Skip to main content

Case Study: Swimmer

It’s 1966.

All athletes competing in women’s events must undergo a physical exam to qualify to compete. They are required to walk naked before a panel of judges (“naked parades”) and/or undergo gynecological examinations. Athletes judged by the panel to have typical female reproductive anatomy are eligible to compete.

Here are the results of the swimmer’s physical exam.

If you were one of the judges in 1966, would you rule that the athlete is eligible to compete in women’s events? Select your answer below.
illustration of notes from exam that reads: Height 178 centimenters. Weight 68 kilograms. Age 20. Female genitalia fully formed. No breasts. No chest or facial hair. Never had a menstrual period. No children.
Text version of image

Illustration of notes from exam that reads: Height 178 centimenters. Weight 68 kilograms. Age 20. Female genitalia fully formed. No breasts. No chest or facial hair. Never had a menstrual period. No children.

Correct.

The physical characteristics of this athlete are typical of those of a woman, and in 1966 she would have qualified to compete in women’s events. Many female athletes don't have menstrual cycles, a condition known as amenorrhea.

Try again.

The physical characteristics of this athlete are typical of those of a woman, and in 1966 she would have qualified to compete in women’s events. The fact that she never had a menstrual cycle would not have disqualified her.

It’s 1968.

Physical exams have been replaced by a less invasive chromosomal test. In cells with two X chromosomes, one is and becomes a Barr body, which appears as a darkly stained structure right up against the nuclear envelope. A positive Barr body test qualifies an athlete to compete in women’s events.

Here are the swimmers’s Barr body test results.

If you were one of the judges in 1968, would you rule that the athlete is eligible to compete in women’s events?
illustration of an irregular round shape representing a human cell, with a dark inner circle labeled nuclear envelope.

Try again.

The athlete’s cells don't have a Barr body. In 1968, these results would have disqualified an athlete from competing in women’s events. The reasoning behind this decision is that absence of a Barr body is more consistent with someone who is 46,XY than 46,XX—although we now know that cells of 45,X women also lack Barr bodies.

Correct.

The athlete’s cells don't have a Barr body. In 1968, these results would have disqualified an athlete from competing in women’s events.

It’s 1992.

The Barr body test has been replaced by testing for a gene on the Y chromosome called SRY. Scientists isolate DNA from the athlete’s blood cells. They a section of SRY DNA using polymerase chain reaction (PCR) and analyze the PCR sample by . Presence on the gel of a DNA band corresponding to SRY would disqualify an athlete from competing in women’s events.

Here is an image of the gel for the swimmer.

If you were one of the judges in 1992, would you rule that the athlete is eligible to compete in women’s events?
illustration of gel electrophoresis with 4 columns and a reference label for S-R-Y along the left side with an arrow pointing right. Lane 1 is the DNA ladder and shows 4 horizontal white lines of varying thicknesses, none of which align with the S-R-Y label. Lane 2 is the positive reference sample (male), which shows one white horizontal line that lines up with the S-R-Y label. Lane 3 is the negative reference sample (female), which has no white horizontal lines. Lane 4 is the Sprinter sample, which has no horizontal white lines.
Text version of image

Illustration of gel electrophoresis with 4 columns and a reference label for S-R-Y along the left side with an arrow pointing right. Lane 1 is the DNA ladder and shows 4 horizontal white lines of varying thicknesses, none of which align with the S-R-Y label. Lane 2 is the positive reference sample (male), which shows one white horizontal line that lines up with the S-R-Y label. Lane 3 is the negative reference sample (female), which has no white horizontal lines. Lane 4 is the Sprinter sample, which has no horizontal white lines.

Correct.

If you look in lane 4, which contains the swimmer’s DNA, there is no PCR product for SRY, indicating that the gene is missing or has a mutation in it. In 1992, this athlete would have qualified to compete in women’s events. The reasoning behind this decision is that a functional SRY gene is important for testes development and the production of large amounts of testosterone.

Try again.

If you look in lane 4, which contains the swimmer’s DNA, there is no PCR product for SRY, indicating that the gene is missing or has a mutation in it. In 1992, this athlete would have qualified to compete in women’s events.

It’s 2011.

Sports officials have abandoned routine sex testing of female athletes. Current policies call for measuring blood testosterone in some athletes, if suspicions are raised about their sex. The cutoff for being able to compete in women’s events is less than of testosterone per liter of blood. These policies are based on the claim that higher levels of naturally produced testosterone are responsible for men’s athletic advantage.

Here is the for the swimmer.

If you were one of the judges in 2011, would you rule that the athlete is eligible to compete in a women’s event?
illustration of testosterone measurement showing test samples reacting to immunoassay

Testosterone level: 3 nmol/L

Correct.

In 2011, athletes with blood testosterone levels below 10 nmol/L would qualify to compete in women’s events. This athlete’s testosterone levels are 3 nmol/L.

Try again.

In 2011, athletes with blood testosterone levels below 10 nmol/L would qualify to compete in women’s events. This athlete’s testosterone levels are 3 nmol/L.

Summary Questions

These are all of the swimmer’s test results. Based on the data, how would you characterize this athlete’s ?
Physical Exam Presence of typical female sex characteristics Absence of typical female sex characteristics
Barr Body Test Barr body present Barr body absent
PCR Test SRY gene absent SRY gene present
Testosterone Above 10 nmol/L Below 10 nmol/L

Female

There is no right or wrong answer for this question. This athlete has some characteristics of a typical biological female (female external reproductive anatomy and some secondary sex characteristics, no SRY gene, and testosterone levels in the female range) and some characteristics of a typical biological male (no Barr body and no breast development).

Male

There is no right or wrong answer for this question. This athlete has some characteristics of a typical biological female (female external reproductive anatomy and some secondary sex characteristics, no SRY gene, and testosterone levels in the female range) and some characteristics of a typical biological male (no Barr body and no breast development).

I don't know

There is no right or wrong answer for this question. This athlete has some characteristics of a typical biological female (female external reproductive anatomy and some secondary sex characteristics, no SRY gene, and testosterone levels in the female range) and some characteristics of a typical biological male (no Barr body and no breast development).

Which of the following genetic conditions could result in an individual who has many secondary sexual characteristics typical of a female, no SRY gene, and low testosterone levels, but appears to have only one X chromosome?
I need to see the phenotypes chart again

Some of the more common DSDs are shown below.

Click on the chromosome(s) for each variation to learn about the .

  • Typical biological female

  • CYP21A2 gene mutation

  • SRY gene mutation

  • AR gene mutation

  • SRY gene present

  • SRD5A2 gene mutation

  • AMH or AMHR2 gene mutations

  • Typical biological male

Select the best possible answer:

A
B
C
D

Try again.

Someone who is 46,XX is most likely to have a positive Barr body test rather than a negative one like this athlete. In addition, this athlete does not have high testosterone levels.

Try again.

Someone who is 45,X is most likely to have neither a Barr body nor SRY gene, like this athlete. However, this athlete does not have high testosterone levels.

Try again.

Someone who is 46, XY is most likely to be negative for Barr body but positive for the SRY gene. There is a better explanation for this athlete’s phenotype.

Correct!

Based on these choices, the genetic variation that best fits this athlete’s phenotype is that of a 46,XY individual with a missing or mutated SRY gene. Since the SRY gene is not present, testes would not develop. Under current regulations, this athlete would be allowed to compete because their testosterone levels are within the accepted range.

Conclusion

Inactivated

One of the two X chromosomes is inactivated, which means that the genes on this chromosome are not expressed (e.g., do not produce RNA and proteins). X chromosome inactivation ensures that all individuals—female and male—have only one functional copy of the X chromosome in each cell. If inactivation did not occur, cells with two X chromosomes would express a potentially harmful double dose of certain genes.

Amplify

Polymerase chain reaction (PCR) results in millions of copies, or amplified numbers, of a specified DNA region.

Gel electrophoresis

Gel electrophoresis is a method used to separate mixtures of DNA, RNA, or proteins by size and charge using an electric field and a gel matrix with small pores. Smaller pieces of DNA (or RNA, or proteins) will move through the gel matrix more quickly than larger pieces. Markers of known sizes are also run in the gel alongside the samples; in the case of DNA, the size markers are referred to as a DNA ladder.

10 nmol (nanomoles) per liter

A mole is an amount of a substance, specifically 6.022 x 1023 atoms of that substance. 10 nanomoles per liter is equivalent to one hundred-millionths of a mole, or 6.022 x 1015 atoms, in a liter of fluid.

Testosterone measurement

Testosterone levels can be measured in blood samples using immunoassay: a technique for determining the concentration of a substance using antibodies. Another common method for measuring testosterone levels uses mass spectrometry.

Biological sex

Biological sex is defined by an individual’s combination of chromosomes, hormone levels, internal and external reproductive anatomy, and sex characteristics. It is usually treated as a binary trait: female or male. Biological sex is different from gender, which is based on social and cultural ideas of what it means to be a woman or man. Gender identity refers to an individual’s concept of who they are. Gender identity does not always match biological sex.

Phenotype

The term phenotype refers to the observable characteristics or traits of an individual. Phenotype is the result of the interaction of the genetic makeup of an individual and environmental factors.

Typical biological female

In typical biological females, the SRY gene is absent. Phenotype: female internal and external reproductive anatomy and secondary sex characteristics, although there are variations among individuals (for example, variations in breast size or muscle mass); estrogens are typically much higher than testosterone, but there is variation in hormone levels and also in the body’s response to hormones.

CYP21A2 gene mutation

CYP21A2 mutations can alter the production of steroid hormones and cause enlargement of the adrenal glands, a condition known as congenital adrenal hyperplasia. Since the adrenal glands are a source of androgens, 46,XX individuals with this condition can produce excess testosterone and other hormones. Phenotype: ovaries present and functional; uterus present; enlarged clitoris; short vaginal canal; elevated testosterone levels (a condition referred to as hyperandrogenism); decreased fertility. Individuals are typically assigned to a female sex at birth.

SRY gene mutation

Mutations in the SRY gene may inactivate its function, and errors in chromosome segregation during meiosis may result in deletion of the SRY gene from the Y chromosome. Without a functioning SRY gene, the gonads do not differentiate into testes. Phenotype: uterus and fallopian tubes are present; ovaries are present but they do not produce eggs; typical female external sex characteristics. Individuals are typically assigned to a female sex at birth.

An error in chromosome segregation during meiosis results in only one complete X chromosome, with the other X chromosome being partially or completely missing. The condition is known as Turner syndrome. Phenotype: highly variable among affected individuals based on the extent and region of the missing X chromosome; female external reproductive anatomy; absent or reduced secondary sex characteristics; infertility; and ovaries may be absent or nonfunctional (e.g., do not produce eggs). Individuals are typically assigned to a female sex at birth.

AR gene mutation

To have an effect on cells, testosterone has to bind to a receptor called the androgen receptor (AR). Some mutations in the AR gene result in cells that don't respond to testosterone. The resulting condition is called androgen insensitivity syndrome. Phenotype: female or ambiguous external reproductive anatomy; male or ambiguous internal anatomy; breasts may develop. Individuals with complete androgen insensitivity syndrome are typically assigned to a female sex at birth, but there is a spectrum of phenotypes depending on the type of AR gene mutation involved.

An error in chromosome segregation during meiosis can cause an individual to have two X chromosomes and a Y chromosome. This condition is known as Klinefelter syndrome. Phenotype: male internal and external reproductive anatomy; low testosterone levels (hypoandrogenism); small testes; infertility; weak muscles; breasts may develop. Individuals are typically assigned to a male sex at birth.

SRY gene present

The SRY gene may be present on one of the X chromosomes as the result of crossing over between the X and Y chromosomes during meiosis. Phenotype: male external reproductive anatomy; small testes; low testosterone (hypoandrogenism); infertility. Individuals are typically assigned to a male sex at birth.

SRD5A2 gene mutation

Mutations in the SRD5A2 gene cause a deficiency in the enzyme 5-alpha reductase. Developing embryos do not produce enough of a hormone called dihydrotestosterone that is important for male sex development. Phenotype: male internal reproductive anatomy; female or ambiguous external reproductive anatomy at birth; surge in testosterone at puberty results in mostly male sex characteristics. Individuals may be assigned to either male or female sex at birth, but may reassign their sex to male after puberty.

AMH or AMHR2 gene mutations

In males, binding of the anti-Müllerian hormone (AMH) to its receptor, AMHR2, prevents the development of the Müllerian ducts into uterus and fallopian tubes. Mutations in the AMH and AMHR2 genes interfere with this process, resulting in the development of uterus and fallopian tubes. Phenotype: male internal and external reproductive anatomy, along with uterus and fallopian tubes; high testosterone; male secondary sex characteristics. Individuals are typically assigned to a male sex at birth.

Typical biological male

SRY gene is present. Phenotype: male internal and external reproductive anatomy and secondary sex characteristics, although there are variations among individuals (for example, variations in penis size, muscle mass, or facial hair); testosterone is typically much higher than estrogens, but there is variation in hormone levels and in the body’s response to hormones.