Case Study Conclusion: Cancer in the Family
Figure 1. Pedigree for Rebecca's family, as described in the beginning of this chapter, showing individuals with cancer (red) and those that do not have cancer (blue). Circles represent women, squares represent men.
Rebecca’s family tree, as illustrated in the pedigree above, shows a high incidence of cancer among close relatives. But are genes the cause of cancer in this family? Only genetic testing, which is the sequencing of specific genes in an individual, can reveal whether a cancer-causing gene is being inherited in this family.
Fortunately for Rebecca, the results of her genetic testing shows that she does not have the mutations in the BRCA1 and BRCA2 genes that most commonly increase a person’s risk of getting cancer. However, it does not mean that she doesn’t have other mutations in these genes that could increase her risk of getting cancer. There are many other mutations in BRCA genes whose effect on cancer risk is not known, and there may be many more yet to be discovered. The picture belowfrom the National Cancer Institute illustrates many of the different types of known mutations in the BRCA1 gene. It is important to continue to study the variations in genes such as BRCA in different people to better assess their possible contribution to the development of disease. As you now know from this chapter, many mutations are harmless, while others can cause significant health effects, depending on the specific mutation and the gene involved.
Figure 2 . Mutations in the BRCA1 gene. Use the knowledge you gained from this chapter to define nonsense, frameshift, and missense mutations. Do these tend to be neutral or harmful mutations?
Mutations in BRCA genes are particularly likely to cause cancer because these genes encode for tumor-suppressor proteins that normally repair damaged DNA and control cell division. If these genes are mutated in a way that causes the proteins to not function properly, other mutations can accumulate and cell division can run out of control, which can cause cancer.
BRCA1 and BRCA2 are on chromosomes 17 and 13, respectively, which are autosomes. As Rebecca’s genetic counselor mentioned, mutations in these genes have a dominant inheritance pattern. Now that you know the pattern of inheritance of autosomal dominant genes, if Rebecca’s grandmother did have one copy of a mutated BRCA gene, what are the chances that Rebecca’s mother also has this mutation? Because it is dominant, only one copy of the gene is needed to increase the risk of cancer, and because it is on autosomes instead of sex chromosomes, the sex of the parent or offspring does not matter in the inheritance pattern. In this situation, Rebecca’s grandmother’s eggs would have had a 50% chance of having a BRCA gene mutation, due to Mendel’s law of segregation. Therefore, Rebecca’s mother would have had a 50% chance of inheriting this gene. Even though Rebecca does not have the most common BRCA mutations that increase the risk of cancer, it does not mean that her also mother does not, because there would also only be a 50% chance that she would pass it on to Rebecca. Therefore, Rebecca’s mother should consider getting tested for mutations in the BRCA genes as well. Ideally, the individuals with cancer in a family should be tested first when a genetic cause is suspected, so that if there is a specific mutation being inherited, it can be identified and the other family members can be tested for that same mutation.
Mutations in both BRCA1 and BRCA2 are often found in Ashkenazi Jewish families. However, these genes are not linked in the chromosomal sense, because they are on different chromosomes and are therefore inherited independently, in accordance with Mendel’s law of independent assortment. Why would certain gene mutations be prevalent in particular ethnic groups? If people within an ethnic group tend to produce offspring with each other, their genes will remain prevalent within the group. These may be genes for harmless variations such as skin, hair, or eye color, or harmful variations such as the mutations in the BRCA genes. Other genetically based diseases and disorders are sometimes more commonly found in particular ethnic groups, such as cystic fibrosis in people of European descent and sickle-cell anemia in people of African descent. You will learn more about the prevalence of certain genes and traits in particular ethnic groups and populations in the chapter on Human Variation.
As you learned in this chapter, genetics is not the sole determinant of phenotype. The environment can also influence many traits, such as adult height and skin color. The environment also plays a major role in the development of cancer. 90 to 95% of all cancers do not have an identified genetic cause, and are often caused by mutagens in the environment such as UV radiation from the sun or toxic chemicals in cigarette smoke. But for families like Rebecca’s, knowing their family health history and genetic makeup may help them better prevent or treat diseases that are caused by their genetic inheritance. If a person knows they have a gene that can increase their risk of cancer, they can make lifestyle changes, have early and more frequent cancer screenings, and may even choose to have preventative surgeries that may help reduce their risk of getting cancer and increase their odds of long-term survival if cancer does occur. The next time you go to the doctor and they ask whether any members of your family have had cancer, you will have a deeper understanding why this information is so important to your health.
In this chapter you learned about genetics — the science of heredity. Specifically you learned that:
- Chromosomes are structures made of DNA and proteins that are encoded with genetic instructions for making proteins. The instructions are organized into units called genes, most of which contain instructions for a single protein.
- Humans normally have 23 pairs of chromosomes. Of these, 22 pairs are autosomes, which contain genes for characteristics unrelated to sex. The other pair consists of sex chromosomes (XX in females, XY in males). Only the Y chromosome contains genes that determine sex.
- Humans have an estimated 20,000 to 22,000 genes. The majority of human genes have two or more possible versions, called alleles.
- Mendel experimented with the inheritance of traits in pea plants, which have two different forms of several visible characteristics. Mendel crossed pea plants with different forms of traits.
- In Mendel's first set of experiments, he crossed plants that only differed in one characteristic. The results led to Mendel's first law of inheritance, called the law of segregation. This law states that there are two factors controlling a given characteristic, one of which dominates the other, and these factors separate and go to different gametes when a parent reproduces.
- In Mendel's second set of experiments, he experimented with two characteristics at a time. The results led to Mendel's second law of inheritance, called the law of independent assortment. This law states that the factors controlling different characteristics are inherited independently of each other.
- Mendel's laws of inheritance, now expressed in terms of genes, form the basis of genetics, the science of heredity. Mendel is often called the father of genetics.
- The position of a gene on a chromosome is its locus. A given gene may have different versions called alleles. Paired chromosomes of the same type are called homologous chromosomes and they have the same genes at the same loci.
- The alleles an individual inherits for a given gene make up the individual's genotype. An organism with two of the same allele is called a homozygote, and an individual with two different alleles is called a heterozygote.
- The expression of an organism's genotype is referred to as its phenotype. A dominant allele is always expressed in the phenotype, even when just one dominant allele has been inherited. A recessive allele is expressed in the phenotype only when two recessive alleles have been inherited.
- In sexual reproduction, two parents produce gametes that unite in the process of fertilization to form a single-celled zygote. Gametes are haploid cells with only one of each pair of homologous chromosomes, and the zygote is a diploid cell with two of each pair of chromosomes.
- Mendelian inheritance refers to the inheritance of traits controlled by a single gene with two alleles, one of which may be completely dominant to the other. The pattern of inheritance of Mendelian traits depends on whether the traits are controlled by genes on autosomes or by genes on sex chromosomes.
- Examples of human autosomal Mendelian traits include dimples and earlobe attachment. Examples of human X-linked traits include red-green color blindness and hemophilia.
- Two tools for studying inheritance are pedigrees and Punnett squares. A pedigree is a chart that shows how a trait is passed from generation to generation. A Punnett square is a chart that shows the expected ratios of possible genotypes in the offspring of two parents.
- Non-Mendelian inheritance refers to the inheritance of traits that have a more complex genetic basis than one gene with two alleles and complete dominance.
- Multiple allele traits are controlled by a single gene with more than two alleles. An example of a human multiple allele trait is ABO blood type.
- Codominance occurs when two alleles for a gene are expressed equally in the phenotype of heterozygotes. A human example of codominance occurs in the AB blood type, in which the IA and IB alleles are codominant.
- Incomplete dominance is the case in which the dominant allele for a gene is not completely dominant to a recessive allele, so an intermediate phenotype occurs in heterozygotes who inherit both alleles. A human example of incomplete dominance is Tay Sachs disease, in which heterozygotes produce half as much functional enzyme as normal homozygotes.
- Polygenic traits are controlled by more than one gene, each of which has a minor additive effect on the phenotype. This results in a continuum of phenotypes. Examples of human polygenic traits include skin color and adult height. Many of these types of traits, as well as others, are affected by the environment as well as by genes.
- Pleiotropy refers to the situation in which a gene affects more than one phenotypic trait. A human example of pleiotropy occurs with sickle cell anemia, which has multiple effects on the body.
- Epistasis is when one gene affects the expression of other genes. An example of epistasis is albinism, in which the albinism mutation negates the expression of skin color genes.
- Genetic disorders are diseases, syndromes, or other abnormal conditions that are caused by mutations in one or more genes or by chromosomal alterations.
- Examples of genetic disorders caused by single-gene mutations include Marfan syndrome (autosomal dominant), sickle cell anemia (autosomal recessive), vitamin D-resistant rickets (X-linked dominant), and hemophilia A (X-linked recessive). Very few genetic disorders are caused by dominant mutations because these alleles are less likely to be passed on to successive generations.
- Nondisjunction is the failure of replicated chromosomes to separate properly during meiosis. This may result in genetic disorders caused by abnormal numbers of chromosomes. An example is Down syndrome, in which the individual inherits an extra copy of chromosome 21. Most chromosomal disorders involve the X chromosome. An example is Klinefelter's syndrome (XXY, XXXY).
- Prenatal genetic testing, for example, by amniocentesis, can detect chromosomal alterations in utero. The symptoms of some genetic disorders can be treated or prevented. For example, symptoms of phenylketonuria (PKU) can be prevented by following a low-phenylalanine diet throughout life.
- Cures for genetic disorders are still in the early stages of development. One potential cure is gene therapy, in which normal genes are introduced into cells by a vector such as a virus to compensate for mutated genes.
Chapter Summary Review
1. Which sentence is correct?
A. Different alleles of the same gene are located at the same locus on homologous chromosomes.
B. Different alleles of the same gene are located at different loci on homologous chromosomes.
C. Different genes of the same alleles are located at the same locus on homologous chromosomes.
D. Different alleles of the same gene are located at different loci on the same chromosome.
2. A person has a hypothetical Aa genotype. Answer the following questions about this genotype.
a. What do A and a represent?
b. If the person expresses only the phenotype associated with A, is this an example of complete dominance, codominance, or incomplete dominance? Explain your answer. Also, describe what the observed phenotypes would be if it were either of the two incorrect answers.
3. Explain how a mutation that occurs in a parent can result in a genetic disorder in their child. Be sure to include which type of cell or cells in the parent must be affected in order for this to happen.
4. What is an allele that is not expressed in a heterozygote called?
5. True or False. Sex is determined by a gene on an autosome.
6. True or False. In sexual reproduction, parents and offspring are never identical.
7. True or False. In humans, a gamete will have 23 chromosomes.
8. True or False. The expression of an organism’s phenotype produces its genotype.
9. True or False. It is entirely likely for a gene to have more than two alleles.
10. Mendel’s law of independent assortment states that
A. two factors of the same characteristic separate into different gametes.
B. there are dominant and recessive factors.
C. factors controlling different characteristics are inherited independently of each other.
D. there are two factors that control inheritance.
11. Linked genes:
A. are on homologous chromosomes.
B. are on the same chromosome.
C. are on adjacent chromosomes.
D. are on non-homologous chromosomes.
12. A woman has red-green color blindness, which is an X-linked recessive trait. Her husband does not have red-green color blindness. Which of the following is correct?
A. Half of their daughters will have red-green color blindness.
B. All of their daughters will have red-green color blindness.
C. All of their sons will have red-green color blindness.
D. All of their children will have red-green color blindness.
13. Which of the following is an example of Mendelian inheritance?
A. A trait that has three alleles
B. A trait that is controlled by two genes
C. A trait that is controlled by a single gene with one dominant and one recessive allele
D. A trait that has two alleles, both of which are expressed equally in the phenotype
14. a. What is gene therapy?
b. Why is gene therapy considered a type of biotechnology?
Credit: Rachel Henderson;
License: CC BY-NC 3.0
Credit: NCI (http://www.cancer.gov) [Public domain], via Wikimedia Commons;
License: CC BY-NC 3.0