If asked for one phrase to define the theme of this text on medical genetics, it might be "the cascade of consequences." This is a major departure from the simple view that a gene causes a trait. Traits can be appearance, behavior, or body chemistry. For much of recent history, and certainly in common discussion, one imagines that a gene has a simple and direct effect on a character. For example, one might say that albinism is caused by the "a" gene (Figure 1-1). While this view is not quite wrong, the reality is both more complex and more interesting. There is in fact an intricate interaction among genes, hormones, enzymes, membrane receptors, neuron networks, and so on that creates a maze of connections that prescribes our individual functional and developmental path. Many of these pathways and interactions are shared by even distantly related animals. There is both unity and diversity in the genetics of life.
Albinism can be traced to homozygosity for a recessive mutation in the pathway for biosynthesis of melanin pigment. (Reprinted with permission from Kelly AP and Taylor ST. Dermatology for Skin of Color. New York: McGraw-Hill, 2009, Fig. 47-1.)
Part 1: Background and Systems Integration
Conception. Development. Birth. Growth. Maturity. Old age. A familiar pattern. A physician's role may have begun months before birth in prenatal care of the mother or may focus decades later when the patient is elderly. But the genetic encyclopedia the patient is drawing from was written at fertilization and will be expressed progressively from the embryo to old age. Deoxyribonucleic acid (DNA) codes for proteins and for various kinds of ribonucleic acid (RNA) made in the many cell types of the body. It can dictate much about an individual's physical abilities and limitations. But it is not a static information resource. Throughout life it changes by mutation and by processes that reduce or block the use of various gene sequences. In addition, environmental factors can influence epigenetic processes, the subsequent chemical interactions that cascade from an initial gene action to have major effects both early and late in life.
With the possible exception of identical twins, each of us begins with a unique genotype that defines our individual biochemistry and form. We recognize that uniqueness in ourselves. We take individuality for granted. Now, as a physician, reflect that perspective on a patient. Clearly, understanding the physiological consequences of a treatment is critical to the medical outcome. But patients come from a diverse human population. Not everyone responds in the same way to any given drug. Normally effective dosages of a prescription medicine might have little effect on some and potentially life-threatening side effects on others. A study cited by National Institute of Health (NIH) (1998) found that 2.2 million serious cases ...