Drosophila Polytene Chromosomes

Duplications and Deletions



Human Diseases Related to Altered Chromosome Structure

Variation in Chromosome Structure WWW Links

Genetic Topics

Human Diseases Related to Altered Chromosome Structure

In humans, several diseases are the result of deletions. For example, muscular dystrophy is often associated with a deletion of the X-chromosome. Muscular dystrophy is found in 1/3500 live male births. This gene has been cloned and appears to cover 1000 kb of the X-chromosome, but the mRNA is only 14 kb. Using probes that were derived from cloning the gene, it was shown that 50% of the individuals with the disease had a deletion. Further, 80% of these deletions could be detected by using two probes that cover only 2 kb of the cDNA, which suggests that certain regions of the gene are more susceptible to deletion events than other.

Two types of cancer in humans have been associated with reciprocal translocations of specific chromosomes. In both cases, the breakpoint of one chromosome occurs near an oncogene.

Oncogene - a gene that causes neoplastic transformations in animal cells growing in culture and tumor formation in animal cells

Extensive molecular analysis has revealed that the human genome has at least 15 unique oncogenes that are located on 14 different chromosomes. The proposed function of some of these oncogenes has been determined, and many appear to be involved in the cell division process. The two types of cancers associated with translocations are chronic myelogenous leukemia and Burkitt's lymphoma. In 85% of the cases of chronic myelogenous leukemia a translocation has occurred between the long arms of chromosomes 22 and 9. The chromosome 22 product is much shorter and is called a Philadelphia chromosome. The break point on chromosome 9 is near the oncogene c-abl and that oncogene resides on the Philadelphia chromosome after the translocation event.

Burkitt's lymphoma is associated, in >80% of the cases, with a translocation between chromosome 8 and chromosome 2, 14, or 22. In these cases, the breakpoint on chromosome 8 is always very near the c-myc oncogene, and the translocated segment is relocated on the other chromosomes in the vicinity of antibody producing genes.

In neither case, Burkitt's lymphoma or chronic myelogenous leukemia, is the reason that the cancer appears understood, although the placement of the oncogene in a new chromosomal location probably has an effect. For example, some of the Burkitt lymphomas are associated with a translocation of the oncogene into the vicinity of an enhancer element involved with antibody expression. Enhancers are sequences which greatly increase the expression of genes which are located nearby. Possibly this enhancer is greatly increasing the expression of the c-myc oncogene product which leads to the cancerous state.

Copyright © 1997. Phillip McClean