Chromosome Aberrations In Humans

-Archana Ramesh

What are chromosomal aberrations?

A chromosome anomaly, abnormality or aberration is a missing, extra, or irregular portion of chromosomal DNA.

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

Cri-du-Chat Syndrome
Also known as chromosome 5p deletion syndrome, 5p minus syndrome or Lejeunes syndrome. Discovered by Jerome Lejeune and his colleagues. Name of the syndrome came from a plaintive catlike mewing cry from small infants because of problems in the larynx and nervous system. Other characteristics include a small head, a saddle nose, broad face, widely shaped eyes with epicanthic folds, unique facial features and mental retardation.

 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.

Chronic Myelocytic Leukemia

Cancer of the blood producing cells of the bone marrow that result in increasing wbcs. Associated with the Philadelphia Chromosome, which was 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 a deficiency behind. Symptoms include enlarged spleen causing pain on the left side, malaise, joint and/or hip pain, low-grade fever, increased susceptibility to infections, anemia, and thrombocytopenia with easy bruising

 CML is now largely treated with targeted drugs called tyrosine kinase inhibitors (TKIs), such as Gleevec/Glivec (imatinib), Sprycel (dasatinib), Tasigna (nilotinib), Iclusig (ponatinib), or Bosulif (bosutinib) which have led to dramatically improved long term survival rates (95.2%) since the introduction of Gleevec in 2001. These drugs have revolutionized treatment of this disease and allow most patients to have a good quality of life when compared to the former chemotherapy drugs.

Philadelphia chromosome
Philadelphia chromosome or Philadelp hia translocation is a specific chromosomal abn ormality that is associated with chronic myelogenous leukemia (CML). It is the result of a reciprocal translocation be tween chromosome 9 and 22.

Malignancy
Chromosomal abnormalities are increasing being associated with malignancies. New staining methods are promoting more precise comparisons of chromosomal arms and differently stained sister chromatids. Banded chromosome causes conditions like: 1. Burkitts Lymphoma 2. Tumor Retinoblastoma: Deletion of chromosome 13q. 3. Wilms tumor 4. Bloom Syndrome

Burkitts Lymphoma
Caused by translocation of Chromosome 14. Cancer of the Lymphatic system.

Wilms Tumor
Deletion in band 11p13. Wilms tumor or nephroblasto ma is cancer of the kidneys that typically occurs in children, rarely in adults.

Bloom Syndrome
also known as Bloom TorreMachacek syndrome. disorder characterized by short stature and predisposition to the development of cancer Sister chromatid exchanges happen indicating instability.

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 intellectual disability. The average full-scale IQ of young adults with Down syndrome is around 50.

Downs Syndrome
The extra chromosome 21 material that causes Down syndrome may be due to a Robertsonian translocation in the karyotype of one of the parents. In this case, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14 .A person with such a translocation is phenotypically normal. During reproduction, normal disjunctions leading to gametes have a significant chance of creating a gamete with an extra chromosome 21, producing a child with Down syndrome. Translocation Down syndrome is often referred to asfamilial Down syndrome. It is the cause of 23% of observed cases of Down syndrome.It does not show the maternal age effect, and is just as likely to have come from fathers as mothers.

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 very short nose, protruding maxilla, etc. Each infant has difficulty sucking and swallowing.

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 duplications that are produced by segregation of translocation chromosome.

BIBLIOGRAPHY
PRINCIPLES OF GENETICS http://en.wikipedia.org/wik http://www.ashg.org/