Genetics

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Examples of single gene disorders

Autosomal recessive:

• Cystic fibrosis (CF) is a very common hereditary disorder (1 out of 2,000 Caucasian births). The normal function of a particular protein is to transport chloride ions into certain cells. Deficiency of this protein somehow results in the accumulation of thick mucus in the lungs and other parts of the body. This situation compromises respiration and greatly increases the chance of pulmonary infections. Affected individuals rarely survive to the age of 40.
• Phenylketonuria (PKU) is a common genetic disorder (1 out of 12,000 births) which results from a deficient enzyme required for the metabolism of the amino acid phenylalanine. Failure to recognize the disorder early in life results in mental retardation. Many states require all newborns to be screened for this disease.
• Alpha-1-antitrypsin (AAT) deficiency is a disorder seen in about 1 out of 10,000 births. The normal function of the protein is to inhibit enzymes which escape from white blood cells in the process of destroying invading bacteria. Affected individuals are much more likely to develop emphysema than usual.
• Sickle cell anemia is a disorder common in individuals with an African ethnic background. The high frequency of the gene probably relates to the fact that the heterozygotes are resistant to malaria. The homozygotes have a predominance of an abnormal hemoglobin in their red blood cells. This abnormal protein causes the red blood cells to assume abnormal shapes and to lyse (a process of disintegration or dissolution) in small blood vessels under conditions of reduced oxygen pressure.
• ADA deficiency is a rare immunodeficiency disorder, sometimes called the "boy in a bubble" disease, which results from the deficiency of an enzyme called adenosine deaminase. This enzyme is important for the normal function of lymphocytes which are the primary components of the immune system. This disease has the distinction of being the first to be treated effectively by genetic engineering. Some of the patient's cells are removed from the body, injected with a normal gene, then reintroduced to the body.

• Duchenne muscular dystrophy is a very common (1 out of 3,500 male births) disorder which results from the presence of an abnormal muscle protein. Muscles of young boys gradually deteriorate until even the muscles required for normal respiration become ineffective. These boys usually die of pulmonary infections before the age of 20.
• Hemophilia A is seen in 1 out of 10,000 male births. The defective protein (coagulation factor VIII) is required for normal blood clotting. Affected individuals require injections of the protein or transfusion of blood products to prevent internal bleeding. Until recently, when the genetically engineered protein became available, many of these individuals contracted viral hepatitis or AIDS as a result of their many transfusions.
• Tay-Sachs disease is a disorder which is seen almost solely in Ashkenazi Jew populations. The incidence in this population has been substantially reduced (from about 1 out of 900) as a result of massive screening programs. The affected protein is an enzyme necessary to breakdown lipids in the membranes of cells. Abnormal membrane fragments accumulate and cause a deterioration of the nervous system. Individuals affected with the severe form of the disease die before the age of 3.

• Familial hypercholesterolemia (FHC) is a fairly common disorder (1 out of 500 individuals are heterozygous). The affected gene codes for a protein which is found on the external surface of most of the body's cells. This so-called receptor protein mediates the uptake of cholesterol into the cells. This cholesterol is transported in the blood by a lipoprotein called LDL. When LDL can't get into cells, it increases to high levels in the blood. High levels of LDL (with its associated cholesterol) increases the risk of developing arteriosclerosis and coronary artery disease. Homozygous individuals (about 1 out of 1,000,000 births) have extremely high levels of LDL and develop coronary heart disease in childhood.
• Huntington's disease is a neurodegenerative disease which doesn't appear until approximately age 30. It has recently become possible to test for the presence of the abnormal gene at any age. This information may be of great interest to individuals who know they will develop the disease later in life since they may wish to modify their plans in regards to marriage and childbearing. Other individuals prefer not to know as the prognosis is grim and there is no effective treatment.

X-linked dominant:
Only a few, very rare, disorders are classified as X-linked dominant. One of these is hypophosphatemic rickets (also called Vitamin D resistant rickets). In this case a protein in the kidneys is defective. This protein normally transports phosphate from the urinary filtrate back into the blood. Since the amount of phosphate in the blood is much lower than normal, the bones are chronically stimulated to release calcium and phosphate by hormones such as parathormone. This results in fragile and abnormally structured bones.