Abstract
In the human paired box-containing (PAX) gene family, only two members, PAX-3 and PAX-6, which are associated with Waardenburg's syndrome and aniridia, respectively have been mapped to human chromosomes. We have now isolated cosmids for six additional human PAX genes (PAX-1,-2,-5,-7,-8,-9) and a polymerase chain reaction fragment for PAX-4. PAX-9 is a novel family member which is closely related in its paired domain to PAX-1. The chromosomal location of all cloned PAX genes was determined by analysis of somatic cell hybrids and (except PAX-4) by fluorescence in situ hybridization to metaphase chromosomes. PAX-1 and PAX-7 map to chromosomal regions containing previously assigned disease loci.
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References
Bopp, D., Burri, M., Baumgartner, S., Frigerio, G. & Noll, M. Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila. Cell 47, 1033–1040 (1986).
Bopp, D., Jamet, E., Baumgartner, S., Burri, M. & Noll, M. Isolation of two tissue-specific Drosophila paired box genes, Pox meso and Pox neuro. EMBO J. 8, 3447–3457 (1989).
Walther, C. et al. Pax: a murine multigene family of paired box-containing genes. Genomics 11, 424–434 (1991).
Gruss, P. & Walther, C. Pax in development. Cell 69, 719–722 (1992).
Treisman, J., Harris, E. & Desplan, C. The paired box encodes a second DNA-binding domain in the Paired homeo domain protein. Genes Dev. 5, 594–604 (1991).
Chalepakis, G. et al. The molecular basis of the undulated/Pax-1 mutation. Cell 66, 873–884 (1991).
Zannini, M., Francis-Lang, H., Plachov, D. & Di Lauro, R. Pax-8, a paired domain-containing protein, binds to a sequence overlapping the recognition site of a homeodomain and activates transcription from two thyroid-specific promoters. Molec. cell. Biol. 12, 4230–4241 (1992).
Barberis, A., Widenhorn, K., Vitelli, L. & Busslinger, M. A novel B-cell lineage-specific transcription factor present at early but not late stages of differentiation. Genes Dev. 4, 849–859 (1990).
Kozmik, Z., Wang, S., Dörfler, P., Adams, B. & Busslinger, M. The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP. Molec. cell. Biol. 12, 2662–2672 (1992).
Adams, B. et al. Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis. Genes Dev. 6, 1589–1607 (1992).
Balling, R., Deutsch, U. & Gruss, P. Undulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of Pax 1. Cell 55, 531–535 (1988).
Epstein, D.J., Vekemans, M. & Gros, P. Splotch (Sp2H), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3. Cell 67, 767–774 (1991).
Hill, R.E. et al. Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature 354, 522–525 (1991).
Foy, C., Newton, V., Wellesley, D., Harris, R. & Read, A.P. Assignment of the locus for Waardenburg syndrome type I to human chromosome 2q37 and possible homology to the Splotch mouse. Am. J. hum. Genet. 46, 1017–1023 (1990).
Glaser, T., Lane, J. & Housman, D. A mouse model of the aniridia-Wilms tumor deletion syndrome. Science 250, 823–827 (1990).
Tassabehji, M. et al. Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. Nature 355, 635–636 (1992).
Baldwin, C.T., Hoth, C.F., Amos, J.A., da-Silva, E.O. & Milunsky, A. An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome. Nature 355, 637–638 (1992).
Morell, R. et al. A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family. Hum. molec. Genet. 1, 243–247 (1992).
Tassabehji, M. et al. Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2. Nature Genet. 3, 26–30 (1993).
Ton, C.C.T. et al. Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell 67, 1059–1074 (1991).
Jordan, T. et al. The human PAX6 gene is mutated in two patients with aniridia. Nature Genet. 1, 328–332 (1992).
Glaser, T., Walton, D.S. & Mans, R.L. Genomic Structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. Nature Genet. 2, 232–239 (1992).
Burri, M., Tromvoukis, Y., Bopp, D., Frigerio, G. & Noll, M. Conservation of the paired domain in metazoans and its structure in three isolated human genes. EMBO J. 8, 1183–1190 (1989).
Tsukamoto, K. et al. Cloning and characterization of the inversion breakpoint at chromosome 2q35 in a patient with Waardenburg syndrome type I. Hum. molec. Genet. 1, 315–317 (1992).
Lichter, P. et al. High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science 247, 64–69 (1990).
Kozmik, Z., Kurzbauer, R., Dörfler, P. & Busslinger, M. Alternative splicing of Pax-8 gene transcripts generates isoforms with distinct transactivation properties and is regulated in early development. EMBO J. (in the press).
Dressler, G.R., Deutsch, U., Chowdhury, K., Nornes, H.O. & Gruss, P. Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system. Development 109, 787–795 (1990).
Martinsson, T., Weith, A., Cziepluch, C. & Schwab, M. Chromosome 1 deletions in human neuroblastomas: generation and fine mapping of microclones from the distal 1p region. Genes Chrom. Cancer 1, 67–78 (1989).
Ellmeier, W. et al. Mutually exclusive expression of a helix-loop-helix gene and N-myc in human neuroblastomas and in normal development. EMBO J. 11, 2563–2571 (1992).
Schnittger, S. et al. PAX1, a member of the paired box-containing class of developmental control genes, is mapped to human chromosome 20p11.2 by in situ hybridization (ISH and FISH). Genomics 14, 740–744 (1992).
Eccles, M.R. et al. Expression of the PAX2 gene in human fetal kidney and Wilms' tumor. Cell Growth Diff. 3, 279–289 (1992).
Nadeau, J.H. et al. Comparative map for mice and humans. Mamm. Genome 3, 480–536 (1992).
Plachov, D. et al. Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland. Development 110, 643–651 (1990).
Jostes, B., Walther, C. & Gruss, P. The murine paired box gene, Pax7, is expressed specifically during the development of the nervous and muscular system. Mech. Dev. 33, 27–37 (1991).
Weith, A. et al. Neuroblastoma consensus deletion maps to 1p36.1–2. Genes Chrom. Cancer 1, 159–166 (1989).
Dracopoli, N.C. et al. Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumor progression. Proc. natn. Acad. Sci. U.S.A. 86, 4614–4618 (1989).
Moley, J.F. et al. Consistent association of 1p loss of heterozygosity with pheochromocytomas from patients with multiple endocrine neoplasia type 2 syndromes. Cancer Res 52, 770–774 (1992).
Harnett, P.R. et al. Loss of allelic heterozygosity on distal chromosome 1p in Merkel cell carcinoma. A marker of neural crest origins? Cancer Genet. Cytogenet. 54, 109–113 (1991).
Vanni, R., Dal, C.P. & Van, D.B.H. Is the chromosome band 1p36 another hot-spot for rearrangements in uterine leiomyoma? Genes Chrom. Cancer 2, 255–256 (1990).
Genuardi, M., Tsihira, H., Anderson, D.E. & Saunders, G.F. Distal deletion of chromosome 1p in ductal carcinoma of the breast. Am. J. hum. Genet. 45, 73–82 (1989).
McKusick, V.A. in Mendelian inheritence in man (Johns Hopkins University Press, Baltimore, 1988).
Schnittger, S., Hofers, C., Heidemann, P., Beermann, F. & Hansmann, I. Molecular and cytogenetic analysis of an interstitial 20p deletion associated with syndromic intrahepatic ductular hypoplasia (Alagille syndrome). Hum. Genet. 83, 239–244 (1989).
Anad, F. et al. Alagille syndrome and deletion of 20p. J. med. Genet. 27, 729–737 (1990).
Zhang, F. et al. Interstitial deletion of the short arm of chromosome 20 in arteriohepatic dysplasia (Alagille syndrome). J. Pediatr. 116, 73–77 (1990).
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Stapleton, P., Weith, A., Urbánek, P. et al. Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9. Nat Genet 3, 292–298 (1993). https://doi.org/10.1038/ng0493-292
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DOI: https://doi.org/10.1038/ng0493-292
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