Their research, published online today in Nature Genetics , identifies a common genetic sequence abnormality that enhances the likelihood of acquiring a mutation in a gene linked to certain blood diseases.

The investigators carried out a genome-wide study to identify inherited DNA sequence changes that frequently occur in patients with myeloproliferative neoplasms, in which several types of blood cells are excessively produced in the bone marrow. They found that an inherited alteration in the gene for JAK2 - a protein with enzymatic activity that is linked to the abnormal production of blood cells - is more common in patients with these disorders. Importantly, patients who inherited this JAK2 alteration were predisposed to acquiring another JAK2 mutation on the same DNA strand. According to the research, these mutations do not arise randomly, but are specifically determined by the DNA sequence.

More than half of patients afflicted with myeloproliferative neoplasms - which affect an estimated 140,000 people in the US - carry the JAK2 mutation and suffer from the overproduction of red blood cells, platelets, or fibrous connective tissue. According to the authors, understanding the underlying inherited sequence partly explains the predisposition for acquiring mutations in certain disease-specific genes and may help explain why some individuals are at higher risk in developing the disease.

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The hypoxia-regulated pattern of BNIP3 expression and the gene's activity in the mole rat echoes its behavior in cancer cells. In both cases waves of normal oxygen levels and hypoxic levels lead to changes in the regulation of hypoxia-induced genes behavior. In mole rats this fluctuation is due to rainfalls that flood their underground tunnels, limiting the availability of oxygen and, moreover, forcing them to rebuild the tunnels and exhaust the limited oxygen; in tumor cells it occurs as they divide faster than blood vessels, which supply oxygen, sprouting into new cells.

Among a growing list of hypoxia-induced genes that were studied in the mole rat by Prof. Avivi and his colleagues and collaborators, this is the third gene that shows a similar pattern of expression as in cancer. In the past it has also been revealed that VEGF (Vascular Endothelial Growth Factor - a major growth factor that regulates the growth of new blood vessels) and p53 (a "master" gene, responsible for activating a battery of other genes engaged in either programmed cell death [apoptosis] or DNA-repair in cells) exhibit a similar mode of action in mole rats and in cancer growths, which is why they are so destructive in human cancer growths, Prof. Avivi pointed out.

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