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A precancerous condition (intestinal polyposis) in a particular human family is determined by a single dominant gene. Among the descendants of one woman who died with cancer of the colon, 10 people have died with the same type of cancer and 6 now have intestinal polyposis. All other branches of the large kindred have been carefully examined, and no cases have been found. In whom did the defective gene originate? In what cells? Be specific and explain your reasoning.

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Roger Maxwell is very health-conscious. He runs, swims, and hikes; follows a lowcarbohydrate 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 elecfrocardiogram (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 reeovery 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.

Question 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-Iinked recessive

.b. autosomal recessive.

c. autosomal dominant.

d. sex-limited.

e. X-Iinked 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. ¾

c. ¼

d. ¼

e. 1/8

7) Roger is relieved that he does not have- LQT7, which affects skeletal as well as cardiac muscle, causing short stature and scoliosis. He is also glad that he doesn't have LQT8, which causes many symptoms, or either of two types that also cause deafness. These other forms of the condition, with more than one symptom, exhibit

a. invariable expressivity.

b. complete penefrance.

c. genetic homogeneity.

d. pleiotropy.

e. phenocopy.

8) The reason that mutations in different genes all cause the same phenotype of extended QT interval on an ECG is that

a. the heart is an extremely complex organ.

b. the genes all encode proteins that affect ion channels essential for maintaining heartbeat.

c. the genes all encode the same protein.

d. the mutations all affect the genes in the same way.

e. the QT interval is highly variable, even within individuals at different times.

9). A phenotypic pattern in a family that could be due to inherited long QT syndrome is

a. sudden cardiac death in one or more young people and individuals who faint easily.

b. many individuals who eat a very fatty diet and are sedentary but do not develop heart disease.

c. many individuals with hypertension.

d. many individuals who suffer heart attacks after age 50.

e. a family with rnany athletes who have very low heart rates because of intense and frequent exercise.

___1. Nationally, the most common cause of Down Syndrome is
a. nondisjunction of Chromosome 21 during meiosis
b. translocation of Chromosome 21 onto another chromosome
c. inversion of a large section of Chromosome 21
d. deletion of the Down Syndrome gene
___2. In humans, sex is determined by
a. The presence or absence of the Y chromosome
b. The ratio of X chromosomes to sets of autosomes
c. The temperature during fetal development
d. Which parent is stronger at the time of conception
___3. A translocation is
a. a chromosomal abnormality in which a piece of one chromosome breaks off and attaches to a different chromosome
b. an abnormality in which the chromosomes are translocated out of the nucleus
c. a condition in which the chromosome has broken in two places and come back together with the middle segment backward
d. an abnormality in which there is an extra copy of one chromosome
___ 4. In snapdragons, a red-flowered plant crossed with a white-flowered plant produces all pink-flowered offspring. But crossing two pink-flowered plants produces red, pink, and white in a 1:2:1 ratio. This is a good example of
a. Incomplete dominance
b. Dominance of the red allele over the white allele
c. Lethal effects of the pink allele
d. Sex-linkage of the flower-color alleles
___ 5. If a person with type AB blood marries a person with Type O blood, what blood types are possible in their children? (Assume this trait is a single-gene trait, not complicated by interaction with other genes).
a. A, B, AB, or O
b. A or B only
c. AB or O only
d. AB only 2
___6. In what phase of meiosis are haploid nuclei first formed? a. Anaphase I b. Metaphase II c. Telophase II d. Metaphase I e. Telophase I
___7. What is the phenotype of a heterozygous tall pea plant? a. tall b. Tt c. TT d. tt e. dominant
___ 8. If genes A and B are far apart on a chromosome, and A and C are close together, which of the following observations is expected?
a. Crossing over will occur more often between A and C than between A and B
b. Crossing over will occur at equal frequencies between A and C, and between A and B
c. Crossing over will occur more often between A and B than between A and C
___9. Sometimes an organism’s genotype for one gene masks the effect of a different gene. This phenomenon is called
a. Dominance
b. Incomplete dominance
c. Co-dominance
d. Epistasis
e. Variable expressivity
___10. The dominant allele of a gene is
a. The one that is expressed most often in a population
b. The one that is expressed most often in any particular cross
c. The one that is expressed in an individual that has two different alleles
d. The one that is most healthy to have, that gives the greatest fitness
___11. In human cells, DNA replication occurs
a. In S phase of interphase
b. In G1 phase of interphase
c. In G2 phase of interphase
d. In prophase of mitosis
e. Whenever the cell needs to read the DNA to make proteins
___ 12. A process in which recipient cells take up genes from DNA molecules floating free in the surrounding medium is called
a. conjugation
b. specialized transduction
c. generalized transduction
d. transformation 3
___ 13. Most calico cats are female. However, a few rare males are observed. What is the genotype of a male calico cat?
a. X BX 0
b. X OY
c. X BY
d. X BYY
e. X BX OY
___ 14. A type of red-green color-blindness is a sex-linked (X-linked) recessive trait in humans. Can a woman have this type of color-blindness?
a. Yes, a woman could be color-blind if her mother and father were both heterozygous.
b. Yes, a woman could be color-blind but only if she has an abnormal number of sex chromosomes.
c. No, women can't show sex-linked traits because they lack a Y chromosome.
d. No, women can't show sex-linked traits because they have two X chromosomes.
e. Yes, a woman could be color-blind if her father was color-blind and her mother was a carrier (heterozygous).

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