Reiner Jennifer, Karger Lisa, Cohen Ninette, Mehta Lakshmi, Edelmann Lisa, Scott Stuart A
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
J Mol Diagn. 2017 May;19(3):397-403. doi: 10.1016/j.jmoldx.2016.11.006. Epub 2017 Mar 18.
Chromosomal microarray (CMA) testing to detect copy number aberrations among individuals with multiple congenital anomalies and/or developmental delay is typically performed on peripheral blood DNA. However, the use of saliva DNA may be preferred for some patients, which prompted our validation study using six saliva DNA samples with a range of bacterial content (approximately 3% to 21%) and 20 paired blood and saliva specimens on the Agilent Technologies, Illumina, and Affymetrix CMA platforms. Ten of the 20 paired specimens were previously determined to carry clinically significant copy number aberrations by clinical CMA testing on blood DNA (100 kb to 2.56 Mb; five deletions, eight duplications). Notably, the quality of saliva DNA (DNA Genotek) was equivalent to blood DNA regardless of bacterial content, as was CMA quality and single-nucleotide polymorphism genotyping quality with all CMA platforms. The number of copy number variants and absence of heterozygosity regions detected by CMA were comparable between paired blood and saliva DNA and, more important, all 13 clinically significant copy number aberrations were detected in saliva DNA by all CMA platforms. These data confirm that the quality of saliva DNA is comparable to blood DNA regardless of bacterial content, including important CMA and single-nucleotide polymorphism quality metrics, and that saliva DNA is a reliable alternative for the detection of clinically significant copy number aberrations by clinical CMA testing.
用于检测患有多种先天性异常和/或发育迟缓个体的拷贝数畸变的染色体微阵列(CMA)检测通常在外周血DNA上进行。然而,对于一些患者来说,唾液DNA可能更受青睐,这促使我们开展了一项验证研究,使用了6份细菌含量范围在约3%至21%的唾液DNA样本以及20对血液和唾液标本,在安捷伦科技公司、Illumina公司和Affymetrix公司的CMA平台上进行检测。在这20对标本中,有10对之前通过血液DNA的临床CMA检测被确定携带具有临床意义的拷贝数畸变(100 kb至2.56 Mb;5个缺失,8个重复)。值得注意的是,无论细菌含量如何,唾液DNA(DNA Genotek)的质量与血液DNA相当,所有CMA平台的CMA质量和单核苷酸多态性基因分型质量也是如此。CMA检测到的拷贝数变异数量以及杂合性缺失区域在配对的血液和唾液DNA之间具有可比性,更重要的是,所有CMA平台在唾液DNA中都检测到了所有13个具有临床意义的拷贝数畸变。这些数据证实,无论细菌含量如何,唾液DNA的质量与血液DNA相当,包括重要的CMA和单核苷酸多态性质量指标,并且唾液DNA是通过临床CMA检测检测具有临床意义的拷贝数畸变的可靠替代物。