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

本研究通过唐氏综合症个体与其兄弟姐妹的比较，促进了对染色体变化如何影响产生颅面表型变异的生物学过程的认识和理解。结论将产生可测试的假设（在动物模型中），关于灵长类动物颅骨进化中的一些转变（如大小/形状变化、牙齿数量、形状、大小和喷发模式变化以及脑大小变化）是如何通过面部发育和整合模式的变化发生的。数据来自与全国唐氏综合症大会、宾夕法尼亚州特奥会、中央县唐氏综合症协会和唐氏综合症伙伴步行协会的合作。所有教育水平的实验室成员（如本科生、研究生、博士后）都接受过收集3D数据的培训，并经常在这些活动中担任志愿者。这些互动让研究团队了解了唐氏综合症组织是如何工作的，也让唐氏综合症社区的成员了解了这项研究从长远来看是如何有益的。这些经历加强了以一种非科学家容易理解的方式解释研究目标的承诺。颅面特征被用来推断人类祖先之间的系统发育关系，并在化石、骨骼种群和法医人类学中估计性别、种族和年龄。本项目研究正常和异常颅面变异，通过了解染色体变化如何影响表型产生的发育过程，最终了解当代人类变异和化石记录中发现的进化变异。对于导致唐氏综合症的特定染色体改变，本研究中颅面形态的形态计量学分析将确定：1)表型变异水平如何被修改；2)发育稳定性如何变化；3)变化模式如何改变；4)这种与生命相适应的染色体改变是如何影响发育从而产生表型变异的。

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.