Neandertal Genomics

尼安德特人基因组学

• 批准号: 7392422
• 负责人: EDWARD M RUBIN
• 金额: $ 29.43万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-03 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7392422
• 关键词: Address; Admixture; Belgium; Biological Preservation; Biological Sciences; Biology; Blood capillaries; Canis familiaris; Cloning; Code; Cognitive; Communities; Croatia; DNA; DNA Library; DNA Resequencing; Data; Depth; Disease; Ensure; Event; Evolution; Facility Construction Funding Category; France; Generations; Genes; Genetic Polymorphism; Genome; Genomic Library; Genomics; Germany; Goals; Human; Human Biology; Human Genome; Institution; Laboratories; Language; Libraries; Mediation; Metagenomics; Methods; Mitochondria; Mitochondrial DNA; Mus; Museums; Nucleotides; Numbers; Orthologous Gene; Pan Genus; Pan troglodytes; Ploidies; Polymerase Chain Reaction; Predisposition; Principal Investigator; Purpose; Rattus; Recovery; Relative (related person); Research; Research Personnel; Resources; Running; Sampling; Site; Source; Standards of Weights and Measures; Ursidae Family; Validation; Y Chromosome; base; capillary; genome sequencing; insight; interest; metagenomic sequencing; research study; trait; vector

DESCRIPTION (provided by applicant): Many aspects of human biology, including cognitive abilities, advanced language, and susceptibility to common diseases, are influenced by genome sequence changes that occurred very recently in human evolution. Genomic sequence from the Neandertal, which most evidence suggests diverged from the modern human lineage -500,000 years ago, would help identify these events. The goal of this study is to obtain Neandertal genome sequences by targeted methods in order to identify fixed sequence changes unique to modern humans. The aims of our proposal are based on extensive preliminary data, including the creation of genomic DNA libraries from Neandertal and cave bear remains, the generation of Neandertal genomic sequences, and the targeted recovery of specific sequences from cave bear genomic libraries. We will first analyze several Neandertal samples available to us to identify those that show the best Neandertal DNA preservation with minimal amounts of modern human contamination. Using these Neandertal samples, we will construct Neandertal metagenomic libraries that will serve as a renewable source of Neandertal genomic DNA for these studies and which we will also make available to the research community at large. We will use these libraries in both direct genomic selection and PCR-based searches for specific Neandertal genomic clones, focusing on sites of human-chimpanzee nucleotide substitution in genes and other functional sequences. The data generated by these methods will be used in an extensive effort to compare human, chimpanzee and Neandertal sequences and identify substitutions that occurred after humans diverged from Neandertals. We will authenticate Neandertal sequences by recovering the same sequences from multiple Neandertal libraries. We will exclude human-Neandertal substitutions polymorphic in modern humans by comparison to known SNPs and by resequencing substituted loci in a diverse panel of human samples. These studies will identify a set of human-chimpanzee sequence differences that are unique to modern humans, yielding fundamental insights into human origins, the rise of human-specific phenotypic traits, and the biology of Neandertals. Lay Summary: Humans are a relatively recent species, arising in the last -160,000 years. However, many aspects of our biology, including our language, our ability to reason, and our susceptibility to many diseases, are unique to us. We hope that by comparing our genome sequence to that of the Neandertal, or closest, but now extinct relative, we will identify the changes that occurred in our genome that led to the rise of unique human traits.

描述（由申请人提供）：人类生物学的许多方面，包括认知能力，先进的语言和对常见疾病的敏感性，受到最近在人类进化中发生的基因组序列变化的影响。大多数证据表明，尼安德特尔（Neandertal）的基因组序列与现代人类血统相差-500，000年前，这将有助于确定这些事件。这项研究的目的是通过靶向方法获得尼安德特基因组序列，以识别现代人类独特的固定序列变化。我们提案的目的是基于广泛的初步数据，包括从尼安德特尔和洞穴熊的基因组DNA库中创建，尼安德特基因组序列的产生以及从洞穴熊基因组基因组库中的特定序列的靶向恢复。我们将首先分析几个可供我们使用的尼安德特尔样本，以识别那些显示出最佳尼安德特人DNA保存的样本，并以最少的现代人类污染物来识别那些样本。使用这些尼安德尔特样品，我们将构建尼安德特元基因组图库，这些库将作为这些研究的尼安德尔特基因组DNA的可再生能源，我们还将为整个研究社区提供。我们将在直接基因组选择和基于PCR的特定尼安德尔特基因组克隆中使用这些文库，重点关注基因和其他功能序列中人类奇异果核苷酸取代的位点。这些方法生成的数据将在广泛的努力中使用，以比较人，黑猩猩和尼安德特尔序列，并确定人类与尼安德特人分歧后发生的替代。我们将通过从多个尼安德特尔库中恢复相同的序列来验证尼安德特尔序列。通过与已知的SNP相比，我们将排除现代人类中的人类北极替代，并通过在人类样本的各种面板中重新陈述取代基因座。这些研究将确定一组现代人类独有的人类 - 奇曼zee序列差异，对人类起源，人类特异性表型特征的兴起和尼安德特人的生物学产生基本见解。外行摘要：人类是一个相对较新的物种，在过去的-160，000年中产生。但是，我们生物学的许多方面，包括我们的语言，推理能力以及我们对许多疾病的敏感性，对我们来说是独一无二的。我们希望，通过将我们的基因组序列与尼安德特尔（Neandertal）或最接近的基因组序列进行比较，但现在灭绝的亲戚，我们将确定基因组中发生的变化导致了独特的人类特征的兴起。