Genetic variation and health; towards individualized medicine

Pediatric endocrine diseases and their adult consequences depend on interactions of environmental exposure factors with the genetic makeup of the individual. Much has been learned over the past two decades about the genetic component in cases of monogenic (Mendelian) disorders due to drastic disruption of a single gene. The majority of children consulting a pediatric endocrinologist, however, suffer from conditions not attributable to a single gene. The nature and mechanisms of more subtle alterations at multiple different genes that are responsible for the genetic component of most human morbidity and mortality is now only beginning to be elucidated, largely thanks to the vast amount of information that is becoming available through the human genome effort.

The purpose of this review is to describe 1. the nature of the information on health-related human variation that is coming our of the genome effort; 2. how this variation can affect biology; 3. which research approaches show promise in linking DNA variation to disease; 4. how this variation is organized in genomic blocks of linkage disequilibrium; and 5. how this knowledge may, in the future, allow clinicians to individualize management of a specific patient according to his/her genetic makeup.