Genetics Program, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S8. doi: 10.1186/1471-2156-6-S1-S8.
Both theoretical and applied studies have proven that the utility of single nucleotide polymorphism (SNP) markers in linkage analysis is more powerful and cost-effective than current microsatellite marker assays. Here we performed a whole-genome scan on 115 White, non-Hispanic families segregating for alcohol dependence, using one 10.3-cM microsatellite marker set and two SNP data sets (0.33-cM, 0.78-cM spacing). Two definitions of alcohol dependence (ALDX1 and ALDX2) were used. Our multipoint nonparametric linkage analysis found alcoholism was nominal linked to 12 genomic regions. The linkage peaks obtained by using the microsatellite marker set and the two SNP sets had a high degree of correspondence in general, but the microsatellite marker set was insufficient to detect some nominal linkage peaks. The presence of linkage disequilibrium between markers did not significantly affect the results. Across the entire genome, SNP datasets had a much higher average linkage information content (0.33 cM: 0.93, 0.78 cM: 0.91) than did microsatellite marker set (0.57). The linkage peaks obtained through two SNP datasets were very similar with some minor differences. We conclude that genome-wide linkage analysis by using approximately 5,000 SNP markers evenly distributed across the human genome is sufficient and might be more powerful than current 10-cM microsatellite marker assays.
理论和应用研究均表明，单核苷酸多态性（SNP）标记在连锁分析中的效用比当前的微卫星标记分析更强大且更具成本效益。在这里，我们对 115 个白种非西班牙裔家庭进行了全基因组扫描，这些家庭分离出酒精依赖症，使用了一套 10.3cM 的微卫星标记和两套 SNP 数据集（0.33cM，0.78cM 间隔）。使用两种酒精依赖症定义（ALDX1 和 ALDX2）。我们的多点非参数连锁分析发现，酗酒症与 12 个基因组区域呈名义连锁。使用微卫星标记集和两套 SNP 集获得的连锁峰通常具有高度的一致性，但微卫星标记集不足以检测到一些名义连锁峰。标记之间存在连锁不平衡并不会显著影响结果。在整个基因组中，SNP 数据集的平均连锁信息量（0.33cM：0.93，0.78cM：0.91）远高于微卫星标记集（0.57）。通过两套 SNP 数据集获得的连锁峰非常相似，略有差异。我们的结论是，使用大约 5000 个 SNP 标记进行全基因组连锁分析，这些 SNP 标记均匀分布在人类基因组中，足以且可能比当前的 10cM 微卫星标记分析更强大。
