Chromosome Aberrations in Humans

7/27/2019 Chromosome Aberrations in Humans

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ChromosomeAberrations In

Humans

-Archana Ramesh


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What are chromosomal aberrations?

A chromosome

anomaly, abnormality or aberration is a

missing, extra, or irregular portion

of chromosomal DNA.


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The various chromosomal aberrations

in humans

Chromosomal anomalies affect humans in the

form of a number of disorders.

Major disorders are:

1. Cri-du-chat Syndrome

2. Myelocytic Leukemia

3. Philadelphia Chromosome

4. Downs Syndrome

5. Chromosome 3 duplication-deletion syndrome


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Cri-du-Chat Syndrome

Also known as chromosome 5p deletionsyndrome, 5p minus syndrome orLejeunessyndrome.

Discovered by Jerome Lejeune and his colleagues.

Name of the syndrome came from a plaintive catlikemewing cry from small infants because of problems inthe larynx and nervous system.

Other characteristics include a small head, a saddlenose, broad face, widely shaped eyes with epicanthicfolds, unique facial features and mental retardation.


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IQs range from 20-40.

Chromosomal deficiency is in the short arm of

chromosome 5.

Patients suffering from this syndrome die early

and dont transmit, unless the deficiency gets

involved in reciprocal translocation.

5 translocates to 15, and carrier is a healthy

parent. If deficient member is carried, then

children exhibit it.


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Chronic Myelocytic Leukemia

Cancer of the blood producing cells of the bone marrowthat result in increasing wbcs.

Associated with the Philadelphia Chromosome, whichwas observed consistently in bone marrow preparations

of patients who had CML. A part of the long chromosome 22 translocated to

another chromosome, usually chromosome 9, leaving adeficiency behind.

Symptoms include enlarged spleen causing pain on theleft side, malaise, joint and/or hip pain, low-grade fever,increased susceptibility to infections, anemia,and thrombocytopenia with easy bruising


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CML is now largely treatedwith targeted drugscalled tyrosine kinase

inhibitors (TKIs), such asGleevec/Glivec (imatinib),Sprycel (dasatinib), Tasigna(nilotinib), Iclusig (ponatinib),or Bosulif (bosutinib) whichhave led to dramatically

improved long term survivalrates (95.2%) since theintroduction of Gleevec in2001. These drugs haverevolutionized treatment ofthis disease and allow most

patients to have a good qualityof life when compared to theformer chemotherapy drugs.


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Philadelphia chromosome

Philadelphia

chromosome or Philadelp

hia translocation is a

specific chromosomal abnormality that is associated

with chronic myelogenous

leukemia (CML). It is the

result of a

reciprocal translocation be

tween chromosome 9 and

22.


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Malignancy

Chromosomal abnormalities are increasing beingassociated with malignancies.

New staining methods are promoting more precisecomparisons of chromosomal arms and differentlystained sister chromatids.

Banded chromosome causes conditions like:

1. Burkitts Lymphoma

2. Tumor Retinoblastoma: Deletion of chromosome 13q.3. Wilms tumor

4. Bloom Syndrome


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Burkitts Lymphoma

Caused by translocation

of Chromosome 14.

Cancer of the Lymphatic

system.


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Wilms Tumor

Deletion in band 11p13.

Wilms

tumor or nephroblasto

ma is cancer ofthe kidneys that

typically occurs

in children, rarely

in adults.


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Bloom Syndrome

also known as BloomTorreMachacek

syndrome.

disorder characterizedby short stature andpredisposition to thedevelopment of cancer

Sister chromatidexchanges happenindicating instability.


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Downs Syndrome

Down syndrome disorders are based on having

too many copies of the genes located on

chromosome 21. In general, this leads to an over

expression of the genes. It is typically associated with physical

growth delays, a particular set of facial

characteristics and a severe degree of intellectualdisability. The average full-scale IQ of young

adults with Down syndrome is around 50.


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Downs Syndrome

The extra chromosome 21 material that causes Downsyndrome may be due to a Robertsonian translocation in thekaryotype of one of the parents. In this case, the long arm ofchromosome 21 is attached to another chromosome,often chromosome 14 .A person with such a translocation isphenotypically normal. During reproduction,normal disjunctions leading to gametes have a significantchance of creating a gamete with an extra chromosome 21,producing a child with Down syndrome. TranslocationDown syndrome is often referred to asfamilial Down

syndrome. It is the cause of 23% of observed cases ofDown syndrome.It does not show the maternal age effect,and is just as likely to have come from fathers as mothers.


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Chromosome 3 duplication-deletion

syndrome

This syndrome includes stillbirths, neonatal

deaths, and spontaneous abortions.

The children who survived this condition suffer

from facial malformation which includes:distorted head shape, thick, low eyebrows, low

hairline, long eyelashes, persistent lanugo,

distended veins on scalp, hypertelorism, a veryshort nose, protruding maxilla, etc.

Each infant has difficulty sucking and swallowing.


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Why translocation is not the bad guy?

It is not the translocation of the chromosome

that produces abnormalities, but rather the

imbalance of genetic material reflected in

chromosome deficiencies and duplicationsthat are produced by segregation of

translocation chromosome.


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BIBLIOGRAPHY

PRINCIPLES OF GENETICS

http://en.wikipedia.org/wik

http://www.ashg.org/
http://en.wikipedia.org/wikhttp://www.ashg.org/http://www.ashg.org/http://en.wikipedia.org/wik

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Chromosome Aberrations in Humans