title: tRNA gene copy number variation in humans.
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.
authors.affiliation: Intramural Research Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Iben
authors.affiliation: Intramural Research Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: maraiar@mail.nih.gov.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Maraia
mesh_terms: D000483:Alleles; D000926:Anticodon / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D014176:Protein Biosynthesis / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics*
chemical_list: D000926:Anticodon; D012343:RNA, Transfer
keywords: Anti-codon; CNV; Chr; Codon; GWAS; Genome-wide; Next-generation; PCR; Sequencing; T2D; Translation; base pair(s); bp; chromosome; copy number variation; genome wide association studies; polymerase chain reaction; tRNA; tRNA gene copy number variation; tgCNV; transfer RNA; type-2 diabetes