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CHAPTER 4 Mendel’s Laws

Peter Maxwell is an aging rock star. Although by day he is a high school music teacher, on the weekends his genetic gifts express themselves on stage. Peter has inherited a lucky combination of traits—hyperextensible fingers (autosomal recessive, genotype hf//hf); a fabulous head of long, red hair just like his paternal grandfather Emmett had; and a high, clear, strong voice that echoes those of the finest rock bands of the 1980s, a trait called rock star voice (RSV), which is autosomal dominant. Over the years Peter has been widely sought after for tribute bands. Each of these traits is inherited on a different autosome.

Alas, Ellie Maxwell, Peter’s wife, is not musical and is, in fact, just the opposite. She has an autosomal dominant condition called congenital amusia or tune (not tone) deafness. Ellie comes from a long line of people who cannot hear the pitch and rhythmic patterns of musical notes as a melody. Instead, they hear a disconnected string of sounds, and this is what they mimic when they attempt to sing. They are always off-key. Her father, an identical twin, was once nicely asked to leave a church choir because he couldn’t correct his off-key notes. Ellie’s paternal grandfather, too, was notorious for his loud, horrible singing. Although she was convinced this lack of talent was inherited, Ellie never sang to her children, for fear that they might imitate her.

Another autosomal dominant trait in the family is distal symphalangism, for which Ellie can blame her tiny toenails and very stiff fingers. Her siblings Jill and Dan luckily escaped both the weird fingers and bad singing voice.

Peter and Ellie have three children (Figure 2). Sean is lead guitarist in a rock band, thanks to his hyperextensible fingers and synesthesia (see Chapter 1). Unfortunately, he has inherited his mother’s tune deafness, which is especially frustrating because he has also inherited rock star voice. He can sing clear, beautiful, soaring notes—but the wrong ones. He has stopped singing since his attempts at harmony made his bandmates ill. Sean hopes he keeps his lustrous hair, which is like his father’s, and doesn’t somehow inherit Uncle Roger’s baldness. How awful it would be to watch those glorious red curls thin and then fall out!

Figure 2 A partial pedigree of the Maxwell family. Different combinations of symbols can be filled in to represent inheritance of specific traits.

Sean’s sister Keri has rock star voice and distal symphalangism. Her stiff fingers don’t bother her, but she always covers her shrunken toenails. Maybe she’ll get fake ones. The only family peculiarity that little sister Anna shares is synesthesia.

Peter’s sister Joan uses her hyperextensible fingers in her career as an eye surgeon. She likes to sing in the operating room, but it is good that her patients are often unconscious because she hasn’t inherited RSV. Peter’s and Joan’s older brother Roger has been unlucky genetically—in addition to the pattern baldness that worries Peter and Sean, Roger has an inherited heart condition called long QT syndrome. The first symptom can be a fatal disturbance of the heart’s rhythm (see extended pedigree, figure i).

MULTIPLE CHOICE

1. In the Maxwell family, the individuals who must be heterozygous (carriers) for hyperextensible fingers are

a. Peter and Sean.

b. Ellie, Anna, and Peter’s parents, Abe and Sarah.

c. Peter’s siblings Joan and Roger and half of their children.

d. all Peter’s grandparents.

e. not clear from the available information.

2. If Keri gets fake toenails, she will be altering

a. her phenotype but not her genotype.

b. her genotype but not her phenotype.

c. her genotype and her phenotype.

d. neither her genotype nor her phenotype.

e. the DNA sequence of the distal symphalangism gene.

3. The probability that Anna inherited normal fingers, assuming that the genes for the two finger traits are on different chromosomes, is___.

a.

b.

c.

d.

e. not possible to determine from the given information

4. Disappointed that his son Sean has his mother’s congenital amusia, Peter looks to his nephew Eric. Although not gripped with tune deafness, Eric has a weak and wandering voice and is more interested in studying physics than in making music. The most likely explanation for the inheritance pattern of rock star voice in this family is that it is

a. autosomal recessive and originated many generations back.

b. carried on a gene on the X chromosome.

c. autosomal dominant and originated in Peter.

d. autosomal recessive and originated in Peter.

e. not inherited at all, but learned.

5. The probability that if Ellie and Peter have another child, he or she inherits Peter’s fortuitous combination of musical traits—hyperextensible fingers and rock star voice—is___.

a.

b.

c.

d. ¼

e. ½

QUESTIONS FOR RESEARCH AND DISCUSSION

6. Which approach to determining the likelihood of various genotypes occurring in the offspring of particular parents is easier for you—constructing a Punnett square, or using the product rule to calculate probabilities?

7. Compare and contrast the inheritance patterns of autosomal recessive and autosomal dominant traits.

CHAPTER 5 Beyond Mendel’s Laws

Long QT Syndrome

Roger Maxwell is very health-conscious. He runs, swims, and hikes; follows a low-carbohydrate diet; and generally feels great. He sees a physician when he needs to, in addition to annual physical exams at the large company where he is an engineer. He’d never allow himself to get so out of shape that heart disease would be a risk. Because of his strict adherence to this healthy lifestyle, Roger is surprised when a medical intern, gazing at his yearly electrocardiogram (ECG) at his work physical, clearly picks up on something.

“What? What are you looking at?” Roger blurts out while buttoning up his shirt.

“Oh, it’s probably nothing.” But she doesn’t look like it’s probably nothing.

“The heart murmur? My mom’s been telling me about it since childhood. Not a big deal. The doctors called it something last year, something I never heard of.”

“Did you check it out?” asks the intern.

“Nah. It wasn’t bothering me, so I forgot about it. Why? What’s wrong?”

“Well, maybe you should ask the doctor to explain it again and suggest what to do.”

“About what?”

“The doctor will explain it. Please don’t worry, though,” says the intern as she rushes off to the next patient.

Roger’s electrocardiograms had in fact been showing that he has had long QT syndrome, and not a heart murmur, for many years. The doctor explains that this is a problem with the heart’s rhythm, and not its valves. Roger goes home and Googles long QT syndrome right away. What he finds concerns him enough to alert his relatives.

Long QT syndrome is a lengthening in the time that it takes the ventricles (the lower two heart chambers) to recover after a contraction, called the QT interval on an electrocardiogram. This delay is called torsade de pointes, and it causes lightheadedness upon standing or even fainting, as blood pressure drops when the heart rhythm becomes abnormal. If the arrhythmia turns into the more erratic condition called ventricular fibrillation, it can be deadly. Some cases of sudden cardiac arrest in people who apparently do not have heart disease are in fact due to long QT syndrome. This may have been the case with Roger’s aunt, Amelia, his mother’s sister, who died at age 34 of what was thought to be a heart attack, but, now Roger realizes, was more likely an arrhythmia. Still, with only one affected relative, Roger had never thought of his aunt’s early demise as a family history, especially since his mother is healthy.

Roger reads that in people with some forms of long QT syndrome, fatal arrhythmia can be triggered by intense emotions or a sudden loud sound. The first recorded case of the condition was a little girl, who collapsed dead when her teacher suddenly yelled at her. Her older brother had died in a similar circumstance. Suddenly, Roger remembers that his daughter Sheila faints very easily. She even passed out once at a rock concert because she got so excited. He’d never panicked over it because his mother fainted easily, too. A pattern was emerging.

Long QT syndrome is caused by mutations in any of at least 10 genes that encode either proteins that form parts of ion channels (potassium, sodium, or calcium) or proteins that affect the functioning of these channels. Ion channels control the spread of nerve impulses and the resulting muscle contraction. The time for the heart’s recovery after a beat, called repolarization, extends the period when ions are trapped inside heart muscle cells because the channels are blocked, too slow to open, or too quick to close in people who are at elevated risk due to inheriting a mutation. People with long QT syndrome can experience arrhythmia if they take certain drugs that prolong the QT interval. These drugs include certain antibiotics, antidepressants, and diuretics (“water pills”).

Roger reads about the different genes and drug combinations that cause long QT syndrome on Wikipedia, and then he scans www.genetests.org to find labs that test for all of them. Only then does he make an appointment with a cardiologist, and he arranges to have his blood and that of his daughter and mother sent to one of the labs. Two weeks later, he learns that they all have a dominant mutation in a gene called HERG (for “human ether-a-go-go”) that causes long QT syndrome type 2 (LQT2). Even healthy family members could have inherited the mutation, because 15 percent of people with long QT syndrome do not have symptoms. The concern is their increased risk of developing symptoms in the future—perhaps suddenly.

MULTIPLE CHOICE

1. Roger is upset that in the past doctors had not been more insistent that he follow up on the abnormal ECG pattern. When he mentions this to his primary care physician, she answers, “I didn’t say anything because you are so healthy, and people who have cardiac arrest from long QT do so in young adulthood. You’re too old to worry about it.” But Roger should be worried, because

a. he looks younger than he is, so could still be at risk.

b. the condition can be inherited, so others in the family could be affected.

c. he could die at any time.

d. he can no longer take antibiotics.

e. long QT syndrome can cause cholesterol to build up in his coronary arteries.

2. Individuals who should take genetic tests for long QT syndrome are

a. all the people in generation IV.

b. Eric, Joan and Peter, and then Dylan, Anika, Sean, Keri, and Anna if a parent has the mutation.

c. Juanita, Larry, Joan, Peter, and Ellie.

d. Abe, Sara, Craig, Philip, Edwin, and Yvonne.

e. Only those who are athletic.

3. The mode of inheritance of long QT syndrome in the Maxwell family is

a. X-linked recessive.

b. autosomal recessive.

c. autosomal dominant.

d. sex-limited.

e. X-linked dominant.

4. Some people who inherit the same mutation as Roger do not experience any symptoms. This means that the mutation is

a. variably expressive.

b. genetically heterogeneic.

c. polygenic.

d. incompletely penetrant.

e. dominant.

5. The fact that mutations in any of several genes can cause long QT syndrome means that the condition is

a. variably expressive.

b. genetically heterogeneic.

c. polygenic.

d. incompletely penetrant.

e. recessive.

6. The risk that Sean, Keri, or Anna has inherited the family’s mutation for long QT syndrome is___.

a. 1

b.

c. ½

d. ¼

e.

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