Human Genomic Polymorphisms And Haplotypes

Johns Hopkins University, Baltimore MD

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): With the availability of known and predicted genes and their regulatory sequences in a reference human genome, studies of complex disorders are expected to be more efficient by a systematic genomic search for functional variants by association studies. Recent data show that common genetic variation is distributed across the genome in a highly non-random manner as haplotypes (blocks) of single nucleotide polymorphisms (SNPs). The identification of these blocks can both establish the specific patterns and be directly used for disease association studies. The goals of this proposal are to implement a novel, accurate and robust genotyping technology that will allow the simultaneous genotyping of thousands of SNPs, distributed genome-wide, per assay on genomic samples. The specific aims are: (1) to identify 493,000 SNPs and genotype at least 370,000 SNPs in 195 human and great ape samples using genomic complexity reduction, whole genome amplification and oligonucleotide array-based hybridization; (2) to assess the repeatability and accuracy of genotyping using duplicate assays and comparison to single-base extension genotyping; (3) to analyze the genotype data using existing and novel techniques to identify SNP composition, length and frequency of major haplotypes in the human genome. All data emanating from this project at each stage will be publicly released daily. This proposal is a collaboration between a group of human geneticists and a biotechnology company. The investigators have a successful history of collaboration, publication and technology development. They have demonstrated experience and expertise in genomic variation technology and their applications to human disease and population genetics and DNA chip technology.