Abstract
After the development of efficient methods for the construction of transcription maps of defined genomic regions, the rate-limiting step in the analysis of the coding potentials of these regions is the elucidation of function of the novel genes and the examination of their possible involvement in hereditary diseases localized to the region. This can be greatly facilitated by the detection of sequence homology to a gene of known function. XAP-4 is one of the genes identified in the G6PD region of the human Xq28 by direct cDNA selection. The rapid assembly of this gene and the determination of its function was possible because of its sequence homology with the bovine smg p25A/rab3A GDP dissociation inhibitor (GDI). Sequence comparison with other GDIs in the databases has revealed that XAP-4 belongs to one of at least two distinct classes of mammalian rab GDIs. The rab GDIs, which play an important role in the regulation of cellular transport, are highly evolutionarily conserved, as are several other genes identified in the neighborhood of XAP-4. This genomic region is very gene dense, and all the cDNA clones from the approximately 2.5-kb-long transcript of XAP-4 map to a single 7.5-kb genomic EcoRI fragment. The genomic organization of XAP-4 has been examined to determine the distribution of the exonic sequences within this short segment of genomic DNA. It was found that, similar to several other genes from the region, XAP-4 is split into exons of average size, which are interrupted by very short introns.
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Adams, M.D., Kelley, J.M., Gocayne, J.D., Dubnick, M., Polymeropoulos, M.H., Xiao, H., Merril, C.R., Wu, A., Olde, B., Moreno, R.F. (1991). Complementary DNA sequencing: expressed sequence tags and human genome project. Science 252, 1651–1656.
Adams, M.D., Soares, M.B., Kerlavage, A.R., Fields, C., Venter, J.C. (1993a). Rapid cDNA sequencing (expressed sequence tags) from a directionally cloned human infant brain cDNA library. Nature Genet. 4, 373–380.
Adams, M.D., Kerlavage, A.R., Fields, C., Venter, J.C. (1993b). 3400 new expressed sequence tags identify diversity of transcripts in human brain. Nature Genet. 4, 256–267
Alcalay, M., Toniolo, D. (1988). CpG islands of the X chromosome are gene associated. Nucleic Acids Res. 16, 9527–9543.
Asada, M., Kaibuchi, K., Takai, Y. (1993). EMBL Nucleotide Sequence Database, Acc. No. D13988.
Bhat, K.S. (1992). EMBL Nucleotide Sequence Database, Acc. No. L05086.
Bione, S., Tamanini, F., Maestrini, E., Triboli, C., Poustka, A., Torri, G., Rivella, S., Toniolo, D. (1993). Transcriptional organization of a 450kb region of the human X chromosome in Xq28. Proc. Natl. Acad. Sci. USA 90, 10977–10981.
Boguski, M.S. (1993). GenBank, Acc. No. U00002.
Brown, M.S., Goldstein, J.L. (1993). Mad Bet for Rab. Nature 366, 14–15.
Buckler, A.J., Chang, D.D., Graw, S.L., Brook, D.J., Naber, D.A., Sharp, P.A., Houseman, D.E. (1991). Exon amplification: a strategy to isolate mammalian genes based on RNA splicing. Proc. Natl. Acad. Sci. USA 88, 4005–4009.
Chen, E.Y., Cheng, A., Lee, A., Kuang, W.-J., Hillier, L.D., Green, P., Schlessinger, D., Ciccodicola, A., D'Urso, M. (1991). Sequence of human glucose-6-phosphate dehydrogenase cloned in plasmids and a yeast artificial chromosome. Genomics 10, 792–800.
Coy, J.F., Kioschis, P., Sedlacek, Z., Poustka, A. (1994). Identification of tissue-specific expressed sequences in human band Xq28 using complex pig cDNA probes. Mamm. Genome, in press.
Cremers, F.P.M., van de Pol, D.J.R., van Kerkhoff, L.P.M., Wieringa, B., Ropers, H.-H. (1990) Cloning of a gene that is rearranged in patients with choroideraemia. Nature 347, 674–677.
Cremers, F.P.M., Molloy, C.M., Van de Pol, D.J.R., van den Hurk, J.A.J.M., Bach, I., van Kessel, A.H.M.G., Ropers, H.-H. (1992). An autosomal homologue of the choroideraemia gene colocalises with the Usher syndrome type II locus on the distal part of the chromosome 1q. Hum. Mol. Genet. 1, 71–75.
Devereux, J., Haeberli, P., Smithies, O. (1984). A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 12, 387–395.
Dowdy, S.F., Lai, K.-M., Weissman, B.E., Matsui, Y., Hogan, B.L.M., Stanbridge, E.J. (1991). The isolation and characterisation of a novel cDNA demonstrating an altered mRNA level in nontumorigenic Wilms' microcell hybrid cells. Nucleic Acids Res. 19, 5763–5769.
Eisinger, D.P., Jiang, H.P., Serrero, G. (1993). A novel mouse gene highly conserved throughout evolution: regulation in adipocyte differentiation and in tumorigenic cell lines. Biochem. Biophys. Res. Commun. 196, 1227–1232.
Filippi, M., Triboli, C., Toniolo, D. (1990). Linkage and sequence conservation of the X-linked genes DXS253E (P3) and DXS254E (GdX) in mouse and man. Genomics 7, 453–457.
Fodor, E., Lee, R.T., O'Donnell, J.J. (1991). Analysis of choroideraemia gene. Nature 351, 614.
Fujioka, H., Kikuchi, A., Yoshida, Y., Kuroda, S., Takai, Y. (1990). A small GTP-binding protein (G-protein) recognised by smg p25A GDP dissociation inhibitor (GDI) in human platelet membranes and GDI for this small G-protein in human platelet cytosol. Biochem. Biophys. Res. Commun. 168, 1244–1252.
Garrett, M.D., Kabcenell, A.K., Zahner, J.E., Kaibuchi, K., Sasaki, T., Takai, Y., Cheney, C.M., Novick, P.J. (1993). Interaction of Sec4 with GDI proteins from bovine brain, Drosophila melanogaster and Saccharomyces cerevisiae. FEBS Lett. 331, 233–238.
Hawkins, J.D. (1988). A survey on intron and exon lengths. Nucleic Acids Res. 16, 9893–9908.
Higgins, D.G., Sharp, P.M. (1988). CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene 73, 237–244.
Khan, A.S., Wilcox, A.S., Polymeropoulos, M.H., Hopkins, J.A., Stevens, T.J., Robinson, M., Orpana, A.K., Sikela, J.M., (1993). Single pass sequencing and physical and genetic mapping of human brain cDNAs. Nature Genet 2, 180–185.
Korn, B., Sedlacek, Z., Manca, A., Kioschis, P., Konecki, D., Lehrach, H., Poustka, A. (1992). A strategy for the selection of transcribed sequences in the Xq28 region. Hum. Mol. Genet. 1, 235–242
Kozak, M. (1987). An analysis of 5′ noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 15, 8125–8148.
Leffers, H., Nielsen, M.S., Andersen, A., Honoré, B., Madsen, P., Vanderkerchove, J., Celis, J.E. (1993). Identification of two human rho GDP dissociation inhibitor proteins whose overexpression leads to disruption of the actin cytoskeleton. Exp. Cell Res. 209, 165–174.
Lovett, M., Kere, J., Hinton, L.M. (1991). Direct selection: a method for the isolation of cDNAs encoded by large genomic regions. Proc. Natl. Acad. Sci. USA 88, 9628–9632.
Matsui, Y., Kikuchi, A., Araki, S., Hata, Y., Kondo, J., Teranishi, Y., Takai, Y. (1990). Molecular cloning and characterisation of a novel type of regulatory protein (GDI) for smg p25A, a ras p21-like GTP-binding protein. Mol. Cell. Biol. 10, 4116–4122.
Merry, D.E., Jänne, P.A., Landers, J.E., Lewis, R.A., Nussbaum, R.L. (1992). Isolation of a candidate gene for choroideraemia. Proc. Natl. Acad. Sci. USA 89, 2135–2139.
Nishimura, N. (1993). EMBL Nucleotide Sequence Database, Acc. Nos. X74401, X74402.
Parimoo, S., Patanjali, S.R., Shukla, H., Chaplin, D.D., Weissman, S.M. (1991). cDNA selection: efficient PCR approach for the selection of cDNAs encoded in large chromosomal DNA fragments. Proc. Natl. Acad. Sci. USA 88, 9623–9627.
Pearson, W.R., Lipman, D.J. (1988). Improved tools for biological sequence comparison. Proc. Natl. Acad. Sci. USA 85, 2444–2448.
Persico, M.G., Viglietto, G., Martini, G., Toniolo, D., Paonessa, G., Moscatelli, C., Dono, R., Vulliamy, T., Luzzato, L., D'Urso, M. (1968). Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA clones: primary structure of the protein and unusual 5′ non-coding region. Nucleic Acids Res. 14, 2511–2522.
Sedlacek, Z., Korn, B., Konecki, D.S., Siebenhaar, R., Coy, J.F., Kioschis, P. Poustka, A. (1993a). Construction of a transcription map of a 300kb region around the human G6PD locus by direct cDNA selection. Hum. Mol. Genet. 2, 1865–1869.
Sedlacek, Z., Konecki, D.S., Siebenhaar, R., Kioschis, P., Poustka, A. (1993b). Direct selection of DNA sequences conserved betwen species. Nucleic Acids Res. 21, 3419–3425.
Shapiro, M.B., Senapathy, P. (1987). RNA splice junctions of different classes of eukaryotes: sequence statisties and functional implications in gene expression. Nucleic Acids Res. 15, 7155–7174.
Simons, K., Zerial, M. (1993). Rab proteins and the road maps for intracellular transport. Neuron 11, 789–799.
Toniolo, D., Persico, M., Alcalay, M. (1988). A housekeeping gene on the X chromosome encodes a protein similar to ubiquitin. Proc. Natl. Acad. Sci. USA 85, 851–855.
Uberbacher, E.C., Mural, R.J. (1991). Locating protein-coding regions in human DNA sequences by a multiple sensor-neural network approach. Proc. Natl. Acad. Sci. USA 88, 11261–11265.
Ueda, T., Takeyama, Y., Ohmori, Y., Ohyanagi, H., Saitoh, Y., Takai, Y. (1991). Purification and characterisation from rat liver cytosol of a GDP dissociation inhibitor (GDI) for liver 24KG, a ras p21-like GTP-binding protein, with properties similar to those of smg p25A GDI. Biochemistry 30, 909–917.
Ullrich, O., Stenmark, H., Alexandrov, K., Huber, L.A., Kaibuchi, K., Sasaki, T., Takai, Y., Zerial, M. (1993). Rab GDP dissociation inhibitor as a general regulator for the membrane association of rab proteins. J. Biol. Chem. 268, 18143–18150.
van den Ouweland, A.M.W., Kioschis, P., Verdijk, M., Tamanini, F., Toniolo, D., Poustka, A., van Oost, B.A. (1992). Identification and characterisation of a new gene in the human Xq28 region. Hum. Mol. Genet. 1, 269–273.
Waldherr, M., Ragnini, A., Schweyen, R.J., Boguski, M.S. (1993). MRS6-yeast homologue of the choroideraemia gene. Nature Genet. 3, 193–194.
Yuzo, M., Takuji, S. (1993). EMBL Nucleotide Sequence Database, Acc. No. D25063.
Zahner, J.E., Cheney, C.M. (1993). A drosophila homolog of bovine smg p25A GDP dissociation inhibitor undergoes a shift in isoelectric point in the developmental mutant quartet. Mol. Cell. Biol. 13, 217–227.
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The nucleotide sequence data reported in this paper have been submitted to EMBL database and have been assigned the accession numbers X79353-X79364.
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Sedlacek, Z., Konecki, D.S., Korn, B. et al. Evolutionary conservation and genomic organization of XAP-4, an Xq28 located gene coding for a human rab GDP-dissociation inhibitor (GDI). Mammalian Genome 5, 633–639 (1994). https://doi.org/10.1007/BF00411459
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DOI: https://doi.org/10.1007/BF00411459