A Subphenotyping Approach To Identifying Genes Responsible For Isolated Clefts Of The Lip And Palate.
Funder
National Health and Medical Research Council
Funding Amount
$679,707.00
Summary
Clefts of the lip and palate are the most common birth defects involving the face. The genes responsible for these conditions have been difficult to find in the past. We have identified a method through which the chances of finding these genes is greatly increased. Detailed measurements of a number of facial features in cleft patients and unaffected first-degree relatives will provide a much clearer picture of those at higher risk of being affected by this debilitating disorder.
Gene Identification In Familial Orofacial Clefts By Genomic Technologies
Funder
National Health and Medical Research Council
Funding Amount
$565,181.00
Summary
Cleft lip/palate (CL/P) is among the most common malformation disorders but the causes of this condition are largely unknown. We do know that gene mutations cause CL/P in some people. We have also shown that the p63 gene may influence the activity level of genes involved in CL/P by attaching to regulatory elements near these genes. Changes in as yet unidentified genes controlled by p63 are strong possibilities for the cause of CL/P. We will test these by next generation sequencing, a technique t ....Cleft lip/palate (CL/P) is among the most common malformation disorders but the causes of this condition are largely unknown. We do know that gene mutations cause CL/P in some people. We have also shown that the p63 gene may influence the activity level of genes involved in CL/P by attaching to regulatory elements near these genes. Changes in as yet unidentified genes controlled by p63 are strong possibilities for the cause of CL/P. We will test these by next generation sequencing, a technique that analyses all human genes.Read moreRead less
Understanding The Regulation Of Craniofacial Development Through Control Of Chromatin And Gene Transcription
Funder
National Health and Medical Research Council
Funding Amount
$616,372.00
Summary
Cleft lip and palate are among the most common birth defects. Key genes regulating palate development are sensitive to disturbance by environmental factors. We use this system to comprehensively determine a molecular pathway that is at the interface between the environment and gene transcription. Knowledge gained in the project will draw a framework for our understanding of how environmental insults affect chromatin configuration and gene expression and will inform the basis of measures to preve ....Cleft lip and palate are among the most common birth defects. Key genes regulating palate development are sensitive to disturbance by environmental factors. We use this system to comprehensively determine a molecular pathway that is at the interface between the environment and gene transcription. Knowledge gained in the project will draw a framework for our understanding of how environmental insults affect chromatin configuration and gene expression and will inform the basis of measures to prevent birth defects.Read moreRead less
The Role Of Nectins In Morphogenesis Of The Primary Palate: Implications For Non-syndromic Cleft Lip And Palate.
Funder
National Health and Medical Research Council
Funding Amount
$439,500.00
Summary
Cleft lip with or without cleft palate may be an isolated feature or part of a wider array of abnormalities, ie. syndrome. Collectively, cleft lip and palate is the fourth most common congenital disorder in humans, occurring with a frequency of between 1 in 600 and 1 in 1000 live births worldwide. This high frequency is reflective of the heightened susceptibility of the developing face to genetic and-or environmental perturbation and likely arises as a direct consequence of the rapid and signifi ....Cleft lip with or without cleft palate may be an isolated feature or part of a wider array of abnormalities, ie. syndrome. Collectively, cleft lip and palate is the fourth most common congenital disorder in humans, occurring with a frequency of between 1 in 600 and 1 in 1000 live births worldwide. This high frequency is reflective of the heightened susceptibility of the developing face to genetic and-or environmental perturbation and likely arises as a direct consequence of the rapid and significant morphological changes that ultimately generate the human face. Yet despite the clinical significance of this abnormality and the psychological and financial burden to the patient and their family, there is relatively little known about the genetic and, in particular, cellular mechanisms responsible. We are seeking to understand the cellular and developmental role(s) of two key proteins in the formation of the upper lip and palate. It is anticipated that these studies will provide valuable new clues as to the molecular events that underlie some forms of cleft lip and palate as well as reveal a likely mechanism to explain some of the marked clinical variability that is seen most prominently in the isolated forms of cleft lip and palate. It is envisaged that these data may ultimately lead to the development of more effective diagnostic and preventative measures.Read moreRead less