Lanzamiento de la Nueva Referencia del Pangenoma Humano

Abstract Human Genome Genetics Concept

Concepto de genética del genoma humano abstracto

El Consorcio de Referencia del Pangenoma Humano ha introducido una secuencia del genoma humano de referencia significativamente más diversa, el «pangenoma», compuesto por 94 secuencias genómicas distintas y con el objetivo de llegar a 700 para 2024, lo que ayuda a identificar variantes genómicas más grandes y mejorar la precisión del análisis genómico.

Una colección más completa y sofisticada de secuencias genómicas captura significativamente más diversidad humana.

Los investigadores han lanzado una nueva colección de alta calidad de secuencias del genoma humano de referencia que captura una diversidad sustancialmente mayor de diferentes poblaciones humanas que la que estaba disponible anteriormente. El trabajo fue dirigido por el Consorcio Internacional de Referencia del Pangenoma Humano, un grupo financiado por el Instituto Nacional de Investigación del Genoma Humano (NHGRI), parte del

Institutos Nacionales de Salud
Los Institutos Nacionales de Salud (NIH) es la principal agencia del gobierno de los Estados Unidos responsable de la investigación biomédica y de salud pública. Fundado en 1887, es parte del Departamento de Salud y Servicios Humanos de los Estados Unidos. El NIH lleva a cabo su propia investigación científica a través de su Programa de Investigación Intramural (IRP) y proporciona importantes fondos de investigación biomédica a instalaciones de investigación ajenas a los NIH a través de su Programa de Investigación Extramural. Con 27 institutos y centros diferentes bajo su paraguas, los NIH cubren un amplio espectro de investigaciones relacionadas con la salud, incluidas enfermedades específicas, salud de la población, investigación clínica y procesos biológicos fundamentales. Su misión es buscar el conocimiento fundamental sobre la naturaleza y el comportamiento de los sistemas vivos y la aplicación de ese conocimiento para mejorar la salud, prolongar la vida y reducir la enfermedad y la discapacidad.

» datos-gt-translate-atributos=»[{» attribute=»»>National Institutes of Health. 

The new “pangenome” reference includes genome sequences of 47 people, with the researchers pursuing the goal of increasing that number to 350 by mid-2024. With each person carrying a paired set of chromosomes, the current reference actually includes 94 distinct genome sequences, with a goal of reaching 700 distinct genome sequences by the completion of the project.

The work, published in the journal Nature, is one of several papers published by consortium members.

New Human Pangenome Reference

The Human Pangenome Reference Consortium has released a new reference human genome sequence collection. The “pangenome” reference, significantly more diverse than previous models, comprises 94 distinct genome sequences from 47 individuals, with plans to reach 700 sequences from 350 people by 2024. Credit: Darryl Leja, National Human Genome Research Institute, NIH

A genome is the set of

To understand these genomic differences, scientists create reference human genome sequences for use as a “standard” — a digital amalgamation of human genome sequences that can be used as a comparison to align, assemble and study other human genome sequences.

The original reference human genome sequence is nearly 20 years old and has been regularly updated as technology advances and researchers fix errors and discover more regions of the human genome. However, it is fundamentally limited in its representation of the diversity of the human

Pangenome Tube Map

The new pangenome reference is a collection of different genomes from which to compare an individual genome sequence. Like a map of the subway system, the pangenome graph has many possible routes for a sequence to take, represented by the different colors. The detouring paths at the top of the image represent single nucleotide variants (SNVs), which are single-letter differences. The yellow path that loops around itself and repeats the same nucleotides represents a duplication variant. The pink path that loops counterclockwise and follows the nucleotide sequence backward represents an inversion variant. At the bottom, the green and dark blue paths miss the C nucleotide in its route and represent a deletion variant. The light blue path, which has extra nucleotides in its route, represents an insertion variant. Credit: National Human Genome Research Institute

The current reference human genome sequence has gaps that reflect missing information, especially in areas that were repetitive and hard to read. Recent technological advances such as long-read DNA sequencing, which reads longer stretches of the DNA at a time, helped researchers fill in those gaps to create the first complete human genome sequence. This complete human genome sequence, released last year as part of the NIH-funded Telomere-to-Telomere (T2T) consortium, is incorporated into the current pangenome reference. In fact, many of the T2T researchers are also members of the Human Pangenome Reference Consortium.

Using advanced computational techniques to align the various genome sequences, the researchers constructed a new human pangenome reference with each assembly in the pangenome covering more than 99% of the expected sequence with more than 99%

Structural variants can involve thousands of bases. Until now, researchers have been unable to identify the majority of structural variants that exist in each human genome using short-read sequencing due to the bias of using a single reference sequence.

“The human pangenome reference will enable us to represent tens of thousands of novel genomic variants in regions of the genome that were previously inaccessible,” said Wen-Wei Liao, a Ph.D. student at Washington University in St. Louis, research affiliate at

“Basic researchers and clinicians who use genomics need access to a reference sequence that reflects the remarkable diversity of the human population. This will help make the reference useful for all people, thereby helping to reduce the chances of propagating health disparities,” said Eric Green, M.D., Ph.D., NHGRI director. “Creating and enhancing a human pangenome reference aligns with NHGRI’s goal of striving for global diversity in all aspects of genomics research, which is crucial to advance genomic knowledge and implement genomic medicine in an equitable way.”

In line with this effort, the Human Pangenome Reference Consortium includes an embedded ethics group that is working to anticipate challenging issues and help guide informed consent, prioritize the study of different samples, explore possible regulatory issues pertaining to clinical adoption, and work with international and Indigenous communities to incorporate their genome sequences in these broader efforts.

For more on this breakthrough, see:

“A draft human pangenome reference” by Wen-Wei Liao, Mobin Asri, Jana Ebler, Daniel Doerr, Marina Haukness, Glenn Hickey, Shuangjia Lu, Julian K. Lucas, Jean Monlong, Haley J. Abel, Silvia Buonaiuto, Xian H. Chang, Haoyu Cheng, Justin Chu, Vincenza Colonna, Jordan M. Eizenga, Xiaowen Feng, Christian Fischer, Robert S. Fulton, Shilpa Garg, Cristian Groza, Andrea Guarracino, William T. Harvey, Simon Heumos, Kerstin Howe, Miten Jain, Tsung-Yu Lu, Charles Markello, Fergal J. Martin, Matthew W. Mitchell, Katherine M. Munson, Moses Njagi Mwaniki, Adam M. Novak, Hugh E. Olsen, Trevor Pesout, David Porubsky, Pjotr Prins, Jonas A. Sibbesen, Jouni Sirén, Chad Tomlinson, Flavia Villani, Mitchell R. Vollger, Lucinda L. Antonacci-Fulton, Gunjan Baid, Carl A. Baker, Anastasiya Belyaeva, Konstantinos Billis, Andrew Carroll, Pi-Chuan Chang, Sarah Cody, Daniel E. Cook, Robert M. Cook-Deegan, Omar E. Cornejo, Mark Diekhans, Peter Ebert, Susan Fairley, Olivier Fedrigo, Adam L. Felsenfeld, Giulio Formenti, Adam Frankish, Yan Gao, Nanibaa’ A. Garrison, Carlos Garcia Giron, Richard E. Green, Leanne Haggerty, Kendra Hoekzema, Thibaut Hourlier, Hanlee P. Ji, Eimear E. Kenny, Barbara A. Koenig, Alexey Kolesnikov, Jan O. Korbel, Jennifer Kordosky, Sergey Koren, HoJoon Lee, Alexandra P. Lewis, Hugo Magalhães, Santiago Marco-Sola, Pierre Marijon, Ann McCartney, Jennifer McDaniel, Jacquelyn Mountcastle, Maria Nattestad, Sergey Nurk, Nathan D. Olson, Alice B. Popejoy, Daniela Puiu, Mikko Rautiainen, Allison A. Regier, Arang Rhie, Samuel Sacco, Ashley D. Sanders, Valerie A. Schneider, Baergen I. Schultz, Kishwar Shafin, Michael W. Smith, Heidi J. Sofia, Ahmad N. Abou Tayoun, Françoise Thibaud-Nissen, Francesca Floriana Tricomi, Justin Wagner, Brian Walenz, Jonathan M. D. Wood, Aleksey V. Zimin, Guillaume Bourque, Mark J. P. Chaisson, Paul Flicek, Adam M. Phillippy, Justin M. Zook, Evan E. Eichler, David Haussler, Ting Wang, Erich D. Jarvis, Karen H. Miga, Erik Garrison, Tobias Marschall, Ira M. Hall, Heng Li and Benedict Paten, 10 May 2023, Nature.
DOI: 10.1038/s41586-023-05896-x

“Increased mutation rate and gene conversion within human segmental duplications” by Mitchell R. Vollger, Philip C. Dishuck, William T. Harvey, William S. DeWitt, Xavi Guitart, Michael E. Goldberg, Allison N. Rozanski, Julian Lucas, Mobin Asri, Human Pangenome Reference Consortium, Katherine M. Munson, Alexandra P. Lewis, Kendra Hoekzema, Glennis A. Logsdon, David Porubsky, Benedict Paten, Kelley Harris, PingHsun Hsieh and Evan E. Eichler, 10 May 2023. Nature.
DOI: 10.1038/s41586-023-05895-y

“Recombination between heterologous human acrocentric chromosomes” by Andrea Guarracino, Silvia Buonaiuto, Leonardo Gomes de Lima, Tamara Potapova, Arang Rhie, Sergey Koren, Boris Rubinstein, Christian Fischer, Human Pangenome Reference Consortium, Jennifer L. Gerton, Adam M. Phillippy, Vincenza Colonna and Erik Garrison, 10 May 2023, Nature.
DOI: 10.1038/s41586-023-05976-y

“Pangenome graph construction from genome alignment with minigraph-cactus” by Glenn Hickey, Jean Monlong, Jana Ebler, Adam M. Novak, Jordan M. Eizenga, Yan Gao, Human Pangenome Reference Consortium, Tobias Marschall, Heng Li and Benedict Paten, 10 May 2023, Nature Biotechnology.
DOI: 10.1038/s41587-023-01793-w

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