Genetics
X-Linked Inheritance
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Get access- The pattern of inheritance carried by genes on the sex chromosomes
- X-linked recessive: only expressed in females if homozygous
- Gene transmitted from an affected man to all his daughters
- Never from father to son
Females can be affected if homozygous or if they are “manifesting” heterozygotes/carriers
Note
Where the trait is fatal (eg. Duchenne’s), selection drives against inheritance of the trait, therefore new mutations comprise a large proportion of cases
In some X-linked recessive conditions, a small number of female heterozygotes are affected due to lyonization: inactivation of one member of a pair of X chromosomes in every female somatic cell.
The inactivated X chromosome is known as the Barr body and inactivation occurs early therefore all subsequent cells have the same inactive X chromosome. Summary of Lyon hypothesis:
- One X chromosome is active in somatic cells
- The second is the inactive Barr body
- Inactivation occurs from between days 3 and 10 after fertilisation
- Inactivation is random
- All clonal descendents of a cell have the same inactive X
Females are mosaics with respect to X-linked genes (hence there is phenotypic variability in X-linked disorders)
This explains the fact that a single X produces the same quantity of product in males as two X chromosomes do in females
- Some segments of the Barr body may still be active
Females have random expression of the either the paternal or maternal X chromosome so there may be variable expression of mutant X-linked genes in carriers
Including in X-linked retinitis pigmentosa, choroidaemia, X-linked Nettleship-Falls ocular albinism, Fabry disease and colour vision disorders
X-linked dominant: used to describe conditions in which heterozygous females are commonly affected. Disease is usually very severe in males eg. Aicardi syndrome (male foetus rarely survives)
- Hypophosphataemic rickets
- Aicardi syndrome. Triad
- Chorioretinal lacunae
- Agenesis of the corpus callosum
- Infantile spasms
- Also: coloboma, microphthalmos
- Incontinentia pigmenti
- Alport’s syndrome (5%, the majority being X-linked recessive)