Year: 2022
Type: article
Abstract: Lymphoblastoid cell lines (LCLs) provide an unlimited source of genomic DNA for genetic studies. Here, we compared mtDNA sequence variants, heteroplasmic or homplasmic, between LCL (sequenced by mitoRCA-seq method) and whole blood samples (sequenced through whole genome sequencing approach) of the same 130 participants in the Framingham Heart Study. We applied harmonization of sequence coverages and consistent quality control to mtDNA sequences. We identified 866 variation sites in the 130 LCL samples and 666 sites in the 130 blood samples. More than 94% of the identified homoplasmies were present in both LCL and blood samples while more than 70% of heteroplasmic sites were uniquely present either in LCL or in blood samples. The LCL and whole blood samples carried a similar number of homoplasmic variants (p = 0.45) per sample while the LCL carried a greater number of heteroplasmic variants than whole blood per sample (p < 2.2e-16). Furthermore, the LCL samples tended to accumulate low level heteroplasmies (heteroplasmy level in 3-25%) than their paired blood samples (p = 0.001). These results suggest that cautions should be taken in the interpretation and comparison of findings when different tissues/cell types or different sequencing technologies are applied to obtain mtDNA sequences.
Source: Scientific Reports
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,190
Awards: G1052645489, G1490530680, Analysis of Heteroplasmic mtDNA Mutations in Whole Genome Sequencing: Methods and Application to Cardiometabolic Disease Traits, G2096685756, Rare variants and NHLBI traits in deeply phenotyped cohorts, G232264632, G250621538, Mitochondrial DNA Copy Number and Sequence Variation in Relation to Age, Alzheimer's Disease Related Phenotypes and Age-related Metabolic Traits, G3667269547, Rare variants and NHLBI traits in deeply phenotyped cohorts, G4978228180, Relations of Mitochondrial Genetic Variation and Function with Atrial Fibrillation, G631129105, The Framingham Heart Study, G6615318374, G7321535475, Studies of Rare Genetic Variation in the Isolated Population of Sardinia
OpenAlex ID: W4210722370