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Ch. 5 - Sex Determination and Sex Chromosomes
Klug - Essentials of Genetics 10th Edition
Klug10th EditionEssentials of GeneticsISBN: 9780135588789Not the one you use?Change textbook
Chapter 5, Problem 25

In mice, the X-linked dominant mutation Testicular feminization (Tfm) eliminates the normal response to the testicular hormone testosterone during sexual differentiation. An XY mouse bearing the Tfm allele on the X chromosome develops testes, but no further male differentiation occurs—the external genitalia of such an animal are female. From this information, what might you conclude about the role of the Tfm gene product and the X and Y chromosomes in sex determination and sexual differentiation in mammals? Can you devise an experiment, assuming you can 'genetically engineer' the chromosomes of mice, to test and confirm your explanation?

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Step 1: Understand the biological context—In mammals, sex determination is typically controlled by the presence of the Y chromosome, specifically the SRY gene, which initiates testis development. The X chromosome carries genes important for sexual differentiation, such as the Tfm gene, which is X-linked dominant and affects the response to testosterone.
Step 2: Analyze the phenotype of the Tfm mutation—An XY mouse with the Tfm mutation develops testes (indicating that the Y chromosome and SRY gene function normally to initiate testis formation), but the external genitalia are female, showing that the mutation disrupts the response to testosterone, preventing male differentiation despite the presence of testes.
Step 3: Formulate a hypothesis about the Tfm gene product—Since the mutation eliminates the normal response to testosterone, the Tfm gene product likely encodes the androgen receptor or a critical component of the testosterone signaling pathway necessary for male sexual differentiation after testis formation.
Step 4: Design an experiment to test the hypothesis—Using genetic engineering, create mice with different combinations of sex chromosomes and Tfm alleles, such as: (a) XY mice with a normal X chromosome, (b) XY mice with the Tfm mutation, (c) XX mice with the Tfm mutation, and (d) XY mice with a Y chromosome lacking SRY but carrying a normal X. Observe the sexual phenotype and hormone responses in each case to confirm the role of the Tfm gene product and the influence of X and Y chromosomes.
Step 5: Predict outcomes and interpret results—If the Tfm gene product is the androgen receptor, then mice with the Tfm mutation will fail to masculinize external genitalia despite having testes, confirming that the Y chromosome initiates testis development but the X-linked Tfm gene is essential for testosterone response and male differentiation.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

X-linked Dominant Mutations and Their Effects

X-linked dominant mutations occur on the X chromosome and can affect both males and females, but males are often more severely impacted due to having only one X. The Tfm mutation disrupts the normal function of the androgen receptor, preventing cells from responding to testosterone, which is crucial for male sexual differentiation despite the presence of testes.
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Role of Sex Chromosomes in Mammalian Sex Determination

In mammals, the presence of the Y chromosome, specifically the SRY gene, initiates testis development, determining genetic sex as male (XY). However, sexual differentiation depends on hormone signaling pathways, where the X chromosome carries genes like the androgen receptor that mediate the body's response to male hormones.
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Experimental Design Using Genetic Engineering to Test Gene Function

To test the role of the Tfm gene product, one could engineer mice with modified X chromosomes carrying either the normal or mutant allele and observe sexual differentiation outcomes. For example, introducing a functional androgen receptor gene into Tfm XY mice should restore male differentiation, confirming the gene's role in hormone response.
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Related Practice
Textbook Question

In mice, the Sry gene is located on the Y chromosome very close to one of the pseudoautosomal regions that pairs with the X chromosome during male meiosis. Given this information, propose a model to explain the generation of unusual males who have two X chromosomes (with an Sry-containing piece of the Y chromosome attached to one X chromosome).

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Textbook Question

The genes encoding the red- and green-color-detecting proteins of the human eye are located next to one another on the X chromosome and probably evolved from a common ancestral pigment gene. The two proteins demonstrate 76 percent homology in their amino acid sequences. A normal-visioned woman (with both genes present on each of her two X chromosomes) has a red-color-blind son who was shown to have one copy of the green-detecting gene and no copies of the red-detecting gene. Devise an explanation for these observations at the chromosomal level (involving meiosis).

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Textbook Question

In chickens, a key gene involved in sex determination has recently been identified. Called DMRT1, it is located on the Z chromosome and is absent on the W chromosome. Like SRY in humans, it is male determining. Unlike SRY in humans, however, female chickens (ZW) have a single copy while males (ZZ) have two copies of the gene. Nevertheless, it is transcribed only in the developing testis. Working in the laboratory of Andrew Sinclair (a co-discoverer of the human SRY gene), Craig Smith and colleagues were able to 'knock down' expression of DMRT1 in ZZ embryos using RNA interference techniques. In such cases, the developing gonads look more like ovaries than testes. What conclusions can you draw about the role that the DMRT1 gene plays in chickens in contrast to the role the SRY gene plays in humans?

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