パンゲノムの画期的な進歩: ヒトゲノムの多様性の非常に鮮明な画像

ロックフェラー大学2023年5月13日

Human Pangenome Reference Consortium は、世界中から 47 人のゲノム配列を収集することにより、より包括的なヒト参照ゲノムの作成において大きな進歩を遂げました。元のヒト参照ゲノムは、アフリカ系ヨーロッパ人を背景とする単一の個人からのデータに基づいており、遺伝的多様性の表現が制限されていました。この新しいパンゲノムは、各配列の 99% 以上を高精度でレンダリングし、これまで見えなかったほぼ 1 億 2,000 万の DNA 塩基対を明らかにします。ヒトの遺伝的多様性をより正確に表現することで、研究者は遺伝子と病気の関係についての理解を深め、臨床研究を加速し、最終的には健康格差への対処に役立てることができます。

大きな進歩として、科学者たちはさまざまな背景を持つ 47 人のゲノム配列を集めてパンゲノムを作成しました。これは、既存の参照ゲノムよりもヒトの遺伝的多様性をより正確に表現するものです。この新しいパンゲノムは、研究者が遺伝子と病気の関係について理解を深めるのに役立ち、最終的には健康格差に対処するのに役立つ可能性があります。

20 年以上にわたり、科学者は他の遺伝データを比較するための標準として、コンセンサス遺伝子配列であるヒト参照ゲノムに依存してきました。数え切れないほどの研究で使用されている参照ゲノムにより、特定の疾患に関係する遺伝子を特定したり、ヒトの形質の進化を追跡したりすることが可能になりました。

But it has always been a flawed tool. One of its biggest problems is that about 70 percent of its data came from a single man of predominantly African-European background whose DNADNA, or deoxyribonucleic acid, is a molecule composed of two long strands of nucleotides that coil around each other to form a double helix. It is the hereditary material in humans and almost all other organisms that carries genetic instructions for development, functioning, growth, and reproduction. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA)." data-gt-translate-attributes="[{"attribute":"data-cmtooltip", "format":"html"}]"> DNA の配列は、人のすべての DNA を捕捉する最初の取り組みであるヒトゲノム計画中に解析されました。その結果、地球上の 70 億人の各人を互いに異なるものにする遺伝子配列の 0.2 ～ 1 パーセントについてはほとんど知ることができず、健康の一部に関与すると考えられる生物医学データに固有の偏りが生じています。今日の患者に影響を与えている格差。たとえば、非ヨーロッパ人集団で見つかった多くの遺伝的変異は、参照ゲノムにはまったく表現されていません。

新しいパンゲノム参照草案には、1 つだけではなく 47 個のゲノムが含まれており、DNA の違いを見つけて理解するために、従来の参照よりもはるかに優れた比較ポイントを提供します。クレジット: 国立ヒトゲノム研究所

For years, researchers have called for a resource more inclusive of human diversity with which to diagnose diseases and guide medical treatments. Now scientists with the Human Pangenome Reference Consortium have made groundbreaking progress in characterizing the fraction of human DNA that varies between individuals. As they recently published in Nature, they’ve assembled genomic sequences of 47 people from around the world into a so-called pangenome in which more than 99 percent of each sequence is rendered with high accuracyHow close the measured value conforms to the correct value." data-gt-translate-attributes="[{"attribute":"data-cmtooltip", "format":"html"}]">正確さ。

これらの配列が重なり合うと、これまで見えなかった約 1 億 2,000 万の DNA 塩基対が明らかになりました。

At the time, Jarvis, one of the consortium’s leaders, was honing advanced sequencing and computational methods through the Vertebrate Genomes Project, which aims to sequence all 70,000 vertebrate speciesA species is a group of living organisms that share a set of common characteristics and are able to breed and produce fertile offspring. The concept of a species is important in biology as it is used to classify and organize the diversity of life. There are different ways to define a species, but the most widely accepted one is the biological species concept, which defines a species as a group of organisms that can interbreed and produce viable offspring in nature. This definition is widely used in evolutionary biology and ecology to identify and classify living organisms." data-gt-translate-attributes="[{"attribute":"data-cmtooltip", "format":"html"}]"species. His and other collaborating labs decided to apply these advances for high-quality diploid genome assemblies to revealing the variation within a single vertebrate: Homo sapiens./p>

With so many genomes represented in a pangenome, that cloudiness threatened to develop into a thunderstorm of confusion. So the HPRC homed in a method developed by Adam Phillippy and Sergey Koren at the National Institutes of HealthThe National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability." data-gt-translate-attributes="[{"attribute":"data-cmtooltip", "format":"html"}]"National Institutes of Health on parent-child “trios”—a mother, a father, and a child whose genomes had all been sequenced. Using the data from mom and dad, they were able to clear up the lines of inheritance and arrive at a higher-quality sequence for the child, which they then used for pangenome analysis./p>

The pangenome assembly also fills in gaps that were due to repetitive sequences or duplicated genes. One example is the major histocompatibility complex (MHC), a cluster of genes that code proteins on the surface of cells that help the immune system recognize antigens, such as those from the SARS-CoV-2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the official name of the virus strain that causes coronavirus disease (COVID-19). Previous to this name being adopted, it was commonly referred to as the 2019 novel coronavirus (2019-nCoV), the Wuhan coronavirus, or the Wuhan virus." data-gt-translate-attributes="[{"attribute":"data-cmtooltip", "format":"html"}]">SARS-CoV-2 virusA virus is a tiny infectious agent that is not considered a living organism. It consists of genetic material, either DNA or RNA, that is surrounded by a protein coat called a capsid. Some viruses also have an outer envelope made up of lipids that surrounds the capsid. Viruses can infect a wide range of organisms, including humans, animals, plants, and even bacteria. They rely on host cells to replicate and multiply, hijacking the cell's machinery to make copies of themselves. This process can cause damage to the host cell and lead to various diseases, ranging from mild to severe. Common viral infections include the flu, colds, HIV, and COVID-19. Vaccines and antiviral medications can help prevent and treat viral infections." data-gt-translate-attributes="[{"attribute":"data-cmtooltip", "format":"html"}]"virus./p>