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Thursday, February 5, 2009

Anna Kiialainen, Uppsala University - “Identification of Regulatory Genetic Variation That Affects Drug Response in Childhood Acute Lymphoblastic Leuk

1.most common in children
2.20% do not respond to treatment
3.multi-factorial disease

Allele specific expression is important. Normally, you only have one copy of each gene, however you can get different ratios of expression from each allele, which leads to very different proportions in the sample of each allele.

Advantages: they can serve as internal standards for each other.

Causes: SNPs that affect transcription or stability. Or, allele specific promotor (regulation or methylation).

Samples: 700 children with acute lymphoblastic leukemia. Yearly follow up data and drug response, in vitro drug sensitivity, immuophenotype, cytogenic data. RNA available for 1/3 of them.

Genotyped over 3531 SNPs in 2529 genes. ASE was detected in 400 (16%) of the informative genes, 67 of which displayed monoallelic gene expression. (Milani L, et al, Genome Research 2009)

Methylation analysis: Selection of 1536 CpG sites from >50,000 CpG sites in genes displaying ASE. Custom GoldenGate methylation panel. (ibid)

SNP discovery: 56 genes displaying ASE selected fro sequencing in 90 ALL samples. Template preparation with Nimblegen seq. capture. Illumina sequencing.

To date: 16 samples hybridzed. 5 samples sequenced with GA I. 81-97% align to genome (Eland), 28-67% align to target region (MAQ).

Overview of sample sequencing coverage.

Initial SNP discovery – 2063-4283 SNPs found with MAQ. 3422 in at least two samples. 818/3422 are novel (not in db.)

My comments: This is an interesting talk, from the big picture view. Dr. Kiialainen is spending a lot of time talking about metrics that haven't really been used much this year (percent alignment, etc.) and explaining figures that are relatively simple. There wasn't much data presented – essentially it's no more than an outline and statistics of the sequences gathered. Not my least favourite talk, but had very little content, unfortunately. Knowing you can do allelic studies is neat, however, which is clearly the best part of the talk. My advisor is chairing the session... and asking the same questions he asks me. Nice to know I'm not the only who answers with “No, I haven't done that yet!”



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