Unit Three. The Continuity of Life


10. Foundations of Genetics


10.11. Counseling and Therapy


Although most genetic disorders cannot yet be cured, we are learning a great deal about them, and progress toward successful therapy is being made in many cases. However, in the absence of a cure, some parents may feel their only recourse is to try to avoid producing children with these conditions. The process of identifying parents at risk of producing children with genetic defects and of assessing the genetic state of early embryos is called genetic counseling. Genetic counseling can help prospective parents determine their risk of having a child with a genetic disorder and advise them on medical treatments or options if a genetic disorder is determined to exist in an unborn child.

High-Risk Pregnancies

If a genetic defect is caused by a recessive allele, how can potential parents determine the likelihood that they carry the allele? One way is through pedigree analysis, often employed as an aid in genetic counseling. As illustrated earlier in this chapter, by analyzing a person’s pedigree, it is sometimes possible to estimate the likelihood that the person is a carrier for certain disorders. For example, if one of your relatives has been afflicted with a recessive genetic disorder such as cystic fibrosis, it is possible that you are a heterozygous carrier of the recessive allele for that disorder. When a pedigree analysis

indicates that both parents of an expected child have a significant probability of being heterozygous carriers of a recessive allele responsible for a serious genetic disorder, the pregnancy is said to be a high-risk pregnancy. In such cases, there is a significant probability that the child will exhibit the clinical disorder.

Another class of high-risk pregnancies is that in which the mothers are more than 35 years old. As we have seen, the frequency of birth of infants with Down syndrome increases dramatically in the pregnancies of older women (see figure 10.26).

Genetic Screening

When a pregnancy is determined to be high risk, many women elect to undergo amniocentesis, a procedure that permits the prenatal diagnosis of many genetic disorders. Figure 10.35 shows how an amniocentesis is performed. In the fourth month of pregnancy, a sterile hypodermic needle is inserted into the expanded uterus of the mother, and a small sample of the amniotic fluid bathing the fetus is removed. Within the fluid are free-floating cells derived from the fetus; once removed, these cells can be grown in cultures in the laboratory. During amniocentesis, the position of the needle and that of the fetus are usually observed by means of ultrasound. The ultrasound image in figure 10.36 clearly reveals the fetus’s position in the uterus. You can see its head and a hand extending up, maybe sucking its thumb. The sound waves used in ultrasound generate a live image that permits the person withdrawing the amniotic fluid to do so without damaging the fetus. In addition, ultrasound can be used to examine the fetus for signs of major abnormalities.



Figure 10.35. Amniocentesis.

A needle is inserted into the amniotic cavity, and a sample of amniotic fluid, containing some free cells derived from the fetus, is withdrawn into a syringe. The fetal cells are then grown in culture and their karyotype and many of their metabolic functions are examined.




Figure 10.36. An ultrasound view of a fetus.

During the fourth month of pregnancy, when amniocentesis is normally performed, the fetus usually moves about actively. The head of the fetus (visualized in green) is to the left.


In recent years, physicians have increasingly turned to another invasive procedure for genetic screening called chorionic villus sampling. In this procedure, the physician removes cells from the chorion, a membranous part of the placenta that nourishes the fetus. This procedure can be used earlier in pregnancy (by the eighth week) and yields results much more rapidly than does amniocentesis, but can increase the risk of miscarriage.

Genetic counselors look at three things in the cultures of cells obtained from amniocentesis or chorionic villus sampling:

1. Chromosomal karyotype. Analysis of the karyotype can reveal aneuploidy (extra or missing chromosomes) and gross chromosomal alterations.

2. Enzyme activity. In many cases, it is possible to test directly for the proper functioning of enzymes involved in genetic disorders. The lack of normal enzymatic activity signals the presence of the disorder. Thus, the lack of the enzyme responsible for breaking down phenylalanine signals PKU (phenylketonuria), the absence of the enzyme responsible for the breakdown of gangliosides indicates Tay-Sachs disease, and so forth.

3. Genetic markers. Genetic counselors can look for an association with known genetic markers. For sicklecell anemia, Huntington’s disease, and one form of muscular dystrophy (a genetic disorder characterized by weakened muscles), investigators have found other mutations on the same chromosomes that, by chance, occur at about the same place as the mutations that cause those disorders. By testing for the presence of these other mutations, a genetic counselor can identify individuals with a high probability of possessing the disorder-causing mutations. Finding such mutations in the first place is a little like searching for a needle in a haystack, but persistent efforts have proved successful in these three disorders. The associated mutations are detectable because they alter the length of the DNA segments that DNA-cleaving enzymes produce when they cut strands of DNA at particular places, an approach described in more detail in chapter 13.

DNA Screening

The mutations that cause hereditary defects are frequently caused by alteration of a single DNA nucleotide within a key gene. Such spot differences between the version of a gene you have and the one another person has are called “single nucleotide polymorphisms,” or SNPs. With the completion of the Human Genome Project (described in detail in chapter 13), researchers have begun assembling a huge database of hundreds of thousands of SNPs. Each of us differs from the standard “type sequence” in several thousand gene-altering SNPs. Screening SNPs and comparing them to known SNP databases should soon allow genetic counselors to screen each patient for copies of genes leading to hereditary disorders such as cystic fibrosis and muscular dystrophy.

Parents conceiving by in vitro fertilization have available a well-established screening procedure known as preimplantation genetic screening. In this test, the egg is fertilized outside the mother, in glassware, and allowed to divide three times, until it contains eight cells. One of the eight cells is then removed from each of several such 8-cell embryos (figure 10.37) and tested for any of 150 genetic defects. The remaining 7-cell embryos are each able to develop into normal fetuses, giving the parents the choice of identifying and implanting an embryo that is disease free.




Figure 10.37. Preimplantation genetic screening.

The photograph shows a human embryo at the eight-cell stage, just before one of the eight cells is to be extracted for genetic testing by researchers.


Key Learning Outcome 10.11. It has recently become possible to detect genetic defects early in pregnancy, allowing for appropriate planning by the prospective parents.


Inouiry & Analysis

Why Woolly Hair Runs in Families

The woman in the photo on the right does not cut her hair. Her hair breaks off naturally as it grows, keeping it from getting long. Other members of her family have the same sort of hair, suggesting it is a hereditary trait. Because of its curly, fuzzy texture, this trait has been given the name "woolly hair.”

While the woolly-hair trait is rare, it flares up in certain families. The extensive pedigree below (drawn curved so as to fit in the large families produced by the second and subsequent generations) records the incidence of woolly hair in five generations (the Roman numerals on the left) of a Norwegian family. As is the convention, affected individuals are indicated by solid symbols, with circles females and squares males. The pedigree below will provide you with the information you need to discover how this trait is inherited within human families.



1. Applying Concepts In the diagram below, how many individuals are documented? Are all of them related?

2. Interpreting Data

a. Does the woolly-hair trait appear in both sexes equally?

b. Does every woolly-hair child have a woolly-hair parent?

c. What percentage of the offspring born to a woolly-haired parent are also woolly haired?

3. Making Inferences

a. Is woolly hair sex-linked or autosomal?

b. Is woolly hair dominant or recessive?

c. Is the woolly-hair trait determined by a single gene, or by several?

4. Drawing Conclusions

a. How many copies of the woolly-hair allele are necessary to produce a detectable change in a person's hair?

b. Are there any woolly-hair homozygous individuals in the pedigree? Explain.




Test Your Understanding

1. Gregor Mendel studied the garden pea plants because

a. pea plants are small, easy to grow, grow quickly, and produce lots of flowers and seeds.

b. he knew about studies with the garden pea that had been done for hundreds of years, and wanted to continue them, using math—counting and recording differences.

c. he knew that there were many varieties available with distinctive characteristics.

d. All of the above.

2. Mendel examined seven characteristics, such as flower color. He crossed plants with two different forms of a character (purple flowers and white flowers). In every case the first generation of offspring (F1) were

a. all purple flowers.

b. half purple flowers and half white flowers.

c. 3/4 purple and 1/4 white flowers.

d. all white flowers.

3. Following question 2, when Mendel allowed the F1 generation to self-fertilize, the offspring in the F2 generation were

a. all purple flowers.

b. half purple flowers and half white flowers.

c. 3/4 purple and 1/4 white flowers.

d. all white flowers.

4. Mendel then studied his results, and proposed a set of hypotheses stating that parents transmit

a. traits directly to their offspring and they are expressed.

b. some factor, or information, about traits to their offspring and it may or may not be expressed.

c. some factor, or information, about traits to their offspring and it will always be expressed.

d. some factor, or information, about traits to their offspring and both traits are expressed in every generation, perhaps in a “blended” form with information from the other parent.

5. A cross between two individuals results in a ratio of 9:3:3:1 for four possible phenotypes. This is an example of a

a. dihybrid cross.

b. monohybrid cross.

c. testcross.

d. None of these is correct.

6. Human height shows a continuous variation from the very short to the very tall. Height is most likely controlled by

a. epistatic genes.

b. environmental factors.

c. sex-linked genes.

d. multiple genes.

7. In the human ABO blood grouping, the four basic blood types are type A, type B, type AB, and type O. The blood proteins A and B are

a. simple dominant and recessive traits.

b. incomplete dominant traits.

c. codominant traits.

d. sex-linked traits.

8. What finding finally determined that genes were carried on chromosomes?

a. heat sensitivity of certain enzymes that determined coat color

b. sex-linked eye color in fruit flies

c. the finding of complete dominance

d. establishing pedigrees

9. Nondisjunction

a. occurs when homologous chromosomes or sister chromatids fail to separate during meiosis.

b. may lead to Down syndrome.

c. results in aneuploidy.

d. All of the above.

10. Which of the following analyses can detect aneuploidy?

a. enzyme activity

b. chromosomal karyotyping

c. pedigrees

d. genetic markers


Apply Your Understanding: Additional Genetics Problems

1. Silky feathers in chickens is a single-gene recessive trait whose effect is to produce shiny plumage. If you had a normal-feathered bird, what would be the easiest cross to perform to determine if a bird is homozygous or heterozygous for the silky allele?

2. Among Hereford cattle there is a dominant allele called polled; the individuals that have this allele lack horns. Suppose you acquire a herd consisting entirely of polled cattle, and you carefully determine that no cow in the herd has horns. Some of the calves born that year, however, grow horns. You remove them from the herd and make certain that no horned adult has gotten into your pasture. Despite your efforts, more horned calves are born the next year. What is the reason for the appearance of the horned calves? If your goal is to maintain a herd consisting entirely of polled cattle, what should you do?

3. Brachydactyly is a rare human trait that causes a shortening of the length of the fingers by a third. A review of medical records reveals that the progeny of marriages between a brachydactylous person and a normal person are approximately half brachydactylous. What proportion of offspring in matings between two brachydactylous individuals would be expected to be brachydactylous?

4. Your instructor presents you with a Drosophila (fruit fly) with red eyes, as well as a stock of white-eyed flies and another stock of flies homozygous for the red-eye allele. You know that the presence of white eyes in Drosophila is caused by homozygosity for a recessive allele. How would you determine whether the single red-eyed fly was heterozygous for the white-eye allele?

5. Hemophilia is a recessive sex-linked human blood disease that leads to failure of blood to clot normally. One form of hemophilia has been traced to the royal family of England, from which it spread throughout the royal families of Europe. For the purposes of this problem, assume that it originated as a mutation either in Prince Albert or in his wife, Queen Victoria.

a. Prince Albert did not have hemophilia. If the disease is a sex-linked recessive abnormality, how could it have originated in Prince Albert, a male, who would have been expected to exhibit sex-linked recessive traits?

b. Alexis, the son of Czar Nicholas II of Russia and Empress Alexandra (a granddaughter of Victoria), had hemophilia, but their daughter Anastasia did not. Anastasia died, a victim of the Russian revolution, before she had any children. Can we assume that Anastasia would have been a carrier of the disease? Would your answer be different if the disease had been present in Nicholas II or in Alexandra?

6. A normally pigmented man marries an albino woman. They have three children, one of whom is an albino. What is the genotype of the father?