Using a MALDI-TOF System for SNP Analysis

  • Jafari, Nadereh (PD/PI)

Project: Research project

Project Details


DESCRIPTION (provided by applicant): Whole Genome Association Studies (GWAS) is a very powerful approach for the genetic analysis of complex traits, and interaction(s) between genetic predisposition and environment. Following the statistical analysis of high-density genome-wide association studies in large cohorts, investigators generally pursue two phases of follow-up genotyping. The first is an immediate, medium-density genotyping of the most highly associated SNPs (<384 SNPs) in a much larger cohort of individuals with an attempt to replicate and confirm the significant association of the initially identified SNPs. The second analysis consists of medium- to high-density genotyping of so called top signals (~1500 SNPs) that are more selectively chosen with the guidance of additional bioinformatics analyses, e.g. pathway analysis tools. The Genomics Core of the Center of Genetic Medicine (CGM) at Northwestern University has the appropriate instrumentation for primary GWAS studies (Affymetrix and Illumina systems with the capacity to run up to 1 M SNPs), and second phase medium- to high-density genotyping of the top signals (Illumina). However, the Genomics Core currently lacks a suitable system for the first immediate phase analysis for the rapid and cost- efficient characterization of less than 384 SNPs. The Sequenom MassARRAY system, requested in this proposal, is a flexible sequence analysis system which uses Matrix-Assisted Laser Desorption/Ionization Time- of-Flight Mass Spectrometry (MALDI-TOF MS) to perform medium- and low-throughput genotyping of regions identified with high-throughput approaches. Availability of a Sequenom genotyping system at the Genomics Core will provide access to this technology to the investigators at Northwestern University and affiliated institutions at a competitive price. Specifically, a Sequenom MassARRAY system will permit several Northwestern university investigators to a) identify genes that account for the genetic underpinnings of fetal growth and maternal metabolism and the interaction of those genes with the environment in determination of their phenotype, b)identify susceptibility loci of Preterm Birth, c) validate the effect of DNA methylation in pathogenesis of Multiple Myeloma, d) Investigate the role of genetic polymorphisms in the TGF-ss signaling axis in the pathogenesis of Scleroderma/Systemic Sclerosis, e) investigate the genetic and structural determinants of heart failure and left ventricular hypertrophy, f)rapidly genotype the Y-chromosome and autosomal SNPs to assess the nature of the evolutionary relationships between prehistoric and modern inhabitants of the North Slope, g) investigate genetic basis for asthma disparities in minorities, h) study the link between diabetes and obesity to postmenopausal breast cancer risk. PUBLIC HEALTH RELEVANCE: Currently available genotyping platforms at the core facility are not ideally suited for genotyping intermediate number of Single Nucleotide Polymorphisms (SNPs), are expensive to use, and do not perform low-density methylation analyses. Acquiring the MassARRAY system from Sequenom is necessary to fill this gap and to permit the efficient and timely completion of NIH- and NSF-funded projects focusing on a broad spectrum of diseases such as heart failure, hyperglycemia and adverse pregnancy outcomes, preterm birth, multiple myeloma, asthma, and scleroderma/ sclerosis at our institution and its affiliates.
Effective start/end date5/20/1011/19/11


  • National Center for Research Resources (1S10RR025669-01A1)


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