Have a HaploCHIP

Searching for common DNA polymorphisms that affect gene regulation in vivo.

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The majority of single nucleotide polymorphisms are found in non-coding DNA but there have been few reliable techniques to predict their functional significance. In an Advanced Online Publication in Nature Genetics, Julian Knight and colleagues at the Wellcome Trust Centre for Human Genetics, Oxford, UK, describe an approach, dubbed HaploCHIP, which uses hapolotype-specific chromatin immunoprecipitation (CHIP) to detect differences in the amount of phosphorylated RNA polymerase II (Pol II) bound to different alleles (Nature Genetics, DOI:10.1038/ng1124,10 March 2003).

Knight et al. tested the HaploCHIP method by studying the imprinted gene SNRPN, encoding the small nuclear ribonucleoprotein polypeptide N. CHIP with antibodies against the phosphorylated Pol II protein could distinguish between transcriptional activation of the two SNRPN alleles. For accurate and sensitive detection of the relative abundance of the two different alleles they used primer extension and MALDI-TOF mass spectrometry. The HaploCHIP approach revealed a correlation between haplotypes and gene expression ...

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