Lyonization or X-chromosome inactivation is the conversion of all but one, X-chromosomes in Females into non-coding heterochromatin (i.e. deactivated) leading to the formation of one or more Barr bodies. The selection of the X-chromosome to be inactivated is different in different animals. In female Marsupials, the inactivation is always of the Paternal X-chromosome while in placental mammals, the selection is random. (Although the extent of lyonization is not completely random and varies directionally with age).

My question is

If the X-chromosome to be inactivated is randomly selected in placental mammals (including humans), then why don't the females heterozygous for a X-linked recessive disorder do not show the phenotype of the disease though the functional gene is equally likely (as compared to the defective) to be the one to be lyonized?

There are some evidences of genes escaping inactivation and managing to exhibit themselves but I don't think they can account for all the recessive x-linked disorders.


1 Answer 1


The simple answer is that which X chromosome is inactivated varies in different cell lineages, so typically a female will have cells exhibiting either wild-type or mutant phenotypes. It was Mary Lyon's observation of mosaicism in heterozygous mouse coat colour that gave the phenomenon its name. So in the case of a recessive disease there will be a phenotype, but in many cases the 50% of cells expressing the normal gene will provide sufficient functional cells to get by. From the Wikipedia article about Mary Lyon:

Her research has allowed us to understand the genetic control mechanisms of chromosome X, which explains the absence of symptoms in numerous healthy women that are carriers of diseases associated with this chromosome.

Edit - response to comments:

Plug, I et al. (2006) Bleeding in carriers of hemophilia. Blood 108: 52-56


A wide range of factor VIII and IX levels is observed in heterozygous carriers of hemophilia as well as in noncarriers. In female carriers, extreme lyonization may lead to low clotting factor levels. We studied the effect of heterozygous hemophilia carriership on the occurrence of bleeding symptoms. A postal survey was performed among most of the women who were tested for carriership of hemophilia in the Netherlands before 2001. The questionnaire included items on personal characteristics, characteristics of hemophilia in the affected family members, and carrier testing and history of bleeding problems such as bleeding after tooth extraction, bleeding after tonsillectomy, and other operations. Information on clotting factor levels was obtained from the hospital charts. Logistic regression was used to assess the relation of carrier status and clotting factor levels with the occurrence of hemorrhagic events. In 2004, 766 questionnaires were sent, and 546 women responded (80%). Of these, 274 were carriers of hemophilia A or B. The median clotting factor level of carriers was 0.60 IU/mL (range, 0.05-2.19 IU/mL) compared with 1.02 IU/mL (range, 0.45-3.28 IU/mL) in noncarriers. Clotting factor levels from 0.60 to 0.05 IU/mL were increasingly associated with prolonged bleeding from small wounds and prolonged bleeding after tooth extraction, tonsillectomy, and operations. Carriers of hemophilia bleed more than other women, especially after medical interventions. Our findings suggest that not only clotting factor levels at the extreme of the distribution, resembling mild hemophilia, but also mildly reduced clotting factor levels between 0.41 and 0.60 IU/mL are associated with bleeding.

Bimler, D & Kirkland, J (2009) Colour-space distortion in women who are heterozygous for colour deficiency. Vision Research 49: 536-543

from the Introduction:

About 15% of women are heterozygous for some form of colour vision deficiency (CVD). That is, they possess a genetic abnormality on one of their two X chromosomes, affecting the photopigments (opsins) which subserve colour vision. The retina of a heterozygous woman is a mosaic in which some cone cells express the aberrant gene while others express the normal copy, depending on which X chromosome is active (inactivation of one X chromosome occurs randomly in retinal stem-cells at some stage of fetal development). The normal cells are sufficient to provide full trichromatic vision.

  • $\begingroup$ Thank you for the answer. In case of a female heterozygous for haemophilia, can we observe the defective $\beta$-Hb chain in atleast a part of the total RBCs? That, if possible, would greatly simplify identification of Heterozygous carriers. $\endgroup$ Oct 20, 2013 at 17:52
  • $\begingroup$ I don't know the answer, but I think that you are getting your diseases mixed up - it's sickle cell anaemia that's a haemoglobin disorder. I seem to recall however that the most common genetic disease in humans, glucose 6-phosphate dehydrogenase deficiency (X-linked) is an example of a blood disorder in which heterozygous females have two populations of red cells. $\endgroup$
    – Alan Boyd
    Oct 20, 2013 at 18:07
  • $\begingroup$ I am sorry. I was in quite a haste and blundered because of it! Thank you anyway. $\endgroup$ Oct 21, 2013 at 1:27
  • $\begingroup$ @SatwikPasani I got quite interested in what you said in the first comment if we apply it to some other disorder as sickle cell anaemia isn't X linked ( As alan boyd already pointed out). Why shouldn't the concentration of say, a clotting factor differ in haemophilia carriers from that of homozygous female ? $\endgroup$
    – biogirl
    Oct 21, 2013 at 14:16
  • $\begingroup$ @biogirl Analysing the cone constitution in females heterozygous for color-blindness is equally intriguing since there is a possibility of there being a random distribution of color-blind and normal cones, in the retina. Anyway, I am looking up the Haemophilia case at the adjacent pathology centre and will keep updating here. P.s.( I know I did a mistake in my first comment but editing comments after 5 min is disallowed :)) $\endgroup$ Oct 21, 2013 at 14:26

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