A pangenome reference of 36 Chinese populations

Area of Science:

• Genomics
• Population Genetics
• Bioinformatics

Background:

• The current human reference genome (GRCh38) lacks representation from diverse global populations, particularly those of Asian ancestry.
• A shift towards a pangenome approach is crucial for a more comprehensive understanding of human genetic variation.

Purpose of the Study:

• To address the underrepresentation of Asian populations in genomics by creating high-quality pangenome assemblies.
• To identify novel genetic variants and sequences missing from current references.

Main Methods:

• Generated 116 high-quality, haplotype-phased de novo genome assemblies from 58 core samples across 36 minority Chinese ethnic groups.
• Utilized high-fidelity long-read sequencing with an average coverage of 30.65×.
• Analyzed assemblies for small and structural variants compared to existing references.

Main Results:

• Added 189 million base pairs of euchromatic polymorphic sequences and 1,367 protein-coding gene duplications to GRCh38.
• Identified 15.9 million small variants and 78,072 structural variants, with millions novel compared to a recent pangenome reference.
• Discovered enriched archaic-derived alleles and functionally important genes in missing sequences.

Conclusions:

• The Chinese Pangenome Consortium data significantly improve genomic representation for underrepresented populations.
• The findings offer insights into human evolution, adaptation, and the genetic basis of complex diseases.
• This work highlights the importance of diverse data in advancing genomic medicine.