Professional Documents
Culture Documents
CHAPTER SUMMARY
This chapter opens with a vignette about the discovery of phenylketonuria that reinforces the
relationship between gene products and phenotype. The role of proteins as the link between
genotype and phenotype is described.
To begin the discussion of metabolic disease, the great variety of protein functions and possible
protein structures are described. Enzyme function is defined, metabolic pathways are described
and Archibald Garrod’s elucidation of alkaptonuria is recalled. To illustrate the role of enzymes
as gene products in the production of phenotype, defects in pathways of amino acid
86 Chapter Ten
metabolism are used as examples. Figure 10.4 summarizes the metabolic pathways that begin
with phenylalanine, and shows several genetic disorders associated with metabolic blocks and
their phenotypic consequences. Phenylketonuria (PKU) is used as a classic example of a
metabolic block that has phenotypic consequences as a result of the accumulation of products in
a secondary pathway. Its progress and treatment are described at length. This is contrasted with
genetic goitrous cretinism, another condition associated with phenylalanine metabolism, but in
which phenotypic consequences result from lack of an important pathway product.
Defects in proteins that function in transport are also covered, using the various hemoglobin
abnormalities as examples. The hemoglobin molecule and the two hemoglobin gene clusters are
described as background to discussion of hemoglobin variants. In this section the point is made
that the defect in sickle cell anemia is caused by the substitution of one out of 146 amino acids in
the structure of beta globin. This is done to provide a graphic example of the relationship
between the nucleotide sequence of a gene, the amino acid sequence of a protein, and the
phenotype. Thalassemias and other variants are described. The section ends with an account of
the novel method of gene switching to treat these disorders.
A section on pharmacogenetics introduces the concept that we live in greatly different sensory
worlds due to genetic differences in our abilities to taste or smell various compounds. This in
turn likely affects our chosen diets and therefore our health. Genetic differences also exist that
cause potentially lethal sensitivity to various drugs; two examples are described.
In the last section, ecogenetics is defined as the branch of pharmacogenetics dealing with
sensitivity to environmental chemicals. A gene whose alleles provide varying degrees of
resistance to both a common insecticide and a toxic nerve gas agent is discussed.
TEACHING/LEARNING OBJECTIVES
By the conclusion of this chapter, students should have a thorough understanding of:
a. The concept that proteins are the end products of genes.
b. The fact that proteins that function as enzymes participate in metabolic pathways.
c. The idea that mutations can produce defects in enzymes that affect metabolic pathways,
producing phenotypic effects due to either lack of a necessary product or accumulation
of a toxic pathway substance; details of PKU provide a useful example.
d. The functional capacities of proteins in other roles, including receptors and transport.
88 Chapter Ten
• Ecogenetics: A branch of genetics that studies genetic traits related to the response to
environmental substances.
TEACHING HINTS
In a definition in a previous chapter and in Table 10.3 the author describes familial
hypercholesterolemia as dominant, and in this chapter thalassemia is defined as recessive, even
though in both cases the heterozygote has markedly milder symptoms than the homozygote. As
in chapter 5, this brings up the fuzziness of these terms and the need, perhaps, to point this out
to students.
Lactose intolerance is a fairly common condition and fairly well known, thanks to advertising.
Students often confuse this with galactosemia since in both cases milk and dairy product
consumption is a problem. It might be a good idea to specifically make sure students
understand the difference.
Even if there is no lab in your course, the PTC tasting test is a popular exercise with students.
Sensitive tasters are astounded that others cannot detect what to them is an obvious and terrible
taste. Although use of one-strength test papers is easy and cheap, use of varied-strength
solutions is both more informative, as the text points out, and also saves sensitive tasters a very
unpleasant experience if they test themselves starting with the weakest solution.
PKU
Online resource and support group for those with PKU and parents of children with PKU.
http://www.pku.com/
90 Chapter Ten
Ecogenetics, Evolutionary Biology, Genomics, and Medicine
Downloadable PowerPoint presentation from conference on Darwin and medicine.
www.pitt.edu/~super7/32011-33001/32211-32221.ppt
ANIMATIONS
Biological Animations
Short animations of biological processes including enzyme activity and metabolism.
http://www.stolaf.edu/people/giannini/biological%20anamations.html
KScience — Enzymes
Animation with an interactive that allows changing parameters to investigate how enzymes act
under varying conditions. Downloadable files.
http://www.kscience.co.uk/animations/anim_2.htm#top
3. C
5. a. Yes. Each will carry the normal gene for the other enzyme. (Individual 1 will be
mutant for enzyme 1 but normal for enzyme 2. This is because enzyme 1 and 2 are
encoded by two different genes)
b. Let D = dominant mutation in enzyme 1, let normal allele = d
Let A = dominant mutation in enzyme 2, let normal allele = a
Ddaa X ddAa
Offspring: DdAa mutation in enzyme 1 and 2, A buildup, no C
Ddaa mutation in enzyme 1, A buildup, no C
ddAa mutation in enzyme 2, B buildup, no C
VI
His first action on awakening was always to stretch out his hand
for the letters that his silent man would have placed by his side, and
to glance at the clock on his dressing table to see how many hours
he had slept. And, indeed, next morning his first sensation was one
of bodily well-being and of satisfaction because the clock appeared
to inform him that he had slept for three hours longer than was his
habit. But with a slight feeling of uneasiness he remembered how
late he had been the night before, and stretching out his hand for the
letters, he heard a voice say:
“Are you 4,259 Mayfair?”
He had answered “What?” before he realized that this question
was nothing more than a very vivid recollection. But even when he
had assured himself that it was only a very vivid recollection, he lay
still and discovered that his heart was beating very quickly. And so
afraid was he that the motion of stretching out his arm would bring
again the voice to his ears, that he lay still, his hand stretched along
the counterpane. And suddenly he got up.
He opened one white-painted cupboard, then the other. Finally,
he went to the door of the room and peered out. His man,
expressionless, carrying over his arm a pair of trousers, and in one
hand a white letter crossed with blue, was slowly ascending the
staircase at the end of the corridor.
“You didn’t ask me a question,” Dudley Leicester said, “about
two minutes ago?”
Saunders said: “No, sir, I was answering the door to the
postman. This, sir.” And he held out the registered letter.
It was as if Dudley Leicester recoiled from it. It bore Pauline’s
handwriting, a large, round, negligent scrawl.
“Did he ask our number?” Dudley inquired eagerly; and
Saunders, with as much of surprise as could come into his impassive
face, answered:
“Why, no, sir; he’s the regular man.”
“Our telephone number, I mean,” Dudley Leicester said.
Saunders was by this time in the room, passing through it to the
door of the bath-cabinet.
“As a matter of fact, sir,” he said, “the only thing he asked was
whether Mrs. Leicester’s mother was any better.”
“It’s very odd,” Dudley Leicester answered. And with Saunders
splashing the water in the white bath-cabinet, with a touch of sun
lighting up the two white rooms—in the midst of these homely and
familiar sounds and reflections, fear suddenly seized Dudley
Leicester. His wife’s letter frightened him; when there fell from it a
bracelet, he started as he had never in his life started at a stumble of
his horse. He imagined that it was a sort of symbol, a sending back
of his gifts. And even when he had read her large, sparse words, and
discovered that the curb chain of the bracelet was broken, and
Pauline desired him to take it to the jeweller’s to be repaired—even
then the momentary relief gave way to a host of other fears. For
Dudley Leicester had entered into a world of dread.
II
III
“No,” she commenced, “do not put down this form of obstinacy
to mental aberration. It is rather to be considered as a manifestation
of passion. You say that Kitty is not of a passionate disposition. I
imagine it may prove that she is actually of a disposition passionate
in the extreme. But all her passion is centred in that one desire—the
desire to excite concern. The cure for this is not medical; it is merely
practical. Nerve treatment will not cure it, nor solicitude, but feigned
indifference. You will not touch the spot with dieting; perhaps by ...
But there, I will not explain my methods to you, old Ellida. I
discussed Kitty’s case, as you set it forth, very fully with the chief in
Philadelphia, and between us we arrived at certain conclusions. I
won’t tell you what they were, not because I want to observe a
professional reticence, but simply so that, in case one treatment
fails, you may not be in agonies of disappointment and fear. I haven’t
myself much fear of non-success if things are as you and Dr.
Tressider say. After all, weren’t we both of us as kiddies celebrated
for fits of irrational obstinacy? Don’t you remember how one day you
refused to eat if Calton, the cat, was in the dining-room? And didn’t
you keep that up for days and days and days? Yet you were awfully
fond of Calton.... Yes; I think I can change Kitty for you, but upon one
condition—that you never plead for Robert Grimshaw, that you never
mention his name to me. Quite apart from any other motive of mine
—and you know that I consider mother’s example before anything
else in the world—if he will not make this sacrifice for me he does
not love me. I do not mean to say that you are to forbid him your
house, for I understand he dines with you every other day. His
pleadings I am prepared to deal with, but not yours, for in you they
savour of disrespect for mother. Indeed, disrespect or no disrespect,
I will not have it. If you agree to this, come to our hotel as soon as
you have read it. If you disagree—if you won’t, dear, make me a
solemn promise—leave me three days in which to make a choice out
of the five patients who wish to have me in London, and then come
and see me, bringing Kitty.
“Not a word, you understand—not one single word!
“On that dreadful day when Robert told us that father had died
intestate and that other—I was going to add ‘horror,’ but, since it was
mother’s doing, she did it, and so it must have been right—when he
told us that we were penniless and illegitimate, I saw in a flash my
duty to mother’s memory. I have stuck to it, and I will stick to it.
Robert must give in, or I will never play the part of wife to him.”
She folded her letter into the stamped envelope, and, having
dropped it deliberately into the ship’s letter-box, she rejoined Mrs.