September 2011: An Israeli scientist at Tel Aviv University has developed a unique fast-track gene-based technology to diagnose hearing loss, one that is faster and cheaper than current methods. Professor Karen Avraham at the university’s Sackler Faculty of Medicine working together in a unique collaboration with Professor Moein Kanaan from Bethlehem University, used “exome deep sequencing”, a method which sequences thousands of genes at a time.

Exome sequencing collects relevant DNA from specific sites of the body. The process was used to identify five genetic mutations leading to deafness in a population of 11 Jewish Israelis and Palestinian Authority Arabs. None were related to each other, but all had deafness in their families. This is the first time scientists have identified some of these genetic mutations in Middle Eastern deaf populations, and the first time this technology has ever been applied to these populations. The research was funded by the U.S. National Institutes of Health.

Avraham’s method provides better diagnosis capabilities and can improve the quality of care for patients with hearing loss, she reported in the latest issue of Genome Biology. For less than $500, researchers can now scan all the known genes for deafness and provide results in a matter of weeks, as opposed to testing that in the past has cost many times more.

More than 28 million Americans are hearing impaired, with at least half of the cases traced to genetic causes. The condition can be especially challenging for children who are born with hearing impairment, because spoken language, reading and cognitive development are all tied to hearing. “That makes early diagnosis essential for identifying appropriate therapy and treatment,” Avraham commented.

“It is a remarkable step forward in helping us to find treatments and even cures for patients,” she added. “This new technology is changing the way we practice genomic medicine, and revolutionizing genetic diagnostics.” The technology can be used to search for genetic mutations that characterize any disease or condition, she noted.

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Israeli scientists at the Weizmann Institute of Science have discovered that it takes two different types of enzymes to carry out an essential form of DNA repair — one that can make the difference between life and death. A recent study conducted by Prof. Tzvi Livneh of the Weizmann Institute’s Biological Chemistry Department, graduate students Sigal Shachar and Omer Ziv, and researchers from the US and Germany, revealed how the error-prone repair works. The findings of the study were published recently in the EMBO Journal. Livneh, has been working on the problem for the past 20 years. Prof. Livneh’s research is supported by the Helen and Martin Kimmel Institute for Stem Cell Research; the estate of Lore F. Leder; and Esther Smidof, Geneva, Switzerland. He is the incumbent of the Maxwell Ellis Professorial Chair in Biomedical Research.
The team found that the repair system proceeds in two steps and requires two types of enzymes, belonging to the family of enzymes called DNA polymerases, which synthesize DNA. First, one repair enzyme, “the inserter,” does its best to fit in a genetic “letter” into the gap, opposite the damaged site in the DNA molecule; several enzymes can perform this initial step, which often results in the insertion of an incorrect genetic letter. Next, another enzyme, “the extender,” helps to restore regular copying of DNA by attaching additional DNA letters after the damaged site; only one repair enzyme is capable of performing this vital second step.

“Considering that the DNA of each cell is damaged about 20,000 times a day by radiation, pollutants and harmful chemicals produced within the body, it’s obvious that without effective DNA repair, life as we know it could not exist,” Livneh said. “Most types of damage result in individual mutations – genetic ‘spelling mistakes’ – that are corrected by precise, error-free repair enzymes,” he continued. “Sometimes, however, the damage results in more than a mere spelling mistake.” That kind of damage can cause gaps in the DNA which prevent the DNA molecule from being copied when the cell divides — much like an ink blot or a hole on a book page interferes with reading, he explained.

“So dangerous are these gaps that the cell resorts to a sloppy but efficient repair technique to avoid them — it fills in the missing DNA in an inaccurate fashion. “Such repair can save the cell from dying, but it comes at a price: this error-prone mechanism is a major source of mutations,” he noted. The “stopgap” process was discovered about 10 years ago by scientists at the Weizmann Institute, and elsewhere around the world.

Understanding how this major form of DNA repair works can have significant clinical implications, Livneh added. Since defects in DNA repair increase the risk of cancer, clarifying the mechanism might one day make it possible to enhance the process in people whose natural DNA repair is deficient. In addition, manipulating this mechanism can improve the effectiveness of cancer drugs, he pointed out, since cancer cells can resist chemotherapy by exploiting their natural repair mechanisms. Blocking these mechanisms may help overcome this resistance, leading to a targeted destruction of the cancerous tumor, he stated.