A Comparison Study of Whole Genome Sequencing (WGS) in Clinical Setting

Posted by beauty33 on November 16th, 2018

Background

In recent years, with the further development of high-throughput sequencing technology, the cost of sequencing has continued to decrease, and whole-exome sequencing (WES) has been increasingly applied to genetic disease detection, which has improved the diagnosis rate of diseases. However, it comes with the question: does the widely used whole-genome sequencing (WGS) currently suitable for clinical application?

The study

On March 22nd, Genet Med. published an article online (PMID: 29565419) entitled Whole-genome sequencing offers additional but limited clinical utility compared with reanalysis of whole-exome sequencing.

There have been few previous comparisons of WGS and WES for the detection rate of genetic diseases. After screening, a total of 108 patients were enrolled in the WGS analysis. Their gene chip and WES test both showed negative results and their clinical data and previous sequencing raw data were preserved intact. After WGS test, the results showed that 10 cases (9%) of positive results, 5 cases were uncertain, and 93 cases were negative.

The authors analyzed the reasons for the positive results of 10 cases of WGS, including three aspects:

(1) The academic background of WES and WGS: Although WES also detected mutation site on the 1st, 2cd, and 3rd case, it was not reported as the pathogenic site, mainly because at the time of detection, the correlation between pathogenic gene and clinical phenotype has not been determined yet;

(2) The influence of structural variation and non-coding region variation: such as the 4th, 5th, and 6th case;

(3) Impact of sequencing platform: The 7th, 8th, 9th and 10th case belongs to this situation. The mutation sites were detected by WES on the Illumina platform.

In summary, among the 10 cases with negative WES previously, 7 cases were detected by WES reanalysis and WGS, and 3 cases were detected by WGS for structural variation and non-coding region variation.