X chromosome inactivation

The inactivation of one the x chromosomes in female

1. X chromosome inactivation Ikram Ullah M.Phil MLSc

2. X Chromosome inactivation Females have two alleles for every gene on the X chromosomes, whereas males have only one. In mammals, a mechanism called X inactivation balances this apparent inequality in the expression of genes on the X chromosome

3. Equaling Out the Sexes By the time a female embryo consists of 8 cells, about 75 percent of the genes on one X chromosome in each cell are inactivated A nd the remaining 25 percent are expressed to different degrees in different women. Which X chromosome is mostly turned off in each cell—the one inherited from the mother or the one from the father—is usually random. A female mammal expresses the X chromosome genes inherited from her father in some cells and those from her mother in others. She is, therefore, a mosaic for expression of most genes on the X chromosome

4. Equaling Out the Sexes

5. By studying rare human females who have lost a small part of one X chromosome researchers identified a specific region The X inactivation center, that shuts off much of the chromosome . Genes in the PARs and some other genes escape inactivation . A gene called XIST controls X inactivation. It encodes an RNA that binds to a specific site on the same ( inactivated) X chromosome. From this point out to the chromosome tip , the X chromosome is inactivated

6. Once an X chromosome is inactivated in one cell All its daughter cells have the same X chromosome inactivated . Because the inactivation occurs early in development the adult female has patches of tissue that differ in their expression of X-linked genes. With each cell in her body having only one active X chromosome, she is roughly equivalent to the male in terms of gene expression X inactivation can alter the phenotype (gene expression ), but not the genotype. It is not permanent, and is reversed in germline cells destined to become oocytes

7. X inactivation is an example of an epigenetic change One that is passed from one cell generation to the next but that does not alter the DNA base sequence. We can observe X inactivation at the cellular level because the turned-off X chromosome absorbs a stain much faster than the active X . This differential staining occurs because inactivated DNA has chemical methyl (CH 3 ) groups that prevent it from being transcribed into RNA and also enable it to absorb stain . X inactivation can be used to check the sex of an individual .

8. The nucleus of a cell of a female, during interphase, has one dark-staining X chromosome called a Barr body. A cell from a male has no Barr body because his one X chromosome remains active Checking for Barr bodies has been done in the Olympics to identify athletes competing as the wrong gender

9. Effect on the Phenotype For homozygous X-linked genotypes, X inactivation has no effect. For heterozygotes, however, X inactivation leads to expression of one allele or the other. This doesn’t affect health if enough cells express the functional gene product . The swirls of skin color in incontinentia pigmenti (IP) patients reflect patterns of X inactivation in skin cells

10. A female who is heterozygous for an X-linked recessive gene can express the associated condition if the normal allele is inactivated in the tissues that the illness affects. Consider a carrier of hemophilia A. If the X chromosome carrying the normal allele for the clotting factor is turned off in the liver Then the woman’s blood will clot slowly enough to cause mild hemophilia . A carrier of an X-linked trait who expresses the phenotype is called a manifesting heterozygote

11. Subtle Effects of X Inactivation Theoretically, X inactivation evens out the sexes for expression of X-linked genes. In actuality, however, a female may not be equivalent, in gene expression, to a male because she has two cell populations, whereas a male has only one. For heterozygous X-linked genes, she would have some cells that manufacture the protein encoded by one allele, and some cells that produce the protein encoded by the other allele. Although most heterozygous genes have the alleles about equally represented, sometimes X inactivation can be skewed. That is, most cells express the X inherited from the same parent.