TY - JOUR
T1 - High-Resolution Genomic Analysis of Human Mitochondrial RNA Sequence Variation
AU - Hodgkinson, Alan
AU - Idaghdour, Youssef
AU - Gbeha, Elias
AU - Grenier, Jean-Christophe
AU - Hip-Ki, Elodie
AU - Bruat, Vanessa
AU - Goulet, Jean-Philippe
AU - de Malliard, T.
AU - Awadalla, Philip
PY - 2014/4/25
Y1 - 2014/4/25
N2 - Mutations in the mitochondrial genome are associated with multiple diseases and biological processes; however, little is known about the extent of sequence variation in the mitochondrial transcriptome. By ultra-deeply sequencing mitochondrial RNA (>6000×) from the whole blood of ~1000 individuals from the CARTaGENE project, we identified remarkable levels of sequence variation within and across individuals, as well as sites that show consistent patterns of posttranscriptional modification. Using a genome-wide association study, we find that posttranscriptional modification of functionally important sites in mitochondrial transfer RNAs (tRNAs) is under strong genetic control, largely driven by a missense mutation in MRPP3 that explains ~22% of the variance. These results reveal a major nuclear genetic determinant of posttranscriptional modification in mitochondria and suggest that tRNA posttranscriptional modification may affect cellular energy production.
AB - Mutations in the mitochondrial genome are associated with multiple diseases and biological processes; however, little is known about the extent of sequence variation in the mitochondrial transcriptome. By ultra-deeply sequencing mitochondrial RNA (>6000×) from the whole blood of ~1000 individuals from the CARTaGENE project, we identified remarkable levels of sequence variation within and across individuals, as well as sites that show consistent patterns of posttranscriptional modification. Using a genome-wide association study, we find that posttranscriptional modification of functionally important sites in mitochondrial transfer RNAs (tRNAs) is under strong genetic control, largely driven by a missense mutation in MRPP3 that explains ~22% of the variance. These results reveal a major nuclear genetic determinant of posttranscriptional modification in mitochondria and suggest that tRNA posttranscriptional modification may affect cellular energy production.
U2 - 10.1126/science.1251110
DO - 10.1126/science.1251110
M3 - Article
SN - 0036-8075
VL - 344
SP - 413
EP - 415
JO - Science
JF - Science
IS - 6182
ER -