A summary of chromosomes and its structure how the division of chromosomes occur, problems during division. What is trisomy how is it occurring. Down syndrome, problems patients with down syndrome has. treatment by XIST gene genetic engineering. Ethical issues regarding Down syndrome treatment. examples of people having a normal life

1. TRISOMY IN
CHROMOSOME 21
AND
ITS
TREATMENT S.BHARGAVI
SUMMER TRAINEE IN CCMB UNDER THE
GUIDENCE OF Dr K. LAKSHMI RAO
STUDENT OF B-TECH BIOTECHNOLOGY
SIKSHA ‘O’ ANUSANDHAN DEEMED TO BE
UNIVERSITY BHUBANESWAR

2. CHRMOSOMES
• Chromosomes are thread-like structures in which DNA is tightly
packaged within the nucleus.
• DNA is coiled around proteins called histones, which provide the
structural support.
• Chromosomes help ensure that DNA is replicated and distributed
appropriately during cell division.

3. • Each chromosome has a centromere, which divides the chromosome
into two sections – the p (short) arm and the q (long) arm.
• The centromere is located at the cell’s constriction point, which may
or may not be the center of the chromosome.

4. Number of chromosomes in humans
• In humans, 46 chromosomes are arranged in 23 pairs, including 22 pairs of
chromosomes called autosomes. Each chromosome pair consists of one
chromosome inherited from the mother and one from the father.
• Humans also have one pair of sex chromosomes called an allosome. Allosomes
are XX and XY. Females have two copies of the X chromosome (one inherited
from the mother and one from the father). Males have one copy of the X
chromosome (inherited from the mother) and one copy of the Y chromosome
(inherited from the father).

5. How does a chromosomes divide
• Chromosomes divide by Mitosis
and Meiosis. In both processes,
diploid cells divide.
• In mitosis, the diploid “parent”
cell divides and produces two
diploid “daughter” cells.
• In meiosis, the parent cell
produces four haploid daughter
cells (each containing half of the
parent cells chromosomes).
• The critical difference between
mitosis and meiosis is that
mitosis produces two genetically
identical daughter cells, whereas
meiosis produces four
genetically different daughter
cells.

6. Trisomy
• Trisomy is the presence of an extra chromosome. This can arise as a
result of non-disjunction, when homologous chromosomes fail to
separate at meiosis resulting in a germ cell containing 24
chromosomes rather than 23.
• Trisomy of any chromosome can occur, but all except trisomies 21, 18,
13, X and Y are lethal in utero.
• The risk of non-disjunction increases with maternal age, particularly
for chromosome 21.

7. Trisomy in Chromosome 21
• Trisomy 21 is the commonest of the
viable trisomies affecting around 1 in
every 650 live births in the absence of
prenatal screening.
• The majority of Down syndrome occurs
due to non-disjunction trisomy 21 and is
associated with maternal age. Around
5% of Down syndrome is associated
with a chromosome translocation.
• It is found that the risk of non-
disjunction Down syndrome increases
with maternal age with a live-born risk
in a 25-year-old woman of under 1 in
1000; in a 30-year-old woman, the risk
(1 in 900) is similar to the population
risk and rises to 1% at a maternal age of
40.

8. Down syndrome symptoms
• It was in the late nineteenth century
when Langford Down who is also
known as the “father” of the syndrome
published an accurate description of a
person suffering from this condition.
• People suffering from Down Syndrome
usually have flat faces, upward slant
eyes, a short neck, a single deep crease
across the palm of their hand, small
stature, and low muscle tone. They
may or may not possess all of these
characteristics.

9. Types of Down syndrome
• Trisomy 21: This occurs when there’s an error in the cell division
called ‘nondisjunction’ which results in three chromosomes in an
embryo instead of two.
• Mosaicism: This occurs when there’s a mix of two types of cells, some
containing 46 chromosomes and some with 47. The ones with 47
contain the extra 21 chromosome.
• Translocation: This type is relatively less common. In this scenario, the
number of chromosomes remains 46 but an additional or partial copy
of chromosome attaches to another chromosome.

10. XIST gene
• XIST gene: XIST (X-inactive specific transcript) is an RNA gene on the X
chromosome of the placental mammals that acts as major effector of
the X inactivation process. X inactivation is an early developmental
process in mammalian females that transcriptionally silences one of
the pair of X chromosomes, thus providing dosage equivalence
between males and females.
• The XIST gene produces a large piece of RNA that coats one of the
two X chromosomes and condenses it into a dense, inaccessible
bundle.
• Jun Jiang from the University of Massachusetts Medical School has
used XIST to shut down chromosome 21.

11. Procedure in brief
• enzymes called zinc finger nucleases were used which cut the DNA at
very specific points, to smuggle the giant XIST gene into a pre-defined
spot on the 21st chromosome.
• XIST gene had “painted” one of the three chromosome-21s, and
condensed it into a tight bundle. The genes on that copy were almost
totally inactivated.
• After XIST, it was found that the Down’s cells grew more quickly,
produced larger colonies, and were far better at dividing into neuron-
making cells.
• Jiang’s work also confirmed that XIST is evolved to shut down the X
chromosome, but it worked on all of them. It is said that the XIST may
be acting on something that’s found on all chromosomes, and it is
thought that the XIST gene may recognize repetitive bits of DNA that
are found throughout our genome.

12. AN ETHICAL DISCUSSION OF DOWN SYNDROME
CHROMOSOME THERAPY
• Chromosome therapy and the idea that Down Syndrome could be
“eliminated” from an individual raises a number of complex ethical
issues. With chromosome therapy, a child with Down Syndrome could
have a chance at a typical life, free of the mental and/or physical
adversities one may face as a person with Down Syndrome. However,
it is possible for people to view people with Down Syndrome in a
nondiscriminatory way. Many would argue that people with Down
Syndrome are able to enjoy the same quality of life as anyone else.
• With chromosome therapy, the child could “live their life to the
fullest.” but the rich would be able to afford chromosome therapy
and services for a child with Down Syndrome, while the poor would
not be able to afford the chromosome therapy nor be able to provide
all the therapies needed to raise a child with disabilities. It is
important to note that such economic privilege exists in all aspects of
society.

15. Treatment of Down syndrome
• Researchers at the University of Massachusetts Medical School found
a way to “switch off” the extra chromosome that causes Down’s
syndrome (DS) by adding a gene called “XIST” to human stem cells.
• The stem cell treatment has only been achieved in singular cells and
there is a good chance of getting full chromosome therapy within 10-
15 years.
• a gene called “XIST” is dropped into the extra chromosome in cells
taken from people with Down’s syndrome. Once in place, the gene
caused a buildup of a version of a molecule called RNA, which coated
the extra chromosome and ultimately shut it down.