Introduction

X-linked dominant inheritance describes a genetic condition that is associated with mutations in genes that are located on the X chromosome. For disease to cause in both males (who possess only one X chromosome) and females (who have two X chromosomes) only a single copy of the mutation is enough. In some cases, the absence of the only functional gene leads to the death of males that are affected. X-linked dominant inheritance is the only way in which the genetic trait or condition must be passed down from parent to child via mutations (i.e. any sudden changes) occurring in a gene present on a single X chromosome. In females (who usually possess two X chromosomes), a mutation in a gene that is present on one of the X chromosomes is generally enough to cause the condition. In males (who only have a single X chromosome), a mutation in the copy of the gene on the single X chromosome leads to the condition. Fathers generally do not pass X-linked dominant conditions to their sons, but all daughters of affected fathers will surely be affected by the condition and can be able to pass it on to their children.

Genetics

Since the X chromosome is mainly one of the sex chromosomes (whereas the other is the Y chromosome), X-linked inheritance can be determined by the sex of the parent carrying that specific gene and this may usually seem complicated. This is mainly because females possess two copies of the X-chromosome, whereas males possess only one copy. The main point of difference between dominant and recessive inheritance patterns also has a crucial role in determining the probability of a child inheriting an X-linked disorder from their parents.

Males can only get an X chromosome from their mother whereas females get an X chromosome from both their parents. This is the main reason, why females tend to show a higher probability of X-linked dominant disorders since they have more of a chance to inherit a faulty X chromosome.

Patterns for X-linked Dominant Inheritance

After completing the genotypes for every individual in several family trees that exhibit this mode of inheritance, other different patterns that can be noticed are discussed below:

All daughters of an affected male will also possess the trait.
No male can be seen in this type of inheritance; this trait follows the inheritance of the X-chromosome.
Sons might have the trait only if their mother also possesses the trait.
The same type of inheritance pattern as that of autosomal dominant traits can be seen in human females.
The father transfers their ‘X’ sex chromosome (and all of its genes) to his daughters and that of his ‘Y’ sex chromosome (with its genes) to his sons.
Genes usually act in pairs, one from each parent for the females. In this type of mode of inheritance, males generally get their genes for the trait from their mother.
Gene pairs separate during meiosis and result in the formation of the sex cells along with the chromosomes.
As the sperm fertilizes the egg, the father’s genes (and chromosomes) join with that of the mother’s, and both of them contribute to the genetic makeup of the offspring.
In this case, one form of a gene might be dominant over another recessive form and the dominant form would be mainly expressed.

X-linked dominant with male lethality

Some of the X-linked dominant conditions are generally lethal only in a hemizygous individual like a male with (‘XY’) or a female with Turner syndrome (‘XO’ or ‘X-‘). Conditions like Rett syndrome, incontinentia pigmenti (IP), oral-facial-digital I (OFD I) syndrome, focal dermal hypoplasia, and X-linked Chondrodysplasia Puncatata Type 2 all of these mainly result in an early gestational male lethality. One exception to this form is an ‘XXY’ genotype, that might lead to an affected male.

X linked Inactivation

In females, though each body cell possesses two X chromosomes, only one is used for making the gene product and the other X chromosome is generally switched off. This process of switching off is referred to as X-inactivation. This mainly happens randomly so that in some of the female’s cells, one particular X will get inactivated (i.e. switched off) and in another cell, then X will get activated (switched on).

Pedigree Analysis Rules

X-linked Dominant Inheritance

Trait must not skip generations.
Affected males should only come from affected mothers.
About half of the children of an affected female are usually affected.
All the daughters, but none of the sons, of an affected father are seen to be affected.
For a female child to get affected, the father or the mother should also be affected.

Disorders related to X linked dominant

Vitamin D resistant rickets: X-linked hypophosphatemia
Rett syndrome (95% of cases are due to sporadic mutations)
Most cases of Alport syndrome
Incontinentia pigmenti
Giuffrè–Tsukahara syndrome
Goltz syndrome
X-linked dominant porphyria
Aicardi Syndrome

Conclusion

Some scholars have suggested discontinuing the use of the terms like dominant and recessive while referring to X-linked inheritance and stating that the highly variable penetrance of X-linked traits in females is the result of mechanisms like skewed X-inactivation or somatic mosaicism is very difficult to reconcile with the present standard definitions of dominance and recessiveness.

Pedigrees are mainly used to analyse the pattern of inheritance of a particular trait in the whole family. Pedigrees help us to know the presence or absence of a trait since it relates to the relationship between parents, offspring, and siblings. With the help of pedigree analysis, we can determine genotypes, identify phenotypes, and predict the transmission of a trait to the next generation. The information from a pedigree makes it easier to determine how certain alleles are inherited: whether they are dominant, recessive, autosomal, or sex-linked. Here we come to an end of this topic, we hope that you were able to grasp a clear concept of X linked dominance.