Functional Genetics Approaches to Investigate Human Evolution

研究人类进化的功能遗传学方法

基本信息

批准号：
10675773
负责人：
Tyler Fair
金额：
$ 4.51万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-11 至 2025-08-10
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10675773
关键词：
ATAC-seq Alleles Apoptosis Area Base Pairing Brain CRISPR interference Cell Proliferation Cell physiology Cells Chromatin Clustered Regularly Interspaced Short Palindromic Repeats Code Collaborations Computational Biology Computational Technique Computing Methodologies Data Set Embryo Equilibrium Evolution Foundations Gene Dosage Gene Expression Gene Targeting Genes Genetic Genetic Transcription Genetic Variation Genome Genomics Goals Growth Guide RNA High-Throughput Nucleotide Sequencing Hominidae Human Human Genome Libraries Link Macaca Macaca mulatta Machine Learning Maps Molecular Mutation Nucleotides Organoids Pan Genus Phenotype Pluripotent Stem Cells Pollen Population Genetics Proliferating Proteins Regulation Regulatory Element Repetitive Sequence Research Personnel Scientist Single Nucleotide Polymorphism Site Statistical Methods System Techniques Telencephalon Testing Untranslated RNA Variant Work cell motility cell type comparative genomics experience genetic approach genetic variant genome-wide genomic locus genomic predictors induced pluripotent stem cell loss of function migration mouse model nerve stem cell nonhuman primate permissiveness public health relevance screening single-cell RNA sequencing skills stable cell line statistics stem cell differentiation stem cell model transcriptome sequencing transcriptomics

项目摘要

Analyses of human and chimpanzee genomes have catalogued the single-nucleotide and structural variants that have emerged since humans diverged from nonhuman primates. Nearly all of these genetic variants remain functionally uncharacterized. Contained within these genetic variants are alterations to cis-regulatory elements, protein-coding genes, noncoding RNAs, gene copy number, repetitive elements, and other genomic features that underlie phenotypic differences between humans and nonhuman primates. Because it is difficult to predict how genomic differences within the hominid lineage contribute to phenotypic differences, there is a critical need for high-throughput, systematic approaches to interrogate functional genetic variation. Therefore, I seek to develop a quantitative genome-scale platform for identifying the phenotypic consequences of human-specific evolutionary mutations at a cellular and molecular level. To accomplish this objective, I will combine advances in chimpanzee pluripotent stem cell-derived models with CRISPR interference (CRISPRi), single-cell RNAsequencing (scRNA-seq), and single-cell ATAC-sequencing (scATAC-seq). This project is of great

对人类和黑猩猩基因组的分析已经对单核苷酸和结构变异进行了分类自人类与非人类灵长类动物分化以来就出现了。几乎所有这些遗传变异都仍然存在功能上未表征。这些遗传变异中包含顺式调控元件的改变，蛋白质编码基因、非编码RNA、基因拷贝数、重复元件和其他基因组特征这是人类和非人类灵长类动物之间表型差异的基础。因为很难预测原始人类谱系内的基因组差异如何导致表型差异，这是一个迫切需要用于询问功能遗传变异的高通量、系统方法。因此，我寻求开发一个定量基因组规模平台，用于识别人类特异性的表型后果细胞和分子水平上的进化突变。为了实现这个目标，我将结合先进的技术在黑猩猩多能干细胞衍生模型中，采用 CRISPR 干扰 (CRISPRi)、单细胞 RNA 测序 (scRNA-seq) 和单细胞 ATAC 测序 (scATAC-seq)。这个项目意义重大

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Comparative landscape of genetic dependencies in human and chimpanzee stem cells.

人类和黑猩猩干细胞遗传依赖性的比较景观。

DOI：
发表时间：
2023-03-20
期刊：
影响因子：
0
作者：
She, Richard;Fair, Tyler;Schaefer, Nathan K;Saunders, Reuben A;Pavlovic, Bryan J;Weissman, Jonathan S;Pollen, Alex A
通讯作者：
Pollen, Alex A

Mapping cis- and trans-regulatory target genes of human-specific deletions.

绘制人类特异性缺失的顺式和反式调控靶基因。

DOI：
发表时间：
2023-12-28
期刊：
影响因子：
0
作者：
Fair, Tyler;Pavlovic, Bryan J;Schaefer, Nathan K;Pollen, Alex A
通讯作者：
Pollen, Alex A

Comparative landscape of genetic dependencies in human and chimpanzee stem cells.

人类和黑猩猩干细胞遗传依赖性的比较景观。

DOI：
发表时间：
2023-07-06
期刊：
影响因子：
64.5
作者：
She, Richard;Fair, Tyler;Schaefer, Nathan K;Saunders, Reuben A;Pavlovic, Bryan J;Weissman, Jonathan S;Pollen, Alex A
通讯作者：
Pollen, Alex A

The human brain's network architecture is genetically encoded by modular pleiotropy

人脑的网络架构是通过模块化多效性进行基因编码的

DOI：
10.1016/bs.irn.2019.10.005
发表时间：
2019-05-18
期刊：
arXiv: Neurons and Cognition
影响因子：
0
作者：
Maxwell A. Bertolero;A. S. Blevins;Graham L. Baum;R. Gur;R. Gur;D. Roalf;T. Satterthwaite;D. Bassett
通讯作者：
D. Bassett