Sex-Linked Diseases

In Chapter 3 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I include a homework problem about color blindness.

Problem 6. Color blindness is a sex-linked defect. The defective gene is located in the X chromosome. Females carry an XX chromosome pair, while males have an XY pair. The trait is recessive, which means that the patient exhibits color blindness only if there is no normal X gene present. Let X_d be a defective gene. Then for a female, the possible gene combinations are

XX, XX_d, X_dX_d.

For a male, they are

XY, X_dY.

In a large population about 8% of the males are color-blind. What percentage of the females would you expect to be color-blind?

In the Textbook of Medical Physiology (often cited in IPMB), Guyton and Hall write

Medical Physiology, by Guyton and Hall

“Red-green color blindness is a genetic disorder that occurs almost exclusively in males. That is, genes in the female X chromosome code for the respective cones. Yet color blindness almost never occurs in females because at least one of the two X chromosomes almost always has a normal gene for each type of cone. Because the male has only one X chromosome, a missing gene can lead to color blindness.

Because the X chromosome in the male is always inherited from the mother, never from the father, color blindness is passed from mother to son, and the mother is said to be a color blindness carrier; this is true in about 8 per cent of all women.”

Color blindness is not the only sex-linked defect. Many others exist, including hemophilia; an inability to clot blood. Those who suffer from hemophilia bleed profusely from minor cuts, and bruise easily. Guyton and Hall explain

“Hemophilia is a bleeding disease that occurs almost exclusively in males. In 85 per cent of cases, it is caused by an abnormality or deficiency of Factor VIII; this type of hemophilia is called hemophilia A or classic hemophilia. About 1 of every 10,000 males in the United States has classic hemophilia. In the other 15 per cent of hemophilia patients, the bleeding tendency is caused by deficiency of Factor IX [hemophilia B]. Both of these factors are transmitted genetically by way of the female chromosome. Therefore, almost never will a woman have hemophilia because at least one of her two X chromosomes will have the appropriate genes. If one of her X chromosomes is deficient, she will be a hemophilia carrier, transmitting the disease to half of her male offspring and transmitting the carrier state to half of here female offspring.”

Hemophilia B was common among the royal families of Europe in the 19th and 20th centuries. Queen Victoria of England was a carrier, and passed the mutation to royal houses in Spain, Germany and Russia. It may have played a role in triggering the Russian Revolution.