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（由适用提供）：非人类脊椎动物的NIH/NHGRI资助的高质量基因组的可用性，包括诸如Zebra Fine和Chicky的禽类物种，使得可以搜索与人类无法研究的特征相关的基因组特征，从而需要实验模型生物体。对一些复杂的学习行为及其相关的大脑电路的研究很好地说明了这一点。我们在这里提出了一组Zebra Fine中的探索性分析，以阐明声带学习的基因组基础，这是一种复杂的行为特征，是一种先决条件用于人类的言语和语言获取。斑马精炼已成为研究声乐学习生物学基础的主要模型有机体。实际上，没有其他有机体（包括啮齿动物和非人类隐私）提供了一个可比的实验平台，该平台使研究人员能够将神经和基因组特征与学习的声音行为联系起来，并与人类的言语紧密联系。最近的研究揭示了在歌手和人类中进行声乐控制的脑电路中的显着收敛分子专业，指出了一系列对鸟鸣和人类言语学习的共享分子要求。这种发现对理解遗传机制具有广泛的影响，这些遗传机制可能是各种人类交流障碍和疾病的基础。在这里，我们建议实施一种新型的计算搜索算法，该算法旨在发现斑马细胞基因组中的新颖和重复的基因，这些基因在紧密相关的声音非学习物种（Manakin）中不存在，因此可能与声音学习有关。我们预计这种探索性工作将确定斑马罚款中约有100个新基因。为了进一步测试与声带学习的可能链接，我们将研究其他多种人声学习者鸟类中鉴定的基因的发生，这些鸟类现在也可以使用。探索性表达分析将试图将新型基因与与人声学习相关的特定脑细胞类型以及与人类健康相关的其他歌手特征，包括成人神经发生，大脑二态性和性别立体声动作以及学习的睡眠调节。我们还将探讨新基因中功能蛋白结构域的扩展是否存在于其他禽类人声学习者以及人类中。如果在后者中发现，则可以将这种特征用于言语水平和疾病的遗传相关性的未来研究。结果还将指导未来的机械研究，以在特定基因与声音学习之间建立严重的联系。最后，我们的目的是实施广泛适用性的计算搜索算法，该算法可用于任何目标物种中的新基因搜索和基因组策展；因此，这种算法应该广泛使用，特别是用于分析质量低或没有注释的最近组装的基因组。

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