18
According to the authors, the most important thing is not to focus disproportionately
on specifi c variants, but rather to integrate across all classes or risk-associated vari-
ants. In some individuals, risk may be caused by an unusual combination of common
variants, whereas in others it will be due to a smaller number of large effect rare vari-
ants. Nevertheless, the extent to which private or rare genetic variation are turning up
in large-scale genome sequencing studies, personal genome analyses, and targeted
gene sequencing work hints that these mutations have a previously unappreciated
infl uence over traits and diseases. There is considerable medically actionable infor-
mation that can be gleaned from genetic and genomic studies of these recent muta-
tions in the genome that are shared between family members. The authors state that
this “clan genomics” model could help in interpreting personal genome and disease
data. This can be leveraged to promote a better gene discovery. Another goal of the
study was to encourage a move away from a preoccupation with accounting for all of
the heritability for a given disease. It is not necessary to account for all of the herita-
bility in order to better understand biology and improve human health. It is also
important to consider the infl uence that rare and common variants can have on one
another, because each personal genome has a collection of deleterious as well as
protective variations, which in combination dictate the health of the individual.
Considering common diseases involving many genes and Mendelian diseases associ-
ated with high penetrance, rare genetic variants are not necessarily separate entities,
since they sometimes involve different types of alterations to the same genes or path-
ways. Common variations in the so-called Mendelian disease genes are also contrib-
ute to more common chronic disease in the population.
Basics Technologies for Developing Personalized Medicine
Defi nitions of Technologies Relevant to Personalized Medicine
Important basics of personalized medicine are derived from the following technolo-
gies and approaches, which will be described in more detail in various chapters of
the report:
- Molecular diagnostics, particularly single nucleotide polymorphism genotyping
- Integration of diagnostics with therapy, particularly monitoring of therapy
- Bioinformatics for evaluation and use of data from various biotechnologies
- Pharmacogenomics is the application of genomics (variations of DNA as well as
RNA) to drug discovery and development. It involves the study of mechanism of
action of the drugs on the cells as revealed by gene expression patterns. - Pharmacogenetics is a term recognized in pharmacology in the pre-genomic era
and concerns the study of infl uence of genetic factors on response to drugs. With
advances in genomics, role of gene polymorphisms on action of drugs has been
added to this.
1 Basic Aspects