Disease-causing mutations may involve a single base pair, a long stretch of DNA, multiple segments of DNA, or even entire chromosomes (as we saw for Down syndrome in Key Concept 11.5).

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POINT MUTATIONS Sickle-cell anemia is just one of many diseases caused by a point mutation. In some cases (sickle-cell anemia, for example), everyone with the disease has the same genetic mutation. In other cases, different loss-of-function point mutations in one gene can lead to the same disease (as we saw above for PKU). Think about it: the three-dimensional structure of an enzyme protein depends on its secondary structure, so any change in the amino acid sequence of a protein has the potential to affect its structure, and consequently its function.

LARGE DELETIONS Larger mutations may involve many base pairs of DNA. For example, deletions in the X chromosome that include the gene for the protein dystrophin result in Duchenne muscular dystrophy. Dystrophin is important in organizing the structure of muscles, and people who have only the abnormal form have severe muscle weakness. Sometimes only part of the dystrophin gene is missing, leading to an incomplete but partly functional protein and a mild form of the disease. In other cases, deletions span the entire sequence of the gene, so that the protein is missing entirely, resulting in a severe form of the disease. In yet other cases, deletions involve millions of base pairs and cover not only the dystrophin gene but adjacent genes as well; the result may be several diseases in the same person.

CHROMOSOMAL ABNORMALITIES Chromosomal abnormalities also cause human diseases. Such abnormalities result from the gain or loss of complete chromosomes (aneuploidy) (see Figure 11.19), or from the gain or loss of chromosomal segments (see Figure 15.3). About 1 newborn in 200 has a chromosomal abnormality. This may be inherited from a parent who also has the abnormality, or it may result from an error in meiosis during the formation of gametes in one of the parents. One example is fragile-X syndrome, which is a constriction in the tip of the X chromosome that can result in intellectual disability (Figure 15.8). About 1 male in 3,000 and 1 female in 7,000 are affected. Although the basic pattern of inheritance is that of an X-linked recessive trait, there are departures from this pattern. Not all people with the fragile-X chromosomal abnormality are intellectually disabled, as we will see.