Genome scan linkage analysis comparing microsatellites and single-nucleotide polymorphisms markers for two measures of alcoholism in chromosomes 1, 4, and 7
Genome scan linkage analysis comparing microsatellites and single-nucleotide polymorphisms markers for two measures of alcoholism in chromosomes 1, 4, and 7
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DOI：
10.1186/1471-2156-6-s1-s4
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发表时间：
2005-12-30
期刊：
影响因子：
2.9
通讯作者：
Rotimi, C
中科院分区：
文献类型：
--
作者：
Chen, GJ;Adeyemo, A;Rotimi, C
背景资料：我们分析了143个家系（364个核心家庭）在酒精中毒遗传学合作研究（COGA）中的数据提供给遗传分析研讨会14（GAW 14）的参与者，目的是比较使用微卫星的基因组连锁分析获得的结果和使用SNP标记获得的两种酒精中毒指标的结果（最大饮酒次数-MAXDRINK和来自EEG-TTTH 1的电生理测量）。首先，我们构建了单倍型块，通过使用整个单核苷酸多态性（SNP）在染色体1，4和7。这些染色体在以前的报告中显示了MAXDRINK或EEG-TTTH 1的连锁信号。其次，我们从每个区组中随机选择1、2、3、4和5个SNP（分别称为Rep 1-Rep 5），使用方差分量法进行连锁分析。最后，所有的SNP分析的结果进行了比较，使用微卫星markers.Results获得的LOD得分略高，但从SNPs获得的曲线没有根本上不同，从微卫星分析。与微卫星标记相比，SNP组的连锁区域的峰值略微左移。减少的SNP组在相同的连锁区域提供信号，但具有较小的LOD得分，表明信息含量的减少对连锁结果有显著影响。与微卫星标记相比，SNP连锁区域的1个LOD支持区间的宽度较小。结论：与微卫星标记相比，单核苷酸多态性标记的连锁区域较窄，LOD值略高。微卫星和SNP标记中使用的遗传图谱的不同构建或/和基因分型中的错误可能解释了使用SNP未识别的7号染色体上的微卫星连锁信号。此外，SNPs和微卫星标记之间未解决的地图问题可能是部分负责移动的连锁峰时，比较两种类型的标记。
Background: We analyzed 143 pedigrees (364 nuclear families) in the Collaborative Study on the Genetics of Alcoholism (COGA) data provided to the participants in the Genetic Analysis Workshop 14 (GAW14) with the goal of comparing results obtained from genome linkage analysis using microsatellite and with results obtained using SNP markers for two measures of alcoholism (maximum number of drinks-MAXDRINK and an electrophysiological measure from EEG-TTTH1). First, we constructed haplotype blocks by using the entire set of single-nucleotide polymorphisms (SNP) in chromosomes 1, 4, and 7. These chromosomes have shown linkage signals for MAXDRINK or EEG-TTTH1 in previous reports. Second, we randomly selected one, two, three, four, and five SNPs from each block (referred to as Rep1-Rep5, respectively) to conduct linkage analysis using variance component approach. Finally, results of all SNP analyses were compared with those obtained using microsatellite markers.Results: The LOD scores obtained from SNPs were slightly higher but the curves were not radically different from those obtained from microsatellite analyses. The peaks of linkage regions from SNP sets were slightly shifted to the left when compared to those from microsatellite markers. The reduced sets of SNPs provide signals in the same linkage regions but with a smaller LOD score suggesting a significant impact of the decrease in information content on linkage results. The widths of 1 LOD support interval of linkage regions from SNP sets were smaller when compared to those of microsatellite markers. However, two linkage regions obtained from the microsatellite linkage analysis on chromosome 7 for LOG of TTTH1 were not detected in the SNP based analyses.Conclusion: The linkage results from SNPs showed narrower linkage regions and slightly higher LOD scores when compared to those of microsatellite markers. The different builds of the genetic maps used in microsatellite and SNPs markers or/and errors in genotyping may account for the microsatellite linkage signals on chromosome 7 that were not identified using SNPs. Also, unresolved map issues between SNPs and microsatellite markers may be partly responsible for the shifted linkage peaks when comparing the two types of markers.