Written by Fazil Hussein: A recent article in Nature describes a draft for human pangenome. In this article, the Human Pangenome Reference Consortium (HPRC) presents a first draft of the human pangenome reference.
The human reference genome has formed the backbone of human genomics since its initial draft release more than 20 years ago. However, the current human reference genome (GRCh38) is incomplete and biased, as it contains many gaps and simulated sequences, and does not capture the genetic diversity of our species.
A recent breakthrough in human genomics was the completion of the first telomere-to-telomere (T2T) sequence of a human chromosome. This sequence provides a continuous representation of each autosome and chromosome X.
However, one genome is not enough to represent the variation among humans. To address this limitation, researchers have proposed to use a pangenome as a reference, which is a collection of genomes that includes all the possible variants in a population. Pangenome methods have advanced rapidly in recent years, enabling more comprehensive and unbiased analyses of human genomic data.
What is the new draft human pangenome?
The Human Pangenome Reference Consortium (HPRC) is a project that aims to better represent the genomic diversity of human populations by sequencing and assembling genomes from individuals of different ancestries. The planned HPRC panel aims to better capture global genomic diversity across 700 haplotypes of 350 individuals.
In their first draft of the human pangenome reference, they report the results of sequencing and assembling 47 diploid genomes from a diverse cohort of individuals, using long-read technologies and improved assembly algorithms. These genomes cover more than 99% of the expected sequence and are more than 99% accurate at both the base pair and structural levels.
They also align these genomes to generate a draft pangenome that captures known and novel variants and haplotypes, especially at complex loci. They add 119 million base pairs of polymorphic sequences and 1,115 gene duplications that are not present in the current reference genome GRCh38. About 90 million of these base pairs are derived from structural variation.
They demonstrate that using their draft pangenome to analyze short-read data reduces small variant discovery errors by 34% and increases the number of structural variants detected per haplotype by 104%, compared to GRCh38-based workflows. Their draft pangenome is a valuable resource for improving the accuracy and completeness of human genomic analyses.
What is next?
The next step is to recruit more participants from different backgrounds to increase the diversity of human genetic data. This will help us understand how genomics works and how we can use it to prevent, diagnose and treat diseases. It will also make sure that the benefits of genomic research and precision medicine are available for everyone.
This project will also set new standards for how to capture and share genetic variation, how to communicate science to diverse audiences, and how to involve different perspectives in this ambitious goal of creating a common global reference resource.
The efforts to get a more complete set of diverse and accurate human reference genomes, with improving and optimizing the pangenome reference, will enable a wide range of applications for both researchers and clinicians.
See also:
Mass Whole Genome Sequencing – Chasing the Dream
One-Hundred-Dollar Genome is Coming
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