Single gene disorders

Single gene disorders are caused by DNA changes in one particular gene and often have predictable inheritance patterns. Over 10,000 human disorders are caused by a change, known as a mutation, in a single gene. These are known as single-gene disorders. The mutated version of the gene responsible for the disorder is known as a mutant, or disease, allele. Individually, single-gene disorders are very rare, but as a whole, they affect about one per cent of the population. Since only a single gene is involved, these disorders can be easily tracked through families and the risk of them occurring in later generations can be predicted. Single gene disorders can be divided into different categories: dominant, recessive and X-linked.

Dominant diseases – Dominant diseases are single-gene disorders that occur in the heterozygous state –when an individual has one mutant copy of the relevant gene and one healthy copy. The effects of the mutant version of the gene (allele) override the effects of the healthy version of the gene. So, the mutant allele causes disease symptoms even though a healthy allele is present. Dominant disorders tend to crop up in every generation of an affected family because very one carrying a dominant mutant allele shows the symptoms of the disease.  Dominant disorders spread vertically down family trees, from parent to child. In rare cases when an individual has two copies of the mutant gene  (also known as being homozygous), the disorder symptoms are generally more severe.  An example of a dominant single gene disorder is Huntington’s disease, which is a disease of the nervous system.

Recessive diseases – Recessive diseases are single-gene disorders that only occur in the homozygous state – when an individual carries two mutant versions (alleles) of the relevant gene. The effects of the healthy allele can compensate for the effects of the mutant allele. The mutant allele does not cause disease symptoms when a healthy allele is also present. However, if a parent inherits two mutant alleles, there are no healthy alleles, so the mutant allele can exert its effect. As shown in the diagram below, affected individuals arise when both of their parents carry a single mutated allele and each pass on that mutated copy to the child so the child then has two mutated copies. In this diagram, the mother of the affected grandson has inherited a mutated copy from the grandmother, and the father has inherited a mutated copy from his family. Recessive diseases are more difficult to trace through family trees because carriers of a mutant allele do not show symptoms of the disease. It, therefore, appears that the disease has skipped a generation when it is seen in groups of children within a family. The risk of an individual having a recessive disorder increases when two closely related people have a child together (consanguinity). This is because there is a much greater chance that the same mutant allele will be present in related parents.

X-linked disorders – X-linked disorders are single-gene disorders that result from the presence of a mutated gene on the X chromosome. Because females (XX) have two copies of the X chromosome, but males (XY) only have one copy, X-linked disorders are more common in males. If a male’s single copy on the X chromosome is mutated, he has no healthy copy to restore healthy function. The inheritance patterns of X-linked diseases are simplified by the fact that males always pass their X chromosome to their daughters but never to their sons. Like other single-gene disorders, X-linked disorders can be either recessive or dominant.

X-linked recessive diseases – Examples of X-linked recessive disorders include red-green color blindness,  hemophilia and the Duchenne and Becker forms of muscular dystrophy.  X-linked recessive disorders are much more common in males than females because two copies of the mutant allele are required for the disorder to occur in females, while only one copy is required in males. The inheritance patterns of X-linked recessive disorders are as follows: The overall pattern of the disease is characterized by the transmission of the disease from a carrier mother, who inherited a copy of the mutant gene from her affected father.

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