Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
Nucleic Acids Res. 2010 Jul;38(12):4027-39. doi: 10.1093/nar/gkq127. Epub 2010 Mar 9.
Trinucleotide repeats (TNRs) are of interest in genetics because they are used as markers for tracing genotype-phenotype relations and because they are directly involved in numerous human genetic diseases. In this study, we searched the human genome reference sequence and annotated exons (exome) for the presence of uninterrupted triplet repeat tracts composed of six or more repeated units. A list of 32 448 TNRs and 878 TNR-containing genes was generated and is provided herein. We found that some triplet repeats, specifically CNG, are overrepresented, while CTT, ATC, AAC and AAT are underrepresented in exons. This observation suggests that the occurrence of TNRs in exons is not random, but undergoes positive or negative selective pressure. Additionally, TNR types strongly determine their localization in mRNA sections (ORF, UTRs). Most genes containing exon-overrepresented TNRs are associated with gene ontology-defined functions. Surprisingly, many groups of genes that contain TNR types coding for different homo-amino acid tracts associate with the same transcription-related GO categories. We propose that TNRs have potential to be functional genetic elements and that their variation may be involved in the regulation of many common phenotypes; as such, TNR polymorphisms should be considered a priority in association studies.
三核苷酸重复（TNR）在遗传学中很有研究价值，因为它们可用作追踪基因型-表型关系的标记，并且直接涉及许多人类遗传疾病。在这项研究中，我们搜索了人类基因组参考序列和注释的外显子（外显子组），以寻找由六个或更多重复单元组成的不间断三核苷酸重复片段。生成并在此提供了 32448 个 TNR 和 878 个包含 TNR 的基因列表。我们发现，一些三核苷酸重复，特别是 CNG，过度表达，而 CTT、ATC、AAC 和 AAT 在外显子中表达不足。这一观察表明，外显子中 TNR 的发生不是随机的，而是受到正或负的选择压力。此外，TNR 类型强烈决定它们在 mRNA 节段（ORF、UTR）中的定位。大多数包含外显子中过度表达 TNR 的基因与基因本体定义的功能相关。令人惊讶的是，许多包含编码不同同源氨基酸片段的 TNR 类型的基因组与相同的转录相关 GO 类别相关。我们提出 TNR 具有成为功能遗传元件的潜力，它们的变异可能参与许多常见表型的调控；因此，TNR 多态性应在关联研究中被视为优先考虑的因素。
