Sex-Linked InheritanceInheritance refers to how genetic information is passed down from parent to child. Mendelian inheritance, or “classic” inheritance, is one of the foundations of genetics. Gregor Mendel, who is often called the founder of modern genetics, performed many experiments on pea plants and was able to make several important observations. Those observations led to “rules” that are still followed to this day, and allowed Mendel to define the basic inheritance patterns.
Each of the inheritance patterns follows certain rules:
The basic patterns of inheritance follow all of these rules, as well as some of their own. Sex-linked inheritance includes some of the major basic patterns of inheritance, as well as some less common patterns.
Sex-linked inheritance refers to an allele being passed on from parent to child on one of the sex chromosomes, either the X or the Y. The allele that is passed down can be either dominant or recessive, but most of the time sex-linked inheritance refers to recessive alleles being passed down on the X chromosome. Dominant and recessive sex-linked inheritance patterns are similar to autosomal dominant and recessive patterns, but there are differences. These differences are mainly due to the fact that autosomes (non-sex chromosomes) are the same in males and females, but the sex chromosomes differ between the sexes.
Females have two X chromosomes. These two chromosomes are a pair, just as the autosomes are found in pairs. As such, females have two copies of each gene on the X chromosome. Males, on the other hand, have only one X chromosome. Even though the Y is considered the X chromosome's “partner,” the two are not a pair. The genes found on the Y chromosome are different from those found on the X chromosome. As such, males have only one copy of each gene on the X chromosome and one copy of each gene on the Y chromosome.
The sex chromosomes are inherited in much the same way as the autosomes. One sex chromosome is inherited from the mother, one sex chromosome is inherited from the father. Since females have two X chromosomes, mothers are only able to pass on an X. Fathers, however, could pass on either an X or a Y. If the father passes on an X, the child will have two X chromosomes and will be female. If the father passes on a Y, the child will have one X and one Y chromosome and be male.
All of these facts are important to sex-linked patterns of inheritance:
X-linked Recessive Inheritance All X-linked recessive conditions involve genes located on the X chromosome. Just like with autosomal recessive inheritance, the appearance of an X-linked recessive condition depends on all copies of the gene having a mutation. For females, this means that the allele on each of their two X chromosomes must carry a mutation. For males, however, only the one allele on their one X chromosome must carry a mutation. In other words, a female can be affected with an X-linked recessive condition only if both alleles of the gene pair carry a mutation. A male can be affected with an X-linked recessive condition if his one allele carries a mutation. It is easier to examine the inheritance of X-linked recessive disorders for males and females separately.
Males can only inherit X-linked recessive conditions through their mother. Males receive a Y chromosome from their father, not an X. A male's one and only X chromosome comes from his mother. If an allele with a mutation is on that X chromosome, there is only that one allele and no other. The male child will have inherited a mutation and will thus be affected. This means that the mother must have an allele with a mutation on at least one of her X chromosomes. It is highly unusual for a woman to have an allele with a mutation on both X chromosomes. If a male child inherits an X chromosome with a mutated allele, it is much more likely that his mother was a carrier for the condition. A carrier for an X-linked recessive condition is much the same as a carrier for an autosomal recessive condition. An allele with a mutation is present on one chromosome, but not the other. The carrier does not usually show signs or symptoms of the condition, but has the ability to pass that mutated allele on to children. Males cannot be carriers of an X-linked recessive condition. If a male has a mutated allele, it is expressed and the male is affected with the condition. Females can be carriers, though, and can pass the condition on to their sons:
A carrier mother can pass on an X-chromosome without a mutated allele or an X-chromosome with a mutated allele. A father will pass on a Y-chromosome to a male child. The Y chromosome does not really matter when it comes to X-linked recessive conditions. If an X-linked recessive carrier mother has male children, there is a 1 in 2 (50%) chance each male child will be unaffected and a 1 in 2 (50%) chance each male child will be affected.
If a male affected with an X-linked recessive condition has children, there is a 0% chance for him to pass the condition on to his sons. Every single male child will inherit a Y chromosome and cannot inherit the mutated allele present on his father's X chromosome.
It is possible, however, for a man to pass a mutated allele on an X chromosome on to his daughter. In fact, that is the only thing that can happen if a male is affected. If a male passes on an X chromosome to his child, that child will be female. If that X chromosome carries a mutated allele, the daughter will inherit a mutated allele from her father. However, this does not necessarily mean she will be affected. In order for a female to be affected, she must have a mutated allele on both of her X chromosomes. This would mean that a daughter would also have to inherit a mutated allele on the X chromosome from her mother. In other words, the mother would have to be a carrier for the same condition present in the father.
As mentioned earlier, females with X-linked recessive conditions are quite rare. The much more likely role for a female to play in the inheritance of X-linked recessive conditions is that of a carrier. That is, to have a mutated allele on one of her two X chromosomes. That mutated allele can come from either her mother or her father:
An affected male can only pass on an allele with a mutation to his daughter. A non-carrier female can only pass on an allele without a mutation. The only possible combination is one X chromosome with a mutated allele and one X chromosome with a non-mutated allele. Thus, if an affected male and non-carrier female have female children, there is a 2 in 2 (100%) chance each female child will be a carrier and a 0 in 2 (0%) chance each female child will be affected.
Female carriers can also be born to an unaffected male father and carrier female mother:
An unaffected male can only pass on an X chromosome without a mutated allele to his daughter. A carrier female can pass on either an X chromosome with a mutated allele, or an X chromosome with a non-mutated allele. Therefore, there are two possible combinations: the daughter may inherit two X chromosomes with non-mutated alleles and be a non-carrier, or she may inherit one X chromosome with a mutated allele and one without and be a carrier. Thus, if an unaffected male and a carrier female have female children, there is a 1 in 2 (50%) chance each female child will be an unaffected non-carrier, and a 1 in 2 (50%) chance each female child will be a carrier. There is a 0 in 2 (0%) chance a female child would be affected.
The takeaway message from each of these examples is that X-linked recessive inheritance is most likely going to be conducted through a carrier mother. Affected males cannot pass a mutated allele on to sons and daughters would be carriers. Affected females are rare. Males cannot be carriers. This leaves the situation of a carrier mother. The overall chance for a carrier mother to have an affected child is shown below:
This is the most likely situation in which an X-linked recessive condition would be found in a family: an unaffected male partnered with a carrier female. If a female carrier for an X-linked recessive condition has children with an unaffected male, there is a 1 in 4 (25%) chance with each pregnancy the child will be an affected male, a 1 in 4 (25%) chance the child will be an unaffected male, a 1 in 4 (25%) chance the child will be female carrier, and a 1 in 4 (25%) chance the child will be a female non-carrier. Overall, there is a 1 in 4 (25%) chance of having an affected child.
Many female carriers for an X-linked recessive condition do not know they are carriers. Sometimes there is a family history of brothers or other males in the family having the condition, but other times there is not. Some women blame themselves for their son's condition upon learning of their carrier status, but it is important to emphasize that it is not her fault . A woman cannot choose which X chromosome she will pass on to her son, nor can she choose to have a mutated allele present on one of her own X chromosomes.
Examples of X-linked recessive conditions include: Duchenne muscular dystrophy, hemophilia, and Friedreich's ataxia.
X-linked Dominant Inheritance X-linked dominant inheritance is similar to autosomal dominant inheritance in that only one allele of a gene pair must carry a mutation in order for disease to occur. This means that both males and females can be affected by X-linked dominant conditions, since both males and females have at least one X chromosome. Sadly, though, X-linked dominant disorders are often (though not always) lethal in males.
Just as in X-linked recessive inheritance, there is no chance the son of an affected male will inherit the condition from his father. Every single male child will inherit a Y chromosome and cannot inherit the mutated allele present on his father's X chromosome. Every single female child of an affected male would have to inherit the X chromosome bearing the mutation; thus, every single daughter of an affected male would also be affected.
An affected female can potentially pass an X-linked dominant condition to sons or daughters:
An affected mother can pass on either an X chromosome with a mutated allele, or an X chromosome with a non-mutated allele. The father can only pass on sex chromosomes with no mutated alleles. Since this is a dominant condition and only one mutated allele is required for symptoms to appear, there are no “carriers.” An individual is either affected or unaffected. Thus, if an affected female and unaffected male have children, there is a 1 in 4 (25%) chance with each pregnancy the child will be an affected male, a 1 in 4 (25%) chance the child will be an unaffected male, a 1 in 4 (25%) chance the child will be an affected female, and a 1 in 4 (25%) chance the child will be an unaffected female. Overall, there is a 2 in 4 (50%) chance of having an affected child, and a 2 in 4 (50%) chance of having an unaffected child.
X-linked dominant conditions are quite rare; examples include incontinentia pigmenti and Coffin-Lowry syndrome. Y-linked Inheritance Y-linked inheritance is an extremely rare phenomenon, owing partially to the fact that there are relatively few genes located on the Y chromosome. However, it can occur, and obviously these genes can be passed down only from fathers to sons, as only males bear a Y chromosome. Male infertility can be inherited in this manner. |
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