TY - JOUR
T1 - Next-Generation Sequencing of Human Mitochondrial Reference Genomes Uncovers High Heteroplasmy Frequency
AU - Sosa, Maria Ximena
AU - Sivakumar, I. K.Ashok
AU - Maragh, Samantha
AU - Veeramachaneni, Vamsi
AU - Hariharan, Ramesh
AU - Parulekar, Minothi
AU - Fredrikson, Karin M.
AU - Harkins, Timothy T.
AU - Lin, Jeffrey
AU - Feldman, Andrew B.
AU - Tata, Pramila
AU - Ehret, Georg B.
AU - Chakravarti, Aravinda
PY - 2012/10
Y1 - 2012/10
N2 - We describe methods for rapid sequencing of the entire human mitochondrial genome (mtgenome), which involve long-range PCR for specific amplification of the mtgenome, pyrosequencing, quantitative mapping of sequence reads to identify sequence variants and heteroplasmy, as well as de novo sequence assembly. These methods have been used to study 40 publicly available HapMap samples of European (CEU) and African (YRI) ancestry to demonstrate a sequencing error rate <5.63×10-4, nucleotide diversity of 1.6×10-3 for CEU and 3.7×10-3 for YRI, patterns of sequence variation consistent with earlier studies, but a higher rate of heteroplasmy varying between 10% and 50%. These results demonstrate that next-generation sequencing technologies allow interrogation of the mitochondrial genome in greater depth than previously possible which may be of value in biology and medicine.
AB - We describe methods for rapid sequencing of the entire human mitochondrial genome (mtgenome), which involve long-range PCR for specific amplification of the mtgenome, pyrosequencing, quantitative mapping of sequence reads to identify sequence variants and heteroplasmy, as well as de novo sequence assembly. These methods have been used to study 40 publicly available HapMap samples of European (CEU) and African (YRI) ancestry to demonstrate a sequencing error rate <5.63×10-4, nucleotide diversity of 1.6×10-3 for CEU and 3.7×10-3 for YRI, patterns of sequence variation consistent with earlier studies, but a higher rate of heteroplasmy varying between 10% and 50%. These results demonstrate that next-generation sequencing technologies allow interrogation of the mitochondrial genome in greater depth than previously possible which may be of value in biology and medicine.
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U2 - 10.1371/journal.pcbi.1002737
DO - 10.1371/journal.pcbi.1002737
M3 - Article
C2 - 23133345
AN - SCOPUS:84868093500
SN - 1553-734X
VL - 8
JO - PLoS computational biology
JF - PLoS computational biology
IS - 10
M1 - e1002737
ER -