Re: Why don't Barr bodies seem to affect the m/f ratios of x-linked traits?

12.4.96

Dear Victoria,

These are good questions. Hope these answers help.

1) Q: If Barr bodies form in females, why do the same phenotypic ratios for x-linked traits appear to be the same as if they didn't?

A: Because inactivation occurs in a mosaic distribution.

To explain further ... Some recessive genetic diseases in humans are X-linked. Because men are XY and women are XX, men are more likely to display X-linked diseases. They have only one chance to get a good copy of a gene whereas women have two chances to get a good copy.

Barr bodies are inactivated X-chromosomes that form in women's cells in a process known as dosage compensation. This inactivation would seem to make women just as susceptible to X-linked diseases as men _but_ the inactivation occurs randomly in individual cells during development. Some cells inactivate the paternal X and others inactivate the maternal X. Inactivation is maintained in the progeny cells of the dividing cells. This results in a mosaic - patches of cells have one X inactivated, patches of cells have the other X inactivated. The women heterozygous for an X-linked disease therefore have some defective cells and some normally functioning cells. The normally functioning cells are generally do a good enough job that no disease results.

Here is one example from a text book (Development) of an X-linked disease for which women have been proven to be mosaic. Lesch-Nyhan Syndrome is the lack of the enzyme HPRT and it is lethal for people lacking the enzyme. Skin cells were removed from a heterozygous women carrier and cultured to form colonies of skin cells on a plate. Half the colonies were HPRT+ and half were HPRT-.

2) Q: When during development of an organism do Barr bodies form?

A: During Embryogenesis.

To explain further...X chromosome inactivation is a mechanism to insure the women and men get the same "genetic dose" of genes on the X chromosome. Mammals generally take care of this "dosage compensation" by inactivating one X in females. Other animals do things like upregulate the transcriptional activity of the one X in males. Although it might not seem like a big deal to have 2X too much of some gene activities, failure of dosage compensation is lethal. The fertilized egg and early embryo can survive without dosage compensation. Inactivation occur during the proliferative stage of early embryogenesis. There are some exceptions to random mosaic inactivation. Germ cells (egg and sperm precursors) reactivate their inactivated X. There are also examples of tissues in mice and marsupials that choose which X to inactivate (paternal or maternal).

3) Q: Is it at all possible that a trait coded for on the Y-chromosome could affect whether or not an x-linked trait or disorder shows up (could it boost the probability that it will show up?)

A: Its definitely possible but I don't know of an example of a Y to X interaction like this in humans.

The interaction that you propose between two different genes is called genetic enhancement - where one allele of gene 1 shows a more prominent phenotype in the background of a particular allele of gene 2. Its a phenomena we observe all the time with genetic experiments in the lab. We also find genetic suppression where an allele of gene 1 looses its phenotype in the background of a particular allele of gene 2. You might also be interested in knowing that the X and Y are not completely unrelated chromosomes. There is a small stretch of the X chromosome that does not inactivate when the Barr body forms and it has a homologous section on the Y. This small section of the X and Y is called the psuedoautosomal region - both men and women have two copies of these genes.

Take care,

Jim