THE GENETIC BASIS OF MORPHOLOGICAL VARIATION IN THE SKULL OF THE GRAY SHORT-TAILED POSSUM, MONODELPHIS DOMESTICA

描述(申请人提供)：这项研究项目的长期目标是通过使用有袋类动物模型来加强我们对哺乳动物头面部骨骼遗传基础的理解。有袋类动物已经成为几种人类疾病的宝贵模式生物，如皮肤癌和眼癌、高胆固醇血症和脊髓损伤。这项研究将它们的使用范围扩大到包括颅面研究，主要有两个原因。首先，人们对这种哺乳动物亚纲物种形态变异的遗传基础知之甚少。其次，德克萨斯生物医学研究所(TBRI)的John VandeBerg博士长期以来一直保持着一个非常有用的人工饲养家养Monodelphis种群，其中包括具有已知系谱的个体和几个准近交系。因此，本研究项目将利用灰色短尾负鼠这一圈养繁殖种群，对该物种的头骨形态变异进行遗传分析。在这项分析中，将使用新的DNA测量技术来产生分子标记，其变异将与通过使用3D数字化设备测量的颅骨形态的个体差异相关。然后，将使用针对复杂家系定制的统计方法来识别导致头面部形态个体差异的数量性状基因座。关于形态变异的发育决定因素的假设也将得到检验。这项工作将增加我们对哺乳动物头面部骨骼遗传基础的稀疏理解。它还将使我们能够识别影响头面部骨骼的几个基因组区域。其中一些基因组区域可能为我们提供有趣的候选基因，这将为这一模式物种开辟新的研究途径。这项工作也将有助于我们理解颅面整合进化的遗传和个体发育机制。

DESCRIPTION (provided by applicant): The long-term objective of this research project is to enhance our understanding of the genetic underpinnings of the mammalian craniofacial skeleton through the use of a marsupial model. Marsupials have already become a valuable model organism for several human conditions, such as skin and eye cancer, hypercholesterolemia and spinal cord injury. This research expands their use to include craniofacial research, for two main reasons. First, little is known about the genetic underpinnings of morphological variation in species from this mammalian infraclass. Second, Dr. John VandeBerg from the Texas Biomedical Research Institute (TBRI) has for long maintained an extremely useful captive breeding population of Monodelphis domestica, containing individuals with known pedigrees and several quasi-inbred lines. Therefore, this research project will take advantage of this captive breeding population of the gray short-tailed opossum and carry out a genetic analysis of cranial morphological variation in this species. In this analysis, novel DNA surveying techniques will be used to generate molecular markers whose variation will be correlated to individual differences in cranial morphology, measured through the use of 3D digitizing equipment. Quantitative trait loci contributing to individual differences in craniofacial morphology will then be identified using statistical methods tailored t complex pedigrees. Hypotheses about the developmental determinants of morphological variation will also be tested. This work will increase our sparse understanding of the genetic underpinnings of the mammalian craniofacial skeleton. It will also allow us to identify several genomic regions that affect the craniofacial skeleton. Some of these genomic regions may provide us with interesting candidate genes that will open up new research avenues for this model species. This work will also contribute to our understanding of the genetic and ontogenetic mechanisms for the evolution of craniofacial integration.