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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
. 1995 Nov 21;92(24):10841–10848. doi: 10.1073/pnas.92.24.10841

How is the Human Genome Project doing, and what have we learned so far?

M S Guyer 1, F S Collins 1
PMCID: PMC40527  PMID: 7479895

Abstract

In this paper, we describe the accomplishments of the initial phase of the Human Genome Project, with particular attention to the progress made toward achieving the defined goals for constructing genetic and physical maps of the human genome and determining the sequence of human DNA, identifying the complete set of human genes, and analyzing the need for adequate policies for using the information about human genetics in ways that maximize the benefits for individuals and society.

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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. Adams M. D., Kerlavage A. R., Fleischmann R. D., Fuldner R. A., Bult C. J., Lee N. H., Kirkness E. F., Weinstock K. G., Gocayne J. D., White O. Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. Nature. 1995 Sep 28;377(6547 Suppl):3–174. [PubMed] [Google Scholar]
  3. Anguiano A., Oates R. D., Amos J. A., Dean M., Gerrard B., Stewart C., Maher T. A., White M. B., Milunsky A. Congenital bilateral absence of the vas deferens. A primarily genital form of cystic fibrosis. JAMA. 1992 Apr 1;267(13):1794–1797. [PubMed] [Google Scholar]
  4. Ballabio A. The rise and fall of positional cloning? Nat Genet. 1993 Apr;3(4):277–279. doi: 10.1038/ng0493-277. [DOI] [PubMed] [Google Scholar]
  5. Bell C. J., Budarf M. L., Nieuwenhuijsen B. W., Barnoski B. L., Buetow K. H., Campbell K., Colbert A. M., Collins J., Daly M., Desjardins P. R. Integration of physical, breakpoint and genetic maps of chromosome 22. Localization of 587 yeast artificial chromosomes with 238 mapped markers. Hum Mol Genet. 1995 Jan;4(1):59–69. doi: 10.1093/hmg/4.1.59. [DOI] [PubMed] [Google Scholar]
  6. Boguski M. S., Lowe T. M., Tolstoshev C. M. dbEST--database for "expressed sequence tags". Nat Genet. 1993 Aug;4(4):332–333. doi: 10.1038/ng0893-332. [DOI] [PubMed] [Google Scholar]
  7. Brennan M. B., Hochgeschwender U. So many needles, so much hay. Hum Mol Genet. 1995 Feb;4(2):153–156. doi: 10.1093/hmg/4.2.153. [DOI] [PubMed] [Google Scholar]
  8. Brook J. D., McCurrach M. E., Harley H. G., Buckler A. J., Church D., Aburatani H., Hunter K., Stanton V. P., Thirion J. P., Hudson T. 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 Feb 21;68(4):799–808. doi: 10.1016/0092-8674(92)90154-5. [DOI] [PubMed] [Google Scholar]
  9. Brumley R. L., Jr, Smith L. M. Rapid DNA sequencing by horizontal ultrathin gel electrophoresis. Nucleic Acids Res. 1991 Aug 11;19(15):4121–4126. doi: 10.1093/nar/19.15.4121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brunner H. G., Nelen M., Breakefield X. O., Ropers H. H., van Oost B. A. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science. 1993 Oct 22;262(5133):578–580. doi: 10.1126/science.8211186. [DOI] [PubMed] [Google Scholar]
  11. Buetow K. H., Weber J. L., Ludwigsen S., Scherpbier-Heddema T., Duyk G. M., Sheffield V. C., Wang Z., Murray J. C. Integrated human genome-wide maps constructed using the CEPH reference panel. Nat Genet. 1994 Apr;6(4):391–393. doi: 10.1038/ng0494-391. [DOI] [PubMed] [Google Scholar]
  12. Carroll J. M., Goldsmith L. A. The latest fashions in skin disease. Mol Med. 1995 Jan;1(2):123–126. [PMC free article] [PubMed] [Google Scholar]
  13. Chance P. F., Alderson M. K., Leppig K. A., Lensch M. W., Matsunami N., Smith B., Swanson P. D., Odelberg S. J., Disteche C. M., Bird T. D. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell. 1993 Jan 15;72(1):143–151. doi: 10.1016/0092-8674(93)90058-x. [DOI] [PubMed] [Google Scholar]
  14. Chen E. Y., Schlessinger D., Kere J. Ordered shotgun sequencing, a strategy for integrated mapping and sequencing of YAC clones. Genomics. 1993 Sep;17(3):651–656. doi: 10.1006/geno.1993.1385. [DOI] [PubMed] [Google Scholar]
  15. Cherry J. L., Young H., Di Sera L. J., Ferguson F. M., Kimball A. W., Dunn D. M., Gesteland R. F., Weiss R. B. Enzyme-linked fluorescent detection for automated multiplex DNA sequencing. Genomics. 1994 Mar 1;20(1):68–74. doi: 10.1006/geno.1994.1128. [DOI] [PubMed] [Google Scholar]
  16. Chissoe S. L., Bodenteich A., Wang Y. F., Wang Y. P., Burian D., Clifton S. W., Crabtree J., Freeman A., Iyer K., Jian L. Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation. Genomics. 1995 May 1;27(1):67–82. doi: 10.1006/geno.1995.1008. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Church D. M., Stotler C. J., Rutter J. L., Murrell J. R., Trofatter J. A., Buckler A. J. Isolation of genes from complex sources of mammalian genomic DNA using exon amplification. Nat Genet. 1994 Jan;6(1):98–105. doi: 10.1038/ng0194-98. [DOI] [PubMed] [Google Scholar]
  19. Church G. M., Kieffer-Higgins S. Multiplex DNA sequencing. Science. 1988 Apr 8;240(4849):185–188. doi: 10.1126/science.3353714. [DOI] [PubMed] [Google Scholar]
  20. Cohen D., Chumakov I., Weissenbach J. A first-generation physical map of the human genome. Nature. 1993 Dec 16;366(6456):698–701. doi: 10.1038/366698a0. [DOI] [PubMed] [Google Scholar]
  21. Collins F. S. Positional cloning moves from perditional to traditional. Nat Genet. 1995 Apr;9(4):347–350. doi: 10.1038/ng0495-347. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Collins F., Galas D. A new five-year plan for the U.S. Human Genome Project. Science. 1993 Oct 1;262(5130):43–46. doi: 10.1126/science.8211127. [DOI] [PubMed] [Google Scholar]
  24. Collins J. E., Cole C. G., Smink L. J., Garrett C. L., Leversha M. A., Soderlund C. A., Maslen G. L., Everett L. A., Rice K. M., Coffey A. J. A high-density YAC contig map of human chromosome 22. Nature. 1995 Sep 28;377(6547 Suppl):367–379. doi: 10.1038/377367a0. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Cox D. R., Green E. D., Lander E. S., Cohen D., Myers R. M. Assessing mapping progress in the Human Genome Project. Science. 1994 Sep 30;265(5181):2031–2032. doi: 10.1126/science.8091223. [DOI] [PubMed] [Google Scholar]
  27. Delabar J. M., Créau N., Sinet P. M., Ritter O., Antonarakis S. E., Burmeister M., Chakravarti A., Nizetic D., Ohki M., Patterson D. Report of the Fourth International Workshop on Human Chromosome 21. Genomics. 1993 Dec;18(3):735–745. doi: 10.1016/s0888-7543(05)80390-8. [DOI] [PubMed] [Google Scholar]
  28. Dickson D. Consortium plans 'public' map of genome. Nature. 1994 Oct 13;371(6498):551–551. doi: 10.1038/371551a0. [DOI] [PubMed] [Google Scholar]
  29. Doggett N. A., Goodwin L. A., Tesmer J. G., Meincke L. J., Bruce D. C., Clark L. M., Altherr M. R., Ford A. A., Chi H. C., Marrone B. L. An integrated physical map of human chromosome 16. Nature. 1995 Sep 28;377(6547 Suppl):335–365. doi: 10.1038/377335a0. [DOI] [PubMed] [Google Scholar]
  30. Donis-Keller H., Dou S., Chi D., Carlson K. M., Toshima K., Lairmore T. C., Howe J. R., Moley J. F., Goodfellow P., Wells S. A., Jr Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet. 1993 Jul;2(7):851–856. doi: 10.1093/hmg/2.7.851. [DOI] [PubMed] [Google Scholar]
  31. Drmanac R., Labat I., Brukner I., Crkvenjakov R. Sequencing of megabase plus DNA by hybridization: theory of the method. Genomics. 1989 Feb;4(2):114–128. doi: 10.1016/0888-7543(89)90290-5. [DOI] [PubMed] [Google Scholar]
  32. Duyk G. M., Kim S. W., Myers R. M., Cox D. R. Exon trapping: a genetic screen to identify candidate transcribed sequences in cloned mammalian genomic DNA. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8995–8999. doi: 10.1073/pnas.87.22.8995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Edery P., Lyonnet S., Mulligan L. M., Pelet A., Dow E., Abel L., Holder S., Nihoul-Fékété C., Ponder B. A., Munnich A. Mutations of the RET proto-oncogene in Hirschsprung's disease. Nature. 1994 Jan 27;367(6461):378–380. doi: 10.1038/367378a0. [DOI] [PubMed] [Google Scholar]
  34. Fischer S. G., Cayanis E., Russo J. J., Sunjevaric I., Boukhgalter B., Zhang P., Yu M. T., Rothstein R., Warburton D., Edelman I. S. Assembly of ordered contigs of cosmids selected with YACs of human chromosome 13. Genomics. 1994 Jun;21(3):525–537. doi: 10.1006/geno.1994.1311. [DOI] [PubMed] [Google Scholar]
  35. Fleischmann R. D., Adams M. D., White O., Clayton R. A., Kirkness E. F., Kerlavage A. R., Bult C. J., Tomb J. F., Dougherty B. A., Merrick J. M. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995 Jul 28;269(5223):496–512. doi: 10.1126/science.7542800. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. 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]
  39. Fuchs E., Coulombe P. A. Of mice and men: genetic skin diseases of keratin. Cell. 1992 Jun 12;69(6):899–902. doi: 10.1016/0092-8674(92)90607-e. [DOI] [PubMed] [Google Scholar]
  40. Gemmill R. M., Chumakov I., Scott P., Waggoner B., Rigault P., Cypser J., Chen Q., Weissenbach J., Gardiner K., Wang H. A second-generation YAC contig map of human chromosome 3. Nature. 1995 Sep 28;377(6547 Suppl):299–319. doi: 10.1038/377299a0. [DOI] [PubMed] [Google Scholar]
  41. Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
  42. Hamer D. H., Hu S., Magnuson V. L., Hu N., Pattatucci A. M. A linkage between DNA markers on the X chromosome and male sexual orientation. Science. 1993 Jul 16;261(5119):321–327. doi: 10.1126/science.8332896. [DOI] [PubMed] [Google Scholar]
  43. Hauge X. Y., Litt M. A study of the origin of 'shadow bands' seen when typing dinucleotide repeat polymorphisms by the PCR. Hum Mol Genet. 1993 Apr;2(4):411–415. doi: 10.1093/hmg/2.4.411. [DOI] [PubMed] [Google Scholar]
  44. Hofstra R. M., Landsvater R. M., Ceccherini I., Stulp R. P., Stelwagen T., Luo Y., Pasini B., Höppener J. W., van Amstel H. K., Romeo G. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature. 1994 Jan 27;367(6461):375–376. doi: 10.1038/367375a0. [DOI] [PubMed] [Google Scholar]
  45. Jabs E. W., Li X., Scott A. F., Meyers G., Chen W., Eccles M., Mao J. I., Charnas L. R., Jackson C. E., Jaye M. Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. Nat Genet. 1994 Nov;8(3):275–279. doi: 10.1038/ng1194-275. [DOI] [PubMed] [Google Scholar]
  46. Khrapko K. R., Lysov YuP, Khorlyn A. A., Shick V. V., Florentiev V. L., Mirzabekov A. D. An oligonucleotide hybridization approach to DNA sequencing. FEBS Lett. 1989 Oct 9;256(1-2):118–122. doi: 10.1016/0014-5793(89)81730-2. [DOI] [PubMed] [Google Scholar]
  47. Khrapko K., Hanekamp J. S., Thilly W. G., Belenkii A., Foret F., Karger B. L. Constant denaturant capillary electrophoresis (CDCE): a high resolution approach to mutational analysis. Nucleic Acids Res. 1994 Feb 11;22(3):364–369. doi: 10.1093/nar/22.3.364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Kieleczawa J., Dunn J. J., Studier F. W. DNA sequencing by primer walking with strings of contiguous hexamers. Science. 1992 Dec 11;258(5089):1787–1791. doi: 10.1126/science.1465615. [DOI] [PubMed] [Google Scholar]
  49. Koop B. F., Rowen L., Wang K., Kuo C. L., Seto D., Lenstra J. A., Howard S., Shan W., Deshpande P., Hood L. The human T-cell receptor TCRAC/TCRDC (C alpha/C delta) region: organization, sequence, and evolution of 97.6 kb of DNA. Genomics. 1994 Feb;19(3):478–493. doi: 10.1006/geno.1994.1097. [DOI] [PubMed] [Google Scholar]
  50. Kostichka A. J., Marchbanks M. L., Brumley R. L., Jr, Drossman H., Smith L. M. High speed automated DNA sequencing in ultrathin slab gels. Biotechnology (N Y) 1992 Jan;10(1):78–81. doi: 10.1038/nbt0192-78. [DOI] [PubMed] [Google Scholar]
  51. Krauter K., Montgomery K., Yoon S. J., LeBlanc-Straceski J., Renault B., Marondel I., Herdman V., Cupelli L., Banks A., Lieman J. A second-generation YAC contig map of human chromosome 12. Nature. 1995 Sep 28;377(6547 Suppl):321–333. doi: 10.1038/377321a0. [DOI] [PubMed] [Google Scholar]
  52. Krizman D. B., Berget S. M. Efficient selection of 3'-terminal exons from vertebrate DNA. Nucleic Acids Res. 1993 Nov 11;21(22):5198–5202. doi: 10.1093/nar/21.22.5198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. La Spada A. R., Wilson E. M., Lubahn D. B., Harding A. E., Fischbeck K. H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature. 1991 Jul 4;352(6330):77–79. doi: 10.1038/352077a0. [DOI] [PubMed] [Google Scholar]
  54. Lajeunie E., Ma H. W., Bonaventure J., Munnich A., Le Merrer M., Renier D. FGFR2 mutations in Pfeiffer syndrome. Nat Genet. 1995 Feb;9(2):108–108. doi: 10.1038/ng0295-108. [DOI] [PubMed] [Google Scholar]
  55. 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]
  56. 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]
  57. Lovett M. Fishing for complements: finding genes by direct selection. Trends Genet. 1994 Oct;10(10):352–357. doi: 10.1016/0168-9525(94)90131-7. [DOI] [PubMed] [Google Scholar]
  58. Mahadevan M., Tsilfidis C., Sabourin L., Shutler G., Amemiya C., Jansen G., Neville C., Narang M., Barceló J., O'Hoy K. Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science. 1992 Mar 6;255(5049):1253–1255. doi: 10.1126/science.1546325. [DOI] [PubMed] [Google Scholar]
  59. Marshall E. A strategy for sequencing the genome 5 years early. Science. 1995 Feb 10;267(5199):783–784. doi: 10.1126/science.7846520. [DOI] [PubMed] [Google Scholar]
  60. Meng X., Benson K., Chada K., Huff E. J., Schwartz D. C. Optical mapping of lambda bacteriophage clones using restriction endonucleases. Nat Genet. 1995 Apr;9(4):432–438. doi: 10.1038/ng0495-432. [DOI] [PubMed] [Google Scholar]
  61. Muenke M., Schell U., Hehr A., Robin N. H., Losken H. W., Schinzel A., Pulleyn L. J., Rutland P., Reardon W., Malcolm S. A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. Nat Genet. 1994 Nov;8(3):269–274. doi: 10.1038/ng1194-269. [DOI] [PubMed] [Google Scholar]
  62. Mulligan L. M., Kwok J. B., Healey C. S., Elsdon M. J., Eng C., Gardner E., Love D. R., Mole S. E., Moore J. K., Papi L. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature. 1993 Jun 3;363(6428):458–460. doi: 10.1038/363458a0. [DOI] [PubMed] [Google Scholar]
  63. Olson M. V., Green P. Criterion for the completeness of large-scale physical maps of DNA. Cold Spring Harb Symp Quant Biol. 1993;58:349–355. doi: 10.1101/sqb.1993.058.01.041. [DOI] [PubMed] [Google Scholar]
  64. 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]
  65. Patel P. I., Lupski J. R. Charcot-Marie-Tooth disease: a new paradigm for the mechanism of inherited disease. Trends Genet. 1994 Apr;10(4):128–133. doi: 10.1016/0168-9525(94)90214-3. [DOI] [PubMed] [Google Scholar]
  66. Pease A. C., Solas D., Sullivan E. J., Cronin M. T., Holmes C. P., Fodor S. P. Light-generated oligonucleotide arrays for rapid DNA sequence analysis. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5022–5026. doi: 10.1073/pnas.91.11.5022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Rave-Harel N., Madgar I., Goshen R., Nissim-Rafinia M., Ziadni A., Rahat A., Chiba O., Kalman Y. M., Brautbar C., Levinson D. CFTR haplotype analysis reveals genetic heterogeneity in the etiology of congenital bilateral aplasia of the vas deferens. Am J Hum Genet. 1995 Jun;56(6):1359–1366. [PMC free article] [PubMed] [Google Scholar]
  68. Reardon W., Winter R. M., Rutland P., Pulleyn L. J., Jones B. M., Malcolm S. Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nat Genet. 1994 Sep;8(1):98–103. doi: 10.1038/ng0994-98. [DOI] [PubMed] [Google Scholar]
  69. Roa B. B., Dyck P. J., Marks H. G., Chance P. F., Lupski J. R. Dejerine-Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene. Nat Genet. 1993 Nov;5(3):269–273. doi: 10.1038/ng1193-269. [DOI] [PubMed] [Google Scholar]
  70. Roach J. C., Boysen C., Wang K., Hood L. Pairwise end sequencing: a unified approach to genomic mapping and sequencing. Genomics. 1995 Mar 20;26(2):345–353. doi: 10.1016/0888-7543(95)80219-c. [DOI] [PubMed] [Google Scholar]
  71. Romeo G., Ronchetto P., Luo Y., Barone V., Seri M., Ceccherini I., Pasini B., Bocciardi R., Lerone M., Käriäinen H. Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease. Nature. 1994 Jan 27;367(6461):377–378. doi: 10.1038/367377a0. [DOI] [PubMed] [Google Scholar]
  72. Rouquier S., Batzer M. A., Giorgi D. Application of bacterial artificial chromosomes to the generation of contiguous physical maps: a pilot study of human ryanodine receptor gene (RYR1) region. Anal Biochem. 1994 Mar;217(2):205–209. doi: 10.1006/abio.1994.1110. [DOI] [PubMed] [Google Scholar]
  73. Russell L. J., DiGiovanna J. J., Rogers G. R., Steinert P. M., Hashem N., Compton J. G., Bale S. J. Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis. Nat Genet. 1995 Mar;9(3):279–283. doi: 10.1038/ng0395-279. [DOI] [PubMed] [Google Scholar]
  74. Rutland P., Pulleyn L. J., Reardon W., Baraitser M., Hayward R., Jones B., Malcolm S., Winter R. M., Oldridge M., Slaney S. F. Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes. Nat Genet. 1995 Feb;9(2):173–176. doi: 10.1038/ng0295-173. [DOI] [PubMed] [Google Scholar]
  75. Schell U., Hehr A., Feldman G. J., Robin N. H., Zackai E. H., de Die-Smulders C., Viskochil D. H., Stewart J. M., Wolff G., Ohashi H. Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome. Hum Mol Genet. 1995 Mar;4(3):323–328. doi: 10.1093/hmg/4.3.323. [DOI] [PubMed] [Google Scholar]
  76. Shiang R., Thompson L. M., Zhu Y. Z., Church D. M., Fielder T. J., Bocian M., Winokur S. T., Wasmuth J. J. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell. 1994 Jul 29;78(2):335–342. doi: 10.1016/0092-8674(94)90302-6. [DOI] [PubMed] [Google Scholar]
  77. Smith M. W., Holmsen A. L., Wei Y. H., Peterson M., Evans G. A. Genomic sequence sampling: a strategy for high resolution sequence-based physical mapping of complex genomes. Nat Genet. 1994 May;7(1):40–47. doi: 10.1038/ng0594-40. [DOI] [PubMed] [Google Scholar]
  78. Tsui L. C. The spectrum of cystic fibrosis mutations. Trends Genet. 1992 Nov;8(11):392–398. doi: 10.1016/0168-9525(92)90301-j. [DOI] [PubMed] [Google Scholar]
  79. 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]
  80. Wilkie A. O., Slaney S. F., Oldridge M., Poole M. D., Ashworth G. J., Hockley A. D., Hayward R. D., David D. J., Pulleyn L. J., Rutland P. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet. 1995 Feb;9(2):165–172. doi: 10.1038/ng0295-165. [DOI] [PubMed] [Google Scholar]
  81. Woolley A. T., Mathies R. A. Ultra-high-speed DNA fragment separations using microfabricated capillary array electrophoresis chips. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11348–11352. doi: 10.1073/pnas.91.24.11348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Wu K. J., Shaler T. A., Becker C. H. Time-of-flight mass spectrometry of underivatized single-stranded DNA oligomers by matrix-assisted laser desorption. Anal Chem. 1994 May 15;66(10):1637–1645. doi: 10.1021/ac00082a007. [DOI] [PubMed] [Google Scholar]
  83. Yoshida K., Strathmann M. P., Mayeda C. A., Martin C. H., Palazzolo M. J. A simple and efficient method for constructing high resolution physical maps. Nucleic Acids Res. 1993 Jul 25;21(15):3553–3562. doi: 10.1093/nar/21.15.3553. [DOI] [PMC free article] [PubMed] [Google Scholar]

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