Genetics Practice Problems

• Photos of the Stages of Mitosis
• Coin Toss Data

You may type in your own answers, then check to see if you were right. If you’re totally stumped, you can tell the computer to show you the answer to a particular question.

Monohybrid Cross:

In humans, brown eyes (B) are dominant over blue (b)*. A brown-eyed man marries a blue-eyed woman and they have three children, two of whom are brown-eyed and one of whom is blue-eyed. Draw the Punnett square that illustrates this marriage. What is the man’s genotype? What are the genotypes of the children?

(* Actually, the situation is complicated by the fact that there is more than one gene involved in eye color, but for this example, we’ll consider only this one gene.)

Testcross:

In dogs, there is an hereditary deafness caused by a recessive gene, “d.” A kennel owner has a male dog that she wants to use for breeding purposes if possible. The dog can hear, so the owner knows his genotype is either DD or Dd. If the dog’s genotype is Dd, the owner does not wish to use him for breeding so that the deafness gene will not be passed on. This can be tested by breeding the dog to a deaf female (dd). Draw the Punnett squares to illustrate these two possible crosses. In each case, what percentage/how many of the offspring would be expected to be hearing? deaf? How could you tell the genotype of this male dog? Also, using Punnett square(s), show how two hearing dogs could produce deaf offspring.

Incomplete Dominance:

Note: at least one textbook I’ve seen also uses this as an example of pleiotropy (one gene – multiple effects), though to my mind, the malaria part of this is not a direct “effect” of the gene.

(For many genes, such as the two mentioned above, the dominant allele codes for the presence of some characteristic (like, “B” codes for “make brown pigment” in someone’s eyes), and the recessive allele codes for something along the lines of, “I don’t know how to make that,” (like “b” codes for the absence of brown pigment in someone’s eyes, so by “default,” the eyes turn out blue). If someone is a heterozygote (Bb), that person has one set of instructions for “make brown” and one set of instructions for, “I don’t know how to make brown,” with the result that the person ends up with brown eyes. There are, however, some genes where both alleles code for “something.” One classic example is that in many flowering plants such as roses, snapdragons, and hibiscus, there is a gene for flower color with two alleles: red and white. However, in that case, white is not merely the absence of red, but that allele actually codes for, “make white pigment.” Thus the flowers on a plant that is heterozygous have two sets of instructions: “make red,” and “make white,” with the result that the flowers turn out mid-way in between; they’re pink.)

In humans, there is a gene that controls formation of hemoglobin, the protein in the red blood cells which carries oxygen to the body tissue. The “normal” allele of this gene codes for “normal” hemoglobin. However, there is another allele for this gene that has one different nitrogenous base in its DNA sequence, and thus, one codon in the middle of the gene codes for a different amino acid in an important place in the hemoglobin molecule. A red blood cell (RBC) that contains this altered hemoglobin will, under stress, crinkle up into a shape that reminded someone of the shape of an old-fashioned sickle. While the letters “S” and“s” are often used to represent these alleles, since both of them code for “make hemoglobin”, in reality, neither is dominant over the other. Someone who is SS makes all normal hemoglobin, someone who is ss makes all abnormal hemoglobin (and we say that person has sickle-cell anemia), and someone who is Ss essentially has two sets of instructions, and so, makes some of each kind of hemoglobin (often referred to as sickle-cell trait).

Because the RBCs of a person who is ss contain all abnormal hemoglobin, they will “sickle” very easily, with very little stress required to provoke that reaction. All those sickled cells tend to get stuck as they try to go through capillaries, and cause things like strokes, heart attacks, pulmonary embolisms, etc. that lead to death. Because only some of the RBCs of a person who is Ss contain abnormal hemoglobin, that person usually only has trouble with a lot of cells sickling if they’re under a lot of stress trying to meet a higher-than-normal oxygen demand, and so the chances of a person dying from sickle-cell trait are much lower than for full-blown sickle-cell anemia.


A photo, taken by Dr. Fankhauser, of a prepared slide of
blood cells infected with Plasmodium vivax Malaria is a parasitic disease that’s prevalent in tropical areas. When a mosquito that’s carrying the parasites bites someone, the parasites enter the person’s bloodstream, and invades and lives in the person’s RBCs. However, if a person has sickle-cell anemia (ss), the presence of a parasite in a RBC is so stressful, it causes the RBC to sickle (crinkle up), and when that happens, that kills the parasite before it can multiply and spread to other RBCs. Thus, coincidentally, a person who is ss is also “immune” to malaria. If a person is Ss and a malaria parasite tries to invade a RBC with abnormal hemoglobin, again, the RBC will sickle, killing the parasite before it has a chance to reproduce. If a parasite invades a RBC with normal hemoglobin, it will be able to live and multiply, but if its offspring invade other RBCs with abnormal hemoglobin, they, too, will be killed. Thus, a person who is Ss is “resistant” (though not totally immune) to malaria. If a person is SS and has all normal hemoglobin, the malaria parasites do just fine, invading RBCs, growing and multiplying, and invading more RBCs. Thus, an SS person usually dies, eventually, from causes tied to the malaria.
A man and woman living in a tropical area where malaria is prevalent and health care is not accessible have seven children. The genotypes of these children are ss, Ss, SS, ss, Ss, Ss, and SS.

Dihybrid Cross:

In humans, there is a gene that controls formation (or lack thereof) of muscles in the tongue that allow people with those muscles to roll their tongues, while people who lack those muscles cannot roll their tongues. The ability to roll one’s tongue is dominant over non-rolling. The ability to taste certain substances is also genetically controlled. For example, there is a substance called phenylthiocarbamate (PTC for short), which some people can taste (the dominant trait), while others cannot (the recessive trait). The biological supply companies actually sell a special kind of tissue paper impregnated with PTC so students studying genetics can try tasting it to see if they are tasters or non-tasters. To people who are tasters, the paper tastes very bitter, but to non-tasters, it just tastes like paper. Let’s let R represent tongue-rolling, r represent a non-roller, T represent ability to taste PTC, and t represent non-tasting.

Suppose a woman who is both a homozygous tongue-roller and a non-PTC-taster marries a man who is a heterozygous tongue-roller and is a PTC taster, and they have three children: a homozygous tongue-roller who is also a PTC taster, a heterozygous tongue-roller who is also a taster, and a heterozygous tongue-roller who is a non-taster. If these parents would have a bunch more children so that they had 12 in all, how many of those 12 would you expect to be non-tasters who are homozygous for tongue-rolling? If the first child (the homozygous tongue-roller who is also a PTC taster) marries someone who is heterozygous for both traits, draw the Punnett square that predicts what their children will be.

If the man is both Rr and Tt (How do we know that?), he would be RrTt and so could produce gametes with either R or r and either T or t (one allele for each gene). There are two choices for the first trait (R or r). No matter which of those go into a given sperm, there are still two choices for the second trait (T or t). Therefore, a total of 2 × 2 = 4 possible types of gametes (sperm) may be produced.

Multiple Alleles and Codominance:

Some genes have more than two alleles. One of the best-known examples is the gene that is referred to as the “ABO Blood Group,” which actually has quite a number of alleles. However, we will discuss/consider only the three most-common of these. This gene codes for the structure of a certain antigen on the surface of our RBCs. The three alleles we will work with are symbolized by I^A, I^B, and i. However, keep in mind that a person can only have two alleles, two copies of a gene. Thus, the possible genotypes are I^AI^A, I^Ai, I^BI^B, I^Bi, I^AI^B, or ii. (Sometimes, you will see these simplified as AA, AO, BB, BO, AB, and OO, but that does make it harder to remember that these are all alleles for the same gene.)

The allele, I^A, codes for, “make type A antigen,” the allele I^B codes for, “make type B antigen,” and (to simplify things somewhat) the i allele codes for, “I don’t know how to make either A or B.” Thus, both I^AI^A and I^Ai individuals receive instructions to “make type A antigen,” and both I^BI^B and I^Bi individuals receive instructions to “make type B antigen.” Individuals who are I^AI^B receive two sets of instructions: “make type A” and “make type B,” so they have both the A and B forms of that antigen on the surface of their RBCs. People who are ii don’t have any instructions to make either A or B, so by “default” they make what we refer to as type O antigens. Since both I^A and I^B code for “make something” whereas i codes for, “I don’t know how, therefore, both I^A and I^B are dominant over i. However, since both I^A and I^A code for “make something,” neither of them is dominant over the other. Thus we say that I^A and I^B are codominant over i.

Suppose a person with type A blood and a person with type B blood get married. What are the possible genotypes their children could have?

There is another gene that codes for another, different antigen that also occurs on the surface of our RBCs, and technically, that gene also has multiple alleles. However, most people either have or do not have one particular allele called the “d” allele. This gene codes for an antigen that is called “Rh factor” because it was first discovered in Rhesus monkeys. People who have instructions to “make d antigen” are referred to as Rh⁺ (the allele is often symbolized by the letter “R”), while those who have “I don’t know how to make d antigen” instructions are called Rh^– (the allele can be symbolized by “r”). Since this is a totally separate gene than the ABO blood group, if you’re doing a genetic cross that involves both ABO and Rh, that would be a dihybrid cross.

Ms. Johnston, Ms. Johnson, and Ms. Johnstone all entered the same hospital and gave birth to baby girls on the same day, and all three babies were taken to the nursery to receive care, there. Someone later claimed that the hospital mixed up the babies. As a hospital administrator, it is your job to make sure that each pair of parents has the correct baby, so you order blood typing to be done on all the parents and all the babies. Here are the results:

Trihybrid Cross:

In Guinea pigs, black hair (B) is dominant over white (b), rough coat texture (R) is dominant over smooth (r), and short hair (S) is dominant over long hair (s). Assuming these genes are on separate chromosomes, draw the Punnett square for a cross between a homozygous black, rough, short-haired Guinea pig and a white, smooth, long-haired one. What would the phenotype(s) of the offspring be? If two of the F₁ offspring were crossed, draw the Punnett square for this cross. Hint: first make a list of the possible gametes, making sure each has exactly one copy of each of the genes (one allele for each gene). What would the genotype and phenotype ratios be for the F₂ generation?

Polygenic Trait:

Some traits, some phenotypes, are controlled by more than one gene. It was mentioned in the monohybrid cross, above, that technically, human eye color is controlled by at least two genes, one which codes for brown vs. blue and another which codes for green vs. blue. In the epistasis crosses, below, you will see other examples of polygenic traits. Human skin color is also a classic example of a polygenic trait. It is known that at least three or four genes control skin color, and for each of those genes, dark pigment has incomplete dominance over light (so a heterozygote would be intermediate — see above). Because we just did a trihybrid cross, let’s assume three genes here (for simplicity), and to avoid confusion among them, let’s arbitrarily call them genes A, B, and C. Then, someone who is AABBCC would have very dark skin color and someone who is aabbcc would have very light skin color. If they would get married and have children, their children would all be AaBbCc.

If two  AaBbCc  people would get married and have children, the Punnett square would look like this:

	ABC	ABc	AbC	Abc	aBC	aBc	abC	abc
ABC	AABBCC	AABBCc	AABbCC	AABbCc	AaBBCC	AaBBCc	AaBbCC	AaBbCc
ABc	AABBCc	AABBcc	AABbCc	AABbcc	AaBBCc	AaBBcc	AaBbCc	AaBbcc
AbC	AABbCC	AABbCc	AAbbCC	AAbbCc	AaBbCC	AaBbCc	AabbCC	AabbCc
Abc	AABbCc	AABbcc	AAbbCc	AAbbcc	AaBbCc	AaBbcc	AabbCc	Aabbcc
aBC	AaBBCC	AaBBCc	AaBbCC	AaBbCc	aaBBCC	aaBBCc	aaBbCC	aaBbCc
aBc	AaBBCc	AaBBcc	AaBbCc	AaBbcc	aaBBCc	aaBBcc	aaBbCc	aaBbcc
abC	AaBbCC	AaBbCc	AabbCC	AabbCc	aaBbCC	aaBbCc	aabbCC	aabbCc
abc	AaBbCc	AaBbcc	AabbCc	Aabbcc	aaBbCc	aaBbcc	aabbCc	aabbcc

Linked Genes:

wild-type female
wild-type male
black, vestigial female
black, vestigial male

Normal fruit flies have grayish-yellow bodies, red eyes, and wings that are long-enough to be able to fly. Some mutant fruit flies have black bodies rather than grayish-yellow, some have stumpy, vestigial wings that are too short and wrinkled to be able to fly, and some have a brighter, orangish-red eye color that is called “cinnabar.” By breeding flies, fruit fly researchers were able to determine that all three of these mutations were recessive and were on the autosomes.

Fruit fly researchers use a different type of symbolism to represent their genetic crosses. They use a plus sign (+) to indicate anything that is the “wild” type and a letter (or sometimes two) to represent a mutant allele (capital if the mutation is a dominant allele, lower case if it’s recessive). Thus a fruit fly with a homozygous grayish-yellow body would be labeled as “++” for body color while a black-bodied fly would be “bb” and a heterozygous fly would be “+b”. The genotype for normal wings would also be symbolized as “++,” while the allele for vestigial wings is “vg” so a fly that is homozygous recessive for that gene would be “vgvg” and a heterozygote would be notated as “+vg”. Similarly, normal red eyes would be “++,” cinnabar eyes would be ”cncn,” and a heterozygote would be “+cn.”

To simplify things, for now, let’s consider just the b and vg genes. Suppose we had some flies that were genotype +b+vg (grayish-yellow body and long wings, but carriers for both the black and vestigal alleles). Let’s do a testcross (= a cross with bbvgvg, remember?) with these heterozygous flies.

If these genes were on different chromosomes, the Punnett square for this cross would look like this:

	++	+vg	b+	bvg
bvg	+b+vg	+bvgvg	bb+vg	bbvgvg

so out of the offspring, we would expect to get ¼ of each of the four types.

If the genes were linked on the same chromosome and one of the fly’s chromosomes contained the alleles for yellowish body and normal wings while the other chromosome contained the alleles for black body and crumpled, vestigial wings, the Punnett square for this cross would look like this:

	++	bvg
bvg	+b+vg	bbvgvg

so out of the offspring, we would expect to get ½ of each of the two types.

Sex-Linked Genes:

In humans, the genes for colorblindness and hemophilia are both located on the X chromosome with no corresponding gene on the Y. Typically an X chromosome with a “normal” allele is notated as a plain X while an X chromosome carrying the mutant allele is notated as X′ or with an appropriate letter, such as X^c for colorblindness or X^h for hemophilia (thus, while it’s not typically used, you could use X^C or X^H to represent the normal allele, especially if you’re dealing with both, simultaneously). Note that besides being sex-linked genes, hemophilia and colorblindness are also linked genes and a man who has both would be X^chY. These are both recessive alleles. If a man and a woman, both with normal vision, marry and have a colorblind son, draw the Punnett square that illustrates this. If the man dies and the woman remarries to a colorblind man, draw a Punnett square showing the type(s) of children could be expected from her second marriage. How many/what percentage of each could be expected?

Sex (It’s a Phenotype, Not a Chromosome!):

In humans, there’s another X-linked gene that codes for androgen (testosterone) receptors in our cells. The dominant allele (X^A) codes for “make functioning receptors that can correctly receive and bind onto testosterone,” but there is a recessive allele (X^a) that either codes for “I don’t know how to make testosterone receptors” or else “make ‘broken’ receptors that can’t receive and bind onto testosterone.” In humans, there is also a Y-linked gene that codes for “make testes,” and when present, they, in turn, make testosterone, and the testosterone, in turn, goes to other cells in the body, and when received by the receptors, triggers other events within those cells. During embryonic development, one such event is growth and development of male genitalia.

Consider a person who is genotype X^AY. Because this person has a Y chromosome including a normally-functioning gene to make testes, at the appropriate time during embryonic development, testes will form and will start to secrete testosterone. Because this person also has the correctly-functioning allele for the androgen (testosterone) receptor gene, those receptors will form and will begin functioning. As they receive the testosterone made by the testes, this will stimulate development of male genitalia, and (assuming all other genes are working “normally”), this baby will be a boy.

Consider a person who is genotype X^AX^A. Because this person does not have a Y chromosome, there is no gene to provide instructions to make testes, therefore no big prenatal surge of testosterone, therefore no stimulus to make male genitalia (in spite of properly-functioning testosterone receptors), so by “default,” female genitalia develop, and (assuming all other genes are working “normally”), this baby will be a girl.

If these two people would get married, the Punnett square for their children would look pretty much like the ones you’ve just done:

	XA	Y
XA	XAXA	XAY
XA	XAXA	XAY

½ of the children will be females, and ½ will be males

Consider a person who is genotype X^AX^a. Because this person does not have a Y chromosome, there is no gene to provide instructions to make testes, therefore no big prenatal surge of testosterone, therefore no stimulus to make male genitalia (in spite of properly-functioning testosterone receptors in many/most cells), so by “default,” female genitalia develop, and (assuming all other genes are working “normally”), this baby will also be a girl. However, she is a carrier for the non-functioning androgen-receptor gene. Because of inactivation of X chromosomes to form Barr bodies, some of the cells in her body will not be able to receive testosterone messages, which might show up in things like having somewhat less pubic and/or armpit hair.

Androgen Insensitivity Syndrome (AIS) — A Sex-Linked Gene that Helps to Determine Sex

Our genes, our genetic make-up, is/are not independent of the rest of our bodies, but rather, are closely integrated in and with all of our body processes. Androgen Insensitivity Syndrome (AIS) may be used to illustrate how a person’s genetic make-up, hormones, biochemistry, embryonic development, and phenotype are all closely tied together and integrated, and may serve as a good example of how our “sex” is also a phenotype that is under genetic control.

Hormones are chemical “messengers” which are made in specific organs in our bodies, called endocrine glands. These hormones travel, via the blood, to other areas of the body where they exert chemical control over some process that is occurring in that location. For example, the hormone insulin is made by the pancreas and travels to the liver, where it “tells” the liver to take sugar out of the blood and store it up by making glycogen. For many of our hormones, reception of their message is dependent upon proper functioning of other chemicals in the cells of the target organs. For example, in type II diabetes, the person’s body is making adequate insulin, but the insulin receptors in his/her liver are not functioning properly, so the liver never gets the message to store up sugar, and the person’s blood sugar level goes too high.

Androgens, including testosterone, are hormones which all of us, both men and women, make in our bodies. In both men and women, testosterone is responsible for the coarse pubic and axillary (armpit) hair which starts to grow at puberty. Since the testes are the primary organs which produce testosterone, people with testes typically have a higher level of testosterone in their bodies than people without testes, and that is responsible for development of most of the traits that we consider “male”. As in the above example, the testosterone produced by the testes is secreted into the blood and travels to many other areas of the person’s body to exert its effects, and also as above, testosterone (androgen) receptors are required in those target locations. By the way, all of us, both men and women, also make at least some estrogen, and for all of us, both men and women, how we look – our phenotype – is typically influenced by the effects of both the testosterone and estrogen in our bodies.

Testosterone exerts its effect in a somewhat indirect fashion. When testosterone reaches a target organ or target tissue, it must be absorbed into the cells of that tissue. Inside those cells is a kind of protein, coded for by the person’s DNA, called an androgen receptor which, as its name implies, receives the testosterone and binds on to it. As the testosterone binds onto the androgen receptor protein, it causes a change in that protein’s native conformation which converts the inactive receptor into an active DNA-binding state, thereby enabling the protein to chemically interact with that cell’s DNA. Thus, once testosterone has attached to the androgen receptor, that pair goes into the nucleus of the cell and interacts with the person’s DNA, thereby controlling transcription of other genes. Many of those genes control “male” traits such as embryonic development of male external genitalia.

All human embryos, whether XX or XY, develop identically for the first 6 weeks of life, all have undifferentiated external genitalia, and all have rudimentary primordial gonadal tissue that can, potentially, form either male or female organs. If the embryo baby has a Y chromosome, that Y chromosome contains a gene which codes for the formation of testes from the primordial gonadal tissue at about 6 weeks. Testes, by the way, form in approximately the same location in the abdomen as ovaries do, with the difference that while ovaries “stay put,” normally, testes later move down lower in the abdomen and eventually, out the bottom of the abdomen and into the scrotum (thus, we say they “descend”). Formation of the testes is not dependent on androgens such as testosterone, but rather, once testes have begun to form, they start to secrete androgens, including testosterone, as well as another hormone called anti-Müllerian hormone. The anti-Müllerian hormone has an inhibitory effect which causes regression of the primordial female system, thus inhibiting the development of Fallopian tubes, uterus, and the upper portion of the vagina. The androgens, including testosterone, have a stimulatory effect on development of the male system, which causes development of the epididymis, vasa deferentia, and seminal vesicles during about the 9^th through 13^th weeks. In the absence of the effects of these hormones, development of the male system does not occur and instead, by “default,” the female external genitalia (labia, vagina) develop.

However, in order for embryonic development of the male organs to take place, the androgen receptor protein has to be functioning properly. As just mentioned, in type II (adult onset) diabetes, the person’s body is making enough insulin, but the insulin receptors in that person’s liver cannot properly receive the insulin. Similarly, the androgen receptors must be functioning properly to receive testosterone. Since the androgen receptor molecules are a kind of protein, that means they’re under the control of the gene that codes for them, and any mutation of that gene – totally missing androgen receptor gene, missing chunk of gene, frameshift mutation, etc. – can cause the protein to be absent or have an abnormal native conformation that is incapable of binding on to testosterone. Thus, even though lots of testosterone is present, the androgen receptor can’t bind on to it, and therefore is unable to control transcription of other genes. This would make that person’s organs/tissues appear to be totally resistant or insensitive to the effects of testosterone, hence the name “Androgen Insensitivity Syndrome.”

Now, consider the effect that would have on the embryonic development of an XY individual. Since the Y chromosome is present, that person has the gene to make testes, so the testes begin to develop and start to secrete testosterone and anti-Müllerian hormone. Since the anti-Müllerian hormone is functioning properly, development of the uterus, Fallopian tubes, and the top end of the vagina will be inhibited. However, despite lots of testosterone, the rest of the body never gets the message, so the epididymis, vasa deferentia, and seminal vesicles will not develop. Also, without the effects of testosterone, external male genitalia (scrotum, penis) will not form, but rather by “default,” as is normally the case in the absence of the influence of testosterone, the external genitalia will be totally female, including the labia and most of the vagina. Thus, even though this person is chromosomally XY and has testes, she is phenotypically female. Actually, since a girl/woman with AIS is totally resistant to the effects of testosterone, it’s kind-of like she’s more female than a “typical” XX female whose phenotype is influenced by the testosterone in her body. Usually her testes do not descend, but remain in her abdomen, and thus, as with any undescended testes, they are more likely to develop testicular cancer. When this baby is born, to her doctors, nurses, and parents she looks like any other normal little girl, but her undescended testes may be discovered later if they are in such a position as to give the appearance of a hernia.

What about later in life? In some girls with AIS, their undescended testes are never apparent, and the condition is discovered when they fail to begin menstruating despite normal body development at puberty. Even XY men produce some estrogen in their bodies. In the bodies of women with AIS, some of the testosterone they produce is converted to estrogen, and that, coupled with the estrogen being produced by their bodies is enough that their estrogen levels are about the same as an XX woman in the ”follicular“ phase of her monthly cycle, and women with AIS go through normal development at puberty (breast development, widening of the hips, etc.). Actually, since the effects of estrogen are unopposed by testosterone in their bodies, breast development is often more significant than XX women whose development is also influenced by testosterone. Since testosterone plays a role in teenage acne, women with AIS typically have very clear, acne-free complexions. Since the testes do produce some estrogen, and since some of the testosterone they produce is converted to estrogen, their presence in her body can aid in development at puberty, but due to the increased risk of testicular cancer in undescended testes, physicians often encourage their removal soon thereafter. Since she doesn’t have a uterus or ovaries, a woman with AIS will not menstruate and will not be able to become pregnant, thus may want to consider adopting children. Since, as mentioned above, growth of axillary and pubic hair is controlled by testosterone, women with AIS will usually not have that type of coarse hair, which can be very upsetting to a teen being ridiculed by her classmates during gym class showers. Depending on the shortness of the woman’s vagina, once she is sexually active, that may help to stretch it, but in some cases, a doctor might advise surgery to lengthen it.

While a girl who has AIS has enough estrogen in her body to stimulate normal (or greater than normal) breast development, size-wise, she lacks the hormones needed to stimulate development of the actual mammary gland tissue. If, however, she is given supplemental hormones during puberty, mammary gland tissue will properly develop, and as an adult, she will be as capable as any other adoptive mother of nursing a baby.

The genetics of AIS is an intriguing part of this story. As mentioned above, AIS may be attributed to a mutation in the gene that codes for the androgen receptor protein. Thus, AIS is, essentially, an allele that influences the sex of the individual, but interestingly, AIS is also an X-linked, recessive allele. In other words, testosterone sensitivity is coded for by a gene on the X chromosome (and the recessive allele codes for a non-functioning receptor). If we let X^A represent the allele that codes for functional androgen receptor and X^a represent the allele that codes for non-functional androgen receptor, then a person who is X^AX^A would be a female who is normally receptive to testosterone. Someone who is X^AX^a would be a carrier female, and because this is an X-linked gene, her body would be a mosaic of tissue types – some of her cells would be sensitive to testosterone while others would be resistant, depending on which X chromosome was active and which had become a Barr body. Some women who are heterozygous have delayed menarche (onset of menstruation) or may have reduced or asymmetrical development of pubic or axillary hair. Someone who is X^AY would be a male who is normally receptive to testosterone. However, unlike other sex-linked alleles, because AIS affects the sex of the person, someone who is X^aY would be a female with AIS. If a carrier woman and a man get married, the Punnett square for their children would look like:

	XA	Y
XA	XAXA	XAY
Xa	XAXa	XaY

Thus, ¾ of their children would be expected to be girls and only ¼ boys. Of the girls, we would expect 33% to have normal testosterone receptors, 33% to be carriers, and 33% to have AIS (of all the children, that would be ¼ each).

When we discussed other sex-linked genes such as hemophilia, red-green colorblindness, and white-eyed fruit flies, we took things one step farther, and showed how a carrier female (XX') and affected male (X'Y) could produce a homozygous recessive female (X'X') offspring. Because AIS affects the sex of the individual, that genetic cross wouldn’t be possible. First of all, someone who is X'Y would be female, not male, and so most likely would get married to a man (XY), not another woman (XX'). Secondly, since she doesn’t have a uterus, she can’t get pregnant. Thirdly, between the fact that her testes, if not surgically removed, are undescended (and therefore sterile) and the fact that her testes, along with the rest of her body, are insensitive to the effects of testosterone (and therefore sterile), they would produce no sperm (and anyway, sperm would have no way out). Unlike other X-linked alleles, a girl would not inherit this from her father. An X'X' individual would be extremely rare because no one could inherit that combination, so the only way to get that would be in the extremely unlikely event that mutations suddenly occurred in the X chromosomes that both parents gave to that daughter.

Several famous actresses and female athletes have or may have AIS. Actually, the idea of a successful female athlete with AIS is of interest because it is generally thought that athletic prowess is related to testosterone, yet here is a woman whose body is totally unaffected by testosterone. Because athletic organizations, including the Olympics, have not understood that, these women have, at times, been unfairly barred from competition, based solely on the fact that they have a Y chromosome, and they have been forced to bring law suits to be permitted to compete. Because of our society’s overall lack of understanding and acceptance, some doctors try to convince parents of an androgen-insensitive daughter to keep that a secret from her, but that never works. Sooner or later, she will find out or figure it out, somehow, often accompanied by feelings of guilt, embarassment, and bewilderment, so wouldn’t it be much better to hear it gradually from loving, supportive parents as she grows up than to, as a young adult, suddenly hear it from someone else?

Some things to discuss with your study group: what would you do if...?

• What if one of your neighbors or another student here at school told you that his/her daughter has AIS? What would you think? What would go through your mind when you met that girl for the first time? What would you say to your own children about her?
• Suppose you are the parent of a cute little girl (pick an age: 2? 4? 8?) who loves dressing up in frilly dresses and playing with baby dolls and who, you were told, had a hernia that would have to be surgically corrected. What if the doctor came out of surgery to tell you your little girl did not have a hernia, but they had just discovered she had testes? What if the doctor, then, recommended getting a karyotype done, and the results came back saying that chromosomally, she’s XY? How would you feel? What would go through your mind?
• What would you say to her as she was growing up? What would you say to her when she told you she was going to be a mommy and have babies when she grows up? What would you say to her before or while she was taking junior high health class? What would you say to her when she didn’t start menstruating like all her peers, so they were making fun of her? What would you say to her when she didn’t want to go to junior-high gym class because, during the mandatory group showers afterwards, the other girls ridiculed her because she lacked pubic hair? What would you say to her when she was going through all the insecurities and self-doubts that teenagers go through?
• One for the men: suppose you started dating a woman, fell deeply in love with her, and the two of you were thinking about getting married. What if, in the course of a conversation one day, she told you that she had AIS, that her karyotype was XY, and that she was scheduled to have surgery next week to remove her undescended testes? What would you think? What would you say to her? What would you do?
• One for the women: there is an analogous condition in which a person can be XX, yet due to influence, or lack thereof, of the sex hormones, be phenotypically male. I recall hearing about a medical case history where a couple was not having success conceiving a child, and so they were undergoing medical testing to determine the cause. In the course of the testing, it was discovered that the man was XX. How do you think you would react if that was your husband?

Sex-Influenced Traits:

Baldness in humans is a dominant, sex-influenced trait. This gene is on the autosomes, not the sex chromosomes, but how it is expressed is influenced by the person’s sex (due to hormones present, etc.). A man who is BB or Bb will be bald and will be non-bald only if he is bb. A woman will only be bald if she is BB and non-bald if she is Bb or bb (it’s almost like B is dominant in males and b is dominant in females). Actually, because of the influence of other sex-related factors, most women who are BB never become totally bald like men do, but rather, their hair may become “thin” or sparse. If two parents are heterozygous for baldness (note: that means he would be bald, but she would not.), what are the chances of their children being bald? Use a Punnett square to illustrate this. Note: because the sex of a person does make a difference in how the gene is expressed, you need to set this up as a dihybrid cross to account for the sex of the children.

A non-bald man marries a non-bald woman. They have a son and a daughter. If the son becomes bald, what are the chances that his sister will, too? Use a Punnett square to show this cross.

Epistasis:

In sweet peas, purple flower color (P) is dominant over white (p), but there is also a control gene such that if the plant has a “C”, the purple has “permission” to express itself. If the plant is “cc,” the purple does not “have permission” to express itself and the flower will be white anyway. If a plant with homozygous purple, controlled flowers is crossed with a plant with white, non-controlled flowers, diagram the Punnett square for the F₁ and F₂ generations and calculate the genotype and phenotype ratios.

Because you must keep track of both the purple/white and the control genes, you need to set this up as a dihybrid cross.

Epistasis can also work in the “opposite” direction (actually, some textbooks give these two cases other names). In corn kernels, purple (P) is dominant over yellow (p), but there is also an inhibiting control gene such that if that corn kernel has a “C”, the purple does not “have permission” to express itself, and the kernel will be yellow. If that kernel is “cc”, then the purple has “permission” to be expressed. If the same cross as above is done, the result would be:

genotypes:			phenotypes:
PPCC	1		P–C–	= yellow bec. of C–	9	}	13 yellow total
PPCc	2		ppC–	= yellow	3
PPcc	1		ppcc	= yellow bec. of pp	1
PpCC	2		P–cc	= purple	3	}	3 purple
PpCc	4
Ppcc	2
ppCC	1
ppCc	2
ppcc	1

There are some other, interesting possibilities. Suppose that in corn kernels, purple (P) is dominant over some other color, say red (p). However, suppose there is a control gene (C) which “permits” the color to be present and “cc” doesn’t “permit” color to be present, resulting in yellow kernels. If the same cross as above is done, the result would be:

genotypes:			phenotypes:
PPCC	1		P–C–	= purple	9	}	9 purple
PPCc	2		P–cc	= yellow bec. of cc	3	}	4 yellow total
PPcc	1		ppcc	= yellow bec. of cc	1
PpCC	2		ppC–	= red bec. of pp	3	}	3 red
PpCc	4
Ppcc	2
ppCC	1
ppCc	2
ppcc	1

Suppose, instead, that “C” inhibits or does not “permit” the color to be present, while “cc” does allow the color to be expressed. If the same cross as above is done, the result would be:

genotypes:			phenotypes:
PPCC	1		P–C–	= yellow bec. of C–	9	}	12 yellow total
PPCc	2		ppC–	= yellow bec. of C–	3
PPcc	1		P–cc	= purple	3	}	3 purple
PpCC	2		ppcc	= red bec. of pp	1	}	1 red
PpCc	4
Ppcc	2
ppCC	1
ppCc	2
ppcc	1

ZW Sex-Linked Inheritance:

Birds and lepidopterans (butterflies and moths) have ZW sex determination, which is so named to distinguish it from XY sex determination (as in humans and fruit flies) because ZW is the “opposite” of XY. In the ZW sex determination system, the females are heterogametic (ZW), and the males are homogametic (ZZ).


Barred Rooster In chickens, there is an autosomal gene called “extended black,” symbolized by E. There is also a sex-linked (Z-linked) dominant gene for barred feathers (causing the feathers of the adults to be black and white striped/barred). Since this is a sex-linked gene, the barred allele would be symbolized as Z^B, and the non-barred allele as Z^b.

A genetic cross that is routinely done in the poultry industry is to cross a Rhode Island Red or New Hampshire breed rooster, both of which are EEZ^bZ^b for these two genes with a Barred Plymouth Rock hen, which breed is EEZ^BW for these two genes. This results in hybrid offspring of a variety (not a true-breeding “breed”) called Black Sex-Linked. When the new Black Sex-Linked chicks hatch, they can be sexed immediately because the females are all black while the males have a cream-colored or whitish spot on their heads. As adults, the hens will be solid-colored while the roosters will have barred feathers.

For purposes of this illustration, since both parents are EE, we can “ignore” that gene, and look just at the sex-linked (Z-linked) barring gene. Thus, the cross to produce Black Sex-Linked chicks can be represented by Z^BW × Z^bZ^b.

The resulting offspring would be Z^bW hens (called pullets when young) and Z^BZ^b roosters (called cockerels when young). It is the Z^B allele inherited by the roosters that gives them their white head spots as chicks and also give them barred feathers as adults.

If one each of those Black Sex-Linked hens and roosters would manage to live to adulthood and mate with each other:

	ZB	Zb
Zb	ZBZb	ZbZb
W	ZBW	ZbW

Thus, with the probability of ¼ of each of four possible types of offspring, clearly this hybrid variety of chickens is not true-breeding.