strains o f the Laboratory Mouse, 2nd edn., pp. 618--619, Oxford University Press, New York, 1989. 11. Davisson, M.T., Johnson, K.R., Seldin, J.F., Suzuki, H., and Watanabe, J.: Mouse Chromosome 18. Mammalian Genome 1 (Suppl): 5301-5305, 1991. 12. Dietrich, W., Katz, H., Loncoln, S.E., Shin, H-S., Friedman, J., Dracopoli, N., and Lander, E.S.: A genetic map of the mouse suitable for typing intraspecific crosses., in press, 1992. 13. Duprey P., Chowdhury, K., Dressier, G.R., Bailing, R., Simon, D., Guenet, J-L., and Gruss, P.: A mouse gene homologous to the Drosophila gene caudal is expressed in epithelial cells from the embryonic intestine. Genes Dev 2: 164%1654, 1988. 14. Eccles, M.R.: Genes encoding the platelet-derived growth (PDGF) receptor and colony-stimulating factor 1 (CSF-1) receptor are physically associated in mice as in humans. Gene 108: 285-288, 1991. 15. Evans, E.P.: Standard idiogram. In M.F. Lyon and A.G. Searle (eds.); Genetic Variants and Strains o f the Laboratory Mouse, 2nd edition, pp. 576-578, Oxford University Press, New York, 1989. 16. Ferrero, E., Hsieh, C-L., Francke, U., and Goyert, S.M.: CD14 is a member of the family of leucine-rich proteins and is encoded by a gene syntenic with multiple receptor genes. J Immuno1145: 331-336, 1990. 17. Francke, U. and Gehring, U.: Chromosome assignment of a murine glucocorticoid receptor gene (Grl-l) using intraspecies somatic cell hybrids. Cell 22: 657-664, 1980. 18. Francke, U., Lalley, P.A., Moss, W., Ivy, J., and Minna, J.D.: Gene mapping in Mus musculus by interspecific cell hybridization: assignment of the genes for tripeptidase-1 to Chromosome 10, dipeptidase-2 to Chromosome 18, acid phosphatase-I to Chromosome I2 and adenylate kinase-I to Chromosome 2. Cytogenet Cell Genet 19: 57-84, 1977. 19. Frankel, W.N., Coffin, J.M., Cote, M., Seyfried, T.N., Rise, M., Rajah, T.V., Nelson, F.K., Selsing, E., and Gerstein, R.:
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$265 38. Roach, A., Takahashi, N., Pravtcheva, D., Ruddle, F., and Hood, L.: Chromosomal mapping of mouse myelin basic protein gene and structure and transcription of the partially deleted gene in shiverer mutant mice. Cell 42: 14%155, 1985. 39. Roberts, W.M., Look, A.T., Roussel, M.F., and Sherr, C.J.: Tandem linkage of human CSF-1 receptor (c-fins) and PDGF receptor genes. Cell 55: 655-661, 1988. 40. Sakaguchi, A.Y., Sylvia, V.L., Martinet, L., Lalley, P.A., Shows, T.B., Han, E.S., Smith, E.A., and Ghosh Choudhury, G.: Assignment of tyrosine-specific T-cell phosphatase to conversed syntenic groups on human Chromosome 18 and mouse Chromosome 18. Genomics 12: 151-154, 1992. 41. Sakai, Y., Miyawaki, S., Shimizu, A., Ohno, K., and Watanabe, T.: A molecular genetic linkage map of mouse Chromosome 18, including spin, Grl-l , Fim-2/c-fms, and Mbp. Biochem Genet 29: 103-113, 1991. 42. Searle, A.G.: Chromosome variants. In M.F. Lyon and A.G. Searle (eds.); Genetic Variants and Strains o f the Laboratory Mouse, 2nd edition, pp. 582-616, Oxford University Press, New York, 1989. 43. Sidman, R.L., Conover, C.S., and Carson, J.H.: Shiverer gene maps near the distal end of Chromosome 18 in the house mouse. Cytogenet Cell Genet 39: 241-245, 1985. 44. Sikela, J.M., Adamson, M.C., Wilson-Shaw, D., and Kozak, C.A.: Genetic mapping of the gene for Ca2+/calmodulin dependent protein kinase IV (Camk-4) to mouse Chromosome 18. Genomics 8: 579-582, 1990. 45. Siracusa, L.D., Jenkins, N.A., and Copeland, N.G.: Identification and applications of repetitive probes for gene mapping in the mouse. Genetics 127: 16%179, 1991. 46. Sola, B., Simon, D., Mattei, M-G., Fichelson, S., Bordereaux, D., Tambourin, P.E., Gu6net, J.-L., and Gisselbrecht, S.: Firel, Fim-2/c-fms, and Fire-3, three common integration sites of Friend murine leukemia virus in myeloblastic leukemias, map to mouse chromosomes 13, 18, and 3, respectively. J Virol 62: 3973-3978, 1988. 47. Sundaresan, S. and Francke, U.: Genes for beta>2
enome 9 Springer-VerlagNew York Inc. 1992
Mouse Chromosome 18 Muriel T. Davisson* and Kenneth R. Johnson The Jackson Laboratory, Bar Harbor, Maine 04609, USA
Received February 25, 1992
This report includes two major changes in the Chromosome (Chr) 18 map since the 1991 report. First, a 13-locus multipoint linkage map, spanning most of the genetic length of the chromosome, has been completed and provides a framework for high-resolution genetic analysis of this chromosome (Johnson and Davisson 1992). Second, several simple sequence markers with PCR primers have been identified on Chr 18, including markers that detect the known loci Grl-1 (Dietrich et al. in press), Csfmr and Ii (Todd et al. 1991), and Mbp (Hearne et al. 1991; Dietrich et al. in press; Montagutelli et al. 1991). All the loci mapped to date on Chr 18 are listed in Table 1. The loci with PCR primers are indicated by P in the Type column in Table I. Note that not all neighboring genes have been mapped with respect to each other, and many genes are not securely positioned. The cM distances from the centromere given in Table 1 are approximate positions. On the basis of map position and frequency of use, we propose the anchor (or reference) loci designated in Table 1. Mbp is still the most solid anchor locus because virtually every multipoint cross uses it, and it marks the distal end of the chromosome. The order of loci and, in general, the genetic distances among the different multipoint crosses involving different genetic backgrounds do not differ from each other, and the data have been combined to generate the composite map of Chr 18 (Fig. 1). The only exception to date is increased recombination between the Csfmr cluster and Mbp in the cross between C57BL/Ks and M.m. molossinus (Sakai et al. 1991) compared with all the other crosses. In the case where a direct statistical comparison can be made, the re-
*Chair of Committee for Mouse Chromosome 18
combination of 39% for the Csfmr-Mbp interval in the C57BL/Ks x M.m. molossinus cross is significantly greater (• = 8.25, p ~ 0.025) than 25% for the same interval in the C57BL/6J x M. spretus cross of Johnson and Davisson (1992). The data are as yet insufficient, however, to determine the basis for this difference. The loci scored in multipoint crosses are summarized in Fig. 2. The crosses include (C57BL/6J x SPRET/Ei)F 1 females x SPRET/Ei (Johnson and Dav i s s o n 1992), (C57BL/6J x M. spretus)F 1 females x C57BL/6J (Cox et al. 1991), (C3H/HeJ-gld/gld x M. spretus)F 1 females x C3H/HeJ-gld/gld (Oakey et al. 1991), (NFS/N x M.m. musculus Skive)F1 females • Skive (Sikela et al. 1990), (C57BL/Ks-spm/ spm x MOL-MIT)F1 males x C57BL/Ks-spm/spm (ovaries) (Sakai et al 1991), (C57BL/6J x M.m. castaneus)F~ females x F l males (Dietrich et al. in press), (C.D2-r x CLA)F l x C.D2-cmo/cmo (Byrd et al. 1991), and backcrosses and intercrosses among laboratory strains or stocks. SPRET/Ei, MOL-MIT, and CLA are inbred strains of M. spretus, M.m. molossinus, and M.m. domesticus, respectively. C.D2 is a BALB/cAnPt.DBA/2J congenic. The centromeric end of Chr 18 was determined by use of a Robertsonian chromosome, Rb(2.18)6Rma (Lane et al. 1981). We estimated the distance between the centromere and loci on proximal 18 by combining data from crosses with Rb(2.18)6Rma, Rb(7.18)9Lub, or a pericentromeric heterochromatin duplication, Dp(Hcl8), in linkage analysis with the twirler (Tw) locus, taking into account that the Robertsonian chromosomes may inhibit recombination (Beechey and Searle 1979; Bechey et al. 1980; Lane et al. 1981; Lane and Eicher 1985). The five genes Csfmr, Cdx-1, Pdea, Pdgfrb, and Rpsl4 appear to be in a cluster because no recombination has been observed among them. Although this
M.T. D a v i s s o n a n d K . R . J o h n s o n : M o u s e C h r 18
$262 Table 1. Locus list for mouse Chr 18. New Locus Adrb-2 a.z
* *
* * * * * * * * * * * * * * * *
* *
*
bc Camk4 Cdl4 Cdx.l Cello Csfmr DlSLehl DlSt.~h2 DlSMitl DlSMit3 D18Mit4 D18Mit5 DlSMit6 DlSMit7 Dl8Mit8 D18Mit9 DlSMit10 D18Mit12 D18Mit14 D18Mit15 D18Mit16 DlSPasl Egr-I Emv.21 Fech Fgfa Fire-2 Fms Grl-1 li nbp Mtv.2 Mtv-38 P dea Pdgfrb Pep-]
# *
* *
*
* * *
Pray-20 Ptpt Rnrl8 Rp$14 shi spm sy Tpi-lO Tw Zfp-6 Z/p-35 Xmv-22 Xmv-23 Xmv-29
C,-enename adrenergic receptor, beta-2 ataxia bouncy calmodulin kinase IV CD14 antigen caudal type borneo box-1 chronic multifocal osteonayelitis colony stimulating factor 1 receptor (Fms, Fire-2) DNA segment, Chr 18, Lehrach- 1 DNA segment, Chr 18, Lehraeh-2 D N A segment, Chr 18, MIT-1 DNA segment, Chr 18, Mrr-3 D N A segment, Chr 18, MIT-4 DNA segment, Chr 18, MIT-5 DNA segment, Chr 18, MIT-6 DNA segment, Chr 18, Mrr-7 DNA segment, Chr 18, MIT-8 DNA segment, Chr 18, MIT-9 DNA segment, Chr 18, MIT-10 DNA segment, Chr 18, MIT- 12 DNA segment, Chr 18, MIT- 14 DNA segment, Chr 18, M/T-15 D N A segment, Chr 18, MIT- 16 DNA segment, Chr 18, Pasteur Institute- 1 early growth response- 1 endogenous ecotropic MuLV-21 * ferrochelatase fibroblast growth factor, acidic former symbol for Csfmr former symbol for Csfmr glueocorticoid receptor- 1 Ia associated invariam chain myelin basic protein
A M (cM) 2 33 10 25 19 synterdc 2 31 45 1 31 3 42 56 56 56 56 56 51 46 44 22 17 18 17 57 40 2 17 30 40 2 19
T D V V D
1 21 2 35 1 56
B,D,P L,S D,P Ie,S D,V,P I,L,S
mammary tumor virus loctas-2* mammary tumor virus locus-38 cGMP-phosphodiesterase alpha platelex-derived growth factor receptor, beta polypeptid 2 poptidase-1 (ex Dip-2) plucked polytropic murine leukemia vires-20 protein tyrosine phosphatase, T-cell rDNA, Chr 18 ribosomal protein S 14 shiverer, mutation at Mbp sphingomyelhaosis shaker- with-syndactyllsm triosephophate isoinerase related sequence- 10 twirler forr~aer symbol for Egr- 1 zinc finger protein-35 xenotropic murine leukemia virus-22 xenotropic routine leukemia vlrus-23 xeaotrol:ric routine leukemia virus-29
D
D V D,P D D D,P D,P D,P D,P D,P D,P D,P D,P D,P D,P D,P D,P D,P D D D V D
Method H. symbol H. location L,S ADRB2 5q31-q32 L L L,S CAMK4 5q21-q23 S CD14 5q31 L L I,L,P,S C S F I R 5q33 L L L L L,R L L L,R L,R R L,R L,R L,R L,R L L I,L EGRI 5q31 L L FECH 18q21.3 L FGFA 5q31-q33
Tw linked D 48 D 31 D 31 D synte~c B 23 V 48 or 54 D syntenic D 0 D 31 D 56 V 12 V 36 V 5 D 9 V
L L L,S L,S S L L S L L L L L L L
syntenic D 48 D 48 D 46 D
I R R L,R
GRL DHLAG MBP
PDEA PDGFRB PEPA
PTPT RPS14 MBP SMPD1
Reference 5,25,35,47 28,30,31,32 28,30 44 16 13,25 5 4,14,21,23,25,41,46,50,51 6 6 12 12 12 12 12 12 12 12 12 12 12 12 12 21 24,25 49 21 6,25
5q31-q32 5,6,12,17,25,35,41 5q31-q33 5,6,37,38,50,52 18q22-qter " 5,6,8,12,21,22,25,26, 27,34,35,36,41,44,45,46,50 33 45 5q31 -q34 8,25,44 5q33 4,14,25,35,47 I8q23 t8 29,49 19 18 40 48 5q31-q33 25 18q22-qter 1,26,43 11p15 41 28,29,30,43 25 2,3,28,29,30,31,32,33,43 7 I2 12 12
An asterisk in the '~New" column denotes a new locus added to last year's list. h " 1 " in the " A " column-denotes a primary anchor locus; a " 2 " denotes a secondary anchor. In the " M " column, estimated distances from the centromere are listed in cM. In the " T " column, D = DNA (any locus defined by a DNA sequence or clone); P = PCR primers; B = biochemical/protein/ immunological; and V = visible/other phenotype. In the " M e t h o d "
column, I = in situ hybridization; S = somatic cell genetics; R = RI strains; L = linkage analysis by backcross or intercross; C = cytogenetic analysis (translocations, visible deletions, etc.); D = deletion anaylsis (molecular); H = radiation hybrid analysis; and P - physical mapping (PFGE, YACs, etc.). Information on human genes was taken from the Human Genomic Database (GDB).
could be the result of recombination suppression by a small inversion difference between the spretus and laboratory mouse chromosomes, preliminary physical and comparative data suggest at least two of these loci are tightly linked in mouse and human chromosomes. In both species Csfrnr and Pdgfrb have been shown to
be physically linked by pulsed-field analysis (Eccles 1991; Roberts et al. 1988). Several important spontaneous mutations already have been localized to mouse Chr 18, including twirler (Tw), ataxia (ax), sphingomyelinosis (spm), plucked (pk), bouncy (bc), shaker-with-syndactylism (sy), and
M.T. Davisson and K.R. Johnson: Mouse Chr 18
$263 Loci Pgk-lrs5
DlCnrt8 1 - - Pgk-lrs5
A
- D18Lehl
-
Tw
Tpi-lO
2
spm
T50H
35 36
D18Mit12 D18Mitl4
2
B
~__HD18MitI2,D18Mit15 mgl 7-.9, E g r - l ~ -Dl8Mitl4 --Carnk4, Fgfa -'Grl.l -D18Mit10 -pk
25
33
spm
1
ax
Mtv-2(Tw)
30 31
D18Mit15 Camk4
bc
bc
Cdx-i
TSOH Emv-21(pk) 9~Tdx.l, Pdgfrb, Csfm~Pdea, R p s l 4 ~Adrb-2 -li
Csfr~ Pdea
m m
Pdgfrb 3
-sy
sy
iN
Adrb-2
-
Fech,D18Pasl
li
-
D18Leh2
Fech
- Dt8Mit9 D18Mit8, Xmv.29 - Mtv.38, Xrnv.22,X my-23
D18Leh2
51
- D18Mit7
D18Mit8
-Prav-20,(Xmv.29) D18Mitl,3,4,5,6, l]~J2~(=shl) -D18Mit16
Mbp
DtSPasl
- CnlO
-
Cdl4 Pep-I Ptpt Zf_o-35 [B3-CI
Fig. 1. Composite genetic and cytological maps of Chr 18. The G-band designations are based on Evans (1989). Human chromosomes to which homologs map are shown at the left in boxes; more precise human locations are given in Table 1. Translocation breakpoints for T I 8 H , T50H, and T12RI are indicated by arrows; the genetic breakpoint ot T12R1 is not published (Searle 1989). Bars to the left of the banded chromosome indicate in situ hybridization localization of underlined loci.
shiverer (shi) (Table 1). Two additional mutations, chronic multifocal osteomyelitis (cmo; Byrd et al. 1991) and multiple intestinal neoplasia (Min; Moser et al. 1990; A.P. Moser, personal communication) have recently been mapped to Chr I8. The precise location of Min has not yet been published. Resources available for fine structure mapping of Chr 18 are still limited. Few loci have been typed in recombinant inbred (RI) strains as compared with most other chromosomes. The strain distribution patterns for loci typed in RI strains are shown in Table 2.
---F--l
Rps14
cmo
Di8Mit7
[] ~]
i m
Grl-I pt
44 45 46 48
54 [~] 56 57
m
Fgfa
" ~ - TI8H
[ ] 40 42
mW
Tw
[ ] 12
23
rpi-lo
Egr-I
9 10
17 18 19 21
DlSLehl
1
D)8Mit6
i
m m mm mm mmm m mm mmm mmm m nm im~mnlm
References Fig. 2. A matrix of loci mapped in multipoint crosses. The loci are listed in order from centromere (top) to telomere (bottom) on the basis of the composite map in Fig. 1. Filled boxes in each column indicated the loci scored in the cross references at the bottom.
Cytologically and genetically mapped translocation breakpoints can be used to relate the cytological and genetic maps; three locations involving Chr 18 have been described (Searle 1989). Robertsonian chromosomes can be used to isolate individual chromosomes to make chromosome-specific libraries; six are available (Searle 1989). Pericentromeric heterochromatin variants and the nucleolus organizer region can be used as cytological markers for the centromere end of Chr 18 but are present in only a few strains (Davisson 1989). A restriction fragment length variant for the nucleolus organizer region, Rnr18, was reported at the Fourth Mouse Gene Mapping Workshop (Suzuki 1990), but no further information on this has been reported and, to our knowledge, it has not been used in any mapping crosses. Chromosome aberrations and variants known for Chr 18 are listed in Table 3 and illustrated on the maps in Fig. 1. They are described in
$264
M.T. Davisson and K.R. Johnson: Mouse Chr 18
Table 2. RI SDPs for Chr 18 loci. This information was provided by B.A.
Taylor. The BXD appear in Dietrich and co-workers (1992). The letters stand for C57BL/6 (B), DBA/2J (D), AKR/J (A, AK), C57/L (L), BALB/cBy (C), and C3H/HeJ (H).
Acknowledgments. We thank Dr. B.A. Taylor for providing the RI strain distribution patterns and Drs. J.H. Nadeau and D.P. Doolittle for critical review of the report.
BXD 0000000001111111111222222 1234567890123456789012345
References
2222333 6789012
D18Mitl5
D
BD BD DDDBDB BBDBDBBB BBB
D18Mit14
D
BD BD DDDDBB DBDBDBBB BBB
D18MitlO
D
DD DD DDBDDD DBDDDBBB BBB
D18Mit9
D
BD BD BDDDDD DBBBDDDB BBB
Xmv~9 D18MiN
BD D
D18Mit7
B
BD BD BDBBDD DBDBDBDB BBB
DISMiN
B
DD B
BD BD BDBBDD DBDBDDDB BBBBDD BD BD BDBBDD DBDBDDDB BBB
BDBBDD DBBBDBBB BDB
AKXD 0000000001 Illi 11111222222222 1234567890123456789012345678 DAA
AAADAADDADADA AADADADAA
Xmv-29
DDA
AAADADDADAA D DADDDDDDA
Xmv-22 Xmv~3
DAA DAA
DAADADDADAADD DADDDDDDA DAADADDADAADD DADDDDDDA
AKXL 0000011111111112222222222333333333 5678901234567890123456789012345678
Xmv~2
AALLL
LAA LL L L
LA
LL
LL
LALLL
LAL LA L L
LA
LL
AL
CXB 0000000 1234567 B
CBBCBBC
BXH 0000000001111111111 1234567890123456789 Xmv~9
BHH BBHBHBB B
H
detail in Searle (1989) and Davisson (1989) respectively. Probes and clones that detect markers on Chr 18 (Table I) are described in J.T. Eppig's probes and clones list. Somatic cell hybrid R44, held by F.H. Ruddie (Yale University), contains only Chrs 18, 17, and a small piece of 3, and can be used to make Chr 18enriched libraries. A cell line containing Chrs 17 and 3 but lacking Chr 18 can be used in combination with R44 to identify clones that contain Chr 18 DNA sequences. Table 3. Chromosome aberrations and variants for Chr 18.
Symbol Dp(Hel8)
Rb(4.18)3H
T7E2;18B2)50H
Hel8
Rb(6.18)2Dn
T(10B4;18C)181t
Rb(l.18)lORma
Rb(7.I8)7Mpl
T(10D;18D)12R1
Rb(2.18)6Rma
Rb(7.18)gLub
Abbreviations: Dp, duplication; Hc, pericentromeric heterochromatin; Rb, Robertsonian chromosome; and T, reciprocal translocation.
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