Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 May 15;90(10):4338–4344. doi: 10.1073/pnas.90.10.4338

The human genome project.

M V Olson 1
PMCID: PMC46506  PMID: 8506271

Abstract

The Human Genome Project in the United States is now well underway. Its programmatic direction was largely set by a National Research Council report issued in 1988. The broad framework supplied by this report has survived almost unchanged despite an upheaval in the technology of genome analysis. This upheaval has primarily affected physical and genetic mapping, the two dominant activities in the present phase of the project. Advances in mapping techniques have allowed good progress toward the specific goals of the project and are also providing strong corollary benefits throughout biomedical research. Actual DNA sequencing of the genomes of the human and model organisms is still at an early stage. There has been little progress in the intrinsic efficiency of DNA-sequence determination. However, refinements in experimental protocols, instrumentation, and project management have made it practical to acquire sequence data on an enlarged scale. It is also increasingly apparent that DNA-sequence data provide a potent means of relating knowledge gained from the study of model organisms to human biology. There is as yet little indication that the infusion of technology from outside biology into the Human Genome Project has been effectively stimulated. Opportunities in this area remain large, posing substantial technical and policy challenges.

Full text

PDF
4341

Selected References

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

  1. Adams M. D., Kelley J. M., Gocayne J. D., Dubnick M., Polymeropoulos M. H., Xiao H., Merril C. R., Wu A., Olde B., Moreno R. F. Complementary DNA sequencing: expressed sequence tags and human genome project. Science. 1991 Jun 21;252(5013):1651–1656. doi: 10.1126/science.2047873. [DOI] [PubMed] [Google Scholar]
  2. Anand R., Ogilvie D. J., Butler R., Riley J. H., Finniear R. S., Powell S. J., Smith J. C., Markham A. F. A yeast artificial chromosome contig encompassing the cystic fibrosis locus. Genomics. 1991 Jan;9(1):124–130. doi: 10.1016/0888-7543(91)90229-8. [DOI] [PubMed] [Google Scholar]
  3. Attree O., Olivos I. M., Okabe I., Bailey L. C., Nelson D. L., Lewis R. A., McInnes R. R., Nussbaum R. L. The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase. Nature. 1992 Jul 16;358(6383):239–242. doi: 10.1038/358239a0. [DOI] [PubMed] [Google Scholar]
  4. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
  5. Barr P. J. Mammalian subtilisins: the long-sought dibasic processing endoproteases. Cell. 1991 Jul 12;66(1):1–3. doi: 10.1016/0092-8674(91)90129-m. [DOI] [PubMed] [Google Scholar]
  6. Botstein D., Fink G. R. Yeast: an experimental organism for modern biology. Science. 1988 Jun 10;240(4858):1439–1443. doi: 10.1126/science.3287619. [DOI] [PubMed] [Google Scholar]
  7. Botstein D., White R. L., Skolnick M., Davis R. W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 1980 May;32(3):314–331. [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Caruthers M. H. Gene synthesis machines: DNA chemistry and its uses. Science. 1985 Oct 18;230(4723):281–285. doi: 10.1126/science.3863253. [DOI] [PubMed] [Google Scholar]
  11. Chelly J., Tümer Z., Tønnesen T., Petterson A., Ishikawa-Brush Y., Tommerup N., Horn N., Monaco A. P. Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein. Nat Genet. 1993 Jan;3(1):14–19. doi: 10.1038/ng0193-14. [DOI] [PubMed] [Google Scholar]
  12. Chumakov I., Rigault P., Guillou S., Ougen P., Billaut A., Guasconi G., Gervy P., LeGall I., Soularue P., Grinas L. Continuum of overlapping clones spanning the entire human chromosome 21q. Nature. 1992 Oct 1;359(6394):380–387. doi: 10.1038/359380a0. [DOI] [PubMed] [Google Scholar]
  13. Collins F. S. Positional cloning: let's not call it reverse anymore. Nat Genet. 1992 Apr;1(1):3–6. doi: 10.1038/ng0492-3. [DOI] [PubMed] [Google Scholar]
  14. Coulson A., Kozono Y., Lutterbach B., Shownkeen R., Sulston J., Waterston R. YACs and the C. elegans genome. Bioessays. 1991 Aug;13(8):413–417. doi: 10.1002/bies.950130809. [DOI] [PubMed] [Google Scholar]
  15. Coulson A., Sulston J., Brenner S., Karn J. Toward a physical map of the genome of the nematode Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7821–7825. doi: 10.1073/pnas.83.20.7821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Daniels D. L., Plunkett G., 3rd, Burland V., Blattner F. R. Analysis of the Escherichia coli genome: DNA sequence of the region from 84.5 to 86.5 minutes. Science. 1992 Aug 7;257(5071):771–778. doi: 10.1126/science.1379743. [DOI] [PubMed] [Google Scholar]
  18. Dietrich W., Katz H., Lincoln S. E., Shin H. S., Friedman J., Dracopoli N. C., Lander E. S. A genetic map of the mouse suitable for typing intraspecific crosses. Genetics. 1992 Jun;131(2):423–447. doi: 10.1093/genetics/131.2.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Donis-Keller H., Green P., Helms C., Cartinhour S., Weiffenbach B., Stephens K., Keith T. P., Bowden D. W., Smith D. R., Lander E. S. A genetic linkage map of the human genome. Cell. 1987 Oct 23;51(2):319–337. doi: 10.1016/0092-8674(87)90158-9. [DOI] [PubMed] [Google Scholar]
  20. Fink G. R. Notes of a bigamous biologist. Genetics. 1988 Apr;118(4):549–550. doi: 10.1093/genetics/118.4.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Foote S., Vollrath D., Hilton A., Page D. C. The human Y chromosome: overlapping DNA clones spanning the euchromatic region. Science. 1992 Oct 2;258(5079):60–66. doi: 10.1126/science.1359640. [DOI] [PubMed] [Google Scholar]
  22. Franco B., Guioli S., Pragliola A., Incerti B., Bardoni B., Tonlorenzi R., Carrozzo R., Maestrini E., Pieretti M., Taillon-Miller P. A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature. 1991 Oct 10;353(6344):529–536. doi: 10.1038/353529a0. [DOI] [PubMed] [Google Scholar]
  23. Fu Y. H., Pizzuti A., Fenwick R. G., Jr, King J., Rajnarayan S., Dunne P. W., Dubel J., Nasser G. A., Ashizawa T., de Jong P. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science. 1992 Mar 6;255(5049):1256–1258. doi: 10.1126/science.1546326. [DOI] [PubMed] [Google Scholar]
  24. Fuller R. S., Brake A. J., Thorner J. Intracellular targeting and structural conservation of a prohormone-processing endoprotease. Science. 1989 Oct 27;246(4929):482–486. doi: 10.1126/science.2683070. [DOI] [PubMed] [Google Scholar]
  25. Gall J. G., Pardue M. L. Formation and detection of RNA-DNA hybrid molecules in cytological preparations. Proc Natl Acad Sci U S A. 1969 Jun;63(2):378–383. doi: 10.1073/pnas.63.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gottesman M. M., Pastan I. The multidrug transporter, a double-edged sword. J Biol Chem. 1988 Sep 5;263(25):12163–12166. [PubMed] [Google Scholar]
  27. Green E. D., Olson M. V. Chromosomal region of the cystic fibrosis gene in yeast artificial chromosomes: a model for human genome mapping. Science. 1990 Oct 5;250(4977):94–98. doi: 10.1126/science.2218515. [DOI] [PubMed] [Google Scholar]
  28. Groden J., Thliveris A., Samowitz W., Carlson M., Gelbert L., Albertsen H., Joslyn G., Stevens J., Spirio L., Robertson M. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991 Aug 9;66(3):589–600. doi: 10.1016/0092-8674(81)90021-0. [DOI] [PubMed] [Google Scholar]
  29. Gusella J. F., Wexler N. S., Conneally P. M., Naylor S. L., Anderson M. A., Tanzi R. E., Watkins P. C., Ottina K., Wallace M. R., Sakaguchi A. Y. A polymorphic DNA marker genetically linked to Huntington's disease. Nature. 1983 Nov 17;306(5940):234–238. doi: 10.1038/306234a0. [DOI] [PubMed] [Google Scholar]
  30. Hall J. M., Friedman L., Guenther C., Lee M. K., Weber J. L., Black D. M., King M. C. Closing in on a breast cancer gene on chromosome 17q. Am J Hum Genet. 1992 Jun;50(6):1235–1242. [PMC free article] [PubMed] [Google Scholar]
  31. Hall J. M., Lee M. K., Newman B., Morrow J. E., Anderson L. A., Huey B., King M. C. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990 Dec 21;250(4988):1684–1689. doi: 10.1126/science.2270482. [DOI] [PubMed] [Google Scholar]
  32. Hunkapiller M., Kent S., Caruthers M., Dreyer W., Firca J., Giffin C., Horvath S., Hunkapiller T., Tempst P., Hood L. A microchemical facility for the analysis and synthesis of genes and proteins. Nature. 1984 Jul 12;310(5973):105–111. doi: 10.1038/310105a0. [DOI] [PubMed] [Google Scholar]
  33. Hunkapiller T., Kaiser R. J., Koop B. F., Hood L. Large-scale and automated DNA sequence determination. Science. 1991 Oct 4;254(5028):59–67. doi: 10.1126/science.1925562. [DOI] [PubMed] [Google Scholar]
  34. Kinzler K. W., Nilbert M. C., Su L. K., Vogelstein B., Bryan T. M., Levy D. B., Smith K. J., Preisinger A. C., Hedge P., McKechnie D. Identification of FAP locus genes from chromosome 5q21. Science. 1991 Aug 9;253(5020):661–665. doi: 10.1126/science.1651562. [DOI] [PubMed] [Google Scholar]
  35. Kohara Y., Akiyama K., Isono K. The physical map of the whole E. coli chromosome: application of a new strategy for rapid analysis and sorting of a large genomic library. Cell. 1987 Jul 31;50(3):495–508. doi: 10.1016/0092-8674(87)90503-4. [DOI] [PubMed] [Google Scholar]
  36. Kremer E. J., Pritchard M., Lynch M., Yu S., Holman K., Baker E., Warren S. T., Schlessinger D., Sutherland G. R., Richards R. I. Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science. 1991 Jun 21;252(5013):1711–1714. doi: 10.1126/science.1675488. [DOI] [PubMed] [Google Scholar]
  37. Kuchler K., Sterne R. E., Thorner J. Saccharomyces cerevisiae STE6 gene product: a novel pathway for protein export in eukaryotic cells. EMBO J. 1989 Dec 20;8(13):3973–3984. doi: 10.1002/j.1460-2075.1989.tb08580.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Landegent J. E., Jansen in de Wal N., Dirks R. W., Baao F., van der Ploeg M. Use of whole cosmid cloned genomic sequences for chromosomal localization by non-radioactive in situ hybridization. Hum Genet. 1987 Dec;77(4):366–370. doi: 10.1007/BF00291428. [DOI] [PubMed] [Google Scholar]
  39. Landegent J. E., Jansen in de Wal N., van Ommen G. J., Baas F., de Vijlder J. J., van Duijn P., Van der Ploeg M. Chromosomal localization of a unique gene by non-autoradiographic in situ hybridization. Nature. 1985 Sep 12;317(6033):175–177. doi: 10.1038/317175a0. [DOI] [PubMed] [Google Scholar]
  40. Lawrence J. B., Villnave C. A., Singer R. H. Sensitive, high-resolution chromatin and chromosome mapping in situ: presence and orientation of two closely integrated copies of EBV in a lymphoma line. Cell. 1988 Jan 15;52(1):51–61. doi: 10.1016/0092-8674(88)90530-2. [DOI] [PubMed] [Google Scholar]
  41. Legouis R., Hardelin J. P., Levilliers J., Claverie J. M., Compain S., Wunderle V., Millasseau P., Le Paslier D., Cohen D., Caterina D. The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules. Cell. 1991 Oct 18;67(2):423–435. doi: 10.1016/0092-8674(91)90193-3. [DOI] [PubMed] [Google Scholar]
  42. Lichter P., Tang C. J., Call K., Hermanson G., Evans G. A., Housman D., Ward D. C. High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science. 1990 Jan 5;247(4938):64–69. doi: 10.1126/science.2294592. [DOI] [PubMed] [Google Scholar]
  43. Litt M., Luty J. A. A hypervariable microsatellite revealed by in vitro amplification of a dinucleotide repeat within the cardiac muscle actin gene. Am J Hum Genet. 1989 Mar;44(3):397–401. [PMC free article] [PubMed] [Google Scholar]
  44. Little R. D., Pilia G., Johnson S., D'Urso M., Schlessinger D. Yeast artificial chromosomes spanning 8 megabases and 10-15 centimorgans of human cytogenetic band Xq26. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):177–181. doi: 10.1073/pnas.89.1.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. McGrath J. P., Varshavsky A. The yeast STE6 gene encodes a homologue of the mammalian multidrug resistance P-glycoprotein. Nature. 1989 Aug 3;340(6232):400–404. doi: 10.1038/340400a0. [DOI] [PubMed] [Google Scholar]
  47. Mercer J. F., Livingston J., Hall B., Paynter J. A., Begy C., Chandrasekharappa S., Lockhart P., Grimes A., Bhave M., Siemieniak D. Isolation of a partial candidate gene for Menkes disease by positional cloning. Nat Genet. 1993 Jan;3(1):20–25. doi: 10.1038/ng0193-20. [DOI] [PubMed] [Google Scholar]
  48. Nathans D. Restriction endonucleases, simian virus 40, and the new genetics. Science. 1979 Nov 23;206(4421):903–909. doi: 10.1126/science.228393. [DOI] [PubMed] [Google Scholar]
  49. Oliver S. G., van der Aart Q. J., Agostoni-Carbone M. L., Aigle M., Alberghina L., Alexandraki D., Antoine G., Anwar R., Ballesta J. P., Benit P. The complete DNA sequence of yeast chromosome III. Nature. 1992 May 7;357(6373):38–46. doi: 10.1038/357038a0. [DOI] [PubMed] [Google Scholar]
  50. Olson M. V. A tale of two cities. Anal Chem. 1991 Apr 1;63(7):416A–420A. [PubMed] [Google Scholar]
  51. Olson M. V., Dutchik J. E., Graham M. Y., Brodeur G. M., Helms C., Frank M., MacCollin M., Scheinman R., Frank T. Random-clone strategy for genomic restriction mapping in yeast. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7826–7830. doi: 10.1073/pnas.83.20.7826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Olson M., Hood L., Cantor C., Botstein D. A common language for physical mapping of the human genome. Science. 1989 Sep 29;245(4925):1434–1435. doi: 10.1126/science.2781285. [DOI] [PubMed] [Google Scholar]
  53. Raymond M., Gros P., Whiteway M., Thomas D. Y. Functional complementation of yeast ste6 by a mammalian multidrug resistance mdr gene. Science. 1992 Apr 10;256(5054):232–234. doi: 10.1126/science.1348873. [DOI] [PubMed] [Google Scholar]
  54. Rommens J. M., Iannuzzi M. C., Kerem B., Drumm M. L., Melmer G., Dean M., Rozmahel R., Cole J. L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. doi: 10.1126/science.2772657. [DOI] [PubMed] [Google Scholar]
  55. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  56. Saiki R. K., Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. doi: 10.1126/science.2999980. [DOI] [PubMed] [Google Scholar]
  57. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Schellenberg G. D., Bird T. D., Wijsman E. M., Orr H. T., Anderson L., Nemens E., White J. A., Bonnycastle L., Weber J. L., Alonso M. E. Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14. Science. 1992 Oct 23;258(5082):668–671. doi: 10.1126/science.1411576. [DOI] [PubMed] [Google Scholar]
  59. Silverman G. A., Jockel J. I., Domer P. H., Mohr R. M., Taillon-Miller P., Korsmeyer S. J. Yeast artificial chromosome cloning of a two-megabase-size contig within chromosomal band 18q21 establishes physical linkage between BCL2 and plasminogen activator inhibitor type-2. Genomics. 1991 Feb;9(2):219–228. doi: 10.1016/0888-7543(91)90245-a. [DOI] [PubMed] [Google Scholar]
  60. Smith H. O. Nucleotide sequence specificity of restriction endonucleases. Science. 1979 Aug 3;205(4405):455–462. doi: 10.1126/science.377492. [DOI] [PubMed] [Google Scholar]
  61. Smith H. O., Wilcox K. W. A restriction enzyme from Hemophilus influenzae. I. Purification and general properties. J Mol Biol. 1970 Jul 28;51(2):379–391. doi: 10.1016/0022-2836(70)90149-x. [DOI] [PubMed] [Google Scholar]
  62. 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]
  63. Stallings R. L., Torney D. C., Hildebrand C. E., Longmire J. L., Deaven L. L., Jett J. H., Doggett N. A., Moyzis R. K. Physical mapping of human chromosomes by repetitive sequence fingerprinting. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6218–6222. doi: 10.1073/pnas.87.16.6218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Sulston J., Du Z., Thomas K., Wilson R., Hillier L., Staden R., Halloran N., Green P., Thierry-Mieg J., Qiu L. The C. elegans genome sequencing project: a beginning. Nature. 1992 Mar 5;356(6364):37–41. doi: 10.1038/356037a0. [DOI] [PubMed] [Google Scholar]
  65. 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]
  66. Tynan K., Olsen A., Trask B., de Jong P., Thompson J., Zimmermann W., Carrano A., Mohrenweiser H. Assembly and analysis of cosmid contigs in the CEA-gene family region of human chromosome 19. Nucleic Acids Res. 1992 Apr 11;20(7):1629–1636. doi: 10.1093/nar/20.7.1629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Verkerk A. J., Pieretti M., Sutcliffe J. S., Fu Y. H., Kuhl D. P., Pizzuti A., Reiner O., Richards S., Victoria M. F., Zhang F. P. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell. 1991 May 31;65(5):905–914. doi: 10.1016/0092-8674(91)90397-h. [DOI] [PubMed] [Google Scholar]
  68. Vulpe C., Levinson B., Whitney S., Packman S., Gitschier J. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nat Genet. 1993 Jan;3(1):7–13. doi: 10.1038/ng0193-7. [DOI] [PubMed] [Google Scholar]
  69. Weber J. L., May P. E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed] [Google Scholar]
  70. Weissenbach J., Gyapay G., Dib C., Vignal A., Morissette J., Millasseau P., Vaysseix G., Lathrop M. A second-generation linkage map of the human genome. Nature. 1992 Oct 29;359(6398):794–801. doi: 10.1038/359794a0. [DOI] [PubMed] [Google Scholar]
  71. Ziemin-van der Poel S., McCabe N. R., Gill H. J., Espinosa R., 3rd, Patel Y., Harden A., Rubinelli P., Smith S. D., LeBeau M. M., Rowley J. D. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10735–10739. doi: 10.1073/pnas.88.23.10735. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES