Scientists release human “pangenome” reference

The first human genome sequence, generated by the Human Genome Project 20 years ago, has served as a reference for researchers to use in their genomics studies. This first human genome reference sequence did not represent a single person; rather, it was assembled with genomic data from about 20 people to be a general-purpose tool, against which scientists could compare other human genome sequences.

Over the years, researchers have regularly improved that reference sequence, fixing errors and adding missing pieces. Recently, new genome sequencing technologies, particularly long-read DNA sequencing methods, have made it possible to read longer stretches of DNA at once. These technologies allowed researchers from the NIH-funded Telomere-to-Telomere (T2T) Consortium to fill in the missing gaps and create the first complete human genome sequence in March of last year. While the original human genome reference sequence has been regularly improved, it still consisted of genomes from only around 20 people, which does not adequately represent the diversity of our species.

On average, any two individuals’ genomes are more than 99% identical, but that still leaves millions of differences. A more inclusive human genome reference sequence will allow researchers and clinicians to identify and understand the small genomic differences that make each person unique, providing genomic insights that could be relevant for health and disease management.

Last month, the NHGRI-funded Human Pangenome Reference Consortium released a high-quality collection of human genome reference sequences, which together comprise a human “pangenome” reference. Encompassing genome sequences from 47 people of diverse ancestries, the human pangenome reference captures significantly more population diversity than the previous reference sequence. Specifically, a set of individuals previously studied in the 1,000 Genomes Project had their genomes sequenced with very high accuracy.

The current human pangenome reference consists of genome sequences from 47 people of different ancestral backgrounds, including people from Africa, Asia, the Americas, and Europe. Scientists in the consortium aim to increase the number of represented genomes to 350 by mid-2024, when the project is expected to be completed. The new human pangenome reference adds 119 million bases to the existing human genome reference sequence. This will allow researchers to identify new genomic variants that were not previously detectable and will better represent human diversity

The main human pangenome reference paper is one of several papers published in Nature that report findings generated with the new human pangenome reference. This included developing a map of single-nucleotide variants within segmental duplications and observing patterns of recombination between different parts of chromosomes. 

As a truly collaborative effort, the Human Pangenome Reference Consortium consists of researchers from various institutions around the world working to create a more complete and sophisticated collection of reference genome sequences. As the construction of a human pangenome reference is still ongoing, researchers from the consortium are working hard to add more genome sequences and improve its quality and diversity. 

Importantly, the Human Pangenome Reference Consortium has an embedded ethical, legal, and social implications (ELSI) research group to guide informed consent, sample prioritization, regulatory policies, and collaborations with international and Indigenous communities. This group ensures that the collection and use of the genomic data are ethical and that communities around the world are engaged with the research process.

Generating the human pangenome reference is part of NHGRI’s ongoing effort to account for global diversity in genomics research, which is important for advancing and implementing genomic medicine in an equitable way.

Read the main paper here and the NHGRI press release here. Find more resources about the human pangenome reference, including videos, multimedia, and news coverage, on the genome.gov website.

NHGRI and its partners will host Healthcare Professionals’ Genomics Education Week on June 5-9 this year. With genomics becoming an increasingly important part of patient care, this social media campaign will promote available healthcare professionals’ genomics education resources and opportunities. The week will feature panel discussions, webinars, Q&As, and the launch of three new resources supported by the Inter-Society Coordinating Committee for Practitioner Education in Genomics: the Pharmacogenomics Learning Series, the Nursing Genomics FAQ and Expert Commentaries, and the G3C Module “Autism Spectrum Disorder and Vaccines.” Each day will feature a different theme, such as direct-to-consumer genetic testing, pharmacogenomics, careers in genomics, cancer genomics/obstetrics and gynecology, and rare diseases/inclusive genetics. The full schedule of events can be found on genome.gov. Follow the events on Twitter using #MedGeneEd23.

Last month, NHGRI released a progress report on the institute’s 2021 action agenda, Building A Diverse Genomics Workforce: An NHGRI Action Agenda. Broadly, the goals of the action agenda are to generate programs for recruiting and supporting members of underrepresented groups in the genomics workforce and to develop methods for evaluating progress. In the two years since the release of the action agenda, NHGRI has launched several programs aimed at enhancing diversity in the genomics workforce. These include collaborations with minority-serving institutions; funding for the comprehensive Human Genetics and Genomics Workforce Survey; and creation of the Training, Diversity and Health Equity (TiDHE) Office, which will continue developing new initiatives and offering sustained support for the action agenda.

As part of its commitment to training a more diverse genomics workforce, NHGRI has created the Future Leaders Advancing Genomic Sciences in Health Innovation Postdoctoral Program (FLAGSHIP). FLAGSHIP aims to train a cadre of early career postdoctoral scientists to become tomorrow’s leaders in genomic sciences and help build a genomics workforce that better represents the diversity of the US population. Ideal candidates will be on a career trajectory to independent research, will want to build diverse research groups, and will aim to apply advanced genetics and genomics approaches to benefit people of all ancestries. NHGRI encourages individuals from racial and ethnic groups who have been underrepresented in biomedical research, individuals with disabilities, and individuals from disadvantaged backgrounds to apply. The deadline to apply is June 15, 2023.

The NIH Common Fund has launched the Somatic Mosaicism across Human Tissues (SMaHT) Network, which seeks to discover the influence of somatic mosaicism — a poorly understood form of genomic variation — on human biology and disease. The SMaHT Network will develop state-of-the-art technologies to catalog the extent of somatic genomic mosaicism in different cell types and tissues as well as across human life stages. By cataloging somatic mosaicism in human tissues, the SMaHT Network will provide foundational knowledge that will enable research on the role that somatic genomic variation plays in human development, aging, and a wide range of diseases and disorders. NIH is providing $150 million in funds over five years to establish the SMaHT Network through grant awards for a Tissue Procurement Center, five Genome Characterization Centers, a Data Analysis Center, 14 Tool Development Projects, and an Organizational Center.

Arang Rhie, Adam Phillippy, and Sergey Koren of NHGRI's intramural Genome Informatics Section in the Computational and Statistical Genomics Branch are finalists in the Science, Technology, and Environment category of the Samuel J. Heyman Service to America Medals, also known as the “Sammies.” Each year, the Sammies honor the remarkable and inspiring accomplishments of federal employees. This group was nominated for their work in the Telomere-to-Telomere (T2T) Consortium, which successfully generated the first complete assembly of a human genome sequence. These researchers filled in the final gaps, which were the most difficult parts of our genetic makeup to assemble, shedding new light on our biological blueprint and opening up scientific frontiers that could advance the study of human disease.