Clinical OMICS

JAN-FEB 2018

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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Page 36 of 51 January/February 2018 Clinical OMICs 35 but which also included at least four individuals with an APOE ε4 allele who lived to advanced age with- out clinical symptoms of cognitive decline. The study ended up includ- ing data from more than 200 subjects. They next used WGS to look for candi- date variants. The BYU team found promising variants in RAB10 and SAR1A, and did further analysis of both. They ulti- mately concluded that Rs142787485 in RAB10 appears to confer significant protection against AD and thus could be a promising target for AD-related drug development. Kauwe noted this result needs to be further replicated. But the team also tested two indepen- dent populations to see if its findings held up. In addition, the team per- formed lab tests to further corroborate their results and demonstrated exper- imentally that RAB10 knockdown results in significant decrease in Aβ42 and in the Aβ42/Aβ40 ratio in neu- roblastoma cells. RAB10 expression is also significantly elevated in the brains of former AD patients. The families studied came from the Utah Population Database (UPDB). This is a unique resource that includes the computerized genealogy of Utah pioneers and their descendants and is linked to other state health data repos- itories including death certificates, which have listed AD as a cause-of- death since 1979. More than 8 million people are included in the UPDB, and for 2.5 million of them, the database has three generations of genealogical data. Over a million of these people have at least a dozen of their 14 imme- diate ancestors in the database. "We don't know if they were resil- ient because of resistance to the pathology or if they were just asymp- tomatic," Kauwe said. "But in any case, they were living cognitively normal lives." The search for variants that impact risk of AD has been long and tortured. Most genetic variance Researchers in the Kauwe Lab at BYU discovered a genetic variant that can protect some people from developing Alzheimer's disease despite the presence of the APOE ε4 allele and a strong family history of developing the disease. New in Vitro Biomarker Improves Genotoxicity Prediction An international team of researchers, led by Albert J. Fornace, Jr., M.D., professor in the departments of biochemistry and molecular & cellular biology, oncology and radiation medicine at Georgetown University School of Medicine, has devel- oped an in vitro transcriptomic biomarker that can predict, with up to 90% accuracy, whether a drug candidate or other chem- ical compound is likely to cause the type of cellular injury that can lead to cancer. The TGx-DDI biomarker comprises a panel of 64 transcribed genes that re- flect cellular stress response due to DNA damage. And unlike current genotoxicity assays, which demonstrate high rates of false-positive results for cancer risk, the TGx-DDI panel can distinguish between DNA-damaging chemicals that are poten- tially carcinogenic and those that may be toxic to cells at high levels, but which do not pose a cancer-causing risk in vivo. "Compared to older tests, our approach allows for very accurate and high-through- put screening of chemical compounds that cause DNA damage and, potentially, cancer in humans," said Fornace, who is also a member of Georgetown Lombardi Comprehensive Cancer Center. n (continued on next page) Frentushax / Getty Images

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