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High-Throughput Polymorphism Detection

April 2014 | eNews

The DF/HCC High-Throughput Polymorphism Detection Core provides services to Cancer Center members conducting molecular analyses of germline and somatic DNA collected as part of a wide range of investigations into the molecular epidemiology of cancer, including Genome Wide Association Studies (GWAS). The Core provides high-throughput assays of specific gene mutations and polymorphisms (SNPs) in the many situations where previously defined specific nucleotide alterations are of interest. The Core also provides flexible, high quality, high-throughput SNP Genotyping to the DF/HCC research community.

Services Offered Through the Core

The HTP Core located at HSPH provides the following assays:

  • Telomere length by qPCR
  • TaqMan and OpenArray SNP genotyping platforms
  • DNA Extraction and Whole Genome Amplification services

The HTP Core located at Partners Center for Personalized Genetic Medicine (PCPGM) provides the following assays:                

  • Illumina GoldenGate Genotyping (384, 768, 1536-plex)
  • Infinium Genotyping (OmniExpress (700,000 markers), Omni2.5-8 (2.5 M markers), Omni5 (5 M markers) and the Exome targeted chip with 12,000 markers for genotyping and copy number analysis
  • Next Generation Sequencing (NGS) Services

Recent Projects

Aspirin use, 8q24 single nucleotide polymorphism rs6983267, and colorectal cancer according to CTNNB1 alterations

Principal Investigators: Andrew Chan (MGH), Matthew Freedman (DFCI), Charles Fuchs (DFCI), Edward Giovanucci (HSPH), Shuji Ogino (BWH) 

Description of Project: Regular aspirin use reduces the risk for colorectal cancer (CRC), possibly through inhibition of WNT/cadherin-associated protein β1 (CTNNB1 or β-catenin) signaling. The single nucleotide polymorphism (SNP) rs6983267 on chromosome 8q24 is a CRC susceptibility locus that affects binding activity of transcription factor 7 like-2 (TCF7L2) to CTNNB1, thereby altering expression of target oncogenes, including MYC. The results support an influence of aspirin on WNT/CTNNB1 signaling and suggest that aspirin chemoprevention may be tailored according to rs6983267 genotype.

Contribution of the Core: The Core performed the DNA Extraction, TaqMan and OpenArray genotyping of all of the SNPs in the study onf 5233 individuals.

Common genetic variation of the calcium-sensing receptor and lethal prostate cancer risk

Principal Investigators: Lorelei Mucci (HSPH), Irene M Shui, Meir Stampfer (BWH)

Description of Project: Bony metastases cause substantial morbidity and mortality from prostate cancer (PCa). The calcium-sensing receptor (CaSR) is expressed on prostate tumors and may participate in bone metastases development. This study assessed whether (i) common genetic variation in CaSR was associated with PCa risk and (ii) these associations varied by calcium intake or plasma 25-hydroxyvitamin D [25(OH)D] levels.

In summary the overall findings of this study showed that joint association of SNPs in CaSR was significant for lethal PCa (P = 0.04) and that this association was stronger in those men with low 25(OH)D (p=0.0009). The findings of this study indicate that CaSR may be involved in PCa progression.

Contribution of the Core: The Core performed the DNA Extraction of 2,924 individuals and TaqMan and OpenArray genotyping of 18 SNPs on 2,924 individuals. 

Plasma vitamin D biomarkers and leukocyte telomere length

Principal Investigators: Immaculata De Vivo (BWH), Edward Giovanucci (HSPH), Jiali Han (BWH), Susan Hankinson (BWH), Jason Liu, Jennifer Prescott, Bernard Rosner (BWH)

Description of Project: In this study, the authors examined the association between vitamin D and relative leukocyte telomere length by using both plasma 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) biomarkers. Overall the authors found that higher 25(OH)D levels were significantly associated with longer telomere length (P for trend = 0.05) and that this association may be modified by calcium intake.

Contribution of the Core: The Core performed DNA Extraction of 1,424 individuals, Telomere Length Analysis on 1,424 individuals and OpenArray genotyping of 12 SNPs on 480 individuals.