CHAPTER

2
Genetic Disease
Shane C. Quinonez, MD, & Gregory Barsh, MD, PhD

Mechanisms of cellular and tissue dysfunction in genetic diseases are as varied

as the organs they affect. To some extent, these mechanisms are similar to those
that occur in nonheritable disorders. For example, a fracture resulting from
decreased bone density in osteoporosis heals in much the same way as one
caused by a defective collagen gene in osteogenesis imperfecta, and the response
to coronary atherosclerosis in most individuals does not depend on whether they
have inherited a defective low-density lipoprotein (LDL) receptor. Thus, the
pathophysiologic principles that distinguish genetic disease focus not so much
on the affected organ system as on the mechanisms of genetic and genomic
changes, inheritance, and molecular pathways from genotype to phenotype.
This chapter begins with a discussion of the terminology used to describe
inherited conditions, the prevalence of genetic disease, and some major
principles and considerations in medical genetics. Important terms and key
words used throughout the chapter are defined in Table 2–1.

TABLE 2–1 Glossary of terms and keywords.