Sex linkage describes the patterns of inheritance and presentation when a mutated gene (an allele) is present on a sex chromosome (an allosome) rather than a non-sex chromosome (an autosome). They are characteristically different from the autosomal forms of dominance and recessiveness.
Since humans have several times as many genes on the female X chromosome than on the male Y chromosome, X-linked traits are much more common than Y-linked traits. Additionally, there are more X-linked recessive conditions than X-linked dominant, and X-linked recessive conditions affect males much more commonly, due to males only having the one X chromosome required for the condition to present.
In humans, X-linked traits are inherited from a carrier or affected mother or from an affected father. In X-linked recessive conditions, a son born to an unaffected father and a carrier mother has a 50% chance of inheriting the mother's X chromosome carrying the mutant allele and presenting with the condition. A daughter on the other hand has a 50% chance of being a carrier, however a fraction of carriers may display a milder (or even full) form of the condition due to their body's normal X-inactivation process preferably inactivating a certain parent's X chromosome (the father's in this case), a phenomenon known as skewed X-inactivation. If the condition is dominant, or if the father is also affected, the daughter has a 50% chance of being affected, with an additional 50% chance of being a carrier in the second case. A son born to an affected father and a non-carrier mother will always be unaffected due to not inheriting the father's X chromosome. A daughter on the other hand will always be a carrier (some of which may present with symptoms due to aforementioned skewed X-inactivation), unless the condition is dominant, in which case she will always be affected. There are a few Y-linked traits; these are inherited by sons from their father and are always expressed.
The incidence of X-linked recessive conditions in females is the square of that in males: for example, if 1 in 20 males in a human population are red-green color blind, then 1 in 400 females in the population are expected to be color-blind (1/20)*(1/20).
The inheritance patterns are different in animals which use different sex-determination systems. In the ZW sex-determination system used by birds, the mammalian pattern is reversed, since the male is the homogametic sex (ZZ) and the female is heterogametic (ZW).
|Illustration of some X-linked heredity outcomes (A) the affected father has one X-linked dominant allele, the mother is homozygous for the recessive allele: only daughters (all) will be affected. (B) the affected mother is heterozygous with one copy of the X-linked dominant allele: both daughters and sons will have 50% probability to be affected. (C) the heterozygous mother is called "carrier" because she has one copy of the recessive allele: sons will have 50% probability to be affected, 50% of unaffected daughters will become carriers like their mother.|
Each child of a mother affected with an X-linked dominant trait has a 50% chance of inheriting the mutation and thus being affected with the disorder. If only the father is affected, 100% of the daughters will be affected, since they inherit their father's X chromosome, and 0% of the sons will be affected, since they inherit their father's Y chromosome.
There are less X-linked dominant conditions than X-linked recessive, because dominance in X-linkage requires the condition to present with only a fraction of the gene expression of autosomal dominance, since roughly half (or as many as 90% in some cases) of a particular parent's X chromosomes are inactivated in females.
- Alport syndrome
- Coffin–Lowry syndrome (CLS)
- Fragile X syndrome
- Idiopathic hypoparathyroidism
- Incontinentia pigmenti
- Rett syndrome (RS)
- Vitamin D resistant rickets (X-linked hypophosphatemia)
Females possessing one X-linked recessive mutation are considered carriers and will generally not manifest clinical symptoms of the disorder, although differences in X chromosome inactivation can lead to varying degrees of clinical expression in carrier females since some cells will express one X allele and some will express the other. All males possessing an X-linked recessive mutation will be affected, since males have only a single X chromosome and therefore have only one copy of X-linked genes. All offspring of a carrier female have a 50% chance of inheriting the mutation if the father does not carry the recessive allele. All female children of an affected father will be carriers (assuming the mother is not affected or a carrier), as daughters possess their father's X chromosome. If the mother is not a carrier, no male children of an affected father will be affected, as males only inherit their father's Y chromosome.
- Aarskog–Scott syndrome
- Adrenoleukodystrophy (ALD)
- Bruton's agammaglobulinemia
- Color blindness
- Complete androgen insensitivity syndrome
- Congenital aqueductal stenosis (hydrocephalus)
- Duchenne muscular dystrophy
- Fabry disease
- Glucose-6-phosphate dehydrogenase deficiency
- Haemophilia A and B
- Hunter syndrome
- Inherited nephrogenic diabetes insipidus
- Menkes disease (kinky hair syndrome)
- Ornithine carbamoyltransferase deficiency
- Wiskott–Aldrich syndrome
- Various failures in the SRY genes
- White eyes in Drosophila melanogaster flies—the first sex-linked gene discovered.
- Fur color in domestic cats: the gene that causes orange pigment is on the X chromosome; thus a Calico or tortoiseshell cat, with both black (or gray) and orange pigment, is nearly always female.
- The first sex-linked gene ever discovered was the "lacticolor" X-linked recessive gene in the moth Abraxas grossulariata by Leonard Doncaster.
It is important to distinguish between sex-linked characters, which are controlled by genes on sex chromosomes, and two other categories.
Sex-influenced or sex-conditioned traits are phenotypes affected by whether they appear in a male or female body. Even in a homozygous dominant or recessive female the condition may not be expressed fully. Example: baldness in humans.
These are characters only expressed in one sex. They may be caused by genes on either autosomal or sex chromosomes. Examples: female sterility in Drosophila; and many polymorphic characters in insects, especially in relation to mimicry. Closely linked genes on autosomes called "supergenes" are often responsible for the latter.
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