Exonizaton of Alu Insertion Polymorphisms

Alu 插入多态性的外显子化

• 批准号: 10227617
• 负责人: KATHLEEN H BURNS
• 金额: $ 29.39万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227617
• 关键词: Alleles; Biological Assay; Burn injury; CRISPR/Cas technology; Catalogs; Complement; Computational Biology; Consult; DNA Insertion Elements; DNA Sequence; DNA Transposable Elements; Data; Data Set; Disease; Elements; Encyclopedia of DNA Elements; European; Event; Exons; Genes; Genetic; Genetic Medicine; Genetic Polymorphism; Genetic Transcription; Genome; Genomic DNA; Genomics; Genotype; Haplotypes; Health; Healthcare; Human; Human Cell Line; Human Genome; Inherited; Institutes; Interspersed Repetitive Sequences; Laboratories; Libraries; Light; Link; Linkage Disequilibrium; Long Interspersed Elements; Maps; Mental Depression; Messenger RNA; Modeling; Molecular; Nonsense-Mediated Decay; Phenotype; Plant Roots; Play; Population; Positioning Attribute; Protein Isoforms; RNA Sequences; RNA Splicing; RNA-Directed DNA Polymerase; Relative Risks; Reporter; Risk; Role; Structure; Testing; The Cancer Genome Atlas; Tissues; Transcript; Universities; Untranslated RNA; Variant; base; causal variant; computerized tools; disorder risk; endonuclease; experimental study; follow-up; genetic variant; genome editing; genome wide association study; genomic locus; human disease; medical schools; mouse genome; novel; personalized approach; reference genome; trait; transcriptome sequencing

Common genetic variants contribute to a wide spectrum of human phenotypes and risks of developing many types of diseases. Differentiating causative from non-functional variants and understanding molecular mechanisms of the former together represent important challenges. Alu interspersed repeats are a common type of structural variant in the human genome. Alu insertions are intrinsically capable of impacting mRNA sequence and resulting in disease - even when the repeat is positioned in apparently non-coding, intronic sequence within the gene locus. Our hypothesis is that some inherited Alu insertion polymorphisms are functioning as causative variants for human disease risk. We propose to narrow the list of candidates by identifying those Alu insertions that associate with disease risk and that impact the structure of a relevant mRNA transcript. We will develop computational approaches to identify Alu exonization events in RNA-seq data, and we will experimentally evaluate Alu insertion polymorphisms for effects on mRNA splicing using reporter assays and genome editing strategies.

常见的遗传变异有助于广泛的人类表型和风险

项目成果

Comprehensive and scalable quantification of splicing differences with MntJULiP.

• DOI: 10.1186/s13059-022-02767-y
• 发表时间: 2022-09-14
• 期刊: Genome biology
• 影响因子: 12.3

Detection of Alu Exonization Events in Human Frontal Cortex From RNA-Seq Data.

• DOI: 10.3389/fmolb.2021.727537
• 发表时间: 2021
• 期刊: Frontiers in molecular biosciences
• 影响因子: 5
• 作者: Florea L;Payer L;Antonescu C;Yang G;Burns K
• 通讯作者: Burns K