Center for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Data Tecnica, Washington, District of Columbia, USA.
Mov Disord. 2024 Nov;39(11):2039-2048. doi: 10.1002/mds.29902. Epub 2024 Sep 16.
Commercial genome-wide genotyping arrays have historically neglected coverage of genetic variation across populations.
We aimed to create a multi-ancestry genome-wide array that would include a wide range of neuro-specific genetic content to facilitate genetic research in neurological disorders across multiple ancestral groups, fostering diversity and inclusivity in research studies.
We developed the Illumina NeuroBooster Array (NBA), a custom high-throughput and cost-effective platform on a backbone of 1,914,934 variants from the Infinium Global Diversity Array and added custom content comprising 95,273 variants associated with more than 70 neurological conditions or traits, and we further tested its performance on more than 2000 patient samples. This novel platform includes approximately 10,000 tagging variants to facilitate imputation and analyses of neurodegenerative disease-related genome-wide association study loci across diverse populations.
In this article, we describe NBA's potential as an efficient means for researchers to assess known and novel disease genetic associations in a multi-ancestry framework. The NBA can identify rare genetic variants and accurately impute more than 15 million common variants across populations. Apart from enabling sample prioritization for further whole-genome sequencing studies, we envisage that NBA will play a pivotal role in recruitment for interventional studies in the precision medicine space.
From a broader perspective, the NBA serves as a promising means to foster collaborative research endeavors in the field of neurological disorders worldwide. Ultimately, this carefully designed tool is poised to make a substantial contribution to uncovering the genetic etiology underlying these debilitating conditions. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
商业全基因组基因分型芯片在历史上忽略了人群中遗传变异的覆盖范围。
我们旨在创建一个多祖系全基因组芯片,其中包括广泛的神经特异性遗传内容,以促进多个祖系的神经疾病遗传研究,在研究中促进多样性和包容性。
我们开发了 Illumina NeuroBooster 阵列(NBA),这是一种基于 Infinium Global Diversity Array 中 1914934 个变体的高通量和具有成本效益的定制平台,并添加了包含与 70 多种神经状况或特征相关的 95273 个变体的定制内容,我们还在 2000 多个患者样本上测试了其性能。这个新平台包括大约 10000 个标记变体,以促进在不同人群中进行与神经退行性疾病相关的全基因组关联研究位点的推断和分析。
在本文中,我们描述了 NBA 作为一种有效的方法,用于研究人员在多祖系框架下评估已知和新的疾病遗传关联。NBA 可以识别罕见的遗传变异,并准确推断出超过 1500 万个常见的变体在人群中的存在。除了能够对进一步的全基因组测序研究进行样本优先级排序外,我们设想 NBA 将在精准医学领域的干预性研究的招募中发挥关键作用。
从更广泛的角度来看,NBA 是促进全球神经疾病领域合作研究努力的一种有前途的手段。最终,这个精心设计的工具有望为揭示这些使人衰弱的疾病的遗传病因做出重大贡献。