Scientists construct human genome microsatellite polymorphism map

A research team led by Profs. XU Tao and HE Shunmin from the Institute of Biophysics of the Chinese Academy of Sciences has recently constructed a global polymorphism genetic map of variable number tandem repeats (VNTRs), termed the NyuWa VNTR Polymorphism Map.

The team has generated maps using high-depth whole-genome sequencing data from 8,222 genomes across 140 countries and regions, provides comprehensive coverage of major repetitive sequence elements (ME and STR in previous studies, VNTR in this study) in the human genome using the NyuWa genomic resource. It serves as a critical reference for systematically analyzing variations in repetitive sequence elements.

The results of the study were published in Cell Genomics on November 27.

VNTRs, also known as microsatellite DNA, can increase disease risk not only through length expansion but also via variations in their repeat motifs, which exhibit independent pathogenic effects.

However, due to limitations in sample size, sequencing depth, population diversity, and identification algorithms, genetic studies on VNTRs in existing large-scale genomic projects have been insufficient, leaving certain heritability within the human genome unexplained.

In this study, the researchers identified over 2.5 million VNTR length polymorphisms (VNTR-LPs) and 11 million VNTR motif polymorphisms (VNTR-MPs). Among them, about 1/3 were unique to the NyuWa population, with most being rare variants.

The researchers systematically analyzed the functional characteristics of VNTRs, particularly their regulatory roles in gene expression.

“We found that VNTRs can influence gene expression through changes in length or motif dosage,” said Prof. HE.

The researchers also examined the distribution patterns of VNTR polymorphisms across different populations and explored their potential impact on human phenotypic differentiation and disease susceptibility.

This work expands the scope of repetitive sequence element variation in genetic studies and offers new insights into the role of these elements in gene regulation. It also provides an essential resource for future clinical research and genotype-phenotype association studies.