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Missing Link
Absence of a gene in the body could
lead to a defective heart, reports Biplab Das
Whether it is the birth of a beating heart or a thinking brain, it is the concerted effort of myriad genes that come into play. Genetic harmony nicely orchestrates the development of a fully grown foetus from a
fertilised ovum. Amidst the coordination, sometimes, several genes go awry. And the fall off is a baby born with deformed organs.
In a recent issue of Science, it was reported that researcher Deepak Srivastava and colleagues from the University of Texas along with the help of Rumiko Matsuoka of Tokyo Women's Medical University have homed in on chromosome 22, which holds the key to defective hearts.
A specific gene on this chromosome holds the code for neural crest cells, which, in turn, form a special type of cell that builds the different tracts of heart. Surprisingly, in many cases, the research team found many bases of the gene absent on chromosome 22. This decrease in the number of bases resulted in the gene directing the faulty development of neural crest cells.
When these special type of cells, which are derived from these improperly developed neural crest cells form the outflow tract of the heart and the vessels arising from it, the ultimate result is a defective heart.
Of the affected patients, 50 per cent are born with interrupted aortic arch, 30 per cent with undivided aorta and pulmonary arteries and rest with mal-alignment of aorta and pulmonary artery with ventricles. Most of the babies born with these defects die within one year.
In the laboratory, researchers worked with mice having heart defects.
Soon, they came up with encouraging results. The research team found a factor called
dHNAD which switches on a gene called Ufd1. In mice, this gene codes for neural crest cells. Moreover, in mice, dHNAD is expressed by another gene called endothelin 1(ET-1). When anything goes wrong with ET-1, it down-regulates
dHNAD which, in turn, disrupts the development of neural crest cells. This leads to heart defects.
After having studied the mice, Srivastava and his teammates turned to humans to look for the flawed part on chromosome 22. In this part of the chromosome resides the gene called UFD1L, which codes for neural crest cells. To find out how many bases of UFD1L are missing, the research team used a special technique called FISH (fluorescence in situ
hybridisation). All the patients who were exposed to this technique showed UFD1L deletion. It is this deletion that predisposes a budding baby to be born with defective heart. According to the research team, another gene called CDC45 may have some role to play in this gene anomaly. But inadequate data thwarted researchers from pinning it down.
Although the research team has not yet found a remedy for this malady, Srivastava and his colleagues hope that a treatment, which may either prevent or correct defective hearts and lengthen the life span of ill-fated babies, could soon be possible.
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