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Comparative Transcriptomics and Genomics of Mammalian Lactation

Christophe Lefèvre, Philip Church, Adam Wong, Amit Kumar, James Stillman, Sam Schmidt, Karensa Menzies, Julie Sharp and Kevin Nicholas - Deakin University

Mammals are characterized by the total dependency of the new born on milk produced by the maternal mammary gland. Mammalian species have evolved a variety of lactation strategies providing a rich biodiversity resource to investigate lactation by comparative analysis. For example, marsupials give birth to a relatively immature embryo after a short gestation period. By contrast, in Eutherian, including all extant mammals outside Australasia and America, most of the development occurs in Utero. Thus, the marsupial young depends on milk for a significant period of time of its development. As a result, the study of lactation in marsupial is not only interesting for the exploration of the evolution of the lactation system in mammals, but also provides a unique model to explore the role of marsupial milk factors on the control of mammalian development and their relationship with eutherian intrauterine factors potentially having similar functions in utero. Monotremes, including platypus and echidna, are extant representatives of the most ancient mammals. Monotremes lay leathery-shelled eggs from which emerges a altricial or poorly developed young that is also totally dependant on milk provision by the mother during an extended lactation period. Thus, the analysis of monotreme milk may provide key insight into the origins, function and evolution of lactation. Other animals present peculiar adaptations relevant to study particular aspects of lactation physiology. For example the fur seal is able to maintain lactation after extended periods spent foraging at sea while in the majority of mammals lactation is irreversibly turned off after a few days of weaning. Thus, the fur seal presents a unique differential model to analyse the control of lactation during involution.

We have deployed a high throughput genomics and transcriptomics platform for the study of gene expression during lactation in marsupials (tamar wallaby and opossum), monotremes (platypus and echidna) and other mammals with extreme lactation strategies (seal, cow, human). A bioinformatics resource has been developed to support storage, retrieval and analysis of the data generated. An e-Resource is being built to integrate lactation data from a variety of mammalian species using a plethora of technologies and data sources available in the public domain or generated in house. These efforts should result in high quality annotation for the mammary function and the lactation system. The benefit from integration into an easily accessible and robust annotation framework with a rapidly customisable data-mining interface is illustrated by the way it is enabling research. This provides an interesting test case for in Silico biology where the nature of molecular information transmitted between mother and child during lactation is explored. Examples will be presented to illustrate the power of the comparative approach for the identification and evolutionary analysis of ubiquitous or specific molecular components of milk and the lactation system.

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