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Research Abstracts Online
January 2009 - March 2010

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University of Minnesota Twin Cities
Medical School
Department of Medicine

PI: Jeffrey S. Miller

High-throughput Sequencing of Killer Immunoglobulin-like Receptor Promoters and Their Methylation Status

The killer immunoglobulin-like receptors (KIR) are expressed on the surface of human natural killer (NK) cells and are relevant in the context of hematopoietic cell transplantation. A clear association exists between particular KIR expression profiles and patient survival post-transplant. The variegated expression of genes within the KIR locus is controlled at the level of transcription, and expression positively correlates with the hypomethylation of CpG dinucleotides within individual KIR promoters. The aim of this project is to elucidate the mechanisms responsible for the establishment of methylation patterns within the KIR locus during human NK cell development. These researchers hypothesize that polymorphisms within the promoters of individual KIR genes influence the epigenetic transcriptional state across the KIR locus. To test this hypothesis, they are carrying out high-throughput sequencing of the fourteen known KIR genes from a large patient population to correlate sequence polymorphisms with quantitative RT-PCR expression of gene transcription. The overarching goal of this project is to understand the mechanisms that underlie KIR transcription so that they can be manipulated for clinical benefit.

Group Members

Frank Cichocki, Graduate Student
Todd Lenvik, Research Associate