X-linked recessive

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X-linked recessive is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed only (1) in males (who are necessarily hemizygous for the gene mutation because they have only one X chromosome) and (2) in females who are homozygous for the gene mutation (i.e., they have a copy of the gene mutation on each of their two X chromosomes).

X-linked inheritance means that the gene causing the trait or the disorder is located on the X chromosome. Females have two X chromosomes, while males have one X and one Y chromosome. Carrier females who have only one copy of the mutation do not usually express the phenotype, 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. The current estimate of sequenced X-linked genes is 499 and the total including vaguely defined traits is 983^[1]

Sex Differences In Phenotype and Frequency

In humans, generally "men are affected and women are carriers" for two reasons. The first is the simple statistical fact that if the X-chromosomes is a population carry a particular X-linked mutation at a frequency of 'f' (for example, 1%) then that will be the frequency that men are likely to express the mutation (since thay have only one X, while women will express it at a frequency of f² (for example 1% * 1% = 0.01%) since they have two X's and hence two chances to get the normal allele. Thus, X-linked mutations tend to be rare in women. The second reason for female rarity is that women who express the mutation must have two X chromosomes that carry the trait and they necessarily got one from their father, who would have also expressed the trait because he only had one X chromosome in the first place. If the trait lowers the probability of fathering a child or induces the father to only have children with women who aren't carriers (so as not to create daughters who are carriers rather than expressers and then only if no genetic screening is used) then women become even less likely to express the trait than the statistical prediction of f² .

Examples

Red-Green color blindness is a classic example of an X-linked trait because it is easy to explain the phenotype and it's relatively common ^[2] (7% to 10% of men are carriers making the above calculations predict 0.49% to 1% for women). It's commonness is possibly attributable to it not being a serious disability in most cases and an actual advantage in some situation (for example, not being distracted by some of the color in color based camouflage). Hemophilia A is another famous example because it was found in European royal families who intermarried and were famous enough that their pedigrees could be established and offered in textbooks as a "famous example" of an X-linked trait that had been documented in history books before mendelian genetics was understood.

Traits or diagnoses known or suspected to be X-linked (at least in some forms of the diagnosis) are:

Adrenoleukodystrophy Alport syndrome Androgen insensitivity syndrome Barth syndrome Becker's muscular dystrophy Centronuclear myopathy Charcot-Marie-Tooth disease Coffin-Lowry syndrome Color blindness Duchenne Fabry disease Fragile X syndrome Glucose-6-phosphate dehydrogenase deficiency Hemophilia A Hemophilia B (Christmas disease) Hunter's Syndrome Hypohidrotic ectodermal dysplasia

Incontinentia pigmenti Kabuki syndrome Kennedy disease Lesch-Nyhan syndrome Menkes disease Myotubular myopathy Nonsyndromic deafness and X-linked nonsyndromic deafness Norrie disease Occipital horn syndrome Ornithine transcarbamylase deficiency Rett syndrome Simpson-Golabi-Behmel syndrome Spinal and bulbar muscular atrophy Wiskott-Aldrich syndrome X-linked agammaglobulinemia (XLA) X-linked ichthyosis X-linked Severe Combined Immunodeficiency (SCID) X-linked sideroblastic anemia

See also

• Sex linkage

External links

• X-linked diseases from the Wellcome Trust

References