title: A 4-Mb high-density single nucleotide polymorphism-based map around human APOE.
abstract: Whole-genome association studies using single-nucleotide polymorphisms (SNPs) are the proposed method of choice for the identification of loci associated with complex diseases. In this report, we address the feasibility of generating high-density SNP maps (with <100-kb spacing). As a pilot study, we concentrated on a 4-Mb region around the human APOE locus on chromosome 19. We compared the efficiency of SNP detection using YAC-based versus BAC/PAC-based maps, sequencing individual DNAs versus a pooled DNA sample, and we evaluated three different software applications for polymorphism detection. A total of 121 SNPs (25 in coding regions) were identified. The frequency of SNP detection was 1 SNP/1.1 kb of genomic sequence. From APOE to CALM3 (approximately 2 Mb), the average marker spacing was approximately 30 kb. Fifty-one SNPs were genotyped in five populations, and 10 SNPs showed an allele frequency differential greater than 0.5 between populations. Our results demonstrated that high-density SNP maps can be efficiently generated using existing technologies and that a genome-wide map with 60,000-100,000 SNPs is achievable in a reasonable time frame.
authors.affiliation: US Discovery Genetics, GlaxoWellcome, Inc., 5 Moore Drive, Research Triangle Park, North Carolina, 27709, USA.
authors.forename: E
authors.initials: E
authors.lastname: Lai
authors.forename: J
authors.initials: J
authors.lastname: Riley
authors.forename: I
authors.initials: I
authors.lastname: Purvis
authors.forename: A
authors.initials: A
authors.lastname: Roses
mesh_terms: D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D020451:Contig Mapping; D005006:Ethnicity / Q000235:genetics; D020224:Expressed Sequence Tags; D005787:Gene Frequency; D006801:Humans; D009711:Nucleotides / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D012984:Software
chemical_list: D001057:Apolipoproteins E; D009711:Nucleotides