Cheek swabs, SNP chips, and CNVs: Assessing the quality of copy number variant calls generated with subject-collected mail-in buccal brush DNA samples on a high-density genotyping microarray
Published Date:Jun 26 2012
Source:BMC Med Genet. 2012; 13:51.
Analytic Sample Preparation Methods
CNVs, Copy Number Variants
DNA Copy Number Variations
Genome-Wide Association Study
NBDPS, National Birth Defects Prevention Study
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
SNPs, Single Nucleotide Polymorphisms
Pubmed Central ID:PMC3506514
Funding:3-U50DD613236-10W1/DD/NCBDD CDC HHS/United States
5-R01-HD039054-08/HD/NICHD NIH HHS/United States
Multiple investigators have established the feasibility of using buccal brush samples to genotype single nucleotide polymorphisms (SNPs) with high-density genome-wide microarrays, but there is currently no consensus on the accuracy of copy number variants (CNVs) inferred from these data. Regardless of the source of DNA, it is more difficult to detect CNVs than to genotype SNPs using these microarrays, and it therefore remains an open question whether buccal brush samples provide enough high-quality DNA for this purpose.
To demonstrate the quality of CNV calls generated from DNA extracted from buccal samples, compared to calls generated from blood samples, we evaluated the concordance of calls from individuals who provided both sample types. The Illumina Human660W-Quad BeadChip was used to determine SNPs and CNVs of 39 Arkansas participants in the National Birth Defects Prevention Study (NBDPS), including 16 mother-infant dyads, who provided both whole blood and buccal brush DNA samples.
We observed a 99.9% concordance rate of SNP calls in the 39 blood–buccal pairs. From the same dataset, we performed a similar analysis of CNVs. Each of the 78 samples was independently segmented into regions of like copy number using the Optimal Segmentation algorithm of Golden Helix SNP & Variation Suite 7.
We observed performance from the subject-collected mail-in buccal brush samples comparable to that of blood. These results show that such DNA samples can be used for genome-wide scans of both SNPs and CNVs, and that high rates of CNV concordance were achieved whether using a change-point-based algorithm or one based on a hidden Markov model (HMM).
image/gif image/jpeg image/gif image/jpeg application/vnd.openxmlformats-officedocument.spreadsheetml.sheet text/plain text/plain
You May Also Like: