Two significant inheritance patterns are observed for X-linked recessive alleles. First, males will preferentially exhibit the recessive X-linked phenotype. This expression pattern of primarily affecting males is shown in figure 4.1.
Because females have two X chromosomes, they can produce phenotypically normal offspring that have either homozygous or heterozygous allelic combinations. Males, with only one copy of the X chromosome, are neither homozygous (two copies of the same allele) nor heterozygous (two different alleles). Instead, males are hemizygous, which describes genes that are present in only one copy, like the X-linked genes in males.
When only a single copy of a gene is present, a single recessive allele can determine the phenotype in a phenomenon called pseudodominance. Thus, a male fly with one recessive w allele is white-eyed, with the w allele acting like a dominant allele to confer the whiteeyed phenotype. This demonstrates that expression of a recessive phenotype is not dependent upon the presence of two recessive alleles, but rather the absence of a dominant allele.
The second major inheritance pattern observed with X-linked genes and the corresponding phenotypes is a crisscross pattern of inheritance. Figure 4.1d demonstrates this pattern as the male parent passes his dominant trait (such as wild-type eyes, fig. 4.1d) to his female offspring, and the female parent passes her recessive phenotype (white eyes) to her male offspring. If we examine the reciprocal cross, we do not observe the crisscross pattern (fig. 4.1a). Thus, the crisscross pattern of phenotypic inheritance is not always observed for X-linked genes.
Because males do not transmit their X chromosome to their male offspring, a recessive X-linked phenotype such as color blindness in humans is never normally transmitted from father to son. However, the male will transmit his X chromosome to his daughter (fig. 4.1a). The daughter of an affected male will be heterozygous if she is phenotypically normal. We call this heterozygous individual a carrier, as she possesses the recessive allele. Thus, the transmission of the X chromosome from the male parent to only his female offspring to produce carriers, along with the pseudodominance of X-linked recessive alleles in males, combine to produce the crisscross pattern of inheritance.
Deviation from Mendelian Patterns
Notice that the two different crosses (see fig. 4.1a and 4.1d) produced different phenotypes in the F1progeny. These differences are not consistent with the Mendelian pattern of inheritance that we described in chapter 2. In figure 4.1a, the recessive white-eyed phenotype is lost in the F1 generation as expected, but in the reciprocal cross it is present in half the progeny (fig. 4.1d).
This does not suggest that Mendel’s laws are incorrect, but rather it demonstrates another level of complexity that Mendel did not observe in his pea crosses. In this case, the increased complexity is due to the two different sex chromosomes and the hemizygous nature of the male. It is comforting that as we uncover the cause of the increased complexity, we see how Mendel’s laws still apply, through the pairing of the X and Y chromosome during meiosis in the male. This observation demonstrates that Mendel’s laws are actually more fundamental than we had expected.
In the following chapter, we will explore other examples of deviations from Mendel’s patterns.
Because both the X and the Y are sex chromosomes, two different patterns of sex-linked inheritance are possible. The terms sex-linked and X-linked usually refer to loci found only on the X chromosome. The term Y-linked refers to loci found only on the Y chromosome, which controls holandric traits (traits found only in males).
There are 1,098 genes that are located on the human X chromosome, whereas 171 genes are known to be on the Y chromosome. The small number of loci on the Y chromosome makes the identification of Y-linked phenotypes difficult. In humans, the best example of a Y-linked trait is a form of retinitis pigmentosa, which results in night blindness that progresses into complete blindness. Retinitis pigmentosa has many different genetic causes, some of which are autosomal and others are sex-linked.
This particular form of retinitis pigmentosa was first described in a four-generation Chinese family. In this family, only males were affected. Furthermore, all of the sons, and none of the daughters, of an affected male were also affected. All of the daughters of an affected male also failed to produce an affected child. This transmission from father to all of his sons and no affected females is consistent with the trait being inherited in a Y-linked manner.
For many years, hairy ear rims was believed to be a Y-linked trait (fig. 4.2) because of the description that it was inherited only in fathers and their sons. NIH’s database, the Online Mendelian Inheritance in Man (OMIM) describes recent data that strongly suggests that hairy ear rims result either from more than one locus on the Y chromosome, with one of the loci located in the pseudoautosomal region, or it is not Y linked at all.