title: Practicability of mitochondrial heteroplasmy detection through an Illumina genotyping array.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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%).
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Samuels
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Shilin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: yan.guo@vanderbilt.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
mesh_terms: D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005470:Fluorometry / Q000379:methods*; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D008928:Mitochondria / Q000145:classification / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial