Doctoral Dissertation Improvement: Understanding Gene Dosage Imbalance and Biological Mechanisms Responsible for Craniofacial Variability and Variation

博士论文改进：了解基因剂量不平衡和导致颅面变异和变异的生物机制

• 批准号: 1061563
• 负责人: Joan Richtsmeier
• 金额: $ 1.08万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1061563&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Improvement; Understanding; Gene

This research advances knowledge and understanding of how chromosomal changes affect biological processes that produce craniofacial phenotypic variation through comparisons of Down Syndrome individuals with their siblings. Conclusions will generate testable hypotheses (in animal models) about how some transitions in primate cranial evolution (e.g. size/shape changes, tooth number, shape, size, and eruption pattern changes, and brain size changes) have occurred through changes in patterns of facial development and integration. Data come from working with the National Down Syndrome Congress, Special Olympics of Pennsylvania, Centre County Down Syndrome Society, and Down Syndrome Buddy Walks. Members of the lab, at all educational levels (e.g., undergraduates, graduate students, post-docs,) are trained to collect 3D data and frequently volunteer at these events. These interactions have educated the research team about how Down syndrome organizations work and have educated members of the Down syndrome community about how the research might be beneficial in the long term. These experiences have strengthened the commitment to explain the research goals in a manner that is easily accessible to non-scientists.Craniofacial characteristics are used to infer phylogenetic relationships between human ancestors and to estimate sex, ethnicity, and age in fossils, skeletal populations, and forensic anthropology. This project examines both normal and abnormal craniofacial variation to eventually understand contemporary human variation and the evolutionary variation found in our fossil record by understanding how chromosomal changes affect developmental processes of phenotypic production. Regarding the specific chromosomal change that causes Down Syndrome, the morphometric analyses of craniofacial morphology in this study will determine: 1) how levels of phenotypic variance are modified; 2) how developmental stability changes; 3) how patterns of variation are altered; and 4) how this particular chromosomal alteration compatible with life affects development to produce phenotypic variation.

这项研究促进了知识和了解如何通过比较唐氏综合症个体与兄弟姐妹的比较来影响生物学过程的生物学过程。结论将产生可检验的假设（在动物模型中），即灵长类动物颅骨进化中的某些过渡（例如，大小/形状变化，牙齿数，形状，大小和喷发模式变化以及脑大小的变化）发生了通过面部发育和整合的模式而发生的。数据来自与国家唐氏综合症大会，宾夕法尼亚州特殊奥运会，中心县唐氏综合症协会和唐氏综合症伙伴步行的合作。实验室的成员在所有教育水平（例如，本科生，研究生，毕业后）都经过培训，可以收集3D数据，并经常自愿参加这些活动。这些互动已向研究团队教育了唐氏综合症组织的工作方式，并教育了唐氏综合症社区的成员，从长远来看研究可能如何有益。这些经历加强了以非科学家容易获得的方式来解释研究目标的承诺。颅面特征用于推断人祖先之间的系统发育关系，并估计化石，骨骼种群和法医人类学的化石，种族和年龄。 该项目研究了正常和异常的颅面变异，以最终了解当代人类变异以及我们化石记录中发现的进化变化，通过了解染色体变化如何影响表型生产的发育过程。 关于导致唐氏综合症的特定染色体变化，本研究中颅面形态的形态计量学分析将确定：1）如何改变表型方差的水平； 2）发展稳定性如何变化； 3）如何改变变异模式； 4）这种特殊的染色体改变与生命兼容的如何影响发育以产生表型变异。