Summary
Fifteen different restriction fragment length polymorphisms (RFLPs) were detected in the human genome using 19 cloned DNA segments, derived from flow-sorted metaphase chromosomes or total genomic DNA, as hybridization probes. Since these clones were selected at random with respect to their coding potential, their analysis permitted an unbiassed estimate of single-copy DNA sequence heterozygosity in the human genome. Since our estimate (h=0.0037) is an order of magnitude higher than previous estimates derived from protein data, most of the polymorphic variation present in the genome must occur in non-coding sequences. In addition, it was confirmed that enzymes containing the dinucleotide CpG in their recognition sequence detect more polymorphic variation than those that do not contain CpG.
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Aldridge J, Kunkel L, Bruns G, Tantravahi U, LaLande M, Brewster T, Moreau E, Wilson M, Bromley W, Roderick T, Latt S (1984) A strategy to reveal high-frequency RFLPs along the human X chromosome. Am J Hum Genet 36:546–564
Barker D, Schäfer M, White R (1984) Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell 36:131–138
Bird AP (1980) DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res 8:1499–1504
Cooper DN (1983) Eukaryotic DNA methylation. Hum Genet 64:315–333
Cooper DN, Schmidtke J (1984) DNA restriction fragment length polymorphisms and heterozygosity in the human genome. Hum Genet 66:1–16
Coulondre C, Miller JH, Farabaugh PJ, Gilbert W (1978) Molecular basis of base substitution hotspots in Escherichia coli. Nature 274:775–778
Denhardt D (1966) A membrane filter technique for the detection of complementary DNA. Biochim Biophys Acta 23:641–646
Helentjaris T, Gesteland R (1983) Evolution of random cDNA clones as probes for human restriction fragment polymorphisms. J Mol Appl Genet 2:237–247
Jeffreys AJ (1979) DNA sequence variants in the GγAγ, δ- and β-globin genes of man. Cell 18:1–10
Karn J, Brenner S, Barnett L, Cesareni G (1980) Novel bacteriophage cloning vector. Proc Natl Acad Sci USA 77:5172–5176
Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, Cambridge
Krumlauf R, Jeanpierre M, Young BD (1982) Construction and characterisation of genomic libraries from specific human chromosomes. Proc Natl Acad Sci USA 79:2971–2975
Lewin B (1980) Gene expression: vol 2, Eukaryotic chromosomes. John Wiley, New York
Lund E, Bostock C, Robertson M, Christie S, Mitchen JL, Dahlberg JE (1983) U1 Small nuclear RNA genes are located on human chromosome 1 and are expressed in mouse-human hybrid cells. Mol Cell Biol 3:2211–2220
Maniatis T, Fritsch EF, Sambrock J (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, New York
Murray JC, Demopulos CM, Lawn RM, Motulsky AG (1983) Molecular genetics of human serum albumin: restriction enzyme fragment length polymorphisms and analbuminemia. Proc Natl Acad Sci USA 80:5951–5955
Nei M (1975) Molecular population genetics and evolution North Holland Publishing Company, Amsterdam
Ohno S (1967) Sex chromosomes and sex-linked genes. Springer, Berlin
Rigby PWJ, Dieckmann M, Rhodes C, Berg P (1977) Labelling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol 113:237–251
Salser W (1978) Globin mRNA sequences: analysis of base pairing and evolutionary implications. Cold Spring Harbor Symp Quant Biol 42:985–1002
Skolnick MH, White R (1982) Strategy for detecting and characterizing restriction fragment length polymorphisms (RFLPs). Cytogenet Cell Genet 32:58–67
Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517
Van der Ploeg LHT, Flavell RA (1980) DNA methylation in the human γδβ-globin locus in erythroid and nonerythroid tissues. Cell 19:947–958
Vogel F (1972) Non-randomness of base replacement in point mutation. J Mol Evol 1:334–367
Vogel F, Kopun M (1977) Higher frequencies of transitions among point mutations. J Mol Evol 9:159–180
Vogel F, Motulsky AG (1982) Human Genetics. Springer, Berlin
Wieacker P, Davies KE, Cooke HJ, Pearson PL, Williamson R, Bhattacharya S, Zimmer J, Ropers HH (1984) Toward a complete linkage map of the human X chromosome: regional assignment of somatic cell hybrids. Am J Hum Genet 36:256–276
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Cooper, D.N., Smith, B.A., Cooke, H.J. et al. An estimate of unique DNA sequence heterozygosity in the human genome. Hum Genet 69, 201–205 (1985). https://doi.org/10.1007/BF00293024
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DOI: https://doi.org/10.1007/BF00293024