Craniofacial Anomalies Research Center

描述(由申请人提供)：一般情况下，唇裂和/或腭裂的颅面畸形是人类常见的出生缺陷。这些异常需要大量的外科、牙科、言语和行为干预，并造成巨大的经济和社会负担。已知有400多种综合征、染色体异常和致畸暴露会导致唇裂。这些疾病继发于基因-基因和基因环境相互作用的复杂相互作用，而基因-基因和基因环境相互作用是这些疾病表型差异较大的原因。虽然包括唇裂在内的颅面畸形的病因已经被深入研究，但直到最近几年才开始成功的基因识别，现在有望在诊断、治疗和预防方面有所改进。这些成功是临床医生和动物模型、表型、统计/定量分析和基因发现专家之间合作互动的结果。在我们的颅面畸形研究中心，我们将以爱荷华大学40多年的历史为基础，对这些疾病进行调查。我们已经组建了一支拥有丰富经验和专业知识的国际团队，他们将通过五个主要项目和五个支持核心进行密切互动，以执行一套旨在提高我们对唇腭裂的理解的综合调查。小鼠模型研究将是对人类基因发现的补充，所有研究都将受益于基因组学方法来表征基因和基因表达。该项目的成果将立即和直接地有助于更好地理解人类和动物模型中裂隙的遗传方面，并更好地洞察颅面发育的基本生物学。它将确认可以理解复杂的人类颅面疾病并改进诊断和预防的原则证据。

DESCRIPTION (provided by applicant): Craniofacial anomalies in general in clefts of the lip and/or palate in particular are common human birth defects. These abnormalities require significant surgical, dental, speech, and behavioral interventions and impose substantial economic and societal burdens. More than 400 syndromes, chromosomal abnormalities and teratogenic exposures are known to result in clefts. These occur secondary to a complex interplay of gene-gene and gene environmental interactions which underly the wide variation in phenotype seen in these disorders. Although the causes of craniofacial anomalies including clefts have been investigated intensively, it has only been in the last few years that successful gene identification has begun and now offers the promise of improvements in diagnosis, treatment, and prevention. The successes have been the result of collaborative interactions between clinicians and scientists expert in animal models, phenotyping, statistical/quantitative analysis and gene-finding. In our Craniofacial Anomalies Research Center we will build on an over forty year history at the University of Iowa in investigations into these disorders. We have assembled an international team with substantial experience and expertise who will closely interact through five primary projects and five support cores to perform an integrated set of investigations aimed at improving our understanding of cleft lip and palate. Mouse model studies will complement those of human gene finding and all investigations will benefit from genomic approaches in characterizing genes and gene expression. The outcome of this project will be immediate and direct contributions to a better understanding of the genetic aspects of clefting in both humans and animal models and far better insights into the basic biology of craniofacial development. It will confirm proof of principle that complex human craniofacial disorders can be understood and diagnosis and prevention improved.