Hemizygous

A cell or organism is hemizygous at a locus (a fixed position on a chromosome, such as the position of a gene) if it possesses only one allele for a given trait. In humans, males are hemizygous for alleles expressed on the sex chromosomes as they have only one of each. Contrast this with females who have two copies of the X chromosome and are thus either homozygous or heterozygous at loci on the sex chromosomes. The classic example of hemizygous inheritance is hemophilia.

Classic hemophilia (hemophilia A) is an X-linked, recessive disorder caused by mutations affecting the factor VIII gene, located on the long arm of the X chromosome but nowhere on the Y chromosome. Thus, men with only one mutant allele for the factor VIII gene show a diseased phenotype because the Y chromosome does not have an allele capable of expressing wildtype factor VIII. Women, on the other hand, are not hemizygous at the locus of the factor VIII gene. As only one wildtype allele is necessary to prevent a diseased state, women who are heterozygous at the factor VIII locus will usually not show signs of disease. Only women who are homozygous for the mutant genotype (or are heterozygous with two different, mutant phenotypes) will show signs of disease. The prevalence of hemophilia (and all X-linked recessive diseases) is thus much higher in men than in women.

The hemizygous nature of men also has consequences for the inheritance of X-linked disease. In the case of X-linked recessive diseases, a man with the disease state will pass on the mutant allele to all of his daughters and none of his sons (because all sons receive the Y chromosome). The fate of both the sons and daughters of a man with the mutant allele thus depends on the status of the mother. On the other hand, consider a man with the wildtype allele at the locus in question. While the status of his sons still depends on the status of the mother, the man can be confident that virtually none of his daughters will be affected because they are guaranteed to inherit a wildtype allele from him.

Not all hemizygous traits are X-linked recessive. Although much less common, certain traits are X-linked dominant and there also some Y-linked disease states. The general considerations for inheritance of X-linked dominant traits are similar to those for X-linked recessive traits. However, because dominant inheritance only requires one mutant allele to be present for disease to manifest itself, all of the daughters of an affected father will be affected, whereas affected mothers stand only a 50 percent chance of passing on an affected allele, regardless of the sex of the offspring. It should also be noted that many X-linked dominant disorders are much more prevalent among women than men, even more so than simple probability would suggest. The most common explanation for this is that hemizygosity for a dominant mutant allele is lethal during gestation. This does not seem to be the case with Y-linked alleles, the inheritance of which is always dominant. Males who carry mutations on Y-linked genes may suffer from infertility but seldom suffer a serious disease state that is incompatible with life.

...