tRNA gene copy number variation in humans

Area of Science:

• Genetics
• Molecular Biology
• Genomics

Background:

• The human tRNAome comprises over 500 tRNA genes across 51 anticodon families with varying copy numbers.
• Differences in tRNA gene copy number can influence mRNA translation, affecting translational efficiency, fidelity, and protein folding.

Purpose of the Study:

• To investigate tRNA gene copy number variation (tgCNV) in the human genome.
• To determine the frequency and distribution of tgCNV across diverse ethnic groups.

Main Methods:

• High-coverage whole genome sequencing was employed to analyze tgCNV in six individuals from two kindreds.
• Semiquantitative PCR was used to assess the frequency of a specific tRNALysCUU gene deletion in 98 DNA samples from various ethnicities.

Main Results:

• Several tRNA gene clusters exhibited copy number variation (CNV), some integrated into larger iterations.
• An isolated tRNALysCUU gene deletion was identified, present in either heterozygous or homozygous state in approximately 50% of the studied population across all ethnic groups.
• This represents the first report of copy number variation in human tRNA genes.

Conclusions:

• Significant levels of tRNA gene copy number variation (tgCNV) are present in the human population.
• tgCNV contributes to human genetic diversity.
• The findings align with genome-wide association studies (GWAS) suggesting the role of tRNALys isoacceptor ratios in Type-2 diabetes susceptibility.