판게놈의 혁신: 인간 게놈 다양성의 선명한 이미지

록펠러 대학교 2023년 5월 13일

인간 판게놈 참조 컨소시엄(Human Pangenome Reference Consortium)은 전 세계 47명의 개인의 게놈 서열을 모아 보다 포괄적인 인간 참조 게놈을 만드는 데 상당한 진전을 이루었습니다. 원래 인간 참조 게놈은 아프리카-유럽 배경의 단일 개인의 데이터를 기반으로 했기 때문에 유전적 다양성 표현이 제한되었습니다. 각 서열의 99% 이상을 높은 정확도로 렌더링하는 이 새로운 팬게놈은 이전에 볼 수 없었던 거의 1억 2천만 개의 DNA 염기쌍을 드러냅니다. 인간의 유전적 다양성을 보다 정확하게 표현함으로써 연구자들은 유전자와 질병 사이의 연관성에 대한 이해를 개선하고 임상 연구를 가속화하며 궁극적으로 건강 격차를 해결하는 데 도움을 줄 수 있습니다.

중요한 진전으로, 과학자들은 다양한 배경을 가진 47명의 게놈 서열을 모아 기존 참조 게놈보다 인간의 유전적 다양성을 더 정확하게 표현하는 판게놈(pangenome)을 만들었습니다. 이 새로운 팬게놈은 연구자들이 유전자와 질병 사이의 연관성에 대한 이해를 개선하는 데 도움이 될 것이며 궁극적으로 건강 불균형을 해결하는 데 도움이 될 수 있습니다.

20년 넘게 과학자들은 다른 유전 데이터를 비교하기 위한 표준으로 합의 유전 서열인 인간 참조 게놈에 의존해 왔습니다. 수많은 연구에 사용된 참조 게놈은 특히 특정 질병과 관련된 유전자를 식별하고 인간 특성의 진화를 추적하는 것을 가능하게 했습니다.

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"}]"> DNA는 인간의 모든 DNA를 포착하려는 최초의 노력인 인간 게놈 프로젝트(Human Genome Project) 중에 서열 분석되었습니다. 결과적으로, 지구상의 70억 인구 각각을 서로 다르게 만드는 유전자 서열의 0.2~1%에 대해 거의 알 수 없으며, 일부 건강에 영향을 미치는 것으로 여겨지는 생물 의학 데이터에 내재된 편견을 생성합니다. 오늘날 환자들에게 영향을 미치는 격차. 예를 들어, 비유럽 인구 집단에서 발견된 많은 유전적 변이체는 참조 게놈에 전혀 표시되지 않습니다.

새로운 초안 판게놈 참조에는 단 하나가 아닌 47개의 게놈이 포함되어 있으며 DNA의 차이점을 찾고 이해하기 위한 기존 참조보다 훨씬 더 나은 비교 지점을 제공할 것입니다. 출처: 국립인간게놈연구소

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"}]">정확성.

서로 겹쳐진 이 서열은 이전에는 볼 수 없었던 거의 1억 2천만 개의 DNA 염기쌍을 드러냈습니다.

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>