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Molecular Medicine: Title and subTitle BreakA Spin-off From the Helix FREE

C. Thomas Caskey, MD
[+] Author Affiliations

Reprint requests to the Institute for Molecular Genetics and Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 (Dr Caskey).


JAMA. 1993;269(15):1986-1992. doi:10.1001/jama.1993.03500150098035
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IN THE 40 years that have passed since the publication of the structure of DNA by Watson and Crick,1 remarkable new DNA technology has emerged that has prompted the Human Genome Initiative at the National Institutes of Health (NIH) and ushered in the era of molecular medicine. Crick made additional contributions to our understanding of the genetic code, which was elucidated in the 1960s,2 and now devotes attention to the study of developmental biology of the central nervous system at the Salk Institute. Watson continues to make contributions to the field of genetics such as training scientists at Harvard and Cold Spring Harbor Laboratories (developing CSHL to modern preeminence) and serving as a visionary leader of the NIH Human Genome Initiative. The scientific community is fortunate to have the continued leadership of Watson and Crick.

In this article, it is my objective to review technological developments in biochemical

REFERENCES

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Roberts RJ.  Restriction and modification enzymes and their recognition sequences. Gene . 1978;;4:183-193.
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Khoury G, Martin MA, Lee TNH, Danna KJ, Nathans D.  A map of simian virus 40 transcription sites expressed in productively infected cells. J Mol Biol . 1973;;78:377-389.
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Cohen SN, Chang ACY, Boyer HW, Helling RB.  Construction of biologically functional bacterial plasmids in vitro. Proc Natl Acad Sci USA . 1973;;70:3240-3244.
Burke DT, Carle GF, Olson MV.  Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science . 1987;;236:806-812.
Maniatis T, Hardison RC, Lacy E, et al.  The isolation of structural genes from libraries of eucaryotic DNA. Cell . 1975;;15:687-701.
Ramirez F, Natta C, O'Donnell JV, et al.  Relative numbers of human globin genes assayed with purified α and β complementary human DNA. Proc Natl Acad Sci U S A . 1975;;72:1550-1554.
Sanger F, Coulson AR.  A rapid method of determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol . 1975;;94:441-448.
Sanger F, Nicklen S, Coulson AR.  DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A . 1977;;74:5463-5467.
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Gibbs RA, Nguyen PN, McBride U, Koepf SM, Caskey CT.  Identification of mutations leading to the Lesch-Nyhan syndrome by automated direct DNA sequencing of in vitro amplified cDNA. Proc Natl Acad Sci U S A . 1989;;86:1919-1923.
Gibbs RA, Nguyen PN, Edwards A, Civitello AB, Caskey CT.  Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyl-transferase gene in Lesch-Nyhan families. Genomics . 1990;;7:235-244.
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Fu YH, Pizzuti A, Fenwick RG Jr, et al.  An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science . 1992;;255:1256-1258.
Mahadevan M, Tsilfidis C, Sabourin L, et al.  Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science . 1992;; 255:1253-1255.
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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

Watson JD, Crick FHC.  Molecular structure of nucleic acids. Nature . 1953;;171:737-738.
Crick FHC, Barnet L, Brenner S, Watts-Tobin RJ.  General nature of the genetic code for proteins. Nature . 1961;;192:1227-1232.
Pauling L, Itano HA, Singer SJ, Wells IC.  Sickle cell anemia, a molecular disease. Science . 1949;;110:543-548.
Smith HO, Wilcox KW.  A restriction enzyme from Haemophilus influenzae, I: purification and general properties. J Mol Biol . 1970;;51:379-391.
Kelly TJ Jr, Smith HO.  A restriction enzyme from Haemophilus influenzae, II: base sequence of the recognition site. J Mol Biol . 1970;;51:393-409.
Roberts RJ.  Restriction and modification enzymes and their recognition sequences. Gene . 1978;;4:183-193.
Danna KJ, Sack GH Jr, Nathans D.  Studies of simian virus 40 DNA, VII: a cleavage map of the SV40 genome. J Mol Biol . 1973;;78:363-376.
Khoury G, Martin MA, Lee TNH, Danna KJ, Nathans D.  A map of simian virus 40 transcription sites expressed in productively infected cells. J Mol Biol . 1973;;78:377-389.
Southern EM.  Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol . 1975;;98:503-517.
Cohen SN, Chang ACY, Boyer HW, Helling RB.  Construction of biologically functional bacterial plasmids in vitro. Proc Natl Acad Sci USA . 1973;;70:3240-3244.
Burke DT, Carle GF, Olson MV.  Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science . 1987;;236:806-812.
Maniatis T, Hardison RC, Lacy E, et al.  The isolation of structural genes from libraries of eucaryotic DNA. Cell . 1975;;15:687-701.
Ramirez F, Natta C, O'Donnell JV, et al.  Relative numbers of human globin genes assayed with purified α and β complementary human DNA. Proc Natl Acad Sci U S A . 1975;;72:1550-1554.
Sanger F, Coulson AR.  A rapid method of determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol . 1975;;94:441-448.
Sanger F, Nicklen S, Coulson AR.  DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A . 1977;;74:5463-5467.
Maxam AM, Gilbert W.  A new method for sequencing DNA. Proc Natl Acad Sci U S A . 1977;;74:560-564.
Ansorge W, Sproat B, Stegemann J, Schwager C, Zenke M.  Automated DNA sequencing: ultrasensitive detection of fluorescent bands during electrophoresis. Nucleic Acids Res . 1987;;15:4593-4602.
Landegren U, Kaiser R, Caskey CT, Hood L.  DNA diagnostics—molecular techniques and automation. Science . 1988;;242:229-237.
Breathnach R, Mandel JL, Chambon P.  Ovalbumin gene is split in chicken DNA. Nature . 1977;;270:314-319.
Jeffreys AJ, Flavell RA.  The rabbit β-globin gene contains a large insert in the coding sequence. Cell . 1977;;12:1097-1108.
Hozumi N, Tonegawa S.  Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. Proc Natl Acad Sci U S A . 1976;;73:3628-3632.
Orkin SH, Kazazian HH Jr, Antonarakis SE, et al.  Linkage of β-thalassaemia mutations and β-globin gene polymorphisms with DNA polymorphisms in human β-globin gene cluster. Nature . 1982;;296:627-631.
Kan YW, Golbus MS, Dozy AM.  Prenatal diagnosis of alpha-thalassemia: clinical application of molecular hybridization. N Engl J Med . 1976;;295:1165-1167.
Mullis K, Faloona F, Scharf S, Saiki R, Horn G, Erlich H.  Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. Cold Spring Harb Symp Quant Biol . 1986;;51:263-273.
Saiki RK, Scharf S, Faloona F, et al.  Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science . 1985;;230:1350-1354.
Barany F.  Genetic disease detection and DNA amplification using cloned thermostable ligase. Proc Natl Acad Sci U S A . 1991;;88:189-193.
Handyside AH, Lesko JG, Tarín JJ, Winston RML, Hughes MR.  Birth of a normal girl after in vitro fertilization and preimplantation diagnostic testing for cystic fibrosis. N Engl J Med . 1992;;327:905-909.
Multicenter Study Group.  Diagnosis of Duchenne and Becker muscular dystrophies by polymerase chain reaction: a multicenter study. JAMA . 1992;;267:2609-2615.
Gibbs RA, Nguyen PN, McBride U, Koepf SM, Caskey CT.  Identification of mutations leading to the Lesch-Nyhan syndrome by automated direct DNA sequencing of in vitro amplified cDNA. Proc Natl Acad Sci U S A . 1989;;86:1919-1923.
Gibbs RA, Nguyen PN, Edwards A, Civitello AB, Caskey CT.  Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyl-transferase gene in Lesch-Nyhan families. Genomics . 1990;;7:235-244.
Vogelstein B, Kinzler KW.  p53 function and dysfunction. Cell . 1992;;70:523-526.
Larder BA, Kemp SD.  Multiple mutations in HIV-1: reverse transcriptase confer high-level resistance to zidovudine (AZT). Science . 1989;;246:1155-1158.
Brook JD, McCurrach ME, Harley HG, et al.  Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell . 1992;; 68:799-808.
Fu YH, Pizzuti A, Fenwick RG Jr, et al.  An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science . 1992;;255:1256-1258.
Mahadevan M, Tsilfidis C, Sabourin L, et al.  Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science . 1992;; 255:1253-1255.
Kremer EJ, Pritchard M, Lynch M, et al.  Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science . 1991;;252:1711-1714.
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To understand the clinical management of acute heart failure syndromes.
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