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. 1995 Nov;57(5):1074–1079.

Physical Mapping of the Holoprosencephaly Critical Region in 21q22.3, Exclusion of SIM2 as a Candidate Gene for Holoprosencephaly, and Mapping of SIM2 to a Region of Chromosome 21 Important for Down Syndrome

Maximilian Muenke, Linda J Bone, Heather F Mitchell, Iris Hart, Katy Walton, Karen Hall-Johnson, Elly F Ippel, Jeanne Dietz-Band, Kirsti Kvaløy, Chen-Ming Fan, Marc Tessier-Lavigne, David Patterson
PMCID: PMC1801356  PMID: 7485157

Abstract

We set out to define the holoprosencephaly (HPE) critical region on chromosome 21 and also to determine whether there were human homologues of the Drosophila single-minded (sim) gene that might be involved in HPE. Analysis of somatic cell hybrid clones that contained rearranged chromosomes 21 from HPE patients defined the HPE minimal critical region in 21q22.3 as D21S113 to qter. We used established somatic cell hybrid mapping panels to map SIM2 to chromosome 21 within subbands q22.2-q22.3. Analysis of the HPE patient–derived somatic cell hybrids showed that SIM2 is not deleted in two of three patients and thus is not a likely candidate for HPE1, the HPE gene on chromosome 21. However, SIM2 does map within the Down syndrome critical region and thus is a candidate gene that might contribute to the Down syndrome phenotype.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aronson D. C., Jansweijer M. C., Hoovers J. M., Barth P. G. A male infant with holoprosencephaly, associated with ring chromosome 21. Clin Genet. 1987 Jan;31(1):48–52. doi: 10.1111/j.1399-0004.1987.tb02766.x. [DOI] [PubMed] [Google Scholar]
  2. Chumakov I. M., Le Gall I., Billault A., Ougen P., Soularue P., Guillou S., Rigault P., Bui H., De Tand M. F., Barillot E. Isolation of chromosome 21-specific yeast artificial chromosomes from a total human genome library. Nat Genet. 1992 Jun;1(3):222–225. doi: 10.1038/ng0692-222. [DOI] [PubMed] [Google Scholar]
  3. Chumakov I., Rigault P., Guillou S., Ougen P., Billaut A., Guasconi G., Gervy P., LeGall I., Soularue P., Grinas L. Continuum of overlapping clones spanning the entire human chromosome 21q. Nature. 1992 Oct 1;359(6394):380–387. doi: 10.1038/359380a0. [DOI] [PubMed] [Google Scholar]
  4. Cohen M. M., Jr Perspectives on holoprosencephaly: Part I. Epidemiology, genetics, and syndromology. Teratology. 1989 Sep;40(3):211–235. doi: 10.1002/tera.1420400304. [DOI] [PubMed] [Google Scholar]
  5. Cohen M. M., Jr, Sulik K. K. Perspectives on holoprosencephaly: Part II. Central nervous system, craniofacial anatomy, syndrome commentary, diagnostic approach, and experimental studies. J Craniofac Genet Dev Biol. 1992 Oct-Dec;12(4):196–244. [PubMed] [Google Scholar]
  6. Collins F. S. Positional cloning moves from perditional to traditional. Nat Genet. 1995 Apr;9(4):347–350. doi: 10.1038/ng0495-347. [DOI] [PubMed] [Google Scholar]
  7. Crews S. T., Thomas J. B., Goodman C. S. The Drosophila single-minded gene encodes a nuclear protein with sequence similarity to the per gene product. Cell. 1988 Jan 15;52(1):143–151. doi: 10.1016/0092-8674(88)90538-7. [DOI] [PubMed] [Google Scholar]
  8. Crews S., Franks R., Hu S., Matthews B., Nambu J. Drosophila single-minded gene and the molecular genetics of CNS midline development. J Exp Zool. 1992 Mar 1;261(3):234–244. doi: 10.1002/jez.1402610303. [DOI] [PubMed] [Google Scholar]
  9. Delabar J. M., Créau N., Sinet P. M., Ritter O., Antonarakis S. E., Burmeister M., Chakravarti A., Nizetic D., Ohki M., Patterson D. Report of the Fourth International Workshop on Human Chromosome 21. Genomics. 1993 Dec;18(3):735–745. doi: 10.1016/s0888-7543(05)80390-8. [DOI] [PubMed] [Google Scholar]
  10. Estabrooks L. L., Rao K. W., Donahue R. P., Aylsworth A. S. Holoprosencephaly in an infant with a minute deletion of chromosome 21(q22.3). Am J Med Genet. 1990 Jul;36(3):306–309. doi: 10.1002/ajmg.1320360312. [DOI] [PubMed] [Google Scholar]
  11. Gardiner K., Watkins P., Münke M., Drabkin H., Jones C., Patterson D. Partial physical map of human chromosome 21. Somat Cell Mol Genet. 1988 Nov;14(6):623–637. doi: 10.1007/BF01535316. [DOI] [PubMed] [Google Scholar]
  12. Glaser T., Housman D., Lewis W. H., Gerhard D., Jones C. A fine-structure deletion map of human chromosome 11p: analysis of J1 series hybrids. Somat Cell Mol Genet. 1989 Nov;15(6):477–501. doi: 10.1007/BF01534910. [DOI] [PubMed] [Google Scholar]
  13. Graw S., Davidson J., Gusella J., Watkins P., Tanzi R., Neve R., Patterson D. Irradiation-reduced human chromosome 21 hybrids. Somat Cell Mol Genet. 1988 May;14(3):233–242. doi: 10.1007/BF01534584. [DOI] [PubMed] [Google Scholar]
  14. Gurrieri F., Trask B. J., van den Engh G., Krauss C. M., Schinzel A., Pettenati M. J., Schindler D., Dietz-Band J., Vergnaud G., Scherer S. W. Physical mapping of the holoprosencephaly critical region on chromosome 7q36. Nat Genet. 1993 Mar;3(3):247–251. doi: 10.1038/ng0393-247. [DOI] [PubMed] [Google Scholar]
  15. Human gene mapping 11. London Conference (1991). Eleventh International Workshop on Human Gene Mapping. London, UK, August 18-22, 1991. Cytogenet Cell Genet. 1991;58(3-4):986–2156. doi: 10.1159/000133716. [DOI] [PubMed] [Google Scholar]
  16. Korenberg J. R., Chen X. N., Schipper R., Sun Z., Gonsky R., Gerwehr S., Carpenter N., Daumer C., Dignan P., Disteche C. Down syndrome phenotypes: the consequences of chromosomal imbalance. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4997–5001. doi: 10.1073/pnas.91.11.4997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Langer J. A., Rashidbaigi A., Lai L. W., Patterson D., Jones C. Sublocalization on chromosome 21 of human interferon-alpha receptor gene and the gene for an interferon-gamma response protein. Somat Cell Mol Genet. 1990 May;16(3):231–240. doi: 10.1007/BF01233359. [DOI] [PubMed] [Google Scholar]
  18. Muenke M., Gurrieri F., Bay C., Yi D. H., Collins A. L., Johnson V. P., Hennekam R. C., Schaefer G. B., Weik L., Lubinsky M. S. Linkage of a human brain malformation, familial holoprosencephaly, to chromosome 7 and evidence for genetic heterogeneity. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8102–8106. doi: 10.1073/pnas.91.17.8102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Münke M. Clinical, cytogenetic, and molecular approaches to the genetic heterogeneity of holoprosencephaly. Am J Med Genet. 1989 Oct;34(2):237–245. doi: 10.1002/ajmg.1320340222. [DOI] [PubMed] [Google Scholar]
  20. Nambu J. R., Franks R. G., Hu S., Crews S. T. The single-minded gene of Drosophila is required for the expression of genes important for the development of CNS midline cells. Cell. 1990 Oct 5;63(1):63–75. doi: 10.1016/0092-8674(90)90288-p. [DOI] [PubMed] [Google Scholar]
  21. Nambu J. R., Lewis J. O., Wharton K. A., Jr, Crews S. T. The Drosophila single-minded gene encodes a helix-loop-helix protein that acts as a master regulator of CNS midline development. Cell. 1991 Dec 20;67(6):1157–1167. doi: 10.1016/0092-8674(91)90292-7. [DOI] [PubMed] [Google Scholar]
  22. Overhauser J., Mitchell H. F., Zackai E. H., Tick D. B., Rojas K., Muenke M. Physical mapping of the holoprosencephaly critical region in 18p11.3. Am J Hum Genet. 1995 Nov;57(5):1080–1085. [PMC free article] [PubMed] [Google Scholar]
  23. Peterson A., Patil N., Robbins C., Wang L., Cox D. R., Myers R. M. A transcript map of the Down syndrome critical region on chromosome 21. Hum Mol Genet. 1994 Oct;3(10):1735–1742. doi: 10.1093/hmg/3.10.1735. [DOI] [PubMed] [Google Scholar]
  24. Report and abstracts of the Fifth International Workshop on Human Chromosome 21 Mapping 1994. Tsukuba, Japan, November 9-11, 1994. Cytogenet Cell Genet. 1995;70(3-4):147–182. doi: 10.1159/000134027. [DOI] [PubMed] [Google Scholar]
  25. Schechter I., Conrad D. G., Hart I., Berger R. C., McKenzie T. L., Bleskan J., Patterson D. Localization of the squalene synthase gene (FDFT1) to human chromosome 8p22-p23.1. Genomics. 1994 Mar 1;20(1):116–118. doi: 10.1006/geno.1994.1135. [DOI] [PubMed] [Google Scholar]
  26. Van Keuren M. L., Watkins P. C., Drabkin H. A., Jabs E. W., Gusella J. F., Patterson D. Regional localization of DNA sequences on chromosome 21 using somatic cell hybrids. Am J Hum Genet. 1986 Jun;38(6):793–804. [PMC free article] [PubMed] [Google Scholar]

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