Haplotype analysis of polymorphic genes and its forensic application

因此，识别信息丰富的基因座作为遗传标记，建立简单实用的分析方法在法医学领域具有重要意义。在这些标记中，祖先信息标记(AIMS)正变得对从例如犯罪现场的DNA图谱样本中法医鉴定表型变得有用。我们分析了富含多态和表现出群体特有变异的遗传区域。此外，我们还通过序列分析确定了在全球范围内观察到编码多态的基因的单倍型。变性高效液相色谱(DHPLC)方法用于突变检测的原理不同于测序或其他电泳法，因此被引入本项目。我们可以得到一些结果。1)我们发现结合珠蛋白启动子的单倍型是一种信息丰富的遗传标记，因为三个主要群体之间共享的单倍型很少。2)C6基因A293C附近的一些SNP，即C6A和C6B之间的差异，在三个主要人群中连锁在一起。统计检验表明，A293C可能是平衡选择的目标位点。3)在FUT2编码区下游发现了3.8kb的STR基因座，该STR基因座的序列和重复序列的多态性不仅显示了FUT2的编码区，而且是一个很好的遗传标记。4)两个斯里兰卡人(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，我们还将DHPLC方法应用于FUT2基因分型，结果表明该方法是可行的。5)统计分析表明，含有AIM-1(AIMS之一)的欧洲特有SNP 374F的单倍型最近通过定向选择在一些地区传播。

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.