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Annual Review of Genomics and Human Genetics

Volume 16, 2015

A Mathematician's Odyssey

Abstract

In this overview of my research, I have aimed to give the background as to how I came to be involved in my various areas of interest, with an emphasis on the early phases of my career, which largely determined my future directions. I had the enormous good fortune to have worked under two of the most outstanding scientists of the twentieth century, R.A. Fisher and Joshua Lederberg. From mathematics and statistics, I went to population genetics and the early use of computers for modeling and simulation. Molecular biology took me into the laboratory and eventually to somatic cell genetics and human gene mapping. One chance encounter led me into the HLA field and another led me into research on cancer, especially colorectal cancer. On the way, I became a champion of the Human Genome Project and of the need for scientists to help promote the public understanding of science.

Keyword(s): Autobiography, cancer, HLA, human genome project, linkage disequilibrium, somatic cell genetics
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2015-08-24
2025-04-24
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Literature Cited

  1. Amiel J. 1.  1967. Study of leucocyte phenotypes in Hodgkin's disease. Histocompatibility Testing 1967: Report of a Conference and Workshop, Torino and Saint-Vincent, Italy, 14–24 June 1967 ES Curtoni, PL Mattiuz, RM Tosi 79–81 Copenhagen, Den: Munksgaard [Google Scholar]
  2. Arce-Gomez B, Jones EA, Barnstable CJ, Solomon E, Bodmer WF. 2.  1978. The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for β2 microglobulin. Tissue Antigens 11:96–112 [Google Scholar]
  3. Arklie J, Taylor-Papadimitriou J, Bodmer WF, Egan M, Millis R. 3.  1981. Differentiation antigens expressed by epithelial cells in the lactating breast are also detectable in breast cancers. Int. J. Cancer 28:23–29 [Google Scholar]
  4. Ashraf SQ, Nicholls AM, Wilding JL, Ntouroupia TG, Mortensen NJ, Bodmer WF. 4.  2012. Direct and immune mediated antibody targeting of ERBB receptors in a colorectal cancer cell-line panel. PNAS 109:21046–51 [Google Scholar]
  5. Barnstable CJ, Bodmer WF, Brown G, Galfre G, Milstein C. 5.  et al. 1978. Production of monoclonal antibodies to group A erythrocytes HLA and other human cell surface antigens—new tools for genetic analysis. Cell 14:8–20 [Google Scholar]
  6. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. 6.  1987. Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329:506–12 [Google Scholar]
  7. Bobrow M, Cross J. 7.  1974. Differential staining of human and mouse chromosomes in interspecific cell hybrids. Nature 251:77–79 [Google Scholar]
  8. Bodmer JG. 8.  1980. The HLA system: the HLA-DR antigens and HLA haplotypes in 24 populations. Population Structure and Genetic Disorders AW Eriksson, H Forsius, HR Nevanlinna, PL Workman, RK Norio 211–38 San Diego, CA: Academic [Google Scholar]
  9. Bodmer JG, Bodmer WF. 9.  1973. Population genetics of the HL-A system. A summary of data from the Fifth International Histocompatibility Testing Workshop. Isr. J. Med. Sci. 9:1257–68 [Google Scholar]
  10. Bodmer JG, Bodmer WF, Payne R, Terasaki P, Vredovoe D. 10.  1966. Leukocyte antigens in man: a comparison of lymphocytotoxic and agglutination assays for their detection. Nature 210:28–31 [Google Scholar]
  11. Bodmer WF. 11.  1960. The genetics of homostyly in populations of Primula vulgaris. Philos. Trans. R. Soc. B 242:517–49 [Google Scholar]
  12. Bodmer WF. 12.  1972. Evolutionary significance of the HL-A system. Nature 237:139–45 [Google Scholar]
  13. Bodmer WF. 13.  1972. Genetic factors in Hodgkin's disease: association with a disease susceptibility locus (DS-A) in the HL-A region. Natl. Cancer Inst. Monogr. 36:127–34 [Google Scholar]
  14. Bodmer WF. 14.  1981. The William Allan Memorial Award Address: Gene clusters, genome organization, and complex phenotypes. When the sequence is known, what will it mean?. Am. J. Hum. Genet. 33:664–82 [Google Scholar]
  15. Bodmer WF. 15.  1986. Human genetics: the molecular challenge. Cold Spring Harb. Symp. Quant. Biol. 51:1–13 [Google Scholar]
  16. Bodmer WF. 16.  1993. The genetics of Celtic populations. The Rhys Lecture to the British Academy, March 1992. Proc. Br. Acad. 82:37–57 [Google Scholar]
  17. Bodmer WF. 17.  1996. The Somatic Evolution of Cancer: The Harveian Oration London: R. Coll. Physicans [Google Scholar]
  18. Bodmer WF. 18.  1999. Familial adenomatous polyposis (FAP) and its gene, APC. Cytogenet. Cell Genet. 86:99–104 [Google Scholar]
  19. Bodmer WF. 19.  2008. Genetic instability is not a requirement for tumor development. Cancer Res. 68:3558–603560–61 [Google Scholar]
  20. Bodmer WF. 20.  2010. Public understanding of science: the BA, the Royal Society and COPUS notes. Rec. R. Soc. 64:S151–61 [Google Scholar]
  21. Bodmer WF. 21.  2013. The Human Genome Project. Brenner's Encyclopedia of Genetics 3 S Maloy, K Hughes 552–54 London: Academic, 2nd. http://www.sciencedirect.com/science/article/pii/B9780123749840007464 [Google Scholar]
  22. Bodmer WF. 22.  2015. Genetic characterization of human populations: from ABO to a genetic map of the British people. Genetics 199:267–79 [Google Scholar]
  23. Bodmer WF, Bailey CJ, Bodmer JG, Bussey HJR, Ellis A. 23.  et al. 1987. Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature 328:614–16 [Google Scholar]
  24. Bodmer WF, Bodmer JG, Adler S, Payne R, Bialek J. 24.  1966. Genetics of “4” and “LA” human leukocyte groups. Ann. N.Y. Acad. Sci. 129:473–89 [Google Scholar]
  25. Bodmer WF, Bonilla C. 25.  2008. Common and rare variants in multifactorial susceptibility to common diseases. Nat. Genet. 40:695–701 [Google Scholar]
  26. Bodmer WF, Cavalli-Sforza LL. 26.  1970. Intelligence and race. Sci. Am. 223:19–29 [Google Scholar]
  27. Bodmer WF, Felsenstein J. 27.  1967. Linkage and selection: theoretical analysis of the deterministic two locus random mating model. Genetics 57:237–65 [Google Scholar]
  28. Bodmer WF, Parsons PA. 28.  1962. Linkage and recombination in evolution. Adv. Genet. 11:1–100 [Google Scholar]
  29. Bodmer WF, Tripp M, Bodmer JG. 29.  1967. Application of a fluorochromatic cytotoxicity assay to human leukocyte typing. Histocompatibility Testing 1967: Report of a Conference and Workshop, Torino and Saint-Vincent, Italy, 14–24 June 1967 ES Curtoni, PL Mattiuz, RM Tosi 341–50 Copenhagen, Den: Munksgaard [Google Scholar]
  30. Botstein D, White RL, Skolnick M, Davis RW. 30.  1980. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am. J. Hum. Genet. 32:314–31 [Google Scholar]
  31. Brodsky FM, Parham P, Barnstable CJ, Crumpton MJ, Bodmer WF. 31.  1979. Monoclonal antibodies for analysis of the HLA system. Immunol. Rev. 47:3–61 [Google Scholar]
  32. Cavalli-Sforza LL, Bodmer WF. 32.  1971. The Genetics of Human Populations San Francisco: Freeman [Google Scholar]
  33. Cavanee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R. 33.  et al. 1983. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305:779–84 [Google Scholar]
  34. Cottrell S, Bicknell D, Kaklamanis L, Bodmer WF. 34.  1992. Molecular analysis of APC mutations in familial adenomatous polyposis and sporadic colon carcinomas. Lancet 340:626–30 [Google Scholar]
  35. Fearnhead NS, Wilding JL, Winney B, Tonks S, Bartlett S. 35.  et al. 2004. Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas. PNAS 101:15992–97 [Google Scholar]
  36. Feldman M, Nabholz M, Bodmer WF. 36.  1969. The evolution of the Rh polymorphism: a model for the interaction of incompatibility, reproductive compensation and heterozygote advantage. Am. J. Hum. Genet. 21:171–93 [Google Scholar]
  37. Frayling IM, Beck N, Ilyas M, Dove-Edwin I, Goodman P. 37.  et al. 1998. The APC variants I1307K and E1317Q are associated with colorectal tumors, but not always with a family history. PNAS 95:10722–27 [Google Scholar]
  38. Grumet FC, Coukell A, Bodmer JG, Bodmer WF, McDevitt HO. 38.  1971. Histocompatibility antigens associated with systemic lupus erythematosus: a possible genetic predisposition to disease. N. Engl. J. Med. 285:193–96 [Google Scholar]
  39. Heisterkamp N, Groffen J, Stephenson JR, Spurr NK, Goodfellow PN. 39.  et al. 1982. Chromosomal localisation of human cellular homologues of two viral oncogenes. Nature 299:747–49 [Google Scholar]
  40. Ilyas M, Tomlinson IPM, Rowan A, Pignatelli M, Bodmer WF. 40.  1997. β-Catenin mutations in cell lines established from human colorectal cancers. PNAS 94:10330–34 [Google Scholar]
  41. Johnston MD, Edwards CM, Bodmer WF, Maini PK, Chapman SJ. 41.  2007. Mathematical modeling of cell population dynamics in the colonic crypt and in colorectal cancer. PNAS 104:4008–13 [Google Scholar]
  42. Jones EA, Goodfellow PN, Bodmer JG, Bodmer WF. 42.  1975. Serological identification of HL-A-linked human “Ia-type” antigens. Nature 256:650–52 [Google Scholar]
  43. Kimura M. 43.  1956. A model of a genetic system which leads to closer linkage by natural selection. Evolution 10:278–87 [Google Scholar]
  44. Lawson DJ, Hellenthal G, Myers S, Falush D. 44.  2012. Inference of population structure using dense haplotype data. PLOS Genet. 8:e1004224 [Google Scholar]
  45. Lee JS, Trowsdale J, Bodmer WF. 45.  1982. cDNA clones coding for the heavy chain of human HLA-DR antigen. PNAS 79:545–49 [Google Scholar]
  46. Lee JS, Trowsdale J, Travers PJ, Carey J, Grosveld F. 46.  et al. 1982. Sequence of an HLA-DR α-chain cDNA clone and intron-exon organization of the corresponding gene. Nature 299:750–52 [Google Scholar]
  47. Leslie S, Winney B, Hellenthal G, Davison D, Boumertit A. 47.  et al. 2015. The fine-scale genetic structure of the British population. Nature 519:309–14 [Google Scholar]
  48. Lewontin RC, Kojima K. 48.  1961. The evolutionary dynamics of complex polymorphisms. Evolution 14:458–72 [Google Scholar]
  49. Makin CA, Bobrow LG, Bodmer WF. 49.  1984. Monoclonal antibody to cytokeratin for use in routine histopathology. J. Clin. Pathol. 37:975–83 [Google Scholar]
  50. Maynard Smith J, Haigh J. 50.  1974. The hitch-hiking effect of a favourable gene. Genet. Res. 23:23–35 [Google Scholar]
  51. Nabholz M, Miggiano V, Bodmer WF. 51.  1969. Genetic analysis using human-mouse somatic cell hybrids. Nature 223:358–63 [Google Scholar]
  52. Parham P, Bodmer WF. 52.  1978. Monoclonal antibody to a human histocompatibility alloantigen HLA-A2. Nature 276:397–99 [Google Scholar]
  53. Payne R, Tripp M, Weigle J, Bodmer WF, Bodmer JG. 53.  1964. A new leukocyte isoantigen system in man. Cold Spring Harb. Symp. Quant. Biol. 29:285–95 [Google Scholar]
  54. Pritchard JK, Stephens M, Donnelly P. 54.  2000. Inference of population structure using multilocus genotype data.. Genetics 155:945–59 [Google Scholar]
  55. 55. R. Soc 1985. The public understanding of science Rep., R. Soc., London [Google Scholar]
  56. Rotman B, Papermaster BW. 56.  1966. Membrane properties of living mammalian cells as studied by enzymatic hydrolysis of fluorogenic esters. PNAS 55:134–41 [Google Scholar]
  57. Rowan AJ, Lamlum H, Ilyas M, Wheeler J, Straub J. 57.  et al. 2000. APC mutations in sporadic colorectal tumors: a new mutational “hotspot” and interdependence of the “two hits.”. PNAS 97:3352–57 [Google Scholar]
  58. Santachiara AS, Nabholz M, Miggiano V, Darlington AJ, Bodmer WF. 58.  1970. Genetic analysis with man-mouse hybrids: linkage between human lactate dehydrogenase B and peptidase B. Nature 227:248–51 [Google Scholar]
  59. Solomon E, Bodmer WF. 59.  1979. Evolution of sickle variant gene. Lancet 313:923 [Google Scholar]
  60. Solomon E, Voss R, Hall V, Bodmer WF, Jass JR. 60.  et al. 1987. Chromosome 5 allele loss in human colorectal carcinomas. Nature 328:616–19 [Google Scholar]
  61. Spielman RS, Lee J, Bodmer WF, Bodmer JG, Trowsdale J. 61.  1984. Six HLA-D region α-chain genes on human chromosome 6: polymorphisms and associations of DCα-related sequences with DR types. PNAS 81:3461–65 [Google Scholar]
  62. Sved JA, Reed TE, Bodmer WF. 62.  1967. The number of balanced polymorphisms which can be maintained in a natural population. Genetics 55:469–81 [Google Scholar]
  63. Terasaki PI, McClelland JD. 63.  1964. Microdropler assay of human scrum cytotoxins. Nature 204:998–1000 [Google Scholar]
  64. Tomlinson IPM, Bodmer WF. 64.  1995. Failure of programmed cell death and differentiation as causes of tumors: some simple mathematical models. PNAS 92:11130–34 [Google Scholar]
  65. Tomlinson IPM, Novelli MR, Bodmer WF. 65.  1996. The mutation rate and cancer. PNAS 93:14800–803 [Google Scholar]
  66. Tomlinson IPM, Sasieni P, Bodmer WF. 66.  2002. How many mutations in a cancer?. Am. J. Pathol 160:755–58 [Google Scholar]
  67. Trowsdale J, Lee J, Carey J, Grosveld F, Bodmer JG, Bodmer WF. 67.  1983. Sequences related to HLA-DRα chain on human chromosome 6: restriction enzyme polymorphism detected with DCα chain probes. PNAS 80:1972–76 [Google Scholar]
  68. Trowsdale J, Young JAT, Kelly AP, Austin PJ, Carson S. 68.  et al. 1985. Structure, sequence and polymorphism in the HLA-D region. Immunol. Rev 85:5–43 [Google Scholar]
  69. van Heyningen V, Bobrow M, Bodmer WF, Gardiner SE, Povey S, Hopkinson DA. 69.  1975. Chromosome assignment of some human enzyme loci: mitochondrial malate dehydrogenase to 7, mannosephosphate isomerase and pyruvate kinase to 15 and probably esterase D to 13. Ann. Hum. Genet 38:295–303 [Google Scholar]
  70. van Heyningen V, Craig I, Bodmer WF. 70.  1973. Genetic control of mitochondrial enzymes in human-mouse somatic cell hybrids. Nature 242:509–12 [Google Scholar]
  71. Weiss MC, Green H. 71.  1967. Human-mouse hybrid cell lines containing partial complements of human chromosomes and functioning human genes. PNAS 58:1104–11 [Google Scholar]
  72. Winney B, Boumertit A, Day T, Davison D, Echeta C. 72.  et al. 2012. People of the British Isles: preliminary analysis of genotypes and surnames in a UK-control population. Eur. J. Hum. Genet 20:203–10 [Google Scholar]
  73. Wong NACS, Britton MP, Choi GS, Stanton TK, Bicknell DC. 73.  et al. 2004. Loss of CDX1 expression in colorectal carcinoma: promoter methylation, mutation, and loss of heterozygosity analyses of 37 cell lines. PNAS 101:574–79 [Google Scholar]
  74. Wright S. 74.  1952. The genetics of quantitative variability. Quantitative Inheritance ECR Reeve, CH Waddington 5–41 London: Her Majesty's Station. Off. [Google Scholar]
  75. Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF. 75.  2010. Cancer stem cells from colorectal cancer-derived cell lines. PNAS 107:3722–27 [Google Scholar]
  76. Zallen DT, Burian RM. 76.  1992. On the beginnings of somatic cell hybridization: Boris Ephrussi and chromosome transplantation. Genetics 132:1–8 [Google Scholar]
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A Mathematician's Odyssey
Annual Review of Genomics and Human Genetics 16, 1 (2015); https://doi.org/10.1146/annurev-genom-090314-045856
/content/journals/10.1146/annurev-genom-090314-045856
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Supplementary Data

  • Download Supplemental Text (PDF).

    Download Supplemental Figures as a single PDF (also reproduced below).

    Supplemental Figure 1. Schematic model for synapsis and integration during Bacillus subtilis transformation. (I) Intact donor and recipient molecules. (II) Synapsis by segmental interchange of hydrogen bonding between donor and recipient strands. (III) Integration by breakage of strands (A, B) followed by repair of unpaired regions (C, D) using the unbroken strand as template and covalent linkage to recipient (donor) material. Figure reproduced from Reference 20 with permission from the Genetics Society of America.





    Supplemental Figure 2. (a) Cell line SW1222 lumens in collagen gels. Panel reproduced from Reference 48 with permission; copyright © 1988 by John Wiley & Sons, Inc. (b) A colony derived from a single SW1222 cell expresses all three types of colorectal epithelial cells. AUA1 stains for EpCAM, CDX1 stains mainly for enterocytes, chromogranin stains for enteroendocrine cells, and PR4D4 stains for goblet cells. Panel reproduced from Reference 63.

  • Article Type: Review Article

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