Cleft Lip Genetics: A Multicenter International Consortium

唇裂遗传学：多中心国际联盟

• 批准号: 7258364
• 负责人: Andrew C Lidral
• 金额: $ 10.17万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-07 至 2008-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7258364
• 关键词: Affect; Animal Model; Award; Biological Process; Candidate Disease Gene; Child; Chromosome Mapping; Cleaved cell; Cleft Lip; Cleft Palate; Clinical; Collaborations; Colombia; Complex; Congenital Abnormality; Data Analyses; Defect; Development; Developmental Biology; Diagnosis; Disease; Dissection; Environmental Risk Factor; Etiology; Family; Fathers; Finland; Foundations; Genes; Genetic; Genome; Genome Scan; Genotype; Goals; Human Genetics; International; Iowa; Knowledge; Laboratories; Life; Linkage Disequilibrium; Literature; Live Birth; Maps; Molecular; Mothers; Mutation; Nuclear; Numbers; Ohio; Patients; Pennsylvania; Phenotype; Population; Prevalence; Prevention therapy; Recruitment Activity; Relative (related person); Research; Resources; Role; Technology; Testing; Time; Washington; base; career; craniofacial; genetic analysis; genetic linkage analysis; genetic pedigree; genetic variant; genome wide association study; member; orofacial; prevent; skills; tool; trait

DESCRIPTION (provided by applicant): The focus of my research career is to identify the causes of craniofaciai anomalies, which will provide the foundation to develop strategies and therapies to prevent this common group of birth defects. The specific goals of this award are to 1) provide intensive research time in order to accomplish the goals of the research plan; 2) immerse myself in the literature to stay abreast of new discoveries and technologies such that they can be rapidly integrated into this project when warranted; and 3) broaden my expertise in human genetics as well as molecular and developmental biology to allow me to develop a set of life long skills as my career progresses from disease gene identification and molecular characterization, to the development and study of animal models to finally the development and implementation of prevention therapies. Cleft lip with or without cleft palate (CL/P) is a common birth defect. Previous studies have indicated that CL/P is a complex trait that is caused by a combination of genetic and environmental factors. This complexity has limited studies, such that disease mutations have only been identified in one unique family. It is also unlikely that all disease loci have been identified. The overall objective of this project is to identify disease genes involved in nonsyndromic CL/P by applying new multistage linkage and linkage disequilibrium (LD) strategies to affected relative pairs and extended pedigrees. This multistage approach, which has not yet been applied to CL/P, is very powerful in that no prior knowledge about the involved genetic or biological processes is needed. Hypothesis to be tested: Nonsyndromic CLIP is caused by Genetic Variants at one or more loci. To test this hypothesis, CL/P families with both multiple affected members and mother/father and affected child trios will be recruited from a variety of clinical centers. The families will be the basis for initially evaluating candidate genes to test the above hypothesis using the genetic tools of linkage and linkage disequilibrium to reject (exclude) or provide evidence for support (i.e. linkage) the hypotheses. A 10 cM genome-wide screen will also be performed to find additional loci. Positive loci will be further evaluated by a combination of multipoint, multi-locus and TDT/association analyses using more densely spaced markers. It will be through multi-center projects such as this one, in which worldwide collaborations have been established to apply a combination of complimentary genetic strategies, that disease loci for CL/P wilt be identified. Ultimately, this will further the understanding of normal and abnormal craniofacial development, such that therapies to prevent CL/P can be developed and implemented.

描述（由申请人提供）：我的研究重点是确定颅面畸形的原因，这将为制定预防这一常见出生缺陷的策略和治疗提供基础。该奖项的具体目标是：1)提供密集的研究时间，以完成研究计划的目标；2)让自己沉浸在文献中，跟上新发现和新技术的步伐，这样它们就可以在有保证的时候迅速集成到这个项目中；3)拓宽我在人类遗传学以及分子和发育生物学方面的专业知识，使我能够在从疾病基因鉴定和分子表征到动物模型的开发和研究，最后开发和实施预防疗法的职业发展中培养一套终身技能。