Characterization of NSCLP gene CRISPLD2

NSCLP 基因 CRISPLD2 的表征

基本信息

批准号：
7669085
负责人：
Brett Thomas Chiquet
金额：
$ 3.65万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7669085
关键词：
Abbreviations Affect Algorithms Alleles Animal Model Biological Assay Birth Child Cleaved cell Cleft Palate Complex Computers Congenital Abnormality Congenital Megacolon Counseling Cysteine DNA Dental Development Diagnosis Disease Embryo Equation Equilibrium Etiology Exons Face Family Future Genes Genetic Genetic Transcription Genetic Variation Goals Haplotypes Health Healthcare In Vitro Interferons Knock-out Knockout Mice Knowledge Lead Lip structure Live Birth Luciferases Modeling Mus National Institute of Dental and Craniofacial Research Operative Surgical Procedures Oral health Palate Patients Persons Play Polymerase Chain Reaction RNA Splicing Research Research Training Risk Role Screening procedure Short Tandem Repeat Single Nucleotide Polymorphism Site Speech Therapy Syndrome Testing Texas Therapeutic Intervention Time United States Untranslated Regions Variant base craniofacial gene function high risk human disease improved in vivo insight intervention program knockout gene meetings mouse model nonsyndromic cleft lip with or without cleft palate novel orofacial popliteal pterygium syndrome proband programs promoter secretory protein

项目摘要

DESCRIPTION (provided by applicant): Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common complex birth disorder that affects 1/700 live births, with 4000 cases each year in the United States. The etiology of NSCLP is not completely understood, but both genetics and environmental influences are known to be involved. An estimated 12-25% of the genetic variation causing NSCLP has been identified. We have recently shown that a novel gene, CRISPLD2, is associated with NSCLP and expressed in the orofacial region of developing mouse embryos at the time of lip and palate formation. We hypothesize that CRISPLD2 plays an important role during craniofacial development and that variation in this gene may cause NSCLP. Little information is known about this novel gene. The goal of this project is to characterize the role of this gene in normal craniofacial development and and how it contributes to NSCLP. To accomplish this goal, the CRISPLD2 sequence will be interrogated for variation. Identified sequence variants will be assessed for predicted function using computer algorithms and then analyzed in vitro to determine the effect on normal gene function. This paradigm has proven successful in identifying causative variants in other complex human diseases (i.e., Hirschsprung disease) and other NSCLP genes (i.e., Msx1), and will be followed to identify CRISPLD2 sequence variants with a potential biologic function. In order to determine CRISPLD2 function in normal vertebrate development, a conditional construct will be used to knock out CRISPLD2 in a mouse. Mouse models have proven useful in studying gene functions of other clefting genes (i.e., WntQb, IRF6 and Msx1). These studies are important first steps to characterize this novel craniofacial gene. This research will help us gain a better understanding craniofacial development and the causes of NSCLP. This project meets the goals of the NIDCR in improving oral health through research, research training and the dissemination of health information. Patients with NSCLP face a significant healthcare burden from surgical, dental and speech therapies. The information gained from this project will identify the function of the new clefting gene, CRISPLD2, that we recently identified and define the changes in the gene that may contribute to NSCLP. This will aid in the understanding of normal facial development, help to better diagnose and counsel families at risk for having a child with a cleft, and may lead to therapeutic intervention of orofacial clefting.

描述（由申请人提供）：有或不带裂口的非乳清裂唇唇（NSCLP）是一种常见的复杂性出生障碍，影响1/700个活产，每年有4000例在美国。 NSCLP的病因尚未完全理解，但已知遗传学和环境影响都涉及。估计导致NSCLP的遗传差异的估计为12-25％。我们最近表明，一种新型的基因crispld2与NSCLP相关，并在嘴唇和味觉形成时在发育中的小鼠胚胎的口面区域表达。我们假设Crispld2在颅面发育中起着重要作用，并且该基因的变化可能会导致NSCLP。关于这个新颖基因的信息知之甚少。该项目的目的是表征该基因在正常颅面发育中的作用及其对NSCLP的贡献。为了实现这一目标，Crispld2序列将被审问以进行变化。将使用计算机算法评估确定的序列变体的预测功能，然后在体外分析以确定对正常基因功能的影响。事实证明，该范式在鉴定其他复杂人类疾病（即Hirschsprung疾病）和其他NSCLP基因（即MSX1）中的病因变异已被证明成功，并将遵循具有潜在生物学功能的Crispld2序列变体。为了确定正常脊椎动物发育中的crispld2功能，有条件的构造将用于敲除鼠标中的crispld2。事实证明，小鼠模型可用于研究其他裂基因的基因功能（即WNTQB，IRF6和MSX1）。这些研究是表征这种新型颅面基因的重要第一步。这项研究将有助于我们更好地了解颅面发展和NSCLP的原因。该项目通过研究，研究培训和健康信息传播来符合NIDCR改善口腔健康的目标。 NSCLP患者面临外科，牙科和语音疗法的重大医疗保健负担。从该项目中获得的信息将确定我们最近确定并定义可能对NSCLP的基因变化的新裂基因Crispld2的功能。这将有助于理解正常的面部发展，有助于更好地诊断和咨询有风险的家庭患有裂缝的孩子，并可能导致口面裂的治疗干预。