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Abstract：
The human tRNAome consists of more than 500 interspersed tRNA genes comprising 51 anticodon families of largely unequal copy number. We examined tRNA gene copy number variation (tgCNV) in six individuals; two kindreds of two parents and a child, using high coverage whole genome sequence data. Such differences may be important because translation of some mRNAs is sensitive to the relative amounts of tRNAs and because tRNA competition determines translational efficiency vs. fidelity and production of native vs. misfolded proteins. We identified several tRNA gene clusters with CNV, which in some cases were part of larger iterations. In addition there was an isolated tRNALysCUU gene that was absent as a homozygous deletion in one of the parents. When assessed by semiquantitative PCR in 98 DNA samples representing a wide variety of ethnicities, this allele was found deleted in hetero- or homozygosity in all groups at ~50% frequency. This is the first report of copy number variation of human tRNA genes. We conclude that tgCNV exists at significant levels among individual humans and discuss the results in terms of genetic diversity and prior genome wide association studies (GWAS) that suggest the importance of the ratio of tRNALys isoacceptors in Type-2 diabetes.
摘要：
人tRNAome由超过500个散布的tRNA基因组成,这些tRNA基因包含51个拷贝数不相等的反密码子家族。我们检查了六个个体的tRNA基因拷贝数变异（tgCNV）；两个父母和一个孩子的两个家族，使用高覆盖率的全基因组序列数据。这种差异可能很重要，因为一些mRNA的翻译对tRNA的相对量敏感，并且因为tRNA竞争决定翻译效率与保真度和原生生产错误折叠的蛋白质。我们鉴定了几个具有CNV的tRNA基因簇，在某些情况下，这是较大迭代的一部分。此外,存在分离的tRNAlysCUU基因,其在亲本之一中作为纯合缺失而不存在。当通过半定量PCR对98个代表不同种族的DNA样本进行评估时，发现该等位基因在所有组中以杂合子或纯合子缺失，频率约为50％。这是人类tRNA基因拷贝数变异的首次报道。我们得出的结论是，tgCNV在人类个体中存在显着水平，并讨论了遗传多样性和先前的全基因组关联研究（GWAS）方面的结果，这些结果表明tRNALys等受体比例在2型糖尿病中的重要性。
