3.2 Generation and feature of NeoEXOME panel
OMIM database was used to standardize and screen out the diseases and
related genes. To design the NBS
NGS panel covering monogenic diseases that are severe, actionable, and
early onset for the Chinese population, we combined the following
categorization of diseases in our study: 1) 248 related genes (249
diseases) that were included in China National Catalog of Rare Diseases.
This catalog includes diseases with low incidence, high risk, and strong
treatability based on the clinical data; 2) 360 genes (312 diseases)
that were included in Preventable and Treatable Rare Diseases in China;
3) 79 genes (71 diseases) that were now in the conventional MS/MS NBS
project in China; 4) 71 genes (71 diseases) that were included in the
conventional NBS in China; 5) 149 genes (148 diseases) that were
recommended by ACMG; 6) 55 genes (57 diseases) that were recommended by
the experts of the Chinese NBS Laboratory Committee. Moreover, a list of
diseases with high prevalence in the Chinese population based on the
database about positive mono-genetic diseases in 40000 ill newborns by
MyGenostics was also included. This list included 141 diseases and 94
related genes. Then Venny analysis was conducted to identify and
generate the disease-genes panel (named NeoEXOME) in our study (Fig 1A).
Our NeoEXOME panel is comprised of 601 genes and 542 kinds of diseases
(Supplementary Table1).
The panel covered diseases with multi-systems, including skeletal,
respiratory, urinary, immune system, nervous system, cardiovascular
system, blood, endocrine system, metabolism, and mitochondria-related
diseases (Fig 1B). Among them, diseases of the metabolic system account
for the most proportion in our NeoEXOME panel. Besides, the onset age of
these gene-related diseases was also collected and shown in Fig 1C. 418
out of 601 gene-diseases were
onset in the neonatal period (<1 year), accounting for the
largest proportion. 577 out of 601 (96%) gene-diseases were onset in
childhood (<18 years).
3.3 Performance of NeoEXOME
Results of
“ 1000
Genomes”
Firstly, we validated our panel using the data of unrelated 301 Chinese
in the “1000 Genomes Project”.
According to the interpretation criteria, 72 were negative, 223 were
carrier, and 23 were positive (7.6%). Variants of FLG andGJB2 account for the most frequent mutant genes, with the
frequency 47.8% (11/23) and 21.7% (5/23), respectively (Supplementary
Table 2).