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.
One goal of this study was to explore facial variation among individuals with trisomy 21, their siblings, and unrelated euploid sibling pairs. We found that approximately 28% of linear distance measures exhibit significantly different variances in Down syndrome faces relative to Down syndrome sibling controls. For each significantly different linear distance the Down syndrome sample exhibited increased variance relative to the homologous measures in the Down syndrome sibling sample. Next, we compared variance of facial linear distance measures between the Down syndrome sample and an unrelated age-matched euploid sample. We found that approximately 18% of linear distance measures exhibit significantly different variance in Down syndrome relative to unrelated age-matched euploid controls. Again, for each significantly different linear distance the Down syndrome sample exhibited increased variance relative to the homologous measures in the unrelated age-matched euploid controls. Taken together, these results suggest that gene-dosage imbalance caused by trisomy 21 is affecting the precision of craniofacial morphogenesis to create Down syndrome faces that are more variable for many facial measures. Interestingly, many significantly different linear distance measures are localized to the midface and lower face around the mouth, inferior to the nasal tip and wings. Another goal of this study was to quantify and compare patterns of morphological integration in the faces of individuals with Down syndrome, their siblings, and euploid sibling pairs. We found that the strength of integration between the upper face, midface, and lower face is very similar in Down syndrome relative to unrelated euploid individuals. However, the strength of integration between facial regions is lower in Down syndrome siblings relative to all other subsamples. Next we explored patterns of morphological integration among linear distance measures between sibling samples. We found twice as many significant differences in integration between the Down syndrome sample and Down syndrome sibling sample than we found between euploid sibling pairs. Moreover, we found that the patterns of positive and negative correlations between paired linear distances are different in both the Down syndrome and Down syndrome sibling samples relative to euploid sibling pairs. Taken together these results suggest that facial integration is strengthened by the presence of trisomy 21 and becomes similar to the levels of integration found in unrelated euploid siblings. However, the low levels of integration in Down syndrome siblings suggest that integration starts out lower in the similar genetic backgrounds that are shared by Down syndrome individuals and their siblings, and integration is then strengthened by the presence of trisomy 21 to reach levels found in the faces of typically developing individuals. The last goal of this study was to estimate and compare levels of facial developmental instability in individuals with Down syndrome, their siblings, and euploid sibling pairs to determine if the faces of individuals with Down syndrome exhibit amplified developmental instability. This goal was accomplished using the metric of fluctuating asymmetry, which is used to estimate developmental instability. Overall, we found that Down syndrome faces exhibit 146-169% more fluctuating asymmetry than the faces of their euploid siblings and unrelated euploid individuals. Thus, Down syndrome faces do exhibit amplified developmental instability. Next, we localized linear distance measures exhibiting significantly different fluctuating asymmetry to specific facial regions based upon craniofacial developmental precursors (e.g. frontal prominence, nasal prominences, maxillary prominences, and mandibular prominence) to determine whether developmental instability is generalized across the face or if different facial regions are more or less developmentally stable. We found that facial regions defined by developmental precursors can be characterized from the most developmentally unstable to the most developmentally stable in the Down syndrome sample as follows: mandibular prominence, maxillary prominence, nasal prominences, and the frontal prominence. Linear distances that exhibit significant differences in fluctuating asymmetry between Down syndrome siblings tend to cross developmental modules rather than being contained within developmental modules. This suggests that trisomy 21 may be changing the boundaries of developing facial regions or changing the ways that facial prominences fold and grow during development, possibly by slowing growth rates of particular prominences (e.g. the mandibular prominence) or reducing the amount of time prominences are in contact before fusion occurs. We hypothesize that this may be occurring because gene-dosage imbalance is altering cell division and migration to affect how facial prominences merge during craniofacial morphogenesis. On a developmental scale, these results help elucidate how trisomy 21 alters the typical human facial blueprint to produce the characteristic facial appearance associated with Down syndrome. However, on an evolutionary scale these results suggest that the mandibular and maxillary regions of human faces exhibit more developmental plasticity than other regions of the face. Considering the range of anatomical variation associated with the mandibular and maxillary regions of the face across mammals, it is possible that these particular facial regions are more developmentally labile and capable of responding to the demands of natural selection.
