Populational pan-ethnic screening panel enabled by deep whole genome sequencing

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Linfeng Yang
  • Zhe Lin
  • Yong Gao
  • Jianguo Zhang
  • Huanhuan Peng
  • Yaqing Li
  • Jingang Che
  • Lijian Zhao

Detail(s)

Original languageEnglish
Article number38
Journal / Publicationnpj Genomic Medicine
Volume8
Online published20 Nov 2023
Publication statusPublished - 2023

Link(s)

Abstract

Birth defect is a global threat to the public health systems. Mitigating neonatal anomalies is hampered by elusive molecular mechanisms of pathogenic mutations and poor subsequent translation into preventative measures. Applying appropriate strategies in China to promote reproductive health is particularly challenging, as the Chinese population compromises complex genomic diversity due to the inclusion of many ethnic groups with distinct genetic backgrounds. To investigate and evaluate the feasibility of implementing a pan-ethnic screening strategy, and guide future reproductive counselling, high-quality variants associated with autosome recessive (AR) diseases derived from the largest publicly available cohort of the Chinese population were re-analysed using a bottom-up approach. The analyses of gene carrier rates (GCRs) across distinct ethnic groups revealed that substantial heterogeneity existed potentially due to diverse evolutionary selection. The sampling population, sequencing coverage and underlying population structure contributed to the differential variants observed between ChinaMAP and the East Asian group in gnomAD. Beyond characteristics of GCR, potential druggable targets were additionally explored according to genomic features and functional roles of investigated genes, demonstrating that phase separation could be a therapeutic target for autosomal recessive diseases. A further examination of estimated GCR across ethnic groups indicated that most genes shared by at least two populations could be utilised to direct the design of a pan-ethnic screening application once sequencing and interpreting costs become negligible. To this end, a list of autosomal recessive disease genes is proposed based on the prioritised rank of GCR to formulate a tiered screening strategy. © 2023, The Author(s).

Research Area(s)

Citation Format(s)

Populational pan-ethnic screening panel enabled by deep whole genome sequencing. / Yang, Linfeng; Lin, Zhe; Gao, Yong et al.
In: npj Genomic Medicine, Vol. 8, 38, 2023.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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