Lyon hypothesis-X-inactivation-mosaic formation

about x chromosome and its function and participation in life of female

1. Lyon hypothesis Brought to you by Ayman Hameed

2. X chromosome dosage How to create equal amount of X chromosome gene products in males and females? Sex Chromosomes: females XX , males XY Genes on X: females 2 , males 1copy

3. X LINKED GENE G6PD, glucose 6 phosphate dehydrogenase, gene is carried on the X chromosome This gene codes for an enzyme that breaks down sugar Females produce the same amount of G6PD enzyme as males XXY and XXX individuals produce the same about of G6PD as anyone else decrease X gene products by half in females (e.g. humans called X-inactivation)

4. LYON HYPOTHESIS The Lyon hypothesis states that during early development, one of the X chromosomes in a female gets turned off and this is maintained in all descendant cells of the clone.

5. LYON HYPOTHESIS 1961 English geneticist Mary Lyon proposed this hypothesis to describe X inactivation Consists of :- 1. Condensed X chromosome is genetically inactive 2. X inactivation in humans occurs early in development when embryo consists of about 32 cells. 1 or 2 days following fertilization

6. LYON HYPOTHESIS 3. At this stage in each of the 32 cells one of the X chromosomes is randomly inactivated 4. Inactivation is mitotically stable 5. Net effect of this is to equalize phenotypes in males and females for genes that are carried on the X chromosome

7. Human Chromosomes

8. X CHROMOSOME Only 1 X chromosome is active in any given cell. The other is inactive In some cells the paternal allele is expressed In other cells the maternal allele is expressed In XXX and XXXX females and XXY males only 1 X is activated in any given cell the rest are inactivated

9. X CHROMOSOME XXX embryo survives because it inactivates 2 X chromosomes and has only 1 functioning X chromosome in any given cell The only chromosome we can inactivate is the X chromosome

10. X REACTIVATION IN FEMALES In the female fetus future germ cells undergo Lyonization along with somatic cells . Following differentiation of female fetus, the inactivated X chromosomes are reactivated during female gametogenesis When germ cells develop into oocytes and enter meiosis their inactivated X chromosomes become reactivated so that every egg produced has an activated X chromosome prior to fertilization

11. mosaic or mosaicism Mosaic is an ancient Romanian word used to describe a decoration on a surface made by pressing small pieces of colored glass or stone into a soft material that then hardens to make pictures or patterns . In   genetics , a  mosaic  or  mosaicism  denotes the presence of two or more populations of  cells  with different  genotypes  in one individual who has developed from a single fertilized egg

12. So if we assume that the pieces of colored glass are the stem cells of a female and the final picture that is formed in the end is the complete body ,,, we can notice that each piece of colored glass (( stem cell )) has expressed its own color ( phenotype = differentiated cell ) to form the full picture ( completed human body ) ,,, in other words ; each stem cell has expressed its own genotype & its descendent cells to form a complete human female body .That called mosaic formation . Female is MOSAIC of cells, each cell is functionally HEMIZYGOUS

13. This phenomenon, which can be observed in the coloration of  tortoiseshell cats  when females are  heterozygous  for the  X-linked gene , in other words ( mosaic is the result of X-inactivation). For an individual cell the inactivation is therefore  skewed   and this can give rise to mild symptoms in female 'carriers' of  X-linked  genetic disorders( in cases of diseases ).

14. Inactivation occurs on a cellular level, resulting in a mosaic expression, in which patches of cells have an inactive maternal X-chromosome, while other patches have an inactive paternal X-chromosome. For example, a female heterozygous for hemophilia (an X-linked disease) would have about half of her liver cells functioning properly, which is typically enough to ensure normal blood clotting. Sequences at the  X inactivation center  ( XIC ), present on the X chromosome, control the silencing of the X chromosome. The hypothetical blocking factor is predicted to bind to sequences within the XIC

15. Only occur in heterozygous females ??? Can occur in XrXb but not in XrXr or XbXb X-linked color blindness disease ??? XcY + XX  mosaic formation (one eye is color blindness and other is normal <not possible ) Could it happen in males ??? Coloration of tortoiseshell cats ??? XbXr XbXb XrXr What about G6PD ????

16. Autosomal MOSAICISM Is due to a mitotic loss of 1 X chromosome in a cell early in zygotic development This produces a combination of both XX and XO cells The more XO cells an individual has the more severely she will be affected Some estimates put mosaic Turner females as high as 60% to 80%