PDF(Pubmed)
Abstract：
Genome-wide genotyping platforms have the capacity to capture genetic variation across different populations, but there have been disparities in the representation of population-dependent genetic diversity. The motivation for pursuing this endeavor was to create a comprehensive genome-wide array capable of encompassing a wide range of neuro-specific content for the Global Parkinson\'s Genetics Program (GP2) and the Center for Alzheimer\'s and Related Dementias (CARD). CARD aims to increase diversity in genetic studies, using this array as a tool to foster inclusivity. GP2 is the first supported resource project of the Aligning Science Across Parkinson\'s (ASAP) initiative that aims to support a collaborative global effort aimed at significantly accelerating the discovery of genetic factors contributing to Parkinson\'s disease and atypical parkinsonism by generating genome-wide data for over 200,000 individuals in a multi-ancestry context. Here, we present the Illumina NeuroBooster array (NBA), a novel, high-throughput and cost-effective custom-designed content platform to screen for genetic variation in neurological disorders across diverse populations. The NBA contains a backbone of 1,914,934 variants (Infinium Global Diversity Array) complemented with custom content of 95,273 variants implicated in over 70 neurological conditions or traits with potential neurological complications. Furthermore, the platform includes over 10,000 tagging variants to facilitate imputation and analyses of neurodegenerative disease-related GWAS loci across diverse populations. The NBA can identify low frequency variants and accurately impute over 15 million common variants from the latest release of the TOPMed Imputation Server as of August 2023 (reference of over 300 million variants and 90,000 participants). We envisage this valuable tool will standardize genetic studies in neurological disorders across different ancestral groups, allowing researchers to perform genetic research inclusively and at a global scale.
摘要：
全基因组基因分型平台有能力捕获不同群体的遗传变异，但是在人口依赖的遗传多样性的代表性方面存在差异。追求这一努力的动机是创建一个全面的全基因组阵列，能够为全球帕金森病遗传学计划（GP2）和阿尔茨海默氏症及相关痴呆症中心（CARD）涵盖广泛的神经特异性内容。CARD旨在增加遗传研究的多样性，使用这个数组作为促进包容性的工具。GP2是第一个支持的资源项目，旨在支持全球协作努力，旨在通过在多血统背景下生成超过200,000个人的全基因组数据，大大加快发现导致帕金森病和非典型帕金森病的遗传因素。这里,我们提出了Illumina神经助推器阵列（NBA），一本小说,高通量和具有成本效益的定制设计的内容平台，以筛选不同人群中神经系统疾病的遗传变异。NBA包含1,914,934种变体（InfiniumGlobalDiversityArray）的骨架，并补充了95,273种变体的自定义内容，涉及70多种神经系统疾病或具有潜在神经系统并发症的特征。此外，该平台包括超过10,000个标记变体,以促进不同人群中神经退行性疾病相关GWAS基因座的填补和分析.NBA可以识别低频变体，并从截至2023年8月的TOPMedImputationServer最新版本中准确估算超过1500万个常见变体（参考了超过3亿变体和90,000名参与者）。我们设想这个有价值的工具将标准化不同祖先群体的神经系统疾病的遗传研究，允许研究人员在全球范围内进行包容性的基因研究。
