Polymorphic analysis of hypervariable mimisatellite related to recombination hot spot

重组热点相关高变微卫星多态性分析

基本信息

批准号：
14570392
负责人：
TAMAKI Keiji
金额：
$ 2.24万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570392/
关键词：
minisatellite MVR-PCR minisatellite mutation forensic application B6.7 CEB1

项目摘要

Human tandem repeats account for about 3% of the human genome and (excluding satellite DNA) are classified into two groups according to the size of the repeat unit and the overall length of the repeat array. Human minisatellites or variable number tandem repeat (VNTR) loci have repeat units from 6 bp to more than 100 bp long depending on the locus, with arrays usually kilobases in length. Human GC-rich minisatellites are preferentially found clustered in the recombination-proficient subtelomeric regions of chromosomes. Some minisatellite loci show very high levels of allele length variability.Most minisatellite loci consist of heterogeneous arrays of two or more subtly different repeat unit types (minisatellite variant repeats). All human hypervariable minisatellites characterized to date vary not only in repeat copy number (allele length) but also in the interspersion pattern of these variant repeat units within the array. This internal variation provides a powerful approach to the st … More udy of allelic variation and processed of mutation. Interspersion patterns can be determined by minisatellite variant repeat (MVR) mapping and reveals far more variability than can be resolved by allele length analysis.We analyse minisatellite B6,7 locus in the Japanese population. Allele size distributions showed that Japanese retain extensive allele length variability but have significantly smaller alleles compared to north Europeans. Ninety-two Japanese alleles were further characterised by MVR-PCR. These alleles showed a wide variety of internal MVR structures with most alleles observed only once in the sample. The true heterozygosity is estimated at 99.95%, with well in express of 2000 different alleles existing in the Japanese population. Dot matrix analysis showed that groups of related alleles sharing structural motifs could be identified within Japanese and in north Europeans, and that these groups are population-specific with no examples of significant similarity between any Japanese and north European alleles. Minisatellite B6.7 therefore shows huge allele variability and fast repeat turnover in Japanese as well as north European populations, and provide novel lineage markers for exploring very recent events in human population history.We also anlaysed the properties of another hypervariable minisatellite CEB1 (D2S90) in the Japanese population. The length heterozygosity is observed at 85.0% and the average length of the alleles is 69 repeats. A new single nucleotide polymorphism (SMP) was found in the flanking the minisatellite. Internal MVR structure was different between alleles and new vase substitutions/deletions were found within repeats, which indicates CEB1 is also one of the most hypervariable minisatellite loci in Japanese. Less

根据重复单元的大小和重复阵列的整体长度，人类串联重复占人类基因组的3％，（不包括卫星DNA）分为两组。人类迷你卫星或可变数字串联重复（VNTR）基因座的重复单元从6 bp到100 bp以上，具体取决于基因座，阵列通常为千倍。最好发现，富含人GC的迷你卫星聚集在染色体的重组式亚近端区域中。一些迷你卫星基因座的等位基因长度可变性非常高。大多数迷你卫星基因座由两种或多个微妙的重复单位类型（微型变种重复序列）组成的异质阵列。所有人类高变化的迷你卫星都不仅在重复拷贝数（等位基因长度）中表征到日期变化，而且还以这些变体重复单元的散布模式在阵列中。这种内部变化为ST提供了一种强大的方法……更加对等位基因变异和突变处理。散布模式可以通过迷你卫星变体重复（MVR）映射来确定，并且揭示了比等位基因长度分析可以解决的多变异。等位基因的大小分布表明，日本人保留了广泛的等位基因长度可变性，但与北欧人相比具有明显小的等位基因。 MVR-PCR进一步表征了92个日本等位基因。这些等位基因显示出多种内部MVR结构，大多数等位基因在样品中仅观察到一次。真正的杂合性估计为99.95％，在日本人口中存在2000个不同等位基因的井中。 DOT矩阵分析表明，可以在日本和北欧人中确定相关等位基因共享结构图案的组，并且这些群体是特定于人群的，没有任何日本和北欧等位基因之间的显着相似之处。因此，在日本和北欧人群中，Minisatellite B6.7显示出巨大的等位基因变异性和快速重复的营业额，并为探索人口历史上最近的事件提供了新颖的谱系标记。我们还赋予了日本人群中另一种高变量的微型钙化物CEB1（D2S90）的特性。长度杂合性观察到85.0％，等位基因的平均长度为69个重复。在微型卫星侧面发现了一种新的单个核苷酸多态性（SMP）。等位基因之间的内部MVR结构有所不同，并且在重复序列中发现了新的花瓶取代/缺失，这表明CEB1也是日语中最高太变量的Minisatellite基因座之一。较少的