The distribution pattern of genetic variation in the transcript isoforms of the alternatively spliced protein-coding genes in the human genome
The distribution pattern of genetic variation in the transcript isoforms of the alternatively spliced protein-coding genes in the human genome
复制标题
人类基因组中可变剪接蛋白质编码基因转录亚型遗传变异的分布模式
DOI：
10.1039/c5mb00132c
复制
发表时间：
2015-01-01
影响因子：
--
通讯作者：
Lin, Kui
中科院分区：
文献类型：
--
作者：
Liu, Ting;Lin, Kui
选择性剪接机制通过使来自同一基因位点的多种异构体能够转录，极大地扩展了人类转录组和蛋白质组的多样性。目前，来自人类基因组中每个蛋白质编码基因位点的可变剪接转录物可以被分类为主要或非主要同种型，只要它们在跨物种保护或生物学特征方面不同。通过将来自1000个基因组计划的变体映射到每种亚型的编码区，在全基因组规模上揭示了这两种类型转录本亚型编码区的遗传变异分布的有趣模式：与主要同种型特异性编码区相比，非主要同种型特异性编码区显著富集氨基酸改变变体，特别是那些对蛋白质功能具有强烈影响并具有较高衍生等位基因频率的等位基因，这表明非主要同种型特异性取代不太可能与表型变化或疾病相关。本文的结果可以帮助我们更好地了解从人口的角度来看，选择性剪接产物的潜在后果。
By enabling the transcription of multiple isoforms from the same gene locus, alternative-splicing mechanisms greatly expand the diversity of the human transcriptome and proteome. Currently, the alternatively spliced transcripts from each protein-coding gene locus in the human genome can be classified as either principal or non-principal isoforms, providing that they differ with respect to cross-species conservation or biological features. By mapping the variants from the 1000 Genomes Project onto the coding region of each isoform, an interesting pattern of the genetic variation distributions of the coding regions for these two types of transcript isoforms was revealed on a whole-genome scale: compared with the principal isoform-specific coding regions, the non-principal isoform-specific coding regions are significantly enriched in amino acid-changing variants, particularly those that have a strong impact on protein function and have higher derived allele frequencies, suggesting that non-principal isoform-specific substitutions are less likely to be related to phenotype changes or disease. The results herein can help us better understand the potential consequences of alternatively spliced products from a population perspective.