U Sudhakar Reddy
New research findings on repetitive DNA in the human genomes that have been considered as junk genes so far has now shown a pathway to the personalized medicine in gene therapy for serious diseases like cancer.
City based Centre for Cellular and Molecular Biology scientists have achieved path breaking results by inserting these Simple Sequence Repeats of humans into transgenic Drosophila (fruit fly) genome to show that they act as boundary elements to stop the selective expression of genes.
CCMB director Dr. Ch Mohan Rao said,”boundary elements may be helpful in designing efficient gene therapy applications to prevent undesired effects of genomic elements when inserted at a gene site as part of therapy. Future studies along these lines are holding promising aspects,”
“All the tissues like that of liver, brain, and intestine have similar genes. But the tissues are different in each of them. Enzymes are produced in intestine and not in brain. This means certain genes express only in certain tissues. They also differ from person to person in expression though all human genome is one and the same,” said Mohan Rao.
For instance cancer causing genes are expressed in some persons resulting in the disease. The new research findings can help in personalized medicines to control the diseases by using these repeat DNA as boundary elements to stop disease causing gene expressions.
He added,”boundary elements are key regulatory elements that help in packaging of genome in small nuclear space and define regions of gene activity. Due to them the closely placed genes on the genome can get independently regulated and do not interfere with the neighbors. There are often instances where on gene expresses in one particular tissue, while the adjacent gene expresses in another one,”
CCCM scientists lead by Dr. Rakesh Mishra used one of the Simple Sequence Repeats known as GATA as boundary element in their experiments in the city lab on drosophila fly.
Dr Rakesh Mishra said “Human genome consists of coding DNA and non coding DNA. Around 98 per cent is non coding and only 2 per cent of genome codes for protein. Each human will have DNA with a length of 100 billion kilometers and there is enough DNA to reach from Earth to Sun and back for more than 300 times. The question is why we have so much of DNA if only two per cent of it codes for proteins. Our research found that these junk repetitive DNA have functional significance and they can separate functional domains of genome by acting as boundary elements,”
Dr Rakesh added ,” Out of 501 possible repeats only 30 are most abundant with some variations and in human beings there are 25 including GATA repeat. During packaging of these repeats loops are formed with a boundary type situation. When we inserted GATA human gene it worked as boundary wall between two genes in Drosophila and it’s eye had shown bipolar pigmentation indicating the genomic site of insertion.The research done by CCMB scientists is published in May 14th issue of jintational ournal ‘Nature Communications’.
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