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DNA restriction fragment length polymorphisms and heterozygosity in the human genome

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Summary

A list is presented of published reports of DNA polymorphisms found in the human genome by restriction enzyme analysis. While the list indicates the large number of restriction fragment length polymorphisms (RFLPs) detected to date, the information collated is insufficient to permit an estimate of heterozygosity for the genome as a whole. Data from our laboratory are therefore also presented on RFLPs detected using a random sample of cloned DNA segments. Such an analysis has permitted a first unbiassed estimate of heterozygosity for the human genome. Since this figure is an order of magnitude higher than previous estimates derived from protein data, the majority of polymorphic variation present in the human genome must, by implication, occur in noncoding sequences. In addition it was confirmed that enzymes containing the dinucleotide CpG in their recognition sequences detect more polymorphic variation than those that do not contain a CpG. Also presented are the clinical applications of DNA polymorphisms in the diagnosis of human genetic disease.

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References

  • Antonarakis SE, Boehm CD, Giardina PJV, Kazazian HH (1982) Nonrandom association of polymorphic restriction sites in the β-globin gene cluster. Proc Natl Acad Sci USA 79:137–141

    Google Scholar 

  • Auffray C, Ben-Nun A, Roux-Dosseto M, Germain RN, Seidman JG, Strominger JL (1983) Polymorphism and complexity of the human DC and murine I-Aα chain genes. EMBO J 2:121–124

    Google Scholar 

  • Bakker E, Wieacker P, Beverstock GC, Pearson PL (1983) Recombinant DNA techniques for mapping the human X chromosome. Clin Genet 23:225

    Google Scholar 

  • Barker D, White R (1982) More base pair change polymorphisms at sites containing CpG. Cytogenet Cell Genet 32:253

    Google Scholar 

  • Bastié-Sigeac F, Lucotte G (1983) Optimal use of restriction enzymes in the analysis of human DNA polymorphism. Hum Genet 63: 162–165

    Google Scholar 

  • Bell GI, Pictet RL, Rutter WJ, Cordell B, Tischer E, Goodman HM (1980a) Sequence of the human insulin gene. Nature 284:26–32

    Google Scholar 

  • Bell GI, Pictet R, Rutter WJ (1980b) Analysis of the regions flanking the human insulin gene and sequence of an Alu family member. Nucleic Acids Res 8:4091–4109

    Google Scholar 

  • Bell GI, Karan JH, Rutter WJ (1981) Polymorphic DNA region adjacent to the 5′ end of the human insulin gene. Proc Natl Acad Sci USA 78:5759–5762

    Google Scholar 

  • Bell GI, Selby MJ, Rutter WJ (1982) The highly polymorphic region near the human insulin gene is composed of simple tandemly repeating sequences. Nature 295:31–35

    Google Scholar 

  • Beutler E, Kuhl W, Johnson C (1981) A common mutant EcoRI restriction endonuclease site in the 5′ flanking portion of the human α-globin gene. Proc Natl Acad Sci USA 78:7056–7058

    Google Scholar 

  • Bird AP (1980) DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res 8:1499–1504

    Google Scholar 

  • Blanc H, Chen K-H, D'Amore MA, Wallace DC (1983) Amino acid change associated with the major polymorphic Hinc II site of Oriental and Caucasian mitochondrial DNAs. Am J Hum Genet 35:167–176

    Google Scholar 

  • Boehm CD, Antonarakis SE, Phillips JA, Stetten G, Kazazian HH (1983) Prenatal diagnosis using DNA polymorphisms. Report on 95 pregnancies at risk for sickle-cell disease or β-thalassemia. N Engl J Med 308:1054–1058

    Google Scholar 

  • Böhme J, Owerbach D, Denaro M, Lernmark A, Peterson PA, Rask L (1983) Human class II major histocompatibility antigen β-chains are derived from at least three loci. Nature 301:82–84

    Google Scholar 

  • Boothby M, Ruddon RW, Anderson C, McWilliams D, Boime I (1981) A single gonadotropin α-subunit gene in normal tissue and tumor-derived cell lines. J Biol Chem 256:5121–5127

    Google Scholar 

  • Botstein D, White RL, Skolnick M, Davis RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 32:314–331

    Google Scholar 

  • Brown WM, George M, Wilson AC (1979) Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci USA 76:1967–1971

    Google Scholar 

  • Calabretta B, Robberson DL, Barrera-Saldaña HA, Lambrou IP, Saunders GF (1982) Genome instability in a region of human DNA enriched in Alu repeat sequences. Nature 296:219–225

    Google Scholar 

  • Camerino G, Mattei MG, Mattei JF, Jaye M, Mandel JL (1983) Close linkage of fragile X-mental retardation syndrome to Haemophilia B and transmission through a normal male. Nature 306:701–704

    Google Scholar 

  • Cann HM, Ascanio L, Paul P, Marcadet A, Dausset J, Cohen D (1983) Polymorphic restriction endonuclease fragment segregates and correlates with the gene for HLA-B8. Proc Natl Acad Sci USA 80:1665–1668

    Google Scholar 

  • Cavenee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie BL, Murphree AL, Strong LC, White RL (1983) Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305:779–784

    Google Scholar 

  • Chandra T, Stackhouse R, Leicht M, Long G, Kurachi K, Davie EW, Woo SLC (1982) DNA polymorphism in the human chromosomal alpha-1-antitrypsin gene. DNA I:210

    Google Scholar 

  • Chu M-L, Williams CJ, Pepe G, Hirsch JL, Prockop DJ, Ramirez F (1983) Internal deletion in a collagen gene in a perinatal lethal form of osteogenesis imperfecta. Nature 304:78–80

    Google Scholar 

  • Conner BJ, Reyes AA, Morin C, Itakura K, Teplitz RL, Wallace RB (1983) Detection of sickle cell β s-globin allele by hybridization with synthetic oligonucleotides. Proc Natl Acad Sci USA 80: 278–282

    Google Scholar 

  • Cooke HJ, Noel B (1979) Confirmation of Y/autosome translocations using recombinant DNA. Hum Genet 50:39–44

    Google Scholar 

  • Cooper DN (1983) Eukaryotic DNA methylation. Hum Genet 64: 315–333

    Google Scholar 

  • Coulondre C, Miller JH, Farabaugh PJ, Gilbert W (1978) Molecular basis of base substitution hotspots in Escherichia coli. Nature 274:775–780

    Google Scholar 

  • Daiger SP, Wildin RS, Su T-S (1982) Sequences on the human Y chromosome homologous to the autosomal gene for argininosuccinate synthetase. Nature 298:682–684

    Google Scholar 

  • Dalla-Favera R, Martinotti S, Gallo RR, Eriksson J, Croce CM (1983) Translocation and rearrangements of the c-myc oncogene locus in human undifferentiated B-cell lymphomas. Science 219: 963–967

    Google Scholar 

  • Darlington GJ, Astrin KH, Muirhead SP, Desnick RJ, Smith M (1982) Assignment of human alpha-I-antitrypsin gene to chromosome 14. Cytogenet Cell Genet 32:262–263

    Google Scholar 

  • Davies KE, Pearson PL, Harper PS, Murray JM, O'Brien TO, Sarfarazi M, Williamson R (1983a) Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome. Nucleic Acids Res 11:2303–2312

    Google Scholar 

  • Davies KE, Jackson J, Williamson R, Harper PS, Ball S, Sarfarazi M, Meredith L, Fey G (1983b) Linkage analysis of myotonic dystrophy and sequences on chromosome 19 using a cloned complement 3 gene probe. J Med Genet 20:259–263

    Google Scholar 

  • De Martinville B, Wyman HR, White R, Francke U (1982a) Assignment of the first random restriction fragment length polymorphism (RFLP) locus (DI4SI) to a region of human chromosome 14. Am J Hum Genet 34:216–226

    Google Scholar 

  • De Martinville B, Wyman A, White R, Francke U (1982b) Assignment of the first highly polymorphic marker locus to a human chromosome region. Cytogenet Cell Genet 32:265

    Google Scholar 

  • Denaro M, Blane H, Johnson MJ, Chen KH, Wilmsen E, Cavalli-Storza LL, Wallace DC (1981). Ethnic variation in Hpa II endonuclease cleavage patterns of human mitochondrial DNA. Proc Natl Acad Sci USA 78:5768–5772

    Google Scholar 

  • Driesel AJ, Schumacher AM, Flavell RA (1982) A Hind III restriction site polymorphism in the human collagen α(I)-like gene on chromosome No. 7. Hum Genet 62:175–176

    Google Scholar 

  • Driscoll MC, Baird M, Bank A (1981) A new polymorphism in the human β-globin gene useful in antenatal diagnosis. J Clin Invest 68:915–919

    Google Scholar 

  • Engel JN, Gunning PW, Kedes L (1981) Isolation and characterization of human actin genes. Proc Natl Acad Sci USA 78:4674–4678

    Google Scholar 

  • Erickson JM, Rushford CL, Dorney DJ, Wilson GN, Schmickel RD (1981) Structure and variation of human ribosomal DNA: molecular analysis of cloned fragments. Gene 16:1–9

    Google Scholar 

  • Erlich HA, Stetler D, Saiki R, Gladstone P, Pious D (1983) Mapping of the genes encoding the HLA-DR α chain and the HLA-related antigens to a chromosome 6 deletion by using genomic blotting. Proc Natl Acad Sci USA 80:2300–2304

    Google Scholar 

  • Farquhar M, Gelinas R, Tatsis B, Murray J, Yagi M, Mueller R, Stamatoyannopoulos G (1983) Restriction endonuclease mapping of γ-δ-β-globin region in Gγ(β) + HPFH and a Chinese Aγ HPFG variant. Am J Hum Genet 35:611–620

    Google Scholar 

  • Geever RF, Wilson LB, Nallaseth FS, Milner PF, Bittner M, Wilson JT (1981) Direct identification of sickle cell anemia by blot hybridization. Proc Natl Acad Sci USA 78:5081–5085

    Google Scholar 

  • Giannelli F, Choo KH, Rees DJG, Boyd Y, Rizza CR, Brownlee GG (1983) Gene deletions in patients with haemophilia B and antifactor IX antibodies. Nature 303:181–182

    Google Scholar 

  • Goldfarb M, Shimizu K, Perucho M, Wigler M (1982) Isolation and preliminary characterization of a human transforming gene from T24 bladder carcinoma cells. Nature 296:404–409

    Google Scholar 

  • Gray PW, Goeddel DV (1982) Structure of the human immune interferon gene. Nature 298:859–863

    Google Scholar 

  • Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sakaguchi AY, Young AB, Shoulson I, Bonilla E, Martin JB (1983) A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306:234–238

    Google Scholar 

  • Haneda M, Chan SJ, Kwok SCM, Rubenstein AH, Steiner DF (1983) Studies on mutant human insulin genes: identification and sequence analysis of a gene encoding [SerB24] insulin. Proc Natl Acad Sci USA 80:6366–6370

    Google Scholar 

  • Harris H, Hopkinson DA (1972) Average heterozygosity per locus in man: an estimate based on the incidence of enzyme polymorphisms. Ann Hum Genet 36:9–20

    Google Scholar 

  • Hieter PA, Hollis GF, Korsmeyer SJ, Waldmann TA, Leder P (1981) Clustered arrangement of immunoglobulin λ constant region genes in man. Nature 294:536–540

    Google Scholar 

  • Higgs DR, Goodbourn SEY, Wainscoat JS, Clegg JB, Weatherall DJ (1981) Highly variable regions of DNA flank the human α globin genes. Nucleic Acids Res 9:4213–4224

    Google Scholar 

  • Hill MEE, Davies KE, Harper P, Williamson R (1982) The Mendelian inheritance of a human X chromosome-specific DNA sequence polymorphism and its use in linkage studies of genetic disease. Hum Genet 60:222–226

    Google Scholar 

  • Hollis GF, Hiefer PA, McBride OW, Swan D, Leder P (1982) Processed genes: a dispersed human immunoglobulin gene bearing evidence of RNA type processing. Nature 296:321–325

    Google Scholar 

  • Jeffreys AJ (1979) DNA sequence variants in the Gγ-, Aγ-, δ-and β-globin genes of man. Cell 18:1–10

    Google Scholar 

  • Kan YW, Dozy AM (1978) Polymorphism of DNA sequence adjacent to human β-globin structural gene: relationship to sickle mutation. Proc Natl Acad Sci USA 75:5631–5635

    Google Scholar 

  • Kan YWK, Lee KY, Furbetta M, Angius A, Cao A (1980) Polymorphism of DNA sequence in the β-globin gene region. N Engl J Med 302:185–188

    Google Scholar 

  • Kao F-T, Hawkins JW, Law ML, Dugaiczyk A (1982) Assignment of the structural gene coding for albumin to human chromosome 4. Hum Genet 62:337–341

    Google Scholar 

  • Karathanasis SK, Norum RA, Zannis VI, Breslow JL (1983a) An inherited polymorphism in the human apolipoprotein A-1 gene locus related to the development of atherosclerosis. Nature 301: 718–720

    Google Scholar 

  • Karathanasis SK, McPherson J, Zannis VI, Breslow J (1983b) Linkage of human apolipoproteins A-I and c-III genes. Nature 304: 371–373

    Google Scholar 

  • Karathanasis SK, Zannis VI, Breslow JL (1983c) A DNA insertion in the apolipoprotein A-I gene of patients with premature atherosclerosis. Nature 305:823–825

    Google Scholar 

  • Karin M, Richards RI (1982) Human metallothionein genes, primary structure of the metallothionein-II gene and a related processed gene. Nature 299:797–802

    Google Scholar 

  • Kidd VJ, Wallace RB, Itakura K, Woo SLC (1983) 14-6 deficiency detection by direct analysis of the mutation in the gene. Nature 304:230–234

    Google Scholar 

  • Kingston HM, Thomas NST, Pearson PL, Sarfarazi M, Harper PS (1983) Genetic linkage between Becker muscular dystrophy and a polymorphic DNA sequence on the short arm of the X chromosome. J Med Genet 20:255–258

    Google Scholar 

  • Kohen G, Philippe N, Godet J (1982) Polymorphism of the Hinf I restriction site located I kb 5′ to the human β-globin gene. Hum Genet 62:121–123

    Google Scholar 

  • Krystal M, D'Eustachio P, Ruddle FH, Arnheim N (1981) Human nucleolar organizers on nonhomologous chromosomes can share the same ribosomal gene variants. Proc Natl Acad Sci USA 78: 5744–5748

    Google Scholar 

  • Lange K, Boehnke M (1982) How many polymorphic marker genes will it take to span the human genome? Am J Hum Genet 34: 842–845

    Google Scholar 

  • Lawn RM, Fritsch EF, Parker RC, Blake G, Maniatis T (1978) The isolation and characterization of linked δ-and β-globin genes from a cloned library of human DNA. Cell 15:1151–1174

    Google Scholar 

  • Lebo RV, Kan YW, Cheung MC, Carrano AV, Yu L-C, Change JC, Cordell B, Goodman HM (1982) Assigning the polymorphic human insulin gene to the short arm of chromosome 11 by chromosome sorting. Hum Genet 60:10–15

    Google Scholar 

  • Lebo RV, Chakravarti A, Buetow KH, Cheung M-C, Cann H, Cordell B, Goodman H (1983) Recombination within and between the human insulin and β-globin gene loci. Proc Natl Acad Sci USA 80:4808–4812

    Google Scholar 

  • Lee JS, Trowsdale J, Bodmer WF (1982) cDNA clones coding for the heavy chain of human HLA-DR antigen. Proc Natl Acad Sci USA 79:545–549

    Google Scholar 

  • Lefranc M-P, Lefranc G, Rabbitts TH (1982) Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals. Nature 300:760–762

    Google Scholar 

  • Leinwand LA, Saez L, McNally E, Nadal-Ginard B (1983a) Isolation and characterization of human myosin heavy chain genes. Proc Natl Acad Sci USA 80:3716–3720

    Google Scholar 

  • Leinwand LA, Fournier REK, Nadal-Ginard B, Shows TB (1983b) Multigene family for sarcomeric myosin heavy chain in mouse and human DNA: Localization on a single chromosome. Science 221:766–769

    Google Scholar 

  • Lerman MI, Thayer RE, Singer MF (1983) Kpn I family of long interspersed repeated DNA sequences in primates: polymorphism of family members and evidence for transcription. Proc Natl Acad Sci USA 80:3966–3970

    Google Scholar 

  • Lie-Injo LE, Herrera AR, Kan YW (1981) Two types of triplicated α-globin loci in humans. Nucleic Acids Res 9:3707–3717

    Google Scholar 

  • Little PFR (1981) DNA analysis and the antenatal diagnosis of hemoglobinopathies. In: Williamson R (ed) Genetic engineering, vol I. Academic Press, London

    Google Scholar 

  • Little PFR, Annison G, Darling S, Williamson R, Camba L, Modell B (1980) Model for antenatal diagnosis of β-thalassaemia and other monogenic disorders by molecular analysis of linked DNA polymorphisms. Nature 285:144–147

    Google Scholar 

  • McKusick VA (1982) The human gene map. 20. October 1982. Clin Genet 22:359–391

    Google Scholar 

  • Matthyssens G, Rabbitts TH (1980) Structure and multiplicity of genes for the human immunoglobulin heavy chain variable region. Proc Natl Acad Sci USA 77:6561–6565

    Google Scholar 

  • Meisler MH (1983) DNA polymorphisms. Nature 303:108

    Google Scholar 

  • Michelson AM, Markham AF, Orkin SH (1983) Isolation and DNA sequence of a full-length cDNA clone for human X-chromosome-encoded phosphoglycerate kinase. Proc Natl Acad Sci USA 80: 472–476

    Google Scholar 

  • Mignone N, Feder J, Cann H, van West B, Hwang J, Takahashi N, Honjo T, Piazza A, Cavalli-Sforza LL (1983) Multiple DNA fragment polymorphisms associated with immunoglobulin μ chain switch-like regions in man. Proc Natl Acad Sci USA 80: 467–471

    Google Scholar 

  • Murray JM, Davies KE, Harper PS, Meredith L, Mueller CR, Williamson R (1982) Linkage relationship of a cloned DNA sequence on the short arm of the X chromosome to Duchenne muscular dystrophy. Nature 300:69–71

    Google Scholar 

  • 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

    Google Scholar 

  • Myers JC, Dickson LA, de Wet WJ, Bernard MP, Chu M-L, Di Liberto M, Pepe G, Sangiorgi FO, Ramirez F (1983) Analysis of the 3′ end of the human pro-α2(1) collagen gene. J Biol Chem 258:10128–10135

    Google Scholar 

  • Naylor SL, Sakaguchi AY, Gusella JF, Housman D, Shows TB (1982a) Mapping of an arbitrary restriction polymorphism (ARP2) to human chromosome 3. Cytogenet Cell Genet 32:302

    Google Scholar 

  • Naylor SL, Sakaguchi AY, Gutai MW, Schmickel RD, Shows TB (1982b) Chromosomal organization of rDNA spacer length variants on human chromosomes 13, 14, 15, 21, and 22 in somatic cell hybrids. Cytogenet Cell Genet 32:302

    Google Scholar 

  • Naylor SL, Sakaguchi AY, Shen L-P, Bell GI, Rutter WJ, Shows TB (1983a) Polymorphic human somatostatin gene is located on chromosome 3. Proc Natl Acad Sci USA 80:2686–2689

    Google Scholar 

  • Naylor SL, Sakaguchi AY, Shows TB, Grzeschik K-H, Holmes M, Zasloff M (1983b) Two nonallelic tRNA iMet genes are located in the p23→q12 region of human chromosome 6. Proc Natl Acad Sci USA 80:5027–5031

    Google Scholar 

  • Nei M (1975) Molecular population genetics and evolution. North Holland Publishing Co, Amsterdam

    Google Scholar 

  • Nishida Y, Miki T, Hisajima H, Honjo T (1982) Cloning of human immunoglobulin ε chain genes: evidence for multiple Cε genes. Proc Natl Acad Sci USA 79:3833–3837

    Google Scholar 

  • Nussbaum RL, Crowder WE, Nyhan WL, Caskey CT (1983) A three-allele restriction-fragment-length polymorphism at the hypoxanthine phosphoribosyltransferase locus in man. Proc Natl Acad Sci USA 80:4035–4039

    Google Scholar 

  • Ohno S (1967) Sex chromosomes and sex-linked genes. Springer, Berlin

    Google Scholar 

  • Old JM, Wainscoat JS (1983) A new DNA polymorphism in the β-globin gene cluster can be used for antenatal diagnosis of β-thalassaemia. Br J Haematol 53:337–341

    Google Scholar 

  • Orkin SH, Alter BP, Altay C, Mahoney MJ, Lazarus H, Hobbins JC, Nathan DG (1978) Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion. N Engl J Med 299:166–172

    Google Scholar 

  • Orkin SH, Kazazian HH, Antonarakis SE, Goff SC, Boehm CD, Sexton JP, Waber PG, Giardina PTV (1982) Linkage of β-thalassaemia mutations and β-globin gene polymorphisms with DNA polymorphisms in human β-globin gene cluster. Nature 296:627–631

    Google Scholar 

  • Owerbach D, Rutter WJ, Cooke NE, Martial JA, Shows TB (1981) The prolactin gene is located on chromosome 6 in humans. Science 212:815–816

    Google Scholar 

  • Owerbach D, Lernmark A, Rask L, Peterson PA, Platz P, Svejgaard A (1983a) Detection of HLA-D/DR-related DNA polymorphism in HLA-D homozygous typing cells. Proc Natl Acad Sci USA 80: 3758–3761

    Google Scholar 

  • Owerbach D, Lernmark A, Platz P, Ryder LP, Rask L, Peterson PA, Ludvigsson J (1983b) HLA-D region β-chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulindependent diabetic individuals. Nature 303:815

    Google Scholar 

  • Page D, De Martinville B, Barker D, Wyman A, White R, Francke U, Botstein D (1982) Single copy sequence hybridizes to polymorphic and homologous loci on human X and Y chromosomes. Proc Natl Acad Sci USA 79:5352–5356

    Google Scholar 

  • Panny SR, Scott AF, Smith KD, Phillips JA, Kazazian HH, Talbot CC, Boehm CD (1981) Population heterogeneity of the Hpa I restriction site associated with the β-globin gene: implications for prenatal diagnosis. Am J Hum Genet 33:25–35

    Google Scholar 

  • Parks JS, Herd JE, Wurzel JM (1981) Human growth hormone (HGH) deficiency and polymorphism within the HGH and human placental lactogen (HPL) gene cluster. Pediatr Res 15:513

    Google Scholar 

  • Pearson PL, Bakker E, Flavell RA (1982) Considerations in designing an efficient strategy for localizing unique sequence DNA fragments to human chromosomes. Cytogenet Cell Genet 32:308

    Google Scholar 

  • Phillips JA, Panny SR, Kazazian HH, Boehm CD, Scott AF, Smith KD (1980) Prenatal diagnosis of sickle cell anemia by restriction endonuclease analysis: Hind III polymorphisms in γ-globin genes extend test applicability. Proc Natl Acad Sci USA 77:2853–2856

    Google Scholar 

  • Phillips JA, Hjelle BL, Seeburg PH, Zachmann M (1981) Molecular basis for familial isolated growth hormone deficiency. Proc Natl Acad Sci USA 78:6372–6375

    Google Scholar 

  • Phillips JA, Parks JS, Hjelle BL, Herd JE, Plotnick LP, Migeon CJ, Seeburg PH (1982) Genetic analysis of familial isolated growth hormone deficiency type 1. J Clin Invest 70:489–495

    Google Scholar 

  • Pope FM, Nicholls AC, Grosveld FG (1983) Similar αI(I)-like gene deletions cause some types of Ehlers Danlos syndrome type II and lethal osteogenesis imperfecta. Clin Genet 24:303

    Google Scholar 

  • Prochownik EV, Markham AF, Orkin SH (1983a) Isolation of a cDNA clone for human antithrombin III. J Biol Chem 258:8389–8394

    Google Scholar 

  • Prochownik EV, Antonarakis S, Bauer KA, Rosenberg RD, Fearon ER, Orkin SH (1983b) Molecular heterogeneity of inherited antithrombin III deficiency. N Engl J Med 308:1549–1552

    Google Scholar 

  • Raugei G, Bensi G, Colantuoni V, Romano V, Santoro C, Costanzo F, Cortese R (1983) Sequence of human haptoglobin cDNA: evidence that the α and β subunits are coded by the same mRNA. Nucleic Acids Res 11:5811–5819

    Google Scholar 

  • Rees A, Shoulders CC, Stocks J, Galton DJ, Baralle FE (1983) DNA polymorphism adjacent to human apoprotein A-1 gene: relation to hypertriglyceridemia. Lancet 1:444

    Google Scholar 

  • Riggin CH, Pitha PM (1982) Methylation and a polymorphic restriction site adjacent to human β-interferon gene. DNA 1:267–271

    Google Scholar 

  • Roberts D (1982) Applications of polymorphisms in anthropogenetic studies. Hum Biol 54:175

    Google Scholar 

  • Rotwein P, Chyn R, Chirgwin J, Cordell B, Goodman HM, Permutt MA (1981) Polymorphism in the 5′-flanking region of the human insulin gene and its possible relation to type 2 diabetes. Science 213:1117–1120

    Google Scholar 

  • Rotwein PS, Chirgwin J, Province M, Knowler WC, Pektitt DJ, Cordell B, Goodman HM, Pettitt MA (1983) Polymorphism in the 5′ flanking region of the human insulin gene: a genetic marker for non-insulin-dependent diabetes. N Engl J Med 308: 65–71

    Google Scholar 

  • Sakaguchi AY, Naylor SL, Schmickel RD, Shows TB (1982) Assignment of an arbitrary restriction fragment, ARF-1 to human chromosome 6. Cytogenet Cell Genet 32:313–314

    Google Scholar 

  • Sakaguchi AY, Naylor SL, Shows TB, Toole JJ, McCoy M, Weinberg RA (1983) Human c-Ki-ras 2 proto-oncogene on chromsome 12. Science 219:1081–1085

    Google Scholar 

  • Salser W (1978) Globin mRNA sequences: analysis of base pairing and evolutionary implications. Cold Spring Harbor Symp Ouant Biol 42:985–1002

    Google Scholar 

  • Santos E, Tronick SR, Aaronson SA, Pulciani S, Barbacid M (1982) T 24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB-and Harvey-MSV transforming genes. Nature 298:343–347

    Google Scholar 

  • Schäfer M, White R (1982) Three random loci in the genome with base pair change polymorphisms. Cytogenet Cell Genet 32: 314–315

    Google Scholar 

  • Schmickel RD, Waterson JR, Knoller M, Szura LL, Wilson GN (1980) HeLa cell identification by analysis of ribosomal DNA segment patterns generated by endonuclease restriction. Am J Hum Genet 32:890–897

    Google Scholar 

  • Schmid M, Gall H, Schempp W, Weber L, Schmidtke J (1981) Characterization of a new aberration of the human Y chromosome by banding methods and DNA restriction endonuclease analysis. Hum Genet 59:26–35

    Google Scholar 

  • Shows TB, Sakaguchi AY, Naylor SL (1982) Mapping the human genome, cloned genes, DNA polymorphisms and inherited disease. Adv Hum Genet 12:341–452

    Google Scholar 

  • Shmookler Reis RJ, Lumpkin CK, McGill JR, Riabowol KT, Goldstein S (1983) Extra-chromosomal circular copies of an “Inter-Alu” unstable sequence in human DNA are amplified during in vitro and in vivo ageing. Nature 301:394–398

    Google Scholar 

  • Skolnick MH, Francke U (1982) Report of the committee on human gene mapping by recombinant DNA techniques. Cytogenet Cell Genet 32:194–204

    Google Scholar 

  • Soriano P, Szabo P, Bernardi G (1982) The scattered distribution of actin genes in the mouse and human genomes. EMBO J 1: 579–583

    Google Scholar 

  • Southern EM (1982) Application of DNA analysis to mapping the human genome. Cytogenet Cell Genet 32:52–57

    Google Scholar 

  • Spritz RA, Forget BG (1983) The thalassemias: molecular mechanisms of human genetic disease. Am J Hum Genet 35:333–361

    Google Scholar 

  • Stetler D, Das H, Nunberg JH, Saiki R, Sheng-Dong R, Mullis KB Weissman SM, Erlich HA (1982) Isolation of a cDNA clone for the human HLA-DR antigen α chain by using a synthetic oligonucleotide as a hybridization probe. Proc Natl Acad Sci USA 79:5966–5970

    Google Scholar 

  • Su T-S, Bock H-GO, Beaudet AL, O'Brien WE (1982) Molecular analysis of argininosuccinate synthetase deficiency in human fibroblasts. J Clin Invest 70:1334–1335

    Google Scholar 

  • Sukumaran PK, Nakatsuji T, Gardiner MB, Reese AL, Gilman JG, Huisman THJ (1983) Gamma thalassemia resulting from the deletion of a γ-globin gene. Nucleic Acids Res 11:4635–4643

    Google Scholar 

  • Tabin CJ, Bradley SM, Bargmann CI, Weinberg RA, Papageorge AG, Scolnick EM, Dhar R, Lowy DR, Chang EH (1982) Mechanism of activation of a human oncogene. Nature 300:143–149

    Google Scholar 

  • Taub RA, Hollis GF, Hieter PA, Korsmeyer S, Waldmann TA, Leder P (1983) Variable amplification of immunoglobulin λ light-chain genes in human populations. Nature 304:172–174

    Google Scholar 

  • Trowsdale J, Lee J, Carey J, Grosveld F, Bodmer J, Bodmer W (1983) Sequences related to HLA-DR α chain on human chromosome 6: restriction enzyme polymorphism detected with DC α chain probes. Proc Natl Acad Sci USA 80:1972–1976

    Google Scholar 

  • Tsipouras P, Myers J, Prockop D, Ramirez F (1983) Genetic analysis of the mild autosomal dominant osteogenesis imperfecta with restriction fragment length polymorphism associated with the pro α 2 (I) collagen gene. Abstracts, 34th annual meeting, American Society of Human Genetics: 182A

  • Tuan D, Biro PA, deRiel JK, Lazarus H, Forget BG (1979) Restriction endonuclease mapping of the γ-globin gene loci. Nucleic Acids Res 6:2519–2544

    Google Scholar 

  • Ullrich A, Dull TJ, Gray A, Phillips JA, Peter S (1982) Variation in the sequence and modification state of the human insulin gene flanking regions. Nucleic Acids Res 10:2225–2240

    Google Scholar 

  • Van der Ploeg LHR, Flavell RA (1980) DNA methylation in the human γδβ-globin locus in erythroid and non-erythroid tissues. Cell 19:947–958

    Google Scholar 

  • Vogel F (1972) Non-randomness of base replacement in point mutation. J Mol Evol 1:334–367

    Google Scholar 

  • Vogel F, Kopun M (1977) Higher frequencies of transitions among point mutations. J Mol Evol 9:159–180

    Google Scholar 

  • Vogel F, Motulsky AG (1982) Human genetics, 2nd edn. Springer, Berlin

    Google Scholar 

  • Wake CT, Long EO, Strubin M, Gross N, Accolla R, Carrel S, Mach B (1982a) Isolation of cDNA clones encoding HLA-DR α chains. Proc Natl Acad Sci USA 79:6979–6983

    Google Scholar 

  • Wake CT, Long EO, Mach B (1982b) Allelic polymorphism and complexity of the genes for HLA-DR β-chains-direct analysis by DNA-DNA hybridization. Nature 300:372–374

    Google Scholar 

  • Whitehead AS, Bruns GAP, Markham AF, Colten HR, Woods DE (1983) Isolation of human C-reactive protein complementary DNA and localization of the gene to chromosome 1. Science 221:69–71

    Google Scholar 

  • Wieacker P, Davies KE, Mevorah B, Ropers HH (1983a) Linkage studies in a family with X-linked recessive ichthyosis employing a cloned DNA sequence from the distal short arm of the X chromosome. Hum Genet 63:113–116

    Google Scholar 

  • Wieacker P, Horn N, Pearson P, Wienker TF, McKay E, Ropers HH (1983b) Menkes kinky hair disease: a search for closely linked restriction fragment length polymorphism. Hum Genet 64: 139–142

    Google Scholar 

  • Wieacker P, Wienker TF, Dallapiccola B, Bender K, Davies KE, Ropers HH (1983c) Linkage relationships between retinoschisis, Xg, and a cloned DNA sequence from the distal short arm of the X chromsome. Hum Genet 64:143–145

    Google Scholar 

  • Wilson JT, Milner PF, Summer MF, Nallaseth FS, Fadel HE, Reindollar RH, McDonough PG, Wilson LB (1982a) Use of restriction endonucleases for mapping the allele for βs-globin. Proc Natl Acad Sci USA 79:3628–3631

    Google Scholar 

  • Wilson GN, Szura LL, Rushford C, Jackson D, Erickson J (1982b) Structure and variation of human ribosomal DNA: the external transcribed spacer and adjacent regions. Am J Hum Genet 34: 32–49

    Google Scholar 

  • Wilson JM, Young AB, Kelley WN (1983) Hypoxanthine-guanine phosphorybosyltransferase deficiency: the molecular basis of the clinical syndromes. N Engl J Med 309:900–910

    Google Scholar 

  • Winichagoon P, Higgs DR, Goodbourn SEY, Lamb J, Clegg JB, Weatherall DJ (1982) Multiple arrangements of the human embryonic zeta globin genes. Nucleic Acids Res 10:5853–5868

    Google Scholar 

  • Woo SLC, Lidsky AS, Güttler F, Chandra T, Robson KJH (1983) Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria. Nature 306:151–155

    Google Scholar 

  • Wyman AR, White R (1980) A highly polymorphic locus in human DNA. Proc Natl Acad Sci USA 77:6754–6758

    Google Scholar 

  • Yang TP, Patel PI, Brennand J, Chinault AC, Laskey CT (1983) Molecular analysis of the human HPRT locus. Abstracts, 34th annual meeting, American Society of Human Genetics: 185A

  • Yokoyama S (1983) Polymorphism in the 5′-flanking region of the human insulin gene and the incidence of diabetes. Am J Hum Genet 35:193–200

    Google Scholar 

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  1. Institut für Humangenetik der Universität Göttingen, Nikolausberger Weg 5a, D-3400, Göttingen, Federal Republic of Germany

    David N. Cooper & Jörg Schmidtke

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  1. David N. Cooper
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Cooper, D.N., Schmidtke, J. DNA restriction fragment length polymorphisms and heterozygosity in the human genome. Hum Genet 66, 1–16 (1984). https://doi.org/10.1007/BF00275182

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  • DOI: https://doi.org/10.1007/BF00275182

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