Mutations are errors in the genotype that create new alleles and can result in a variety of genetic disorders. In order for a mutation to be inherited from one generation to another, it must occur in sex cells, such as eggs and sperm, rather than in somatic cells. The best way to detect whether a genetic disorder exists is to use a karyotype, a photograph of the chromosomes from an individual cell, usually lined up in homologous pairs, according to size.
Autosomal Mutations
Some human genetic illnesses are inherited in a Mendelian fashion. The disease phenotype will have either a clearly dominant or clearly recessive pattern of inheritance, similar to the traits in Mendel’s peas. Such a pattern will usually only occur if the disease is caused by an abnormality in a single gene. The mutations that cause these diseases occur in genes on the autosomal chromosomes, as opposed to sex-linked diseases, which we cover later in this chapter. (Be careful not to confuse autosomal chromosomes with somatic cells; autosomal chromosomes are the chromosomes that determine bodily and exist in all cells, both sex and somatic.)
Recessive Disorders
A Mendelian genetic illness initially arises as a new mutation that changes a single gene so that it no longer produces a protein that functions normally. Some mutations, however, result in an allele that produces a nonfunctional protein. A disease resulting from this sort of mutation will be inherited in a recessive fashion: the disease phenotype will only appear when both copies of the gene carry the mutation, resulting in a total absence of the necessary protein. If only one copy of the mutated allele is present, the individual is a heterozygous carrier, showing no signs of the disease but able to transmit the disease gene to the next generation. Albinism is an example of a recessive illness, resulting from a mutation in a gene that normally encodes a protein needed for pigment production in the skin and eyes. The pedigree shown below diagrams three generations of a hypothetical family affected by albinism.
The pedigree demonstrates the features of autosomal recessive inheritance. The parents of an affected individual usually show no signs of disease, but both must at least be heterozygous carriers of the disease gene. Among the offspring of two carriers, 25 percent will have the disease, 50 percent will be carriers, and 25 percent will be noncarriers. No offspring produced by a carrier and a noncarrier will have the disease, but 50 percent will be carriers. Although not shown in this pedigree, offspring produced by two individuals who have the disease in their phenotype, which means both parents are recessive homozygous, will all develop the disease.
Many recessive illnesses occur with much greater frequency in particular racial or ethnic groups that have a history of intermarrying within their own community. For example, Tay-Sachs disease is especially common among people of Eastern European Jewish descent. Other well-known autosomal recessive disorders include sickle-cell anemia and cystic fibrosis.
Dominant Disorders
Usually, a dominant phenotype results from the presence of at least one normal allele producing a protein that functions normally. In the case of a dominant genetic -illness, there is a mutation that results in the production of a protein with an abnormal and harmful action. Only one copy of such an allele is needed to produce disease, because the presence of the normal allele and protein cannot prevent the harmful action of the mutant protein. If a recessive mutation is like a car with an engine that cannot start, a dominant mutation is like a car with an engine that explodes. A spare car will solve the problem in the first case, but will do nothing to protect the garage in the second case.
