The effects of scale: Variation in the APOA1/C3/A4/A5 gene cluster

摘要: While there is considerable appeal to the idea of selecting a few SNPs represent all, or much, DNA sequence variability in local chromosomal region, it also important quantify what detail lost adopting such an approach. To address this issue, we compared high- and low-resolution depictions diversity for same genomic APOA1/C3/A4/A5 gene cluster on chromosome 11. First, extensive re-sequencing identified all nucleotide haplotype variation linked apolipoprotein genes 72 individuals from three populations: African-Americans Jackson, Miss., Europeans North Karelia, Finland, European-Americans Rochester, Minn.. We 124 17.7 kb significant differences among genes. APOC3 was particularly distinctive at high resolution, showing large allele frequency (F ST values >0.250) between Jackson other two samples, divergent population-specific lineages. Next, selected haplotype-tagging (htSNPs) each gene, density approximately one SNP per kb, using algorithm suggested by Stram et al. (2003). The 17 htSNPs were then used reconstruct haplotypes, which inferences about structure drawn. This comparison showed that while successfully tagged common variation, they left much underlying undetected failed, some cases, co-classify groups closely related haplotypes. implications these findings haplotype-based descriptions human are discussed.