Gregory E. Crawford


Professor in Pediatrics

My research involves identifying gene regulatory elements across the genome to help us understand how chromatin structure dictates cell function and fate. For the last 30 years, mapping chromatin accessible sites has been the gold standard method to identify the location of active regulatory elements, including promoters, enhancers, silencers, and locus control regions. I have developed technologies that can identify most DNase I hypersensitive sites from potentially any cell type from any species with a sequenced genome. We are combining this data with other wet-lab and computational data types to better understand how these regulatory regions control global gene expression in a set of diverse tissues (normal and diseased) representative of the human body.

Appointments and Affiliations

  • Professor in Pediatrics
  • Associate Professor in Molecular Genetics and Microbiology
  • Affiliate of the Duke Regeneration Center

Contact Information

  • Office Location: Room 2111 CIEMAS, Durham, NC 27708
  • Office Phone: (919) 684-8196
  • Email Address:
  • Websites:


  • National Institutes of Health, 2006
  • Ph.D. University of Michigan, Ann Arbor, 2001

Courses Taught

  • UPGEN 778A: University Program in Genetics and Genomics Biological Solutions Module I
  • UPGEN 778B: University Program in Genetics and Genomics Biological Solutions Module Il

In the News

Representative Publications

  • Shibata, Y; Sheffield, NC; Fedrigo, O; Babbitt, CC; Wortham, M; Tewari, AK; London, D; Song, L; Lee, B-K; Iyer, VR; Parker, SCJ; Margulies, EH; Wray, GA; Furey, TS; Crawford, GE, Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection., Plos Genet, vol 8 no. 6 (2012) [10.1371/journal.pgen.1002789] [abs].
  • Reddy, TE; Gertz, J; Pauli, F; Kucera, KS; Varley, KE; Newberry, KM; Marinov, GK; Mortazavi, A; Williams, BA; Song, L; Crawford, GE; Wold, B; Willard, HF; Myers, RM, Effects of sequence variation on differential allelic transcription factor occupancy and gene expression., Genome Research, vol 22 no. 5 (2012), pp. 860-869 [10.1101/gr.131201.111] [abs].
  • Bischof, JM; Ott, CJ; Leir, S-H; Gosalia, N; Song, L; London, D; Furey, TS; Cotton, CU; Crawford, GE; Harris, A, A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function., Thorax, vol 67 no. 5 (2012), pp. 385-391 [10.1136/thoraxjnl-2011-200880] [abs].
  • Balasubramanian, D; Akhtar-Zaidi, B; Song, L; Bartels, CF; Veigl, M; Beard, L; Myeroff, L; Guda, K; Lutterbaugh, J; Willis, J; Crawford, GE; Markowitz, SD; Scacheri, PC, H3K4me3 inversely correlates with DNA methylation at a large class of non-CpG-island-containing start sites., Genome Medicine, vol 4 no. 5 (2012) [10.1186/gm346] [abs].
  • Degner, JF; Pai, AA; Pique-Regi, R; Veyrieras, J-B; Gaffney, DJ; Pickrell, JK; De Leon, S; Michelini, K; Lewellen, N; Crawford, GE; Stephens, M; Gilad, Y; Pritchard, JK, DNase I sensitivity QTLs are a major determinant of human expression variation., Nature, vol 482 no. 7385 (2012), pp. 390-394 [10.1038/nature10808] [abs].
  • Gaffney, DJ; Veyrieras, J-B; Degner, JF; Pique-Regi, R; Pai, AA; Crawford, GE; Stephens, M; Gilad, Y; Pritchard, JK, Dissecting the regulatory architecture of gene expression QTLs., Genome Biology, vol 13 no. 1 (2012) [10.1186/gb-2012-13-1-r7] [abs].
  • Lee, BK; Bhinge, AA; Battenhouse, A; McDaniell, RM; Liu, Z; Song, L; Ni, Y; Birney, E; Lieb, JD; Furey, TS; Crawford, GE; Iyer, VR, Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells., Genome Res, vol 22 no. 1 (2012), pp. 9-24 [10.1101/gr.127597.111] [abs].
  • Zhang, W; Wu, Y; Schnable, JC; Zeng, Z; Freeling, M; Crawford, GE; Jiang, J, High-resolution mapping of open chromatin in the rice genome., Genome Res, vol 22 no. 1 (2012), pp. 151-162 [10.1101/gr.131342.111] [abs].
  • Wu, W; Cheng, Y; Keller, CA; Ernst, J; Kumar, SA; Mishra, T; Morrissey, C; Dorman, CM; Chen, K-B; Drautz, D; Giardine, B; Shibata, Y; Song, L; Pimkin, M; Crawford, GE; Furey, TS; Kellis, M; Miller, W; Taylor, J; Schuster, SC; Zhang, Y; Chiaromonte, F; Blobel, GA; Weiss, MJ; Hardison, RC, Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration., Genome Res, vol 21 no. 10 (2011), pp. 1659-1671 [10.1101/gr.125088.111] [abs].
  • Song, L; Zhang, Z; Grasfeder, LL; Boyle, AP; Giresi, PG; Lee, B-K; Sheffield, NC; Gräf, S; Huss, M; Keefe, D; Liu, Z; London, D; McDaniell, RM; Shibata, Y; Showers, KA; Simon, JM; Vales, T; Wang, T; Winter, D; Zhang, Z; Clarke, ND; Birney, E; Iyer, VR; Crawford, GE; Lieb, JD; Furey, TS, Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity., Genome Res, vol 21 no. 10 (2011), pp. 1757-1767 [10.1101/gr.121541.111] [abs].
  • Tsumagari, K; Chang, S-C; Lacey, M; Baribault, C; Chittur, SV; Sowden, J; Tawil, R; Crawford, GE; Ehrlich, M, Gene expression during normal and FSHD myogenesis., Bmc Medical Genomics, vol 4 (2011) [10.1186/1755-8794-4-67] [abs].
  • Boyle, AP; Song, L; Lee, B-K; London, D; Keefe, D; Birney, E; Iyer, VR; Crawford, GE; Furey, TS, High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells., Genome Res, vol 21 no. 3 (2011), pp. 456-464 [10.1101/gr.112656.110] [abs].
  • Stitzel, ML; Sethupathy, P; Pearson, DS; Chines, PS; Song, L; Erdos, MR; Welch, R; Parker, SCJ; Boyle, AP; Scott, LJ; NISC Comparative Sequencing Program, ; Margulies, EH; Boehnke, M; Furey, TS; Crawford, GE; Collins, FS, Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci., Cell Metab, vol 12 no. 5 (2010), pp. 443-455 [10.1016/j.cmet.2010.09.012] [abs].
  • Birney, E; Lieb, JD; Furey, TS; Crawford, GE; Iyer, VR, Allele-specific and heritable chromatin signatures in humans., Hum Mol Genet, vol 19 no. R2 (2010), pp. R204-R209 [10.1093/hmg/ddq404] [abs].
  • Balasubramani, A; Shibata, Y; Crawford, GE; Baldwin, AS; Hatton, RD; Weaver, CT, Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli., Immunity, vol 33 no. 1 (2010), pp. 35-47 [10.1016/j.immuni.2010.07.004] [abs].
  • Schnetz, MP; Handoko, L; Akhtar-Zaidi, B; Bartels, CF; Pereira, CF; Fisher, AG; Adams, DJ; Flicek, P; Crawford, GE; Laframboise, T; Tesar, P; Wei, C-L; Scacheri, PC, CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression., Plos Genet, vol 6 no. 7 (2010) [10.1371/journal.pgen.1001023] [abs].
  • Mukasa, R; Balasubramani, A; Lee, YK; Whitley, SK; Weaver, BT; Shibata, Y; Crawford, GE; Hatton, RD; Weaver, CT, Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage., Immunity, vol 32 no. 5 (2010), pp. 616-627 [10.1016/j.immuni.2010.04.016] [abs].
  • McDaniell, R; Lee, B-K; Song, L; Liu, Z; Boyle, AP; Erdos, MR; Scott, LJ; Morken, MA; Kucera, KS; Battenhouse, A; Keefe, D; Collins, FS; Willard, HF; Lieb, JD; Furey, TS; Crawford, GE; Iyer, VR; Birney, E, Heritable individual-specific and allele-specific chromatin signatures in humans., Science, vol 328 no. 5975 (2010), pp. 235-239 [10.1126/science.1184655] [abs].
  • Song, L; Crawford, GE, DNase-seq: a high-resolution technique for mapping active gene regulatory elements across the genome from mammalian cells., Cold Spring Harbor Protocols, vol 2010 no. 2 (2010) [10.1101/pdb.prot5384] [abs].
  • Xu, X; Tsumagari, K; Sowden, J; Tawil, R; Boyle, AP; Song, L; Furey, TS; Crawford, GE; Ehrlich, M, DNaseI hypersensitivity at gene-poor, FSH dystrophy-linked 4q35.2., Nucleic Acids Research, vol 37 no. 22 (2009), pp. 7381-7393 [10.1093/nar/gkp833] [abs].
  • Ott, CJ; Blackledge, NP; Kerschner, JL; Leir, S-H; Crawford, GE; Cotton, CU; Harris, A, Intronic enhancers coordinate epithelial-specific looping of the active CFTR locus., Proc Natl Acad Sci U S A, vol 106 no. 47 (2009), pp. 19934-19939 [10.1073/pnas.0900946106] [abs].
  • Heintzman, ND; Hon, GC; Hawkins, RD; Kheradpour, P; Stark, A; Harp, LF; Ye, Z; Lee, LK; Stuart, RK; Ching, CW; Ching, KA; Antosiewicz-Bourget, JE; Liu, H; Zhang, X; Green, RD; Lobanenkov, VV; Stewart, R; Thomson, JA; Crawford, GE; Kellis, M; Ren, B, Histone modifications at human enhancers reflect global cell-type-specific gene expression., Nature, vol 459 no. 7243 (2009), pp. 108-112 [10.1038/nature07829] [abs].
  • Ott, CJ; Suszko, M; Blackledge, NP; Wright, JE; Crawford, GE; Harris, A, A complex intronic enhancer regulates expression of the CFTR gene by direct interaction with the promoter., Journal of Cellular and Molecular Medicine, vol 13 no. 4 (2009), pp. 680-692 [10.1111/j.1582-4934.2008.00621.x] [abs].
  • Bina, M; Wyss, P; Lazarus, SA; Shah, SR; Ren, W; Szpankowski, W; Crawford, GE; Park, SP; Song, XC, Discovering sequences with potential regulatory characteristics., Genomics, vol 93 no. 4 (2009), pp. 314-322 [10.1016/j.ygeno.2008.11.008] [abs].
  • Schnetz, MP; Bartels, CF; Shastri, K; Balasubramanian, D; Zentner, GE; Balaji, R; Zhang, X; Song, L; Wang, Z; Laframboise, T; Crawford, GE; Scacheri, PC, Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns., Genome Research, vol 19 no. 4 (2009), pp. 590-601 [10.1101/gr.086983.108] [abs].
  • Shibata, Y; Crawford, GE, Mapping regulatory elements by DNaseI hypersensitivity chip (DNase-Chip)., Methods in Molecular Biology (Clifton, N.J.), vol 556 (2009), pp. 177-190 [10.1007/978-1-60327-192-9_13] [abs].
  • Boyle, AP; Guinney, J; Crawford, GE; Furey, TS, F-Seq: a feature density estimator for high-throughput sequence tags., Bioinformatics, vol 24 no. 21 (2008), pp. 2537-2538 [10.1093/bioinformatics/btn480] [abs].
  • Boyle, AP; Davis, S; Shulha, HP; Meltzer, P; Margulies, EH; Weng, Z; Furey, TS; Crawford, GE, High-resolution mapping and characterization of open chromatin across the genome., Cell, vol 132 no. 2 (2008), pp. 311-322 [10.1016/j.cell.2007.12.014] [abs].
  • Eguchi, J; Yan, Q-W; Schones, DE; Kamal, M; Hsu, C-H; Zhang, MQ; Crawford, GE; Rosen, ED, Interferon regulatory factors are transcriptional regulators of adipogenesis., Cell Metabolism, vol 7 no. 1 (2008), pp. 86-94 [10.1016/j.cmet.2007.11.002] [abs].
  • Xi, H; Shulha, HP; Lin, JM; Vales, TR; Fu, Y; Bodine, DM; McKay, RDG; Chenoweth, JG; Tesar, PJ; Furey, TS; Ren, B; Weng, Z; Crawford, GE, Identification and characterization of cell type-specific and ubiquitous chromatin regulatory structures in the human genome., Plos Genet, vol 3 no. 8 (2007) [10.1371/journal.pgen.0030136] [abs].
  • ENCODE Project Consortium, ; Birney, E; Stamatoyannopoulos, JA; Dutta, A; Guigó, R; Gingeras, TR; Margulies, EH; Weng, Z; Snyder, M; Dermitzakis, ET; Thurman, RE; Kuehn, MS; Taylor, CM; Neph, S; Koch, CM; Asthana, S; Malhotra, A; Adzhubei, I; Greenbaum, JA; Andrews, RM; Flicek, P; Boyle, PJ; Cao, H; Carter, NP; Clelland, GK; Davis, S; Day, N; Dhami, P; Dillon, SC; Dorschner, MO; Fiegler, H; Giresi, PG; Goldy, J; Hawrylycz, M; Haydock, A; Humbert, R; James, KD; Johnson, BE; Johnson, EM; Frum, TT; Rosenzweig, ER; Karnani, N; Lee, K; Lefebvre, GC; Navas, PA; Neri, F; Parker, SCJ; Sabo, PJ; Sandstrom, R; Shafer, A; Vetrie, D; Weaver, M; Wilcox, S; Yu, M; Collins, FS; Dekker, J; Lieb, JD; Tullius, TD; Crawford, GE; Sunyaev, S; Noble, WS; Dunham, I; Denoeud, F; Reymond, A; Kapranov, P; Rozowsky, J; Zheng, D; Castelo, R; Frankish, A; Harrow, J; Ghosh, S; Sandelin, A; Hofacker, IL; Baertsch, R; Keefe, D; Dike, S; Cheng, J; Hirsch, HA; Sekinger, EA; Lagarde, J; Abril, JF; Shahab, A; Flamm, C; Fried, C; Hackermüller, J; Hertel, J; Lindemeyer, M; Missal, K; Tanzer, A; Washietl, S; Korbel, J; Emanuelsson, O; Pedersen, JS; Holroyd, N; Taylor, R; Swarbreck, D; Matthews, N; Dickson, MC; Thomas, DJ; Weirauch, MT; Gilbert, J; Drenkow, J; Bell, I; Zhao, X; Srinivasan, KG; Sung, W-K; Ooi, HS; Chiu, KP; Foissac, S; Alioto, T; Brent, M; Pachter, L; Tress, ML; Valencia, A; Choo, SW; Choo, CY; Ucla, C; Manzano, C; Wyss, C; Cheung, E; Clark, TG; Brown, JB; Ganesh, M; Patel, S; Tammana, H; Chrast, J; Henrichsen, CN; Kai, C; Kawai, J; Nagalakshmi, U; Wu, J; Lian, Z; Lian, J; Newburger, P; Zhang, X; Bickel, P; Mattick, JS; Carninci, P; Hayashizaki, Y; Weissman, S; Hubbard, T; Myers, RM; Rogers, J; Stadler, PF; Lowe, TM; Wei, C-L; Ruan, Y; Struhl, K; Gerstein, M; Antonarakis, SE; Fu, Y; Green, ED; Karaöz, U; Siepel, A; Taylor, J; Liefer, LA; Wetterstrand, KA; Good, PJ; Feingold, EA; Guyer, MS; Cooper, GM; Asimenos, G; Dewey, CN; Hou, M; Nikolaev, S; Montoya-Burgos, JI; Löytynoja, A; Whelan, S; Pardi, F; Massingham, T; Huang, H; Zhang, NR; Holmes, I; Mullikin, JC; Ureta-Vidal, A; Paten, B; Seringhaus, M; Church, D; Rosenbloom, K; Kent, WJ; Stone, EA; NISC Comparative Sequencing Program, ; Baylor College of Medicine Human Genome Sequencing Center, ; Washington University Genome Sequencing Center, ; Broad Institute, ; Children's Hospital Oakland Research Institute, ; Batzoglou, S; Goldman, N; Hardison, RC; Haussler, D; Miller, W; Sidow, A; Trinklein, ND; Zhang, ZD; Barrera, L; Stuart, R; King, DC; Ameur, A; Enroth, S; Bieda, MC; Kim, J; Bhinge, AA; Jiang, N; Liu, J; Yao, F; Vega, VB; Lee, CWH; Ng, P; Yang, A; Moqtaderi, Z; Zhu, Z; Xu, X; Squazzo, S; Oberley, MJ; Inman, D; Singer, MA; Richmond, TA; Munn, KJ; Rada-Iglesias, A; Wallerman, O; Komorowski, J; Fowler, JC; Couttet, P; Bruce, AW; Dovey, OM; Ellis, PD; Langford, CF; Nix, DA; Euskirchen, G; Hartman, S; Urban, AE; Kraus, P; Van Calcar, S; Heintzman, N; Kim, TH; Wang, K; Qu, C; Hon, G; Luna, R; Glass, CK; Rosenfeld, MG; Aldred, SF; Cooper, SJ; Halees, A; Lin, JM; Shulha, HP; Zhang, X; Xu, M; Haidar, JNS; Yu, Y; Iyer, VR; Green, RD; Wadelius, C; Farnham, PJ; Ren, B; Harte, RA; Hinrichs, AS; Trumbower, H; Clawson, H; Hillman-Jackson, J; Zweig, AS; Smith, K; Thakkapallayil, A; Barber, G; Kuhn, RM; Karolchik, D; Armengol, L; Bird, CP; de Bakker, PIW; Kern, AD; Lopez-Bigas, N; Martin, JD; Stranger, BE; Woodroffe, A; Davydov, E; Dimas, A; Eyras, E; Hallgrímsdóttir, IB; Huppert, J; Zody, MC; Abecasis, GR; Estivill, X; Bouffard, GG; Guan, X; Hansen, NF; Idol, JR; Maduro, VVB; Maskeri, B; McDowell, JC; Park, M; Thomas, PJ; Young, AC; Blakesley, RW; Muzny, DM; Sodergren, E; Wheeler, DA; Worley, KC; Jiang, H; Weinstock, GM; Gibbs, RA; Graves, T; Fulton, R; Mardis, ER; Wilson, RK; Clamp, M; Cuff, J; Gnerre, S; Jaffe, DB; Chang, JL; Lindblad-Toh, K; Lander, ES; Koriabine, M; Nefedov, M; Osoegawa, K; Yoshinaga, Y; Zhu, B; de Jong, PJ, Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project., Nature, vol 447 no. 7146 (2007), pp. 799-816 [10.1038/nature05874] [abs].
  • Heintzman, ND; Stuart, RK; Hon, G; Fu, Y; Ching, CW; Hawkins, RD; Barrera, LO; Van Calcar, S; Qu, C; Ching, KA; Wang, W; Weng, Z; Green, RD; Crawford, GE; Ren, B, Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome., Nature Genetics, vol 39 no. 3 (2007), pp. 311-318 [10.1038/ng1966] [abs].
  • Nagel, S; Scherr, M; Kel, A; Hornischer, K; Crawford, GE; Kaufmann, M; Meyer, C; Drexler, HG; MacLeod, RAF, Activation of TLX3 and NKX2-5 in t(5;14)(q35;q32) T-cell acute lymphoblastic leukemia by remote 3'-BCL11B enhancers and coregulation by PU.1 and HMGA1., Cancer Research, vol 67 no. 4 (2007), pp. 1461-1471 [10.1158/0008-5472.CAN-06-2615] [abs].
  • Bernat, JA; Crawford, GE; Ogurtsov, AY; Collins, FS; Ginsburg, D; Kondrashov, AS, Distant conserved sequences flanking endothelial-specific promoters contain tissue-specific DNase-hypersensitive sites and over-represented motifs., Human Molecular Genetics, vol 15 no. 13 (2006), pp. 2098-2105 [10.1093/hmg/ddl133] [abs].
  • Crawford, GE; Davis, S; Scacheri, PC; Renaud, G; Halawi, MJ; Erdos, MR; Green, R; Meltzer, PS; Wolfsberg, TG; Collins, FS, DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays., Nature Methods, vol 3 no. 7 (2006), pp. 503-509 [10.1038/nmeth888] [abs].
  • Lewinski, MK; Yamashita, M; Emerman, M; Ciuffi, A; Marshall, H; Crawford, G; Collins, F; Shinn, P; Leipzig, J; Hannenhalli, S; Berry, CC; Ecker, JR; Bushman, FD, Retroviral DNA integration: viral and cellular determinants of target-site selection., Plos Pathog, vol 2 no. 6 (2006) [10.1371/journal.ppat.0020060] [abs].
  • Scacheri, PC; Davis, S; Odom, DT; Crawford, GE; Perkins, S; Halawi, MJ; Agarwal, SK; Marx, SJ; Spiegel, AM; Meltzer, PS; Collins, FS, Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis., Plos Genet, vol 2 no. 4 (2006) [10.1371/journal.pgen.0020051] [abs].
  • Yan, J; Xu, L; Crawford, G; Wang, Z; Burgess, SM, The forkhead transcription factor FoxI1 remains bound to condensed mitotic chromosomes and stably remodels chromatin structure., Molecular and Cellular Biology, vol 26 no. 1 (2006), pp. 155-168 [10.1128/MCB.26.1.155-168.2006] [abs].
  • Crawford, GE; Holt, IE; Whittle, J; Webb, BD; Tai, D; Davis, S; Margulies, EH; Chen, Y; Bernat, JA; Ginsburg, D; Zhou, D; Luo, S; Vasicek, TJ; Daly, MJ; Wolfsberg, TG; Collins, FS, Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS)., Genome Research, vol 16 no. 1 (2006), pp. 123-131 [10.1101/gr.4074106] [abs].
  • Scacheri, PC; Crawford, GE; Davis, S, Statistics for ChIP-chip and DNase hypersensitivity experiments on NimbleGen arrays., Methods in Enzymology, vol 411 (2006), pp. 270-282 [10.1016/S0076-6879(06)11014-9] [abs].
  • Crawford, GE; Holt, IE; Mullikin, JC; Tai, D; Blakesley, R; Bouffard, G; Young, A; Masiello, C; Green, ED; Wolfsberg, TG; Collins, FS; National Institutes Of Health Intramural Sequencing Center,, Identifying gene regulatory elements by genome-wide recovery of DNase hypersensitive sites., Proceedings of the National Academy of Sciences of the United States of America, vol 101 no. 4 (2004), pp. 992-997 [10.1073/pnas.0307540100] [abs].
  • Crawford, GE; Lu, QL; Partridge, TA; Chamberlain, JS, Suppression of revertant fibers in mdx mice by expression of a functional dystrophin., Human Molecular Genetics, vol 10 no. 24 (2001), pp. 2745-2750 [10.1093/hmg/10.24.2745] [abs].
  • Crawford, GE; Faulkner, JA; Crosbie, RH; Campbell, KP; Froehner, SC; Chamberlain, JS, Assembly of the dystrophin-associated protein complex does not require the dystrophin COOH-terminal domain., The Journal of Cell Biology, vol 150 no. 6 (2000), pp. 1399-1410 [10.1083/jcb.150.6.1399] [abs].
  • Lumeng, C; Phelps, S; Crawford, GE; Walden, PD; Barald, K; Chamberlain, JS, Interactions between beta 2-syntrophin and a family of microtubule-associated serine/threonine kinases., Nature Neuroscience, vol 2 no. 7 (1999), pp. 611-617 [10.1038/10165] [abs].