Genetics of craniofacial anomalies

The birth of a child with a craniofacial malformation is usually an unexpected and devastating event for the parents. One of the first questions asked is ‘Why did this happen?’ Later, they may go on to ask ‘Could this happen again and if so, can it be avoided?’ A clinical genetics assessment can make an important contribution to answering these and other questions. In general, craniofacial malformations represent defects in embryogenesis, which can arise either from altered genetic information (abnormal developmental programming of the embryo), environmental insult (disruption of development), or a combination of adverse genetic and environmental factors. The clinical geneticist’s approach is primarily directed towards deciding which of these scenarios is most likely to be correct and, if a specific genetic cause is suspected, to advising on the most appropriate genetic tests to perform.

A Shift from Glycolytic and Fatty Acid Derivatives toward One-Carbon Metabolites in the Developing Lung During Transitions of the Early Postnatal Period

During postnatal lung development, metabolic changes that coincide with stages of alveolar formation are poorly understood. Responding to developmental and environmental factors, metabolic changes can be rapidly and adaptively altered. The objective of the present study was to determine biological and technical determinants of metabolic changes during postnatal lung development. Over 118 metabolic features were identified by liquid chromatography with tandem mass spectrometry (LC-MS/MS, Sciex QTRAP 5500 Triple Quadrupole). Biological determinants of metabolic changes were the transition from the postnatal saccular to alveolar stages and exposure to 85% hyperoxia, an environmental insult. Technical determinants of metabolic identification were brevity and temperature of harvesting, both of which improved metabolic preservation within samples. Multivariate statistical analyses revealed the transition between stages of lung development as the period of major metabolic alteration. Of 3 distinctive groups that clustered by age, the saccular stage was identified by its enrichment of both glycolytic and fatty acid derivatives. The critical transition between stages of development were denoted by changes in amino acid derivatives. Of the amino acid derivatives that significantly changed, a majority were linked to metabolites of the one-carbon metabolic pathway. The enrichment of one-carbon metabolites was independent of age and environmental insult. Temperature was also found to significantly influence the metabolic levels within the post-mortem sampled lung, which underscored the importance of methodology. Collectively, these data support not only distinctive stages of metabolic change but also highlight amino acid metabolism, in particular one-carbon metabolites as metabolic signatures of the early postnatal lung.

Hashiri, Sakari, Nagori

Japanese gastronomy relies upon seasonality and centuries-old Zen Buddhist principles in methods of cooking, types of ingredients, and colors of food on the plate. But its practitioners and proponents have also mythologized its high-end cuisine. At the same time as Japan was undergoing the most rapid industrialization in history, fantasies about nature, and its role in cooking, developed. These fantasies exist within Japan as well as when its gastronomy is discussed with outsiders to the culture. Long ago, the fantasies served Japan's expansionist goals, and nowadays they contribute to the creation of a global brand—the idea that Japanese food has a native superiority. In addition, the fantasies distract consumers from environmental insult; the talk of Japanese love and respect of nature is at odds with the reality of its industrialization and urban sprawl. When Japanese chefs discuss the ideas behind the food they cook, they can resort to fables, and the psychology of what the food is said to be about has little to do with the pragmatic demands of what goes on in the kitchen. In fact, Japanese gastronomy, as is true of any other national cuisine, has examples of food that represent the nation, but are not rooted in myth. Such food has more to do with cooking than myth.

INVESTIGATING THE MOLECULAR AND DEVELOPMENTAL EFFECTS OF VARIOUS CULTURE REGIMES IN A MOUSE MODEL SYSTEM

Background/Purpose: Genomic imprinting is a specialized transcriptional mechanism that results in the unequal expression of alleles based on their parent-of-origin [1]. Many imprinted genes are critical for proper embryonic and fetaldevelopment [2] and disruption of genomic imprinting are associated with many development disorders [3]. Recently, increased frequencies of imprinting disorders have been correlated with the use of assisted reproductive technologies (ARTs)[2]. Rigorous and thorough testing of ARTs is required to determine their influence on genomic imprinting and development. I hypothesize that imprinting maintenance mechanisms are disrupted during early mouse development by the environmental insult of culture media used in human ARTs, and that loss of imprinting correlates with delayed embryonic development. Methods: The specific aims of my project are to develop a method to evaluate the methylation and expression patterns of 4 known imprinted genes in individual blastocysts. Results: We have successfully developed a novel method to evaluate both imprinted methylation and expression from a single mouse blastocyst. This method has been tested and results compared to methods used to evaluate imprinted methylation and expression separately; we have determined that results obtained with a combined protocol are equivalent to either alone. I will use this method to evaluate relationships between development rates in culture andgenomic imprinting, as well as the effects of various culture media used formouse and human embryo culture on genomic imprinting. Conclusion: This analysis allow for a more comprehensive study ofthe effects of environmental insult on genomic imprinting and preimplantation embryo development. References: 1. Reik W, Walter J. Genomic imprinting:parental influence on the genome. Nat Rev Genet 2001;2:21-32. 2. Rodenhiser D, Mann M. Epigenetics andhuman disease: translating basic biology into clinical applications. CMAJ. 2006;174:341-8. 3.Paoloni-Giacobino A. Epigenetics in reproductive medicine. Pediatr Res 2007;61:51R-57R.

Longitudinal glia in the fly CNS: pushing the envelope on glial diversity and neuron-glial interactions

Interactions between neurons and glial cells are crucial for nervous system development and function in all complex organisms, and many functional, morphological and molecular features of glia are well conserved among species. Here we review studies of the longitudinal glia (LG) in the Drosophila CNS. The LG envelop the neuropil in a membrane sheath, and have features resembling both oligodendrocytes and astrocytes. Because of their unique lineage, morphology and molecular features, the LG provide an excellent model to study the genetic mechanisms underlying glial subtype differentiation and diversity, glial morphogenesis and neuron–glial interactions during development. In addition, they are proving useful in understanding how glial cells maintain ion and neurotransmitter homeostasis and protect neurons from environmental insult.