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relevant in decisions about prescribing. Ultimately, pharmacogenetics may be a
much greater driving force for the application of genetic medicine in primary care
than specifi c genetic screening programs. Genetics will not remain the exclusive
prerogative of specialist centers but every physician will need to use genetic knowl-
edge to aid prescribing and clinical management.
Human Disease and Genes
The Human Gene Nomenclature Committee defi nes a gene as “a DNA segment that
contributes to phenotype/function”. In the absence of demonstrated function, a gene
may be characterized by sequence, transcription or homology. For practical pur-
poses, a gene is a physical and functional unit of heredity, which carries information
from one generation to the next. In molecular terms, it is the entire DNA sequence
including exons, introns, and noncoding transcription control regions that are neces-
sary for production of a functional protein or RNA.
The sequencing of the human genome has revealed considerable information to
study the genetic basis of disease. The identifi cation of all human genes and their
regulatory regions provides the framework to expedite our understanding of the
molecular basis of disease. More than 1,000 human genes have been implicated in
specifi c diseases in the database of Online Mendelian Inheritance in Man ( http://
http://www.ncbi.nlm.nih.gov/Omim/ ). It is expected that the causative lesions in most
monogenic diseases (resulting from mutation in a single gene) will be characterized
in the next few years. Geneticists are now using sophisticated methods to track
genes in polygenic disorders (caused by defects in more than one gene). Even
though genes and proteins related to a disease are discovered, the underlying mech-
anism of how these genes cause the disease is not always understood. The study of
model organisms often provides the fi rst clues to the identity of a genetic defect in
human disease. Sequencing of the genomes of some model organisms has provided
an opportunity to use comparative genomics to study gene function. Along with
Caenorhabditis elegans , zebrafi sh and other small creatures, the fruit fl y has now
entered a new stage of discovery, in which modeling of specifi c cellular pathways
implicated inhuman disease may contribute to the search for new treatments.
Genetic and Environmental Interactions in Etiology
of Human Diseases
Most common diseases are caused by the interplay of genes and environment, with
adverse environmental exposures acting on a genetically susceptible individual to
produce disease. In contrast to single gene disorders such as cystic fi brosis, genes
underlying common diseases are likely to be multiple, each with a small effect,
but act in concert or with environmental infl uences to lead to clinical disease.
1 Basic Aspects