A 4-Mb high-density single nucleotide polymorphism-based map around human APOE

Genomics. 1998 Nov 15;54(1):31-8. doi: 10.1006/geno.1998.5581.


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.

MeSH terms

  • Alleles
  • Apolipoproteins E / genetics*
  • Chromosome Mapping / methods*
  • Chromosomes, Artificial, Yeast / genetics
  • Chromosomes, Human, Pair 19 / genetics
  • Contig Mapping
  • Ethnicity / genetics
  • Expressed Sequence Tags
  • Gene Frequency
  • Humans
  • Nucleotides / genetics*
  • Polymerase Chain Reaction / methods
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Sequence Analysis, DNA
  • Software


  • Apolipoproteins E
  • Nucleotides