| First Author | Pilz A | Year | 1996 |
| Journal | Mouse Genome | Volume | 94 |
| Issue | 4 | Pages | 877-9 |
| Mgi Jnum | J:38089 | Mgi Id | MGI:85478 |
| Citation | Pilz A, et al. (1996) High resolution genetic linkage analysis of mouse Chromosome 2 in the region of homology with human Chromosome 9. Mouse Genome 94(4):877-9 |
| abstractText | Full text of Mouse Genome contribution: HIGH RESOLUTION GENETIC LINKAGE ANALYSIS OF MOUSE CHROMOSOME 2 IN THE REGION OF HOMOLOGY WITH HUMAN CHROMOSOME 9. Alison Pilz1, Sue Povey2 and Cathy Abbott3. 1Department of Biology, The Galton Laboratory, University College London, Wolfson House, 4 Stephenson Way, London, NW1 2HE, UK. 2MRC Human Biochemical Genetics Unit, Wolfson House, 4 Stephenson Way, London, NW1 2HE. 3MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. Introduction. The distal long arm of human chromosome 9 (HSA9) is the subject of a number of intensive positional cloning efforts. The genes for tuberous sclerosis 1 (TSC1), torsion dystonia (DYT1), nail patella syndrome (NPS1) and a tumour suppressor gene involved in ovarian cancer all map to the 9q22-9q34 region (reviewed in [1]). In order to investigate genome evolution, we carried out a comparative mapping study involving this area of the human genome and the mouse genome [2]. 26 markers from human chromosome 9 were mapped to the region of conserved synteny with mouse chromosome 2. Since very little recombination was observed in this region, it was not possible to deduce gene order for many of the markers. The aim of the present study was to develop high resolution linkage maps of mouse chromosome 2 using the European Interspecific backcross (EUCIB; [3]) in order to establish whether there has been conservation of gene order between HSA9q and MMU2. If this is found to be so, then the mouse gene map can have a predictive value for the human gene map, and vice-versa. Materials and Methods. Mice: European Interspecific backcross (EUCIB). This backcross was as described in [3]. Inbred C57BL/6 females were mated to Mus spretus males to produce fertile F1 females that were subsequently backcrossed to either C57BL/6 or Mus spretus males. Probes typed by Southern blot analysis. The cloned, RT-PCR derived and PCR derived probes used were as described in [2]. Southern blot analysis was carried out as described in [4]. Results and Discussion. RFLVs between C57BL/6 and Mus spretus were found with each of the probes and are listed in Table 1. 199 D2Mit6 - D2Mit11 recombinants were analysed out of a total of 857 animals. The number of mice carrying recombinant chromosomes, based on minimising the number of double recombinants, are:- D2Mit6 -12- Grin1 -1- C8g -1- Abc2 -1- Ptgds -14- Notch1 -1- Vav2 -1- (Dbh, Surf1, D2H9S10E) -3- D2H9S114E -1- (Rxra, Col5al) -1- Cel -5- Spna2 -3- Assl -1- (D2H9S46E, Abl) -1- Fpgs -1- Eng -1- Akl -2- Pbx3 -1- Grp78 -3- Hc -1- Epb7.2 -3- Gsn -4- Ggtal -137- D2Mit11. The recombination distances +/- standard error obtained (in cM) are shown in Fig. 1. Figure 1 also shows the linkage map for MMU2 in comparison with the consensus gene order for human (taken from [1], [5] and [6]). The conserved segment between MMU2 and HSA9q is inverted relative to the centromere in one species compared to the other. Within the segment the gene order is the same except for 2 small groups of loci, (Col5a1, Rxra, and D2H9S114E; the mouse homologues of COL5Al, RXRA and D9S114E), and (Spna2 and Ass1; the mouse homologues of SPTAN1 and ASS). In mouse Spna2 and Assl map proximal to Abl, and Rxra, Col5al and D2H9S114E map distal to Dbh. These differences between the mouse and human gene maps probably indicate real evolutionary differences. If both maps are an accurate reflection of gene order in the two species, then the simplest explanation of the evolutionary change would be that there have been two inversions (in mouse with respect to human or vice versa) within the syntenic group. One inversion involves the segment of DNA containing the RXRA, COL5A1 and D9S114E genes and the segment containing the DBH, VAV2 and D9S10E genes, and the other inversion involves the segment of DNA containing the SPTAN1 and ASS genes and the segment containing the ABL and D9S46E genes (see Fig. 1). It would be of interest to establish the precise organisation of this region in man and mouse by detailed physical mapping. Projects are underway to clone 9q34, the target area for TSC1, into cosmid contigs prior to gene isolation studies. As nail patella syndrome, idiopathic torsion dystonia, and tuberous sclerosis (NPS1, DYT1 and TSC1) all map to the region of HSA9 where differences in gene order appear to occur, it is not possible to use information from the mouse to predict gene order in man in the region of HSA9 containing these genes. Acknowledgements. We would like to thank the HGMP Resource Centre for DNA from the EUCIB backcross. We are grateful to Drs. J. Mallet, B. Shane, G. Chimini, D. Kwiatkowski, K. Monica, M. Fried, C. Birkenmeier, P. Brett, B. Le Bourdelles, and P. Whiting (Merck, Sharp and Dohme Research Laboratories) for the gift of probes. This work was supported by the MRC Human Genome Mapping Project Comparative Mapping Initiative. References. 1. Pericak-Vance, M.A., Bale, A.E., Haines, J.L., Kwiatkowski, D.J., Pilz, A., Slaugenhaupt, S., White, J.A., Edwards, J.H., Marchuk, D., Olopade, O.I., Attwood, J., and Povey, S. (1995). Ann. Hum. Genet. 59: 347-365. 2. Pilz, A., Woodward, K., Povey, S. and Abbott, C. (1995). Genomics 25: 139-149. 3. European Backcross Collaborative Group (1994). Hum. Mol. Genet. 3: 621-627. 4. Pilz, A., Moseley, H., Peters, J. and Abbott, C. (1992). Genomics 12: 715-719. 5. Woodward, K., Nahmias, J., Hornigold, N., West, L., Pilz, A., Benham, F., Kwiatkowski, D., Wolfe, J., and Povey, S. (1995). Genomics 29: 257-260. 6. Nahmias, J., Hornigold, N., Fitzgibbon, J., Woodward, K., Pilz, A., Griffin, D., Henske, E.P., Nakamura, Y., Graw, S., Florian, F., Benham, F., Povey, S., and Wolfe, J. (1995). Eur. J. Biochem. 3: 65-77. Table 1. RFLVs used for mapping each probe in the backcross. Name: Abelson murine leukemia viral oncogene homologue; Mouse symbol: Abl; Restriction endonuclease used to detect RFLV: BglII; Fragment sizes (kb)**: C57BL/6: 12; Mus spretus: 16. Name: adenylate kinase 1; Mouse symbol: Ak1; Restriction endonuclease used to detect RFLV: BglII; Fragment sizes (kb)**: C57BL/6: 11, 6; Mus spretus: 7.2, 7, 5.8. Name: argininosuccinate synthetase 1; Mouse symbol: Ass1; Restriction endonuclease used to detect RFLV: BglII; Fragment sizes (kb)**: C57BL/6: 11, 10, 7, 6, 2.5, 1.6; Mus spretus: 9, 7, 6, 2.5, 1.6. Name: ATP binding cassette 2; Mouse symbol: Abc2; Restriction endonuclease used to detect RFLV: TaqI; Fragment sizes (kb)**: C57BL/6: 1.3, 1.2; Mus spretus: 1.4, 1.1. Name: carboxyl ester lipase; Mouse symbol: Cel; Restriction endonuclease used to detect RFLV: TaqI; Fragment sizes (kb)**: C57BL/6: 4.3, 1.2; Mus spretus: 7. Name: procollagen typeV alpha1; Mouse symbol: Col5a1; Restriction endonuclease used to detect RFLV: TaqI; Fragment sizes (kb)**: C57BL/6: 13; Mus spretus: 11. Name: haemolytic complement component 5; Mouse symbol: Hc; Restriction endonuclease used to detect RFLV: BglII; Fragment sizes (kb)**: C57BL/6: 11; Mus spretus: 9. Name: complement component 8 gamma polypeptide; Mouse symbol: C8g; Restriction endonuclease used to detect RFLV: BglII; Fragment sizes (kb)**: C57BL/6: 5.4; Mus spretus: 6. Name: D9S10E, mouse homologue; Mouse symbol: D2H9S10E; Restriction endonuclease used to detect RFLV: BamHI; Fragment sizes (kb)**: C57BL/6: 8, 9; Mus spretus: 9.5, 7.5. Name: D9S114E, mouse homologue; Mouse symbol: D2H9S114E; Restriction endonuclease used to detect RFLV: BglII; Fragment sizes (kb)**: C57BL/6: 2.8; Mus spretus: 4. Name: D9S46E, mouse homologue; Mouse symbol: D2H9S46E; Restriction endonuclease used to detect RFLV: BamHI; Fragment sizes (kb)**: C57BL/6: 6; Mus spretus: 4, 2.8. Name: dopamine Beta-hydroxylase; Mouse symbol: Dbh; Restriction endonuclease used to detect RFLV: BglII; Fragment sizes (kb)**: C57BL/6: 3.5; Mus spretus: 4. Name: endoglin; Mouse symbol: Eng; Restriction endonuclease used to detect RFLV: BamHI; Fragment sizes (kb)**: C57BL/6: 4.5, 3.6, 2.8; Mus spretus: 4.5, 3.4, 2.8. Name: erythrocyte membrane protein band 7.2; Mouse symbol: Epb7.2; Restriction endonuclease used to detect RFLV: BglII; Fragment sizes (kb)**: C57BL/6: 9, 5; Mus spretus: 8, 4.5. Name: folylpolyglutamate synthase; Mouse symbol: Fpgs; Restriction endonuclease used to detect RFLV: BglII; Fragment sizes (kb)**: C57BL/6: 5; Mus spretus: 15, 6.5. Name: glycoprotein, alpha-galactosyltransferase 1; Mouse symbol: Ggta1; Restriction endonuclease used to detect RFLV: TaqI; Fragment sizes (kb)**: C57BL/6: 12, 5; Mus spretus: 6.2. Name: gelsolin; Mouse symbol: Gsn; Restriction endonuclease used to detect RFLV: EcoRV; Fragment sizes (kb)**: C57BL/6: 6, 5; Mus spretus: 7.5, 6. Name: 78kDa glucose regulated protein; Mouse symbol: Grp78; Restriction endonuclease used to detect RFLV: TaqI; Fragment sizes (kb)**: C57BL/6: 1.2; Mus spretus: 1.5. Name: N-methyl-D-aspartate glutamate receptor; Mouse symbol: Grin1; Restriction endonuclease used to detect RFLV: TaqI; Fragment sizes (kb)**: C57BL/6: 6, 5.2, 2.8; Mus spretus: 6, 4, 3. Name: translocation-associated Notch (Drosophila) homologue 1; Mouse symbol: Notch1; Restriction endonuclease used to detect RFLV: PstI; Fragment sizes (kb)**: C57BL/6: 3.5, 2.2; Mus spretus: 3.5, 2.5. Name: pre B-cell leukaemia transcription factor 3; Mouse symbol: Pbx3; Restriction endonuclease used to detect RFLV: BglII; Fragment sizes (kb)**: C57BL/6: 16, 7, 6.9, 3; Mus spretus: 12, 6.5. Name: prostaglandin D2 synthase; Mouse symbol: Ptgds; Restriction endonuclease used to detect RFLV: BglII; Fragment sizes (kb)**: C57BL/6: 4.4; Mus spretus: 6. Name: retinoid X receptor alpha subunit; Mouse symbol: Rxra; Restriction endonuclease used to detect RFLV: PstI; Fragment sizes (kb)**: C57BL/6: 3.7, 2; Mus spretus: 4, 2.1. Name: non-erythrocytic alpha-spectrin; Mouse symbol: Spna2; Restriction endonuclease used to detect RFLV: BamHI; Fragment sizes (kb)**: C57BL/6: 6.5, 3.6; Mus spretus: 6.5, 4. Name: surfeit 1; Mouse symbol: Surf1; Restriction endonuclease used to detect RFLV: BamHI; Fragment sizes (kb)**: C57BL/6: 3, 1.3; Mus spretus: 8.5, 1.3. Name: vav 2 oncogene; Mouse symbol: Vav2; Restriction endonuclease used to detect RFLV: TaqI; Fragment sizes (kb)**: C57BL/6: 8.5; Mus spretus: 3. **Restriction fragments followed in the backcross are underlined. Fig. 1. (Legend). The linkage map of MMU2 with recombination frequencies produced in this study (left) compared to the consensus map of human chromosome 9q33-9qter (right; taken from [I], [5], and [6]). The orientation of the human chromosome has been inverted to make comparison with MMU2 easier. |
