Pleiotropy

Pleiotropy is the phenomenon whereby a single gene has multiple consequences in numerous tissues. Pleiotropic effects stem from both normal and mutated genes, but those caused by mutations are often more noticeable and easier to study. Pleiotropy is actually more common than its opposite, since in a complex organism, a protein from a single gene is likely to be expressed in more than one tissue, and the cascade of problems caused by a mutation is likely to lead to numerous complications throughout the organism. Single-gene defects with effects in only one tissue are more common for nonessential features such as hair texture or eye color.

Sickle cell disease is a classic example of pleiotropy. This disease develops in persons carrying two defective alleles for a blood protein, beta-hemoglobin. Mutant beta-hemoglobins are misaligned inside a blood cell and cause misshapen red blood cells at low oxygen concentrations. Deformed blood cells impair circulation. Impaired circulation damages kidneys and bone. In this case, the gene defect itself only affects one tissue, the blood. The consequences of that defect are found in other tissues and organs.

One baby in three thousand to four thousand births is born with neurofibromatosis, an autosomal dominant disease caused by mutation in a tumor suppressor gene that helps regulate cell division and cell-cell contacts. A truncated version of the tumor suppression protein, neurofibromin (NF I) is implicated in the disease. This mutant protein can come from mis-sense or nonsense mutations, or from reading-frame shifts after a repetitive element called Alu is inserted upstream of the NF I reading frame (a reading frame is the DNA that codes for proteins). Because the mutant protein is unable to regulate cell division, tumors grow on the nerves throughout the body. The tumors produce collateral damage: low blood sugar, intestinal bleeding, café-au-lait spots on the skin, mental retardation, heart problems, high blood pressure, fractures, spinal cord lesions, blindness, aneurysms, arthritis, and respiratory distress.