Most variations in the human genome refer to single-nucleotide variation (SNV), small fragment insertions and deletions, and genomic copy number variation (CNV). Many human diseases including genetic disorders are associated with variations in the genome. These disorders are often difficult to be diagnosed because of their complex clinical conditions, therefore, an effective detection method is needed to facilitate clinical diagnosis and prevent birth defects. With the development of high-throughput sequencing technology, the method of targeted sequence capture chip has been extensively used owing to its high throughput, high accuracy, fast speed, and low cost. In this study, we designed a chip that potentially captured the coding region of 3043 genes associated with 4013 monogenic diseases, with an addition of 148 chromosomal abnormalities that can be identified by targeting specific regions. To assess the efficiency, a strategy of combining the BGISEQ500 sequencing platform with the designed chip was utilized to screen variants in 63 patients. Eventually, 67 disease-associated variants were found, 31 of which were novel. The results of the evaluation test also show that this combined strategy complies with the requirements of clinical testing and has proper clinical application value.

Genetic testing: One-step targeted sequencing helps diagnose genetic disordersA new DNA screening method potentially offers a one-step solution to the challenge of diagnosing genetic diseases. A team from China led by Xiaoming Wei from BGI Genomics in Shenzhen and Yang Wan from the Fuyang People's Hospital has designed a DNA chip that captures the coding regions of 4,013 disease-causing genes plus another 148 common chromosomal abnormalities. The targeted next-generation sequencing strategy can detect a variety of genomic alterations including single-letter mutations as well as chromosomal abnormalities including insertions, deletions and duplications of larger pieces of DNA. The researchers ran the test on blood samples from 63 patients with genetic disorders. In 52 of these individuals, they found a total of 67 different disease-related variants, including 31 novel variants, demonstrating the clinical utility of the approach.