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# Protection and Survival ## Genetic Basis of Disease ### Learning Outcomes After studying this section, you should be able to: - Outline the link between cancer and cell mutation - Distinguish between genetic disorders caused by gene mutation and chromosomal abnormalities, giving examples of each...

# Protection and Survival ## Genetic Basis of Disease ### Learning Outcomes After studying this section, you should be able to: - Outline the link between cancer and cell mutation - Distinguish between genetic disorders caused by gene mutation and chromosomal abnormalities, giving examples of each. --- ## Cancer Cancer (malignant growth of new tissue, p. 57) is caused by mutation (p. 477) of cellular DNA, causing its growth pattern to become disorganized and uncontrolled. - Cells acquire increasing numbers of mutations as they get older, explaining why the incidence of cancer rises sharply with increasing age. - The more mutations a cell suffers, the more likely it is to acquire the characteristics of a tumor, including failure to respond to normal growth controls and immortality. - Some mutations are inherited, increasing the risk of some cancers in families, but most cancer is due to acquired mutations caused by aging or other risk factors, such as irradiation or exposure to mutagenic chemicals (see also p. 57). --- ## Inherited Disease Box 17.1 lists a number of diseases with an inherited component. ### Gene Mutations Many diseases, such as cystic fibrosis (p. 288) and haemophilia (p. 79), are passed directly from parent to child via a faulty gene. Many of these genes have been located by mapping of the human genome, e.g., the gene for cystic fibrosis is carried on chromosome 7. Other diseases (e.g., asthma, some cancers, and cardiovascular disease) have a genetic component (run in the family). In these cases: - A single faulty gene has not been identified, and inheritance is not as predictable as when a single gene is responsible. - The likelihood of developing the disease depends on the genetic makeup as well as the influence of other factors, such as lifestyle and environment. ### Specific Disorders #### Phenylketonuria - In this disorder, an example of an inherited metabolic error, the gene responsible for producing the enzyme phenylalanine hydroxylase is faulty, and the enzyme is absent. - This enzyme normally converts phenylalanine to tyrosine in the liver, but in its absence, phenylalanine accumulates in the liver and overflows into the blood (Fig. 17.12). - In high quantities, phenylalanine is toxic to the central nervous system and, if the condition is untreated, results in brain damage and mental retardation within a few months. - There are low levels of tyrosine, which is needed to make melanin, and so depigmentation occurs; affected children are fair-skinned and blond. - The incidence of this disease is now low in developed countries because screening of newborn babies detects the condition and treatment is provided. #### Mitochondrial Abnormalities - Mitochondrial DNA contains only 37 genes, but defects in these genes can cause inherited disorders with a wide range of potentially fatal signs and symptoms, most commonly involving the central nervous system and skeletal or cardiac muscle. - Spontaneous mutations in this DNA can also occur in maturity, leading to onset of disease in adults. - There is evidence that mitochondrial mutations may be associated with some forms of important diseases, e.g., diabetes mellitus, Parkinson’s disease, and Alzheimer’s disease. --- ### Box 17.1: Some Disorders with an Inherited Component #### Single Gene Disorders - Phenylketonuria - Duchenne muscular dystrophy (p. 472) - Huntington disease - Haemophilia (p. 79) - Achondroplasia (p. 469) - Some cancers, including a proportion of breast, ovarian, and bowel cancers - Myotonic dystrophy - Cystic fibrosis (p. 288) - Polycystic kidney disease (p. 388) #### More Complex Inheritance - More than one gene is likely to be involved, leading to increased susceptibility and “running in families”. Lifestyle and other factors are involved in determining risk. - Asthma (p. 286) - Cleft lip (p. 349) - Hypertension (p. 136) - Atheroma (p. 125) - Some cancers, e.g., breast and gastric cancer - Types 1 and 2 diabetes mellitus (p. 255) - Epilepsy - Schizophrenia - Neural tube defects, e.g., spina bifida (p. 202)