Methylomics

The sequencing of the human genome facilitated the application of the bisulphite methodology to the clinically significant methylated genome, or Methylome, a term coined by Feinberg (1). In this context, Human Genetic Signatures has focussed its Personalized Methylomics programs on the commercialization of early risk assessment for cancers and the commercialization of therapeutic avenues involving aging, cell reprogramming and autologous cell transplantation. This methylomics-based cellular therapeutics may allow for the amelioration of complex human diseases and drug treatment effects.

ref 1; 2001, Feinberg, Nature Genetics, 27, 9-10.

Historical Background

The modern era of Methylomics had its origins in the fields of genetics and embryology. It began in 1939 with Conrad Waddingtons concept of the epigenotype, a character whose mode of impression was over and above, or in addition to, the classical genotype (8). Waddington used this descriptor in terms of interrelated developmental pathways, a view which culminated in his famous description of the Epigenetic Landscape. Epigenetics moved from a genetics-based, to a methylation-based, to a CpG island-based, and more recently to genome-wide Methylomics, initiated by the seminal articles of Art Riggs, Robin Holliday and Adrian Bird and their associates(9-13). Robin Holliday is now a member of the Institutional Review Board of Human Genetic Signatures.

Molecular progress accelerated with the achievement of two significant milestones. The first was the development of a user-friendly technology for methylation assessment by Geoffrey Grigg, Douglas Millar and Marianne Frommer (2), and the second was the generation of the primary sequence of the human genome. Until the sequence of the human genome became available, snapshots of the methylation signatures of genomic regions were piecemeal. The combination of shotgun sequencing methodologies implemented by Craig Venter, Hamilton Smith and colleagues, together with the rapid bioinformatic genomic reconstruction pipelines developed by Gene Myers, and the cloning approaches adopted by the Genome Sequencing Consortium, provided the human sequence data.

The new era of Clinical Methylomics has now arrived, with the development of early risk assessment technologies for disease detection in humans.

ref 2;1992, Frommer et al., Proc. Natl. Acad. Sci. USA, 89,1827-1831
ref 8; 1939, Waddington, An Introduction to Modern Genetics, Allen and Unwin.
ref 9; 1975, Riggs, Cytogenet. Cell Genetics, 14, 9-25.
ref 10; 1975, Holliday and Pugh, Science, 187, 226-232.
ref 11; 1980, Razin and Riggs, Science, 210, 604-610.
ref 12; 1987, Holliday, Science, 238, 163-169.
ref 13; 1986, Bird et al., Cell, 40, 91-99.