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NIA to Fund Studies Using Stem Cell Tools to Understand Alzheimer's Variants

NEW YORK (GenomeWeb News) – Genome-wide association studies have in recent years turned up a number of genetic variants that may contribute to the risk of late-onset Alzheimer's disease, and now the National Institute on Aging plans to fund efforts to further investigate the functional relationships between these variants and AD.

NIA said in a funding announcement yesterday that it plans to use $1 million in 2014 to fund two or three projects using human pluripotent stem cells and genome-editing that seek to establish functional genotype-phenotype relationships of genes and genetic variants that cause, modify, or alter the risk of AD.

“Functional evaluation of AD risk genes and genetic variants in human neurons and glial cells derived from hPSCs may confirm the role in AD of the genes identified in GWAS, DNA sequencing, and other studies,” NIA said in the funding announcement. “Studies on the contribution of multiple genes or genetic variants in producing molecular disease phenotypes using hPSCs will help define the role of common genetic variants in pathways underlying AD.”

Investigators may seek to use this funding to link AD risk candidate genes or variants to molecular, genetic, and biological phenotypes in human neurons or glial cells, to generate and characterize isogeneic hPSC expressing gene variants, or to study different AD-linked variants in hPSC-derived neural cells to identify synergistic gene effects on molecular and cellular phenotypes.

They also may aim to identify non-cell autonomous contributions to molecular and cellular phenotypes involved in AD risk, as well as modifiers of AD cell phenotypes, or to generate an integrated human cell-based genetic or molecular pathway model of AD gene or variant function in neurons and glial cells derived from hPSCs.