Lyon’s hypothesis

In support of Mary Lyon s hypothesis is the fact that the number of chromatin bodies found in individuals is equal to the number of X chromosomes in the karyotype minus one. However, the second X chromosome cannot be considered to be totally unnecessary. If it were, the XO karyotype would not lead to the clinical symptomatology found in Turner s syndrome, nor would an XXY karyotype result in a phenotype different from XY. It has been proposed that the second X chromosome might affect the expression of the genotype in the phenotype simply by its presence. The number of ridges in the fingerprint decreases as the number of genetically inactive X chromosome increases. The Y chromosome unquestionably determines the male sex characteristics, and the male sex characteristics develop in the phenotype even if the karyotypes contain as many as three X chromosomes. Whether the Y chromosome determines the appearance of the phenotype because it stores specific genes or simply because of its presence in the karyotype has not been established. 

Hansen, R.S. (2003) X inactivation-specific methylation of LINE-1 elements by DNMT3B implications for the Lyon repeat hypothesis. Human Molecular Genetics, 12, 2559-2567. 

The answer is a. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 97-158. Wilson, pp 23—39.) Females have two alleles for each locus on the X chromosome because of their 46,XX karyotype. One normal allele is by definition sufficient for normal function in X-linked recessive disorders, so that females with one abnormal allele are carriers instead of affected individuals. Only when the companion normal allele is disrupted or missing does the abnormal allele cause disease. The Lyon hypothesis predicts that X inactivation is early, irreversible, and random, but some females inactivate only the X chromosome carrying the normal allele. X autosome translocations may disrupt an X chromosome locus and cause disease because the translocated autosome must remain active to avert embryonic death nonrandom inactivation of the normal X chromosome thus ablates expression of its normal allele. Females with Turner s syndrome, like males with 46,XY karyotypes, have only one X chromosome and can be affected with X-linked recessive diseases. Conversely, females with triple X or trisomy X syndrome have three alleles at each X chromosome locus and are not affected with X-linked recessive disorders. Since choices c, d, and e each require two genetic changes, they are less common than choice a. 

Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (Takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008 5(1) 22-9. 

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