Abstract
A map encompassing 300 kilobases (kb) in and around the human alpha-globin gene complex shows features with important implications for understanding the structure and function of the human genome. In contrast to other segments of the mammalian genome that have been analysed by pulsed field gradient electrophoresis (PFGE), this region contains an unusually high density of sites for infrequently cutting restriction enzymes that recognise GC rich motifs including the under-represented CpG doublet. This suggests that the 26 kilobase (kb) stretch of DNA containing the alpha-globin gene family, which is known from sequence analysis to be 60% GC rich, is itself embedded within a region of high GC content. This long-range structure, identified by PFGE, corresponds to a class of GC rich isochores that are thought to represent early replicating DNA present in Giemsa negative chromosomal bands. The identification of such regions by PFGE will be of value in understanding the organisation of human chromosomes and will influence the strategies used to construct a physical map of the genome.
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- Adams R. L., Eason R. Increased G + C content of DNA stabilizes methyl CpG dinucleotides. Nucleic Acids Res. 1984 Jul 25;12(14):5869–5877. doi: 10.1093/nar/12.14.5869. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aota S., Ikemura T. Diversity in G + C content at the third position of codons in vertebrate genes and its cause. Nucleic Acids Res. 1986 Aug 26;14(16):6345–6355. doi: 10.1093/nar/14.16.6345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernardi G., Olofsson B., Filipski J., Zerial M., Salinas J., Cuny G., Meunier-Rotival M., Rodier F. The mosaic genome of warm-blooded vertebrates. Science. 1985 May 24;228(4702):953–958. doi: 10.1126/science.4001930. [DOI] [PubMed] [Google Scholar]
- 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]
- Bird A. P., Taggart M. H., Nicholls R. D., Higgs D. R. Non-methylated CpG-rich islands at the human alpha-globin locus: implications for evolution of the alpha-globin pseudogene. EMBO J. 1987 Apr;6(4):999–1004. doi: 10.1002/j.1460-2075.1987.tb04851.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bird A., Taggart M., Frommer M., Miller O. J., Macleod D. A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell. 1985 Jan;40(1):91–99. doi: 10.1016/0092-8674(85)90312-5. [DOI] [PubMed] [Google Scholar]
- Carle G. F., Olson M. V. Separation of chromosomal DNA molecules from yeast by orthogonal-field-alternation gel electrophoresis. Nucleic Acids Res. 1984 Jul 25;12(14):5647–5664. doi: 10.1093/nar/12.14.5647. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Choo K. H., Filby G., Greco S., Lau Y. F., Kan Y. W. Cosmid vectors for high efficiency DNA-mediated transformation and gene amplification in mammalian cells: studies with the human growth hormone gene. Gene. 1986;46(2-3):277–286. doi: 10.1016/0378-1119(86)90412-9. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Furst A., Brown E. H., Braunstein J. D., Schildkraut C. L. alpha-Globulin sequences are located in a region of early-replicating DNA in murine erythroleukemia cells. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1023–1027. doi: 10.1073/pnas.78.2.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kenwrick S., Patterson M., Speer A., Fischbeck K., Davies K. Molecular analysis of the Duchenne muscular dystrophy region using pulsed field gel electrophoresis. Cell. 1987 Jan 30;48(2):351–357. doi: 10.1016/0092-8674(87)90438-7. [DOI] [PubMed] [Google Scholar]
- Schwartz D. C., Cantor C. R. Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis. Cell. 1984 May;37(1):67–75. doi: 10.1016/0092-8674(84)90301-5. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Yunis J. J. Mid-prophase human chromosomes. The attainment of 2000 bands. Hum Genet. 1981;56(3):293–298. doi: 10.1007/BF00274682. [DOI] [PubMed] [Google Scholar]
- Zerial M., Salinas J., Filipski J., Bernardi G. Gene distribution and nucleotide sequence organization in the human genome. Eur J Biochem. 1986 Nov 3;160(3):479–485. doi: 10.1111/j.1432-1033.1986.tb10064.x. [DOI] [PubMed] [Google Scholar]