TY - JOUR
T1 - Practicability of mitochondrial heteroplasmy detection through an Illumina genotyping array
AU - Zhang, Pan
AU - Samuels, David C.
AU - Zhao, Shilin
AU - Wang, Jing
AU - Shyr, Yu
AU - Guo, Yan
N1 - Funding Information:
This study was supported by NIH grants P30 CA68485 , R01CA064277 , R01CA118229 . We should also like to thank Stephanie Page Hoskins for editorial support.
Publisher Copyright:
© 2016 Elsevier B.V. and Mitochondria Research Society
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Motivation High-throughput genomic data often contain unexpected information that can be mined for alternative applications. Despite the rise of high-throughput sequencing, Illumina genotyping arrays remain a driving force in large scale genetic and epidemiology studies. By processing and analyzing genotyping data of over 100,000 samples genotyped on Illumina genotyping arrays, we discovered evidence that indicates that mitochondrial heteroplasmy can be estimated from the fluorescence intensity data of the array. To verify our hypothesis, we conducted a sequencing validation study. Result Mitochondrial DNA targeted sequencing was performed on three samples that had been genotyped using the Illumina exome genotyping array. In each sample chosen, one heteroplasmy target was identified from the genotyping array, and sequencing data verified all three putative heteroplasmic sites. The estimated heteroplasmy level difference between that estimated from the genotyping fluorescence intensity and that directly measured from sequencing was 3.2% on average. Our analysis showed that an Illumina genotyping array can accurately and reliably estimate high-level heteroplasmy (> 40%); however, intensity data from a genotyping array is not suitable for estimating low level heteroplasmy (< 25%).
AB - Motivation High-throughput genomic data often contain unexpected information that can be mined for alternative applications. Despite the rise of high-throughput sequencing, Illumina genotyping arrays remain a driving force in large scale genetic and epidemiology studies. By processing and analyzing genotyping data of over 100,000 samples genotyped on Illumina genotyping arrays, we discovered evidence that indicates that mitochondrial heteroplasmy can be estimated from the fluorescence intensity data of the array. To verify our hypothesis, we conducted a sequencing validation study. Result Mitochondrial DNA targeted sequencing was performed on three samples that had been genotyped using the Illumina exome genotyping array. In each sample chosen, one heteroplasmy target was identified from the genotyping array, and sequencing data verified all three putative heteroplasmic sites. The estimated heteroplasmy level difference between that estimated from the genotyping fluorescence intensity and that directly measured from sequencing was 3.2% on average. Our analysis showed that an Illumina genotyping array can accurately and reliably estimate high-level heteroplasmy (> 40%); however, intensity data from a genotyping array is not suitable for estimating low level heteroplasmy (< 25%).
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U2 - 10.1016/j.mito.2016.08.018
DO - 10.1016/j.mito.2016.08.018
M3 - Article
C2 - 27628068
AN - SCOPUS:84994486620
VL - 31
SP - 75
EP - 78
JO - Mitochondrion
JF - Mitochondrion
SN - 1567-7249
ER -