A mistake during meiosis affects the way a gamete is formed. If abnormal gametes are a product of nondisjunction, the chance of the same parents having another child with the same disorder is minimal. However, if abnormal gametes are produced due to a balanced translocation, the chance of having another similarly affected child increases. A mistake during meiosis is only one way damaged DNA can be inherited by an offspring. Sometimes parents can carry a damaged gene that has been passed down to them through generations. Many times they are not aware they carry the gene until they have an affected child.

Cystic fibrosis affects the lungs, sweat glands, and digestive system. Because of the gene defect, the bodies of people who are affected with cystic fibrosis produce unusually thick, sticky mucus. Mucus is usually a thin, watery substance that keeps the lining of the lungs, digestive system, reproductive system, and other organ systems moist and protects them from infection. But the thick, sticky mucus of a person affected by cystic fibrosis clogs the lungs, making it difficult to breathe and allowing lung infections to develop. Repeated lung infections can damage the lungs. Mucus also clogs the ducts that allow digestive enzymes to reach the appropriate areas during digestion. This prevents the proper absorption of nutrients and, without medication to replace these digestive enzymes, can affect the patient’s growth and weight. The disease also affects the sweat glands, causing them to secrete more salt than they should. This can upset the mineral balance in the body and cause heat-related illnesses.

Cystic fibrosis is one of the most common fatal genetic disorders in the United States. It is more common in Caucasian (white) people than in any other race. One in 3,200 Caucasian babies born in the United States is born with cystic fibrosis. It is an autosomal recessive disease, so both parents must carry a defective copy of the gene in order to have an affected child. People who carry the cystic fibrosis gene are heterozygous for the disease and show no symptoms. One in 29 Caucasians carry the defective gene. If a carrier marries a noncarrier, none of their children will have cystic fibrosis; however, they have a 50% chance of having a child who is a healthy, heterozygous carrier of the disease.

If two carriers marry and have children, there is a 25% chance (1 in 4) that their child will inherit two defective copies of the gene (cc) and be affected with cystic fibrosis. There is also a 25% chance that their child will neither have the disease nor carry it (CC). Again, there is a 50% chance that their child will be a carrier of the disease (Cc) and can pass it on to future generations.

Not only will every child of this couple have an equal chance of being a carrier or noncarrier, he or she also will have an equal chance of being aff ected by the disease The gene that causes cystic fibrosis, called CFTR, was identified in 1989. It is found on chromosome 7 and controls the fl ow of chlorine in and out of certain cells. Th e normal CFTR gene is about 250,000 base pairs long. In 70% of cystic fibrosis cases, three base pairs are deleted within the CFTR gene. This deletion causes the 508th amino acid (phenylalanine) in the protein that this gene codes for to be omitted during protein synthesis.

Much research has been done on cystic fibrosis. As a result, people born with cystic fibrosis now live longer and with fewer medical problems than they have in the past—on average, into their mid-tolate thirties. Research continues today to find better treatments and, ultimately, a cure for the disease.

Tay-Sachs disease is another recessive autosomal inherited disorder. Tay-Sachs disease causes the progressive loss of nerve cells in the brain and spinal cord. Infants born with Tay-Sachs may appear normal for the first three to six months of life, but then they begin to lose some of their motor skills, such as rolling over, sitting up, or crawling. Seizures, vision and hearing loss, paralysis, and developmental delays result as the disease progresses. Tay-Sachs disease is most common in people of Ashkenazi (Eastern and Central European) Jewish descent. It also has a higher prevalence in some French- Canadian communities of Québec, the Old Order Amish community in Pennsylvania, and the Cajun population of Louisiana than it does in the general population. Most children with Tay-Sachs disease do not live past the age of four or five.

Sickle cell disease is also an autosomal recessive inherited disease. It is caused by a mutation on chromosome 11 that deforms the red blood cells into a crescent, or sickle, shape. These sickle-shaped red blood cells die faster than normal red blood cells and can cause a shortage of red blood cells (anemia). Also, because of their sickle shape, these abnormal red blood cells can get stuck and clump up in small blood vessels, causing pain and organ damage.

Sickle cell disease is most common in people of African, Mediterranean, Indian, and South and Central American descent. In the United States, sickle cell disease is the most common inherited blood disorder. Like cystic fibrosis and Tay-Sachs disease, a child must inherit two copies of a mutated gene in order to show symptoms of the disease. About 1 in 12 African Americans carry the sickle cell trait.

Not all autosomal genetic disorders are recessive. In an autosomal dominant disorder, a child only needs to inherit one copy of a mutated gene to show symptoms of the disorder.

Achondroplasia, the most common form of short-limbed dwarfism, for example, is an autosomal dominant inherited disorder. Achondroplasia is characterized by an average-sized trunk but short arms and legs, and occurs in 1 in 15,000 to 40,000 births. It is caused by a mutation in a gene found on chromosome 4. Th e gene codes for a protein that limits the way cartilage is turned into bone through a process called ossification, especially in the long bones of the arms and legs. Almost all of the cases of achondroplasia are caused by one of two mutations in the FGFR3 gene. These mutations cause the protein to be overactive and disrupt the normal development of bone tissue.

Huntington’s disease (or Huntington’s chorea) is also an autosomal dominant disease. People who inherit it usually do not show any symptoms of the disease until they are in their thirties or forties. Huntington’s disease is a progressive brain disorder that causes symptoms that include uncontrolled movements and loss of thinking ability (cognition). Many people who suffer from it also undergo personality changes. Once symptoms begin, Huntington’s disease suffers usually survive only 15 to 25 years longer.

Huntington’s disease is caused by a mutation of the HD (Huntington) gene found on chromosome 4. Usually a child inherits a mutation of the HD gene from an affected parent, but in rare cases the disease can be the result of a random mutation. Scientists are not exactly sure how the HD gene’s protein product functions, but they believe it has something to do with the development of nerve cells. Mutation of the HD gene is found in 3 to 7 out of 100,000 people of European descent. It is rarer in people whose ancestors are from Japan, China, or Africa.

The type of mutation that causes Huntington’s disease is a duplication. A mutated HD gene has duplications of a sequence of DNA at the top of chromosome 4. The nitrogen bases that are duplicated are CAG. They can be duplicated anywhere from 36 to more than 120 times. Scientists have found that even if a patient inherits a mutated HD gene, it does not necessarily mean that they will develop the disease. If the number of CAG repeats is between 27 and 35, for example, the patient will probably not develop Huntington’s disease. However, as the mutated HD gene is passed down from generation to generation, repeats are often added. So, people with 27 to 35 CAG repeats may have children who will be affected by the disease. If the number of CAG repeats is between 36 and 40, the patient may or may not develop symptoms of HD. However, if more than 40 repeats are present, the patient will almost certainly develop symptoms during their lifetime.

In an autosomal dominant disorder, only one parent needs to carry a mutated allele in order to have an affected child. As the following Punnett square shows, if one parent is heterozygous for Huntington’s disease (Hh), there is a 50% probability of having a child with the disease.

Because the symptoms for Huntington’s disease do not show up until the thirties and forties, past the usual time frame of reproduction, many people who are affected by Huntington’s disease are not aware that they carry a gene that they may pass on to their children.

Not all hereditary diseases are linked to one of the 22 autosomes. Some are the result of a mutated sex chromosome—almost always the X chromosome. X-linked diseases are usually passed down from mother to son. Th e mother’s daughters are usually unaffected because they have two copies of the X chromosome. In the fi rst Punnett square on page 80, Xa is a mutated X chromosome. XA is normal. Hypothetically, this couple’s child would have a 50% chance of not having, nor carrying, an X-linked genetic disease (X^AX^A, normal girl; X^AY, normal boy). If the couple has a daughter, she would have a 50% chance of being a carrier (X^AX^a) and 50% chance of being “normal.” None of the couple’s daughters will have the disease. Their sons would have a 50% chance of being affected by the disease (X^aY).

If the father of a child is affected with an X-linked genetic disease and his partner carries the trait for the same X-linked genetic disease, the couple has a 50% chance of having a child affected by the disease (X^aX^a or X^aY). The couple also has a 50% chance of having an unaffected child (X^AX^a: carrier girl; X^AY: normal boy).

Hemophilia is an example of an X-linked genetic disease—it prevents the blood from clotting normally, leading to excessive bleeding. The most common form of hemophilia, hemophilia A, occurs in one of about 4,000 males. The condition is caused by a mutation in a gene on the long (q) arm of the X chromosome. Duchenne and Becker, two forms of muscular dystrophy, are also caused by a mutation in the X chromosome. But this time, the gene involved, the DMD (Duchenne muscular dystrophy) gene, is on the short (p) arm of the X chromosome. About 400 to 600 boys are born with one of these types of muscular dystrophy every year. Both Duchenne and Becker muscular dystrophy are caused by a mutation in the same gene, and both have similar symptoms, which include muscle weakness and atrophy (wasting away) of the skeletal and heart muscles.

Children affected by Duchenne muscular dystrophy usually show signs of the disease in early childhood and are often wheelchair bound by adolescence. Duchenne muscular dystrophy usually progresses fairly rapidly. People affected with Becker muscular dystrophy, on the other hand, usually do not show signs of the disease until later in childhood and possibly not until they are already in adolescence. The symptoms of Becker muscular dystrophy are generally milder, and the disease progresses slower than Duchenne muscular dystrophy. Females who carry a mutated DMD gene may sometimes experience muscle weakness or develop heart abnormalities, but their symptoms are usually much milder than in males affected by the disease.

Although Punnett squares are very useful tools, genetic professionals also study family history using a tool called a pedigree. In a pedigree, symbols of different shapes and colors are used to indicate male, female, parent, child, affected, and unaffected. Mating is indicated by a horizontal line connecting a circle and a square. A vertical line stands for an offspring.

A couple may make an appointment to see a genetic counselor (a professional trained in genetics and counseling who helps families understand and cope with genetic test results) to discuss their family history. In a case like this, the genetic counselor might draw a pedigree, a pictorial representation of the family.

If, for example, the couple in the third (III) generation consulted a genetic counselor and the counselor drew the pedigree similar to the previous one, the pedigree would show that the female is carrying the couple’s child and that child is affected with a genetic disease. It also shows that this child’s mother has a brother and a sister, both of whom are affected by the same genetic disease (or, at least, have the same type of symptoms). The mother’s father (the filled-in square in the second [II] generation) was also affected. The unborn child’s affected grandfather also had an affected brother who died before reproducing (the diagonal line through the other affected male in the second generation shows that he is dead).

Not all genetic traits are inherited by the simple rules Gregor Mendel discovered in pea plants, however. In fact, most traits are a result of complicated genetic relationships between multiple (more than two) alleles. Human blood types, for example, are determined by a gene that can have one of three different alleles: A, B, or O. The O allele is recessive. But the A and B alleles are codominant to each other, which means that they are both expressed at the same time. Therefore, humans can have one of four blood types: A, B, AB, or O. A person with A type blood can have a genotype of either AA or AO, but a person with O type blood must carry two O alleles. If a person with an AO blood type mates with a person with a BO blood type, their child would have a 25% chance of having type AB, a 25% chance of having type B (genotype: BO), a 25% chance of having type A (genotype: AO), and a 25% chance of having type O (genotype: OO) blood.

If someone has a phenotype that shows type A blood, they can be heterozygous for A (AO) or homozygous for A (AA). If the family history is known, it is possible to determine their genotype.

For example, in this pedigree, the woman in the third generation (III) who is pregnant (signified by the unknown sex diamond), has blood type A. By studying her family history, a geneticist could determine if her genotype is AA or AO. Because her mother (in the second generation) has a blood type of O and, therefore, a genotype of OO, and her father’s blood type is A (his genotype could be AA or AO), the geneticist sets up the following Punnett squares to show the possible genotypes of the children of this match.

Looking at these two possibilities and the family’s pedigree, it can be determined that the woman’s father must have a genotype of AO. If he had a genotype of AA, all of his children would have A blood types. But there is one female in the third generation that has blood type O, so the father’s genotype must contain the O allele. This means that the pregnant woman must also have a genotype of AO. Other traits such as skin color, height, intelligence, and behavior cannot be explained by any of the means of inheritance discussed in this chapter. These traits are assumed to be controlled by many different
genes, often on different chromosomes, and have much more complicated inheritance patterns.