GenotypesPhenotypesMalesHemizygous XHUnaffectedHemizygous XhAffectedFemalesHomozygous XH/XHUnaffectedHeterozygous XH/XhCarrier (may or may not be affected)Homozygous (or compound heterozygous) Xh/XhAffected

X Inactivation, Dosage Compensation, and the Expression of X-Linked Genes


Figure 7-11 Immunostaining for dystrophin in muscle specimens. A, A normal female (×480). B, A male with Duchenne muscular dystrophy (DMD) (×480). C, A carrier female (×240). Staining creates the bright signals seen here encircling individual muscle fibers. Muscle from DMD patients lacks dystrophin staining. Muscle from DMD carriers exhibits both positive and negative patches of dystrophin immunostaining, representing fibers with either the normal or mutant allele on the active X. See Sources & Acknowledgments.

Recessive and Dominant Inheritance of X-Linked Disorders

Nearly a third of X-linked disorders are penetrant in some but not all female heterozygotes and cannot be classified as either dominant or recessive. Even for disorders that can be so classified, they show incomplete penetrance that varies as a function of X inactivation patterns, not inheritance patterns. Because clinical expression of an X-linked condition does not depend strictly on the particular gene involved or even the particular mutation in the same family, some geneticists have recommended dispensing altogether with the terms recessive and dominant for X-linked disorders. Be that as it may, the terms are widely applied to X-linked disorders, and we will continue to use them, recognizing that they describe extremes of a continuum of penetrance and expressivity in female carriers of X-linked diseases.

X-Linked Recessive Inheritance


Figure 7-12 Pedigree pattern demonstrating an X-linked recessive disorder such as hemophilia A, transmitted from an affected male through females to an affected grandson and great-grandson.

Hemophilia A is a classic X-linked recessive disorder in which the blood fails to clot normally because of a deficiency of factor VIII, a protein in the clotting cascade (Case 21). The hereditary nature of hemophilia and even its pattern of transmission have been recognized since ancient times, and the condition became known as the “royal hemophilia” because of its occurrence among descendants of Britain’s Queen Victoria, who was a carrier.

As in the earlier discussion, suppose Xh represents the mutant factor VIII allele causing hemophilia A, and XH represents the normal allele. If a male with hemophilia mates with a normal female, all the sons receive their father’s Y chromosome and a maternal X and are unaffected, but all the daughters receive the paternal X chromosome with its hemophilia allele and are obligate carriers. If a daughter of the affected male mates with an unaffected male, four genotypes are possible in the progeny, with equal probabilities:

X-Linked Recessive Inheritance


The wild-type allele at the X-linked hemophilia locus is denoted as XH with an uppercase H, and the mutant allele is denoted as Xh with a lowercase h.

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Nov 27, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Inheritance

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