Abdulkina, L.R.; Agabekian, I.A.; Valeeva, L.R.; Kozlova, O.S.; Sharipova, M.R.; Shakirov, E.V. Comparative Application of Terminal Restriction Fragment Analysis Tools to Large-Scale Genomic Assays. Int. J. Mol. Sci.2023, 24, 17194.
Abdulkina, L.R.; Agabekian, I.A.; Valeeva, L.R.; Kozlova, O.S.; Sharipova, M.R.; Shakirov, E.V. Comparative Application of Terminal Restriction Fragment Analysis Tools to Large-Scale Genomic Assays. Int. J. Mol. Sci. 2023, 24, 17194.
Abdulkina, L.R.; Agabekian, I.A.; Valeeva, L.R.; Kozlova, O.S.; Sharipova, M.R.; Shakirov, E.V. Comparative Application of Terminal Restriction Fragment Analysis Tools to Large-Scale Genomic Assays. Int. J. Mol. Sci.2023, 24, 17194.
Abdulkina, L.R.; Agabekian, I.A.; Valeeva, L.R.; Kozlova, O.S.; Sharipova, M.R.; Shakirov, E.V. Comparative Application of Terminal Restriction Fragment Analysis Tools to Large-Scale Genomic Assays. Int. J. Mol. Sci. 2023, 24, 17194.
Abstract
Analysis of telomere length is an important component of many studies aiming to characterize the role of telomere maintenance mechanisms in cellular lifespan, disease, or in general chromosome protection and DNA replication pathways. Several powerful methods to accurately measure telomere length from Southern blots have been developed, but their utility for large-scale genomic studies has not been previously evaluated. Here we performed comparative analysis of two recently developed programs, TeloTool and WALTER, for extracting mean telomere length values from Southern blots. Using both software packages, we measured telomere length in two extensive experimental datasets for the model plant Arabidopsis thaliana, consisting of 537 natural accessions and 65 T-DNA mutant lines in the Col-0 reference background. We report that TeloTool substantially overestimates telomere length in comparison to WALTER, especially for values over 4,500 bp. Importantly, TeloTool and WALTER-calculated telomere length values correlate the most in the 2,100-3,500 bp range, suggesting that telomeres in this size interval can be estimated by both programs equally well. We further show that genome-wide association studies using datasets from both telomere length analysis tools can detect the most significant SNP candidates equally well. However, GWAS analysis with the WALTER dataset consistently detects fewer significant SNPs than analysis with the TeloTool dataset, regardless of the GWAS method used. These results imply that telomere length data generated by WALTER may represent a more stringent approach to GWAS and SNP selection for downstream molecular screening of candidate genes. Overall, our work revealed the unanticipated impact of telomere length analysis method on the outcomes of large-scale genomic screens.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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