This document discusses X chromosome inactivation and mosaicism. It explains that females have two X chromosomes while males have one, so females inactivate one X chromosome randomly in each cell early in development. This process, called Lyonization, equalizes X-linked gene expression between males and females. As a result, females are mosaics with some cells expressing genes from the maternal X and others from the paternal X. This can cause mild symptoms in carriers of X-linked disorders. Mosaicism can also occur when cells lose an X chromosome during development, producing a mixture of XX and XO cells.

1. 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

9. 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

10. 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

11. 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

12. 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

13.  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

14. 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).

15.  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

16.  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 ????

17. 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%