Haplotype analysis of polymorphic genes and its forensic application

鉴定信息位点作为遗传标记和建立简单、实用的分析方法可能是法医鉴定的重要内容。在这些标记中，祖先信息标记（AIMs）对于从DNA图谱样本（例如从犯罪现场）进行表型的法医鉴定越来越有用。我们分析了多态性丰富的遗传区域和显示群体特异性变异的遗传区域。此外，我们还通过序列分析确定了编码多态性在世界范围内观察到的基因的单倍型。由于变性高效液相色谱（DHPLC）检测突变的原理不同于测序或其他电泳，因此本项目引入了DHPLC。我们可以得到一些结果。1)结合珠蛋白启动子的单倍型是一种信息丰富的遗传标记，因为在三个主要群体中很少有相同的单倍型。2)在三个主要人群中，围绕C6的A293C（即C6A与C6B之间的差异）的一些snp存在连锁。统计检验表明A293C可能是平衡选择的目标位点。3)我们在FUT2编码区下游3.8 kb处发现了STR位点，该STR的序列和重复多态性模式表明该STR位点不仅是FUT2编码区，而且是一个很好的遗传标记。4)两个斯里兰卡人群（泰米尔人和僧伽罗人）的遗传背景相似，但FUT2和FUT3的遗传变异并不相同。此外，我们将DHPLC方法引入到FUT2的基因分型中，证明了该方法的适用性。5)统计分析表明，含有黑素发生基因AIM-1 （AIMs之一）的欧洲特异性衍生SNP 374F的单倍型最近在一些地区通过定向选择传播。

It is possible that the identification of informative loci as genetic marker and establishments of simple and useful analytical methods are important in forensic field. Among the markers, Ancestral informative markers (AIMs) are becoming useful for forensic identification of the phenotype from a DNA profile samples for example from a crime scene. We analyzed genetic regions that are rich in polymorphism and that show population specific variation. In addition, we also determined the haplotypes of the genes of which coding polymorphisms are observed around the world by sequence analysis. The Denaturing High-performance Liquid Chromatography (DHPLC) method was introduced to this project because of its different principle for mutation detection from that of sequencing or other electrophoresis. We could get some results. 1)We showed the haplotypes of promoter of the haptoglobin is one of informative genetic marker because few haplotypes were shared among three major populations. 2)Some SNPs surrounding the A293C of C6, that is difference between C6A and C6B, were linked together among three major human populations. A293C was shown to be possible target site of balancing selection by statistical tests. 3)We found STR locus 3.8 kb downstream of the FUT2 coding region and the pattern of sequence and repeat polymorphism of this STR showed not only the coding region of the FUT2 but this locus is good genetic marker. 4)The genetic background of two Sri Lankan populations (Tamils and Sinhalese) is shown to be similar but not identical by genetic variation of the FUT2 and FUT3. In addition, we introduced DHPLC method to genotyping of the FUT2 and showed this method is applicable. 5)The haplotype containing the European specific derived SNP,374F of melanogenetic gene AIM-1 (one of AIMs) was shown to be spread recently by directional selection in some regions by statistical analyses.