A focus on personal genomics.

Abstract

Since the completion of the human reference genome [1], human geneticists have been using this ‘encyclopedia’ as a baseline for discovering the variation of the human genome at many levels, from SNPs to copy number variation, to complex structural variation. Such studies have largely focused on characterizing the genomic context of disease or disease susceptibility, initially through genome-wide association studies carried out on SNP arrays of ever-increasing density, with varying levels of success. More recently, by applying next-generation sequencing technology to re sequence and characterize entire human genomes, geneticists have set the stage for a revolution in personal genomics that will ultimately progress towards the reality of personalized medicine. Namely genomic data can be collected in a relatively straightforward manner within a matter of hours or days depending upon the technology, yielding a dataset that consists of an individual’s genotype (the unique combination of > 1 million single nucleotide variants as identified by a genotyping array) or of each of the approximately 6 billion nucleotide bases comprising the diploid genome. As a result, companies have been founded that offer ‘direct-to-consumer’ (DTC) genomic profiling and interpretation, individuals have had their own genomes sequenced [2–7] and mutated genes have been discovered in an unbiased fashion by sequencing complete cancer genomes [8,9]. Several scientific meetings have been organized around personal genomics, reflecting the dramatic increase in scientific efforts and interest in this area. The fields of human origins and pharmacogenetics, among others, have been re-energized by the emergence of the personal genome, with the anticipated results improving our understanding of migratory patterns and changing medical practice, respectively. The aforementioned advances in genomics technology and its applications have had unprece dented impacts on the fields of ethics and governance. The established framework of ethical, legal and social issues (ELSI) in genomics has been shaken to its foundations by something as simple as the emergence of personal genomics. Experts in the areas of ethics, social and political sciences, and governance, have been called to arms in order to restore the steady state that ELSI brought to genomics [10]. There are two tiers to the developments that result from technological progress, each of which confronts the ELSI disciplines with specific challenges. First, there are the aforementioned spectacular advances in sequencing. We have progressed from gene ana lysis to whole-genome scans in just half a decade. The availability of information regarding substantial parts of genomes, and even of full human genome sequences, has changed the way we look at such information – the building blocks of the human–organism are no longer hidden and it is becoming ever clearer that integrative personal genomics will enable rational and effective personalized medicine. Increasingly, individualized diagnostics and therapies require a rethinking in terms of justice and equity in healthcare delivery. In addition, new designs and strategies must be developed for both clinical trials and epidemiological studies. This means that substantial innovation in the field of research ethics will be needed. The integrative ‘omics’ sciences will not only change our concepts of health and disease, they will also redefine the interactions of the individual–human–organism and the environment. The second tier consists of the very sudden appearance in the market place of DTC genotyping services that, until recently, mainly provided certain types of selective genome scans. The established disciplines in the field of clinical genetics and in the ELSI area, as well as the various regulatory authorities, have been taken by surprise and, obviously, they are not able to