Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1992 Dec;51(6):1251–1264.

Analysis of chromosome 21 yeast artificial chromosome (YAC) clones.

F Tassone 1, S Cheng 1, K Gardiner 1
PMCID: PMC1682922  PMID: 1463009

Abstract

Chromosome 21 contains genes relevant to several important diseases. Yeast artificial chromosome (YAC) clones, because they span > 100 kbp, will provide attractive material for initiating searches for such genes. Twenty-two YAC clones, each of which maps to a region of potential relevance either to aspects of the Down syndrome phenotype or to one of the other chromosome 21-associated genetic diseases, have been analyzed in detail. Clones total approximately 6,000 kb and derive from all parts of the long arm. Rare restriction-site maps have been constructed for each clone and have been used to determine regional variations in clonability, methylation frequency, CpG island density, and CpG island frequency versus gene density. This information will be useful for the isolation and mapping of new genes to chromosome 21 and for walking in YAC libraries.

Full text

PDF
1251

Images in this article

1255Figure 2
on p.1255
1255Figure 1
on p.1255

Selected References

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

  1. Berdichevskii F. B., Chumakov I. M., Kiselev L. L. Rasshifrovka pervichnoi struktury uchastka son3 genoma cheloveka: identifikatsiia novogo belka, imeiushchego neobychnuiu strukturu i gomologiiu s DNK-sviazyvaiushchimi belkami. Mol Biol (Mosk) 1988 May-Jun;22(3):794–801. [PubMed] [Google Scholar]
  2. Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
  3. Brahe C., Tassone F., Millington-Ward A., Serra A., Gardiner K. Potential gene sequence isolation and regional mapping in human chromosome 21. Am J Med Genet Suppl. 1990;7:120–124. doi: 10.1002/ajmg.1320370724. [DOI] [PubMed] [Google Scholar]
  4. Brownstein B. H., Silverman G. A., Little R. D., Burke D. T., Korsmeyer S. J., Schlessinger D., Olson M. V. Isolation of single-copy human genes from a library of yeast artificial chromosome clones. Science. 1989 Jun 16;244(4910):1348–1351. doi: 10.1126/science.2544027. [DOI] [PubMed] [Google Scholar]
  5. Burke D. T., Carle G. F., Olson M. V. Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science. 1987 May 15;236(4803):806–812. doi: 10.1126/science.3033825. [DOI] [PubMed] [Google Scholar]
  6. Burmeister M., Kim S., Price E. R., de Lange T., Tantravahi U., Myers R. M., Cox D. R. A map of the distal region of the long arm of human chromosome 21 constructed by radiation hybrid mapping and pulsed-field gel electrophoresis. Genomics. 1991 Jan;9(1):19–30. doi: 10.1016/0888-7543(91)90216-2. [DOI] [PubMed] [Google Scholar]
  7. Butler R., Ogilvie D. J., Elvin P., Riley J. H., Finniear R. S., Slynn G., Morten J. E., Markham A. F., Anand R. Walking, cloning, and mapping with yeast artificial chromosomes: a contig encompassing D21S13 and D21S16. Genomics. 1992 Jan;12(1):42–51. doi: 10.1016/0888-7543(92)90404-g. [DOI] [PubMed] [Google Scholar]
  8. Cox D. R., Burmeister M., Price E. R., Kim S., Myers R. M. Radiation hybrid mapping: a somatic cell genetic method for constructing high-resolution maps of mammalian chromosomes. Science. 1990 Oct 12;250(4978):245–250. doi: 10.1126/science.2218528. [DOI] [PubMed] [Google Scholar]
  9. Davidson J. N., Rumsby G., Niswander L. A. Expression of genes on human chromosome 21. Ann N Y Acad Sci. 1985;450:43–54. doi: 10.1111/j.1749-6632.1985.tb21482.x. [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. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  12. Gao J. Z., Erickson P., Patterson D., Jones C., Drabkin H. Isolation and regional mapping of NotI and EagI clones from human chromosome 21. Genomics. 1991 May;10(1):166–172. doi: 10.1016/0888-7543(91)90497-3. [DOI] [PubMed] [Google Scholar]
  13. Gao J., Erickson P., Gardiner K., Le Beau M. M., Diaz M. O., Patterson D., Rowley J. D., Drabkin H. A. Isolation of a yeast artificial chromosome spanning the 8;21 translocation breakpoint t(8;21)(q22;q22.3) in acute myelogenous leukemia. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4882–4886. doi: 10.1073/pnas.88.11.4882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gardiner-Garden M., Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987 Jul 20;196(2):261–282. doi: 10.1016/0022-2836(87)90689-9. [DOI] [PubMed] [Google Scholar]
  15. Gardiner K., Aissani B., Bernardi G. A compositional map of human chromosome 21. EMBO J. 1990 Jun;9(6):1853–1858. doi: 10.1002/j.1460-2075.1990.tb08310.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gardiner K., Horisberger M., Kraus J., Tantravahi U., Korenberg J., Rao V., Reddy S., Patterson D. Analysis of human chromosome 21: correlation of physical and cytogenetic maps; gene and CpG island distributions. EMBO J. 1990 Jan;9(1):25–34. doi: 10.1002/j.1460-2075.1990.tb08076.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gardiner K. Physical mapping of the long arm of chromosome 21. Prog Clin Biol Res. 1990;360:1–14. [PubMed] [Google Scholar]
  18. Gnirke A., Barnes T. S., Patterson D., Schild D., Featherstone T., Olson M. V. Cloning and in vivo expression of the human GART gene using yeast artificial chromosomes. EMBO J. 1991 Jul;10(7):1629–1634. doi: 10.1002/j.1460-2075.1991.tb07685.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Goate A., Chartier-Harlin M. C., Mullan M., Brown J., Crawford F., Fidani L., Giuffra L., Haynes A., Irving N., James L. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 1991 Feb 21;349(6311):704–706. doi: 10.1038/349704a0. [DOI] [PubMed] [Google Scholar]
  20. Green E. D., Olson M. V. Systematic screening of yeast artificial-chromosome libraries by use of the polymerase chain reaction. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1213–1217. doi: 10.1073/pnas.87.3.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Imai T., Olson M. V. Second-generation approach to the construction of yeast artificial-chromosome libraries. Genomics. 1990 Oct;8(2):297–303. doi: 10.1016/0888-7543(90)90285-3. [DOI] [PubMed] [Google Scholar]
  22. Korenberg J. R., Bradley C., Disteche C. M. Down syndrome: molecular mapping of the congenital heart disease and duodenal stenosis. Am J Hum Genet. 1992 Feb;50(2):294–302. [PMC free article] [PubMed] [Google Scholar]
  23. Korenberg J. R., Kawashima H., Pulst S. M., Ikeuchi T., Ogasawara N., Yamamoto K., Schonberg S. A., West R., Allen L., Magenis E. Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype. Am J Hum Genet. 1990 Aug;47(2):236–246. [PMC free article] [PubMed] [Google Scholar]
  24. Lehesjoki A. E., Koskiniemi M., Sistonen P., Miao J., Hästbacka J., Norio R., de la Chapelle A. Localization of a gene for progressive myoclonus epilepsy to chromosome 21q22. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3696–3699. doi: 10.1073/pnas.88.9.3696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lemaire H. G., Salbaum J. M., Multhaup G., Kang J., Bayney R. M., Unterbeck A., Beyreuther K., Müller-Hill B. The PreA4(695) precursor protein of Alzheimer's disease A4 amyloid is encoded by 16 exons. Nucleic Acids Res. 1989 Jan 25;17(2):517–522. doi: 10.1093/nar/17.2.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lutfalla G., Gardiner K., Proudhon D., Vielh E., Uzé G. The structure of the human interferon alpha/beta receptor gene. J Biol Chem. 1992 Feb 5;267(4):2802–2809. [PubMed] [Google Scholar]
  27. McCormick M. K., Schinzel A., Petersen M. B., Stetten G., Driscoll D. J., Cantu E. S., Tranebjaerg L., Mikkelsen M., Watkins P. C., Antonarakis S. E. Molecular genetic approach to the characterization of the "Down syndrome region" of chromosome 21. Genomics. 1989 Aug;5(2):325–331. doi: 10.1016/0888-7543(89)90065-7. [DOI] [PubMed] [Google Scholar]
  28. Mendez M. J., Klapholz S., Brownstein B. H., Gemmill R. M. Rapid screening of a YAC library by pulsed-field gel Southern blot analysis of pooled YAC clones. Genomics. 1991 Jul;10(3):661–665. doi: 10.1016/0888-7543(91)90449-o. [DOI] [PubMed] [Google Scholar]
  29. Miyoshi H., Shimizu K., Kozu T., Maseki N., Kaneko Y., Ohki M. t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10431–10434. doi: 10.1073/pnas.88.23.10431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nelson D. L., Ledbetter S. A., Corbo L., Victoria M. F., Ramírez-Solis R., Webster T. D., Ledbetter D. H., Caskey C. T. Alu polymerase chain reaction: a method for rapid isolation of human-specific sequences from complex DNA sources. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6686–6690. doi: 10.1073/pnas.86.17.6686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Neve R. L., Stewart G. D., Newcomb P., Van Keuren M. L., Patterson D., Drabkin H. A., Kurnit D. M. Human chromosome 21-encoded cDNA clones. Gene. 1986;49(3):361–369. doi: 10.1016/0378-1119(86)90372-0. [DOI] [PubMed] [Google Scholar]
  32. Owen M. J., James L. A., Hardy J. A., Williamson R., Goate A. M. Physical mapping around the Alzheimer disease locus on the proximal long arm of chromosome 21. Am J Hum Genet. 1990 Feb;46(2):316–322. [PMC free article] [PubMed] [Google Scholar]
  33. Patterson D. Report of the Second International Workshop on Human Chromosome 21 mapping. Cytogenet Cell Genet. 1991;57(4):168–174. [PubMed] [Google Scholar]
  34. Rahmani Z., Blouin J. L., Creau-Goldberg N., Watkins P. C., Mattei J. F., Poissonnier M., Prieur M., Chettouh Z., Nicole A., Aurias A. Critical role of the D21S55 region on chromosome 21 in the pathogenesis of Down syndrome. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5958–5962. doi: 10.1073/pnas.86.15.5958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Riley J., Butler R., Ogilvie D., Finniear R., Jenner D., Powell S., Anand R., Smith J. C., Markham A. F. A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones. Nucleic Acids Res. 1990 May 25;18(10):2887–2890. doi: 10.1093/nar/18.10.2887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Salbaum J. M., Weidemann A., Lemaire H. G., Masters C. L., Beyreuther K. The promoter of Alzheimer's disease amyloid A4 precursor gene. EMBO J. 1988 Sep;7(9):2807–2813. doi: 10.1002/j.1460-2075.1988.tb03136.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schellenberg G. D., Anderson L., O'dahl S., Wisjman E. M., Sadovnick A. D., Ball M. J., Larson E. B., Kukull W. A., Martin G. M., Roses A. D. APP717, APP693, and PRIP gene mutations are rare in Alzheimer disease. Am J Hum Genet. 1991 Sep;49(3):511–517. [PMC free article] [PubMed] [Google Scholar]
  38. Siddique T., Figlewicz D. A., Pericak-Vance M. A., Haines J. L., Rouleau G., Jeffers A. J., Sapp P., Hung W. Y., Bebout J., McKenna-Yasek D. Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity. N Engl J Med. 1991 May 16;324(20):1381–1384. doi: 10.1056/NEJM199105163242001. [DOI] [PubMed] [Google Scholar]
  39. St George-Hyslop P. H., Tanzi R. E., Polinsky R. J., Haines J. L., Nee L., Watkins P. C., Myers R. H., Feldman R. G., Pollen D., Drachman D. The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science. 1987 Feb 20;235(4791):885–890. doi: 10.1126/science.2880399. [DOI] [PubMed] [Google Scholar]
  40. Stefani L., Galt J., Palmer A., Affara N., Ferguson-Smith M., Nevin N. C. Expression of chromosome 21 specific sequences in normal and Down's syndrome tissues. Nucleic Acids Res. 1988 Apr 11;16(7):2885–2896. doi: 10.1093/nar/16.7.2885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tanzi R. E., Gusella J. F., Watkins P. C., Bruns G. A., St George-Hyslop P., Van Keuren M. L., Patterson D., Pagan S., Kurnit D. M., Neve R. L. Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science. 1987 Feb 20;235(4791):880–884. doi: 10.1126/science.2949367. [DOI] [PubMed] [Google Scholar]
  42. Trask B., Pinkel D., van den Engh G. The proximity of DNA sequences in interphase cell nuclei is correlated to genomic distance and permits ordering of cosmids spanning 250 kilobase pairs. Genomics. 1989 Nov;5(4):710–717. doi: 10.1016/0888-7543(89)90112-2. [DOI] [PubMed] [Google Scholar]
  43. Van Camp G., Cruts M., Backhovens H., Wehnert A., Van Broeckhoven C. Unique sequence homology in the pericentromeric regions of the long arms of chromosomes 13 and 21. Genomics. 1992 Jan;12(1):158–160. doi: 10.1016/0888-7543(92)90420-w. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES