Learning Objectives

By the end of this section, you will be able to do the following:

• Describe the unique inheritance patterns exhibited by sex-linked genes.
• Build and interpret Punnett Squares modeling inheritance of sex-linked genes.
• Compare and contrast the terms homozygous, heterozygous, and hemizygous.

Introduction

In humans, as well as in many other animals and some plants, the sex of the individual is determined by sex chromosomes. The sex chromosomes are one pair of chromosomes. Non-sex chromosomes are called autosomes. In addition to 22 homologous pairs of autosomes, human females have two X chromosomes, whereas human males have an XY chromosome pair. Although the Y chromosome contains a small region of similarity to the X chromosome so that they can pair during meiosis, the Y chromosome is much shorter and contains fewer genes (Fig 12.1). When a gene is present on the X chromosome but not on the Y chromosome, it is described as X-linked.

Sex-Linked Inheritance

Eye color in Drosophila was one of the first X-linked traits to be identified. Thomas Hunt Morgan mapped this trait to the X chromosome in 1910. Drosophila males have an XY chromosome pair like humans, and females are XX. In flies, the wild-type eye color is red (X^W), and it is dominant to white eye color (X^w).

For X-linked traits, males are described as hemizygous because they have only one allele for any X-linked characteristic. Hemizygosity makes the descriptions of dominance and recessiveness irrelevant for XY males. Drosophila males lack a second allele copy on the Y chromosome; their genotype can only be X^WY or X^wY. In contrast, females have two allele copies of this gene which can be X^WX^W, X^WX^w, or X^wX^w.

Because of the location of the eye-color gene, reciprocal crosses do not produce the same offspring ratios. This means, in an X-linked cross, F₁ and F₂ offspring genotypes depend on whether the male or female in the parental (P) generation expressed the recessive trait. With regard to Drosophila eye color, when the Parental generation male expresses the white-eye phenotype and the female is homozygously red-eyed, all members of the F₁ generation exhibit red eyes. The F₁ females are heterozygous (X^WX^w), and the males are all X^WY, receiving their X chromosome from the homozygous dominant P female and their Y chromosome from the P male. A subsequent cross between the X^WX^w female and the X^WY male would produce only red-eyed females (with X^WX^W or X^WX^w genotypes) and both red- and white-eyed males (with X^WY or X^wY genotypes). Now, consider a cross between a homozygous white-eyed female and a male with red eyes (Figure 12.2). The F₁ generation would exhibit only heterozygous, red-eyed females (X^WX^w) and only white-eyed males (X^wY). Half of the F₂ females would be red-eyed (X^WX^w), and half would be white-eyed (X^wX^w). Similarly, half of the F₂ males would be red-eyed (X^WY), and half would be white-eyed (X^wY).

In some groups of organisms with sex chromosomes, the sex with the non-homologous sex chromosomes is the female rather than the male. This is the case for all birds and some insects, such as butterflies. In this case, sex-linked traits will be more likely to appear in the female, since they are hemizygous.

Human Sex-Linked Disorders

Discoveries in fruit fly genetics can be applied to human genetics. When a female parent is homozygous for a recessive X-linked trait, she will pass the trait on to 100% of her offspring. Her male offspring are, therefore, destined to express the trait, as they will inherit their father’s Y chromosome. In humans, the alleles for certain conditions (some forms of color blindness, hemophilia, and muscular dystrophy) are X-linked. Females who are heterozygous for these diseases are said to be carriers and may not exhibit any phenotypic effects. These females will pass the disease to half of their sons and will pass carrier status to half of their daughters; therefore, recessive X-linked traits appear more frequently in males than females.

Sex-linkage studies in Morgan’s laboratory provided the fundamentals for understanding X-linked recessive disorders in humans, which include red-green color blindness and Types A and B hemophilia. Because human males need to inherit only one recessive mutant X allele to be affected, X-linked disorders are disproportionately observed in males. Females must inherit recessive X-linked alleles from both parents to express the trait. When they inherit one recessive X-linked mutant allele and one dominant X-linked wild-type allele, they are carriers of the trait and are typically unaffected. Carrier females can manifest mild forms of the trait due to the inactivation of the dominant allele located on one of the X chromosomes. However, female carriers can contribute the trait to their sons, resulting in the son exhibiting the trait, or they can contribute the recessive allele to their daughters, resulting in the daughters being carriers of the trait (Figure 12.3). Although some Y-linked recessive disorders exist, they are typically associated with male infertility and are not transmitted to subsequent generations.

Acknowledgements

Adapted from Clark, M.A., Douglas, M., and Choi, J. (2018). Biology 2e. OpenStax. Retrieved from https://openstax.org/books/biology2e/pages/1introduction

Adapted from Fowler, S., Roush, R., Wise, J., Avissar, Y., Choi, J., DeSaix, J., Jurukovski, V., Wise, R., Rye, C., College, O., Molnar, C., & Gair, J. (n.d.). 8.3 extensions of the laws of inheritance. Concepts of Biology1st Canadian Edition. https://ecampusontario.pressbooks.pub/biology/chapter/8-3-extensions-of-the-laws-of-inheritance/