In addition to the differences between populations in transcriptional and translational regulation of genes, alternative pre-mRNA splicing (AS) is also likely to play an important role in regulating gene expression and generating variation in mRNA and protein isoforms. Recently, the genetic contribution to transcript isoform variation has been reported in individuals of recent European descent. We report here results of an investigation of the differences in AS patterns between human populations. AS patterns in 176 HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry were evaluated using the Affymetrix GeneChip® Human Exon 1.0 ST Array. A variety of biological processes such as response to stimulus and transcription were found to be enriched among the differentially spliced genes. The differentially spliced genes also include some involved in human diseases that have different prevalence or susceptibility between populations. The genetic contribution to the population differences in transcript isoform variation was then evaluated by a genome-wide association using the HapMap genotypic data on single nucleotide polymorphisms (SNPs). The results suggest that local and distant genetic variants account for a substantial fraction of the observed transcript isoform variation between human populations. Our findings provide new insights into the complexity of the human genome as well as the health disparities between the two populations.
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机译：除了在基因的转录和翻译调控中不同群体之间的差异外，替代性的前mRNA剪接（AS）也可能在调节基因表达以及产生mRNA和蛋白质同工型的变异中起重要作用。最近，在最近欧洲血统的个体中已经报道了遗传对转录亚型变异的贡献。我们在这里报告了人口之间AS模式差异的调查结果。使用AffymetrixGeneChip®Human Exon 1.0 ST Array评估了源自欧洲和非洲血统的176个HapMap淋巴母细胞细胞系中的AS模式。发现各种生物学过程，例如对刺激和转录的反应，在差异剪接的基因中得到了丰富。差异剪接基因还包括一些与人类疾病有关的基因，其在人群之间具有不同的流行或易感性。然后，使用单核苷酸多态性（SNP）上的HapMap基因型数据，通过全基因组关联评估对转录本同工型变异中的群体差异的遗传贡献。结果表明，局部和远距离的遗传变异占人口之间观察到的转录异构体变异的很大一部分。我们的发现为人类基因组的复杂性以及两个人群之间的健康差异提供了新的见解。
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