Monday, July 2, 2007

"Common KIBRA alleles are associated with human memory performance

Genetics of Human Memory Performance

December 2006

Researchers at the Translational Genomics Research Institute (TGen) in Phoenix and the University of Zurich have discovered a genetic variation in the human KIBRA gene associated with short-term memory performance, a finding that may shed light on devastating memory-based diseases such as Alzheimer's and Parkinson's.

"This is a generally applicable association finding," said Dietrich Stephan, head of the Neurobehavioral Research Unit at TGen. "In fact, probably about 50 percent of people worldwide have the at-risk haplotype and about 50 percent have the good haplotype."

The team, led by Stephan and Andreas Papassotiropoulos, made the discovery using the Affymetrix Human Mapping 500K Array Set; the study is the first published research using genotype data from 500,000 SNPs for whole-genome association analyses.

"Whole-genome association works at this density in outbred populations," said Stephan. "The ramifications for understanding disease process and for early diagnostics are huge."

Stephan's team discovered that genetic changes in the gene encoding the KIBRA protein correlated with the ability to perform memory-based tasks in a cohort of 341 students at the University of Zurich. They confirmed this association in additional Swiss and U.S. cohorts.

Gene expression studies showed that the KIBRA transcript is present at high levels in the human brain, especially in the hippocampus, a part of the brain critical in memory function. The team also performed functional magnetic resonance imaging, which showed that activation in the hippocampus during memory retrieval differs depending on the KIBRA allele.

The study, "Common KIBRA alleles are associated with human memory performance," appears in the October 20, 2006, issue of Science.



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