Abstract
A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4p16.1 region by using somatic cell hybrids containing specific deletions of human chromosome 4. Linkage data from a single-stranded conformational polymorphism derived from the 3' untranslated region of the H6 cDNA placed this homeobox gene more than 20 centimorgans proximal of the previously mapped HOX7 gene on chromosome 4. Identity comparisons of the H6 homeodomain with previously reported homeodomains reveal the highest identities to be with the Nk class of homeobox genes in Drosophila melanogaster.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bender W., Akam M., Karch F., Beachy P. A., Peifer M., Spierer P., Lewis E. B., Hogness D. S. Molecular Genetics of the Bithorax Complex in Drosophila melanogaster. Science. 1983 Jul 1;221(4605):23–29. doi: 10.1126/science.221.4605.23. [DOI] [PubMed] [Google Scholar]
- Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
- Boncinelli E., Somma R., Acampora D., Pannese M., D'Esposito M., Faiella A., Simeone A. Organization of human homeobox genes. Hum Reprod. 1988 Oct;3(7):880–886. doi: 10.1093/oxfordjournals.humrep.a136802. [DOI] [PubMed] [Google Scholar]
- Buetow K. H., Shiang R., Yang P., Nakamura Y., Lathrop G. M., White R., Wasmuth J. J., Wood S., Berdahl L. D., Leysens N. J. A detailed multipoint map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates. Am J Hum Genet. 1991 May;48(5):911–925. [PMC free article] [PubMed] [Google Scholar]
- Bürglin T. R., Finney M., Coulson A., Ruvkun G. Caenorhabditis elegans has scores of homoeobox-containing genes. Nature. 1989 Sep 21;341(6239):239–243. doi: 10.1038/341239a0. [DOI] [PubMed] [Google Scholar]
- Bürglin T. R., Ruvkun G., Coulson A., Hawkins N. C., McGhee J. D., Schaller D., Wittmann C., Müller F., Waterston R. H. Nematode homeobox cluster. Nature. 1991 Jun 27;351(6329):703–703. doi: 10.1038/351703a0. [DOI] [PubMed] [Google Scholar]
- Capecchi M. R. Altering the genome by homologous recombination. Science. 1989 Jun 16;244(4910):1288–1292. doi: 10.1126/science.2660260. [DOI] [PubMed] [Google Scholar]
- Chisaka O., Capecchi M. R. Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Nature. 1991 Apr 11;350(6318):473–479. doi: 10.1038/350473a0. [DOI] [PubMed] [Google Scholar]
- Chisaka O., Musci T. S., Capecchi M. R. Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox gene Hox-1.6. Nature. 1992 Feb 6;355(6360):516–520. doi: 10.1038/355516a0. [DOI] [PubMed] [Google Scholar]
- Dausset J., Cann H., Cohen D., Lathrop M., Lalouel J. M., White R. Centre d'etude du polymorphisme humain (CEPH): collaborative genetic mapping of the human genome. Genomics. 1990 Mar;6(3):575–577. doi: 10.1016/0888-7543(90)90491-c. [DOI] [PubMed] [Google Scholar]
- Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diederich R. J., Merrill V. K., Pultz M. A., Kaufman T. C. Isolation, structure, and expression of labial, a homeotic gene of the Antennapedia Complex involved in Drosophila head development. Genes Dev. 1989 Mar;3(3):399–414. doi: 10.1101/gad.3.3.399. [DOI] [PubMed] [Google Scholar]
- Duprey P., Chowdhury K., Dressler G. R., Balling R., Simon D., Guenet J. L., Gruss P. A mouse gene homologous to the Drosophila gene caudal is expressed in epithelial cells from the embryonic intestine. Genes Dev. 1988 Dec;2(12A):1647–1654. doi: 10.1101/gad.2.12a.1647. [DOI] [PubMed] [Google Scholar]
- 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. 1991 Nov 15;67(4):767–774. doi: 10.1016/0092-8674(91)90071-6. [DOI] [PubMed] [Google Scholar]
- Fainsod A., Greunbaum Y. A chicken homeo box gene with developmentally regulated expression. FEBS Lett. 1989 Jul 3;250(2):381–385. doi: 10.1016/0014-5793(89)80760-4. [DOI] [PubMed] [Google Scholar]
- Galliot B., Dollé P., Vigneron M., Featherstone M. S., Baron A., Duboule D. The mouse Hox-1.4 gene: primary structure, evidence for promoter activity and expression during development. Development. 1989 Oct;107(2):343–359. doi: 10.1242/dev.107.2.343. [DOI] [PubMed] [Google Scholar]
- Gehring W. J. Homeo boxes in the study of development. Science. 1987 Jun 5;236(4806):1245–1252. doi: 10.1126/science.2884726. [DOI] [PubMed] [Google Scholar]
- Hewitt J. E., Clark L. N., Ivens A., Williamson R. Structure and sequence of the human homeobox gene HOX7. Genomics. 1991 Nov;11(3):670–678. doi: 10.1016/0888-7543(91)90074-o. [DOI] [PubMed] [Google Scholar]
- Hill R. E., Favor J., Hogan B. L., Ton C. C., Saunders G. F., Hanson I. M., Prosser J., Jordan T., Hastie N. D., van Heyningen V. Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature. 1991 Dec 19;354(6354):522–525. doi: 10.1038/354522a0. [DOI] [PubMed] [Google Scholar]
- Hill R. E., Jones P. F., Rees A. R., Sime C. M., Justice M. J., Copeland N. G., Jenkins N. A., Graham E., Davidson D. R. A new family of mouse homeo box-containing genes: molecular structure, chromosomal location, and developmental expression of Hox-7.1. Genes Dev. 1989 Jan;3(1):26–37. doi: 10.1101/gad.3.1.26. [DOI] [PubMed] [Google Scholar]
- Ivens A., Flavin N., Williamson R., Dixon M., Bates G., Buckingham M., Robert B. The human homeobox gene HOX7 maps to chromosome 4p16.1 and may be implicated in Wolf-Hirschhorn syndrome. Hum Genet. 1990 Apr;84(5):473–476. doi: 10.1007/BF00195823. [DOI] [PubMed] [Google Scholar]
- Kim Y., Nirenberg M. Drosophila NK-homeobox genes. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7716–7720. doi: 10.1073/pnas.86.20.7716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ko H. S., Fast P., McBride W., Staudt L. M. A human protein specific for the immunoglobulin octamer DNA motif contains a functional homeobox domain. Cell. 1988 Oct 7;55(1):135–144. doi: 10.1016/0092-8674(88)90016-5. [DOI] [PubMed] [Google Scholar]
- Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laughon A., Scott M. P. Sequence of a Drosophila segmentation gene: protein structure homology with DNA-binding proteins. Nature. 1984 Jul 5;310(5972):25–31. doi: 10.1038/310025a0. [DOI] [PubMed] [Google Scholar]
- MORTON N. E. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318. [PMC free article] [PubMed] [Google Scholar]
- McGinnis W., Levine M. S., Hafen E., Kuroiwa A., Gehring W. J. A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes. 1984 Mar 29-Apr 4Nature. 308(5958):428–433. doi: 10.1038/308428a0. [DOI] [PubMed] [Google Scholar]
- Mihara H., Kaiser E. T. A chemically synthesized Antennapedia homeo domain binds to a specific DNA sequence. Science. 1988 Nov 11;242(4880):925–927. doi: 10.1126/science.2903553. [DOI] [PubMed] [Google Scholar]
- Mills K. A., Buetow K. H., Xu Y., Weber J. L., Altherr M. R., Wasmuth J. J., Murray J. C. Genetic and physical maps of human chromosome 4 based on dinucleotide repeats. Genomics. 1992 Oct;14(2):209–219. doi: 10.1016/s0888-7543(05)80208-3. [DOI] [PubMed] [Google Scholar]
- Monaghan A. P., Davidson D. R., Sime C., Graham E., Baldock R., Bhattacharya S. S., Hill R. E. The Msh-like homeobox genes define domains in the developing vertebrate eye. Development. 1991 Aug;112(4):1053–1061. doi: 10.1242/dev.112.4.1053. [DOI] [PubMed] [Google Scholar]
- Ning Y., Weber J. L., Killary A. M., Ledbetter D. H., Smith J. R., Pereira-Smith O. M. Genetic analysis of indefinite division in human cells: evidence for a cell senescence-related gene(s) on human chromosome 4. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5635–5639. doi: 10.1073/pnas.88.13.5635. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orita M., Iwahana H., Kanazawa H., Hayashi K., Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2766–2770. doi: 10.1073/pnas.86.8.2766. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
- Padanilam B. J., Stadler H. S., Mills K. A., McLeod L. B., Solursh M., Lee B., Ramirez F., Buetow K. H., Murray J. C. Characterization of the human HOX 7 cDNA and identification of polymorphic markers. Hum Mol Genet. 1992 Sep;1(6):407–410. doi: 10.1093/hmg/1.6.407. [DOI] [PubMed] [Google Scholar]
- Regulski M., McGinnis N., Chadwick R., McGinnis W. Developmental and molecular analysis of Deformed; a homeotic gene controlling Drosophila head development. EMBO J. 1987 Mar;6(3):767–777. doi: 10.1002/j.1460-2075.1987.tb04819.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruiz i Altaba A., Melton D. A. Involvement of the Xenopus homeobox gene Xhox3 in pattern formation along the anterior-posterior axis. Cell. 1989 Apr 21;57(2):317–326. doi: 10.1016/0092-8674(89)90969-0. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scott M. P., Tamkun J. W., Hartzell G. W., 3rd The structure and function of the homeodomain. Biochim Biophys Acta. 1989 Jul 28;989(1):25–48. doi: 10.1016/0304-419x(89)90033-4. [DOI] [PubMed] [Google Scholar]
- Scott M. P., Weiner A. J., Hazelrigg T. I., Polisky B. A., Pirrotta V., Scalenghe F., Kaufman T. C. The molecular organization of the Antennapedia locus of Drosophila. Cell. 1983 Dec;35(3 Pt 2):763–776. doi: 10.1016/0092-8674(83)90109-5. [DOI] [PubMed] [Google Scholar]
- Shepherd J. C., McGinnis W., Carrasco A. E., De Robertis E. M., Gehring W. J. Fly and frog homoeo domains show homologies with yeast mating type regulatory proteins. Nature. 1984 Jul 5;310(5972):70–71. doi: 10.1038/310070a0. [DOI] [PubMed] [Google Scholar]
- Singh G., Kaur S., Stock J. L., Jenkins N. A., Gilbert D. J., Copeland N. G., Potter S. S. Identification of 10 murine homeobox genes. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10706–10710. doi: 10.1073/pnas.88.23.10706. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Su M. W., Suzuki H. R., Solursh M., Ramirez F. Progressively restricted expression of a new homeobox-containing gene during Xenopus laevis embryogenesis. Development. 1991 Apr;111(4):1179–1187. doi: 10.1242/dev.111.4.1179. [DOI] [PubMed] [Google Scholar]
- Tassabehji M., Read A. P., Newton V. E., Harris R., Balling R., Gruss P., Strachan T. Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. Nature. 1992 Feb 13;355(6361):635–636. doi: 10.1038/355635a0. [DOI] [PubMed] [Google Scholar]
- Walldorf U., Fleig R., Gehring W. J. Comparison of homeobox-containing genes of the honeybee and Drosophila. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9971–9975. doi: 10.1073/pnas.86.24.9971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wasmuth J. J., Carlock L. R., Smith B., Immken L. L. A cell hybrid and recombinant DNA library that facilitate identification of polymorphic loci in the vicinity of the Huntington disease gene. Am J Hum Genet. 1986 Sep;39(3):397–403. [PMC free article] [PubMed] [Google Scholar]
- Wedeen C. J., Kostriken R. G., Matsumura I., Weisblat D. A. Evidence for a new family of evolutionarily conserved homeobox genes. Nucleic Acids Res. 1990 Apr 11;18(7):1908–1908. doi: 10.1093/nar/18.7.1908. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wharton R. P., Ptashne M. Changing the binding specificity of a repressor by redesigning an alpha-helix. Nature. 1985 Aug 15;316(6029):601–605. doi: 10.1038/316601a0. [DOI] [PubMed] [Google Scholar]
- Wilson M. G., Towner J. W., Coffin G. S., Ebbin A. J., Siris E., Brager P. Genetic and clinical studies in 13 patients with the Wolf-Hirschhorn syndrome [del(4p)]. Hum Genet. 1981;59(4):297–307. doi: 10.1007/BF00295461. [DOI] [PubMed] [Google Scholar]
- Wood W. I., Gitschier J., Lasky L. A., Lawn R. M. Base composition-independent hybridization in tetramethylammonium chloride: a method for oligonucleotide screening of highly complex gene libraries. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1585–1588. doi: 10.1073/pnas.82.6.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]