当前位置： SCI文献检索 > BMC Medical Genomics期刊下所有文献 > Clinical utility of the low-density Infinium QC genotyping Array in a genomics-based diagnostics laboratory.

Clinical utility of the low-density Infinium QC genotyping Array in a genomics-based diagnostics laboratory.

Abstract：

BACKGROUND:With 15,949 markers, the low-density Infinium QC Array-24 BeadChip enables linkage analysis, HLA haplotyping, fingerprinting, ethnicity determination, mitochondrial genome variations, blood groups and pharmacogenomics. It represents an attractive independent QC option for NGS-based diagnostic laboratories, and provides cost-efficient means for determining gender, ethnic ancestry, and sample kinships, that are important for data interpretation of NGS-based genetic tests. METHODS:We evaluated accuracy and reproducibility of Infinium QC genotyping calls by comparing them with genotyping data of the same samples from other genotyping platforms, whole genome/exome sequencing. Accuracy and robustness of determining gender, provenance, and kinships were assessed. RESULTS:Concordance of genotype calls between Infinium QC and other platforms was above 99%. Here we show that the chip's ancestry informative markers are sufficient for ethnicity determination at continental and sometimes subcontinental levels, with assignment accuracy varying with the coverage for a particular region and ethnic groups. Mean accuracies of provenance prediction at a regional level were varied from 81% for Asia, to 89% for Americas, 86% for Africa, 97% for Oceania, 98% for Europe, and 100% for India. Mean accuracy of ethnicity assignment predictions was 63%. Pairwise concordances of AFR samples with the samples from any other super populations were the lowest (0.39-0.43), while the concordances within the same population were relatively high (0.55-0.61). For all populations except African, cross-population comparisons were similar in their concordance ranges to the range of within-population concordances (0.54-0.57). Gender determination was correct in all tested cases. CONCLUSIONS:Our results indicate that the Infinium QC Array-24 chip is suitable for cost-efficient, independent QC assaying in the settings of an NGS-based molecular diagnostic laboratory; hence, we recommend its integration into the standard laboratory workflow. Low-density chips can provide sample-specific measures for variant call accuracy, prevent sample mix-ups, validate self-reported ethnicities, and detect consanguineous cases. Integration of low-density chips into QC procedures aids proper interpretation of candidate sequence variants. To enhance utility of this low-density chip, we recommend expansion of ADME and mitochondrial markers. Inexpensive Infinium-like low-density human chips have a potential to become a "Swiss army knife" among genotyping assays suitable for many applications requiring high-throughput assays.

journal_name

BMC Med Genomics

journal_title

BMC medical genomics

authors

Ponomarenko P,Ryutov A,Maglinte DT,Baranova A,Tatarinova TV,Gai X

doi

10.1186/s12920-017-0297-7

subject

Has Abstract

pub_date

2017-10-06 00:00:00

pages

issue

issn

1755-8794

pii

10.1186/s12920-017-0297-7

journal_volume

pub_type

杂志文章

在线工具

Clinical utility of the low-density Infinium QC genotyping Array in a genomics-based diagnostics laboratory.