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Novel gene discovery in zebra finches

斑胸草雀的新基因发现

基本信息

批准号：
9173458
负责人：
Claudio V Mello
金额：
$ 22.83万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-01 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9173458
关键词：
Address Algorithms Animal Model Animals Area Behavior Behavioral Biological Birds Brain Brain region Cell Nucleus Characteristics Chickens Chiroptera Cognition Columbidae Communication impairment Complement Complex Corpus striatum structure Data Databases Disease Elements Exhibits Experimental Models FOXP2 gene Family Psittacidae Funding Future Gene Duplication Gene Expression Profiling Genes Genetic Genetic study Genome Genomics Gonadal Steroid Hormones Health Human Impairment In Situ Hybridization Investigation Language Language Development Language Disorders Learning Link Mammals Methods Modeling Molecular Molecular Genetics National Human Genome Research Institute Neurobiology Organism Orthologous Gene Outcome Process Production Property Proteins Research Research Personnel Rodent Sensory Sleep Songbirds Speech Speech Disorders Strigiformes Synteny System Tertiary Protein Structure Testing United States National Institutes of Health Vertebrates adult neurogenesis auditory feedback base bird song brain cell cell type comparative comparative genomics critical period design dimorphism duplicate genes gene discovery genome annotation genome-wide innovation interest learned behavior mind control nonhuman primate novel novel strategies paralogous gene public health relevance relating to nervous system tool trait vocal control vocal learning vocalization zebra finch

项目摘要

DESCRIPTION (provided by applicant): The availability of NIH/NHGRI-funded high quality genomes for non-human vertebrates, including avian species like the zebra finch and chicken, has made it possible to search for genomic features that are associated with traits whose mechanisms cannot be investigated in humans, thus requiring experimental model organisms. The study of some complex learned behaviors and their associated brain circuits illustrate well this point. We propose here a set of exploratory analyses in the zebra finch, a songbird, in order to elucidate the genomic basis of vocal learning, a complex behavioral trait that is a prerequisite for speech and language acquisition in humans. Zebra finches have emerged as the premier model organism for investigating the biological basis of vocal learning. In fact, no other organism, including rodents and non-human primates, provides a comparable experimental platform that allows investigators to relate neural and genomic features to a learned vocal behavior with close ties to human speech. Recent studies have revealed remarkable convergent molecular specializations in brain circuits for vocal control in songbirds and humans, pointing to a set of shared molecular requirements for birdsong and human speech learning. Such findings have broad implications for understanding genetic mechanisms that may underlie a variety of human communication impairments and disorders. Here we propose to implement a novel computational search algorithm that is designed to discover novel and duplicated genes in the genome of the zebra finch that are absent in a closely related vocal non-learning species (manakin), and thus possibly related to vocal learning. We anticipate that this exploratory effort will identify ~100 novel genes in zebra finches. To further test for a possible link to vocal learning, we will examine the occurrance of the identified genes in multiple other vocal learner birds whose genomes are now also available. An exploratory expression analysis will attempt to link the novel genes to specific brain cell types associated with vocal learning, as well as with other songbird traits of relevance to human health, including adult neurogenesis, brain dimorphisms and sex steroid action, and sleep modulation of learning. We will also explore whether expansions of functional protein domains in the novel genes are present in other avian vocal learner species, as well as in humans. If found in the latter, such features could potentiall be used in future studies of genetic correlates of speech proficiency and disorders. The outcomes will also guide future mechanistic studies to establish causal links between specific genes and vocal learning. Lastly, our intent is to implement a computational search algorithm of broad applicability that can be utilized for novel gene searches and genome curations in any target species of interest; such an algorithm should therefore be of broad use, particularly for analysis of recently assembled genomes that have low quality or no annotations.

描述（由申请人提供）：NIH/NHGRI 资助的非人类脊椎动物（包括斑胸草雀和鸡等鸟类物种）的高质量基因组的可用性使得搜索与无法在人类中研究其机制的性状相关的基因组特征成为可能，因此需要实验模型生物。对一些复杂的习得行为及其相关大脑回路的研究很好地说明了这一点。我们在这里提出了对斑胸草雀（一种鸣鸟）进行一系列探索性分析，以阐明声音学习的基因组基础，这是一种复杂的行为特征，是先决条件用于人类言语和语言习得。斑胸草雀已成为研究声音学习生物学基础的首要模式生物。事实上，没有其他生物体，包括啮齿动物和非人类灵长类动物，能够提供类似的实验平台，使研究人员能够将神经和基因组特征与与人类语音密切相关的习得发声行为联系起来。最近的研究揭示了鸣禽和人类声音控制的大脑回路中显着趋同的分子专业化，指出了鸟类鸣叫和人类语音学习的一系列共同的分子需求。这些发现对于理解可能构成各种人类沟通障碍和疾病的遗传机制具有广泛的意义。在这里，我们建议实施一种新颖的计算搜索算法，旨在发现斑胸草雀基因组中的新颖和重复基因，这些基因在密切相关的发声非学习物种（侏儒鸟）中不存在，因此可能与发声学习有关。我们预计这项探索性工作将在斑胸草雀中鉴定出约 100 个新基因。为了进一步测试与声音学习之间的可能联系，我们将检查已识别基因在其他多种声音学习鸟类中的出现情况，这些鸟类的基因组现在也可用。探索性表达分析将尝试将新基因与与声音学习相关的特定脑细胞类型以及与人类健康相关的其他鸣禽特征联系起来，包括成年神经发生、大脑二态性和性类固醇作用以及学习的睡眠调节。我们还将探索新基因中功能蛋白结构域的扩展是否存在于其他鸟类发声学习者物种以及人类中。如果在后者中发现，这些特征可能会用于未来语言能力和障碍的遗传相关性的研究。研究结果还将指导未来的机制研究，以确定特定基因和声音学习之间的因果关系。最后，我们的目的是实现一种具有广泛适用性的计算搜索算法，可用于任何感兴趣的目标物种的新基因搜索和基因组管理；因此，这种算法应该具有广泛的用途，特别是对于分析最近组装的低质量或没有注释的基因组。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The constitutive differential transcriptome of a brain circuit for vocal learning.

DOI：
10.1186/s12864-018-4578-0
发表时间：
2018-04-03
期刊：
BMC genomics
影响因子：
4.4
作者：
Lovell PV;Huizinga NA;Friedrich SR;Wirthlin M;Mello CV
通讯作者：
Mello CV

Avian genomics lends insights into endocrine function in birds.

DOI：
10.1016/j.ygcen.2017.05.023
发表时间：
2018-01-15
期刊：
General and comparative endocrinology
影响因子：
2.7
作者：
Mello CV;Lovell PV
通讯作者：
Lovell PV

Correspondence on Lovell et al.: response to Bornelöv et al.

洛弗尔等人的通讯：对博内洛夫等人的回应

DOI：
10.1186/s13059-017-1234-y
发表时间：
2017
期刊：
Genome biology
影响因子：
12.3
作者：
Lovell,PeterV;Mello,ClaudioV
通讯作者：
Mello,ClaudioV

Curation of microarray oligonucleotides and corresponding ESTs/cDNAs used for gene expression analysis in zebra finches.

用于斑胸草雀基因表达分析的微阵列寡核苷酸和相应的 EST/cDNA 的管理。

DOI：
10.1186/s13104-018-3402-x
发表时间：
2018
期刊：
BMC research notes
影响因子：
1.8
作者：
Lovell,PeterV;Huizinga,NicoleA;Getachew,Abel;Mees,Brianna;Friedrich,SamanthaR;Wirthlin,Morgan;Mello,ClaudioV
通讯作者：
Mello,ClaudioV