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Barr Bodies

Copyrighted 2013 Richard Frey

A Barr Body is the result of Inactivation of one or more X


Chromosomes in Female Mammals.
Inactivation occurs by Condensing the X Chromosome into
Heterochromatin therefore inactivating it.
Heterochromatin stains more darkly than Euchromatin
therefore a Barr Body appears a dark staining body
pushed up against the nuclear envelope.
Carbol Fuchsin Stain is a DNA specific stain use to view
Barr Bodies

Barr Bodies
Lyonization, named after Dr. Mary Lyon, is the name of the
process that gives rise to a Barr Body.
The number of Barr Bodies present can be determined by:
# of X chromosomes 1. A woman with Trisomy X would
have 2 Barr Bodies. A Klinefelter male, XXY, would have
one.
Barr Bodies are viewed during Interphase of the cell cycle.

Barr Bodies
Barr Bodies are made to accomplish Gene Dosage
Compensation.
Gene Dosage Compensation is the inactivation of one or
more X chromosomes in female mammals (or XXY
males) to allow expression of only one X chromosome
giving males and females the same gene dose from the X
chromosome.

Barr Bodies
Lyonization occurs early in development around the 16 th
day of gestation.
Each cell randomly inactivates one of its X chromosomes.
All progeny or daughter cells resulting from mitosis will
inactivate the same X chromosome and leads to a
mosaic pattern of expression for X genes.

Mosaic

Mosaics in Nature
The calico cat is the classic example of a Mosaic. The X
chromosomes carries a gene for fur color on them. The
gene usually codes either the tabby color or the black
color. A calico cat has a white base color with patches of
tabby or black depending on which X chromosome has
been inactivated through Lyonization. Because the
inactivation is initially random, the tabby and black
patches should roughly be equal in area due to 50%
chance any given X would be chosen for inactivation.

Mosaics in Nature
Human Females are indeed mosaics.
Hemophilia is a well known X-linked trait.
Female carriers of hemophilia will have mosaic liver
tissue. Some portions of the liver will produce
appropriate amounts of clotting agent and others will not
produce any.
How different would our world be if dermal melanin
content, i.e. human skin color, was a gene carried on the
X chromosome?

X Chromosome Inactivation
X inactivation is not fully understood but is regulated by
several factors.
In Mammals there is an important region of DNA on the X
chromosomes called the X Inactivation Center, XIC.
The XIC has genes encoding at least five non-translated
RNAs and seven protein encoding Genes.
The X-inactive Specific Transcript, Xist, is a major factor
in the X inactivation process.

X-inactive Specific Transcript, Xist


In Humans, the Xist gene encodes a large, 17 kB
transcript (RNA) that is highly expressed on the inactive X
Chromosome but is not expressed on the active X
Chromosome.
This transcript is processed like a mRNA through gene
splicing (removal of introns) and polyadenylation
(Poly A tails).
The Xist transcript is not translated into a protein.

X-inactive Specific Transcript, Xist


The Xist gene product, an RNA, is highly expressed by
the inactive X chromosome (Xi) and not expressed by the
active X chromosome (Xa).
The Xist RNA is responsible for silencing the X
chromosome from which it is transcribed.
Many copies of the Xist RNA will coat Xi.
Xa is not coated by the Xist transcript.

X-inactive Specific Transcript, Xist


Any X Chromosome lacking the Xist gene will not become
inactive.
Placing the Xist gene on another chromosome and
expressing the gene will cause that chromosome to
become inactivated.
The Xist gene is only expressed from the Xic of the
inactive X chromosome.

X-inactive Specific Transcript, Xist


In early development, both X chromosomes weakly
express the Xist gene.
During inactivation, the future Xi dramatically increases
Xist RNA transcription. The future Xa stops transcribing
the Xist gene.
Xist RNA progressively coats the Xi chromosome starting
at Xic and moving outward.
Silencing of Xi genes occurs soon after coating by Xist
RNA.

Tsix Transcript: Antisense RNA


Notice that Tsix is Xist backwards, for good reason.
The Tsix gene encodes a large RNA molecule that also is
transcribed by not translated.
The Tsix transcript is antisense to the Xist transcript.
This is due to Tsix being transcribed from the DNA strand
which is complementary to the Xist gene. As the DNA
helix is unwound to expose single stranded template, one
strand would contain the Xist gene and the other strand
would contain the Tsix gene and be antisense to Xist.

Tsix Transcript: Antisense RNA


Tsix is a negative regulator to Xist through some unknown
mechanism.
X chromosomes lacking Tsix transcription have high
levels of Xist transcription and become inactive much
more frequently than normal chromosomes.
Before X inactivation, Tsix is expressed weakly from both
X chromosomes.
During X inactiviation, Tsix expression stops from Xi and
continues for several days from Xa.

DNA Methylation
DNA methylation may help silence X chromosome genes.
In mammals, the cytosine of the dinucleotide, 5-CpG-3,
can be enzymatically methylated after DNA synthesis.
Methylated CpG can repress RNA transcription and a
great majority of methylated CpG in cells can be found on
the inactive X chromosome.

DNA Methylation
CpG methylation may play a role in expression of Xist.
On the Xa chromosome, where Xist is not expressed, the
CpG islands found in the promoter region of Xist become
methylated during X inactivation.
On the Xi chromosome, where Xist is expressed,
hypomethylation of the CpG islands is observed.

Histone Acetylation
Histone acetylation, the addition of COCH 3, is thought to
be involved in genetic expression.
Hyperacetylation of Histones relaxes DNA condensation
and promotes gene expression.
Hypoacetylation is associated with gene silencing.
Regions of Xi (not Xic) that have been silenced show low
levels of histone acetylation.

Psuedoautosomal Regions
Up to 25% of the genes on the human Xi escape
inactivation or silencing and reside in clusters on Xi.
Unlike a majority of the genes on the X chromosome, a
copy these genes are also found on the Y chromosome.
Therefore, expression of these genes from both X
chromosomes in females would create the same gene
dose as found in males.
These regions are called psuedoautosomal regions.

Epigenetic Inheritance
Once an X chromosome is inactivated, all daughter cells
will inactivate the same X chromosome.
However, the DNA sequence of these cells remains
unaltered so no mutation of the DNA has taken place.
Yet, the progeny cells continue to inactivate the same X
chromosome and exhibit an inherited trait.
This is termed Epigenetic Inheritance.

Barr Bodies and Sports


During the Cold War between Western and Eastern
Bloc countries, success in sporting events such as the
Olympics was thought to be an indicator as to which
social philosophy was best for society.
Increasing success of Eastern Bloc Women in strength
sports cause Western Countries to question the femininity
of these athletes.
In 1966, the International Amateur Athletic Federation
announced gender tester of all female athletes.

Barr Bodies and Sports


After this announcement, several dozen women
competitors retired from active competition including the
two world renowned athletes: Tamera and Irina Press.
The femininity of the Press sisters had long been
questioned as they garnered 5 Olympic gold medals and
set 8 world records.

Gender Testing of Female


Athletes
Tamara Press won the Gold
medal for Shot put and Silver
medal for Discus in 1960. She
also won gold in both events
in 1964.
She retired from competition
upon the announcement of
gender testing.

Gender Testing
Ewa Klobukowska won Gold and Bronze
medals in the 1964 Olympics.
Subsequent Karyotyping revealed she was
a mosaic. (XX) and (XXY).
She was stripped of her titles.
Ironically, She would have passed the
1968 Olympic standard of having a Barr
Body.
She retired from competition and
proceeded to give birth to a healthy boy.
Female? You decide.

Gender and Olympics Today


There is currently no gender testing in Olympic sports.
Trans-sexual individuals can now compete as their
chosen sex if they meet requirements outlined by IOC.
Surgical modification at least 2 years prior to competition.
Legal recognition of assigned sex by appropriate authority.
A least 2 years hormone therapy prior to competition.

A students Barr Body