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
Characterising The Role Of MID1 In X-linked Opitz Syndrome: Implications For CATCH22 And Related Disorders
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Opitz syndrome is a debilitating genetic disorder which affects the normal development of many organs and tissues of the human embryo. Patients with Opitz syndrome commonly present with facial deformities (such as cleft lip and palate) as well as both genital and heart defects. Males are usually more severely affected than females although the severity of the disease can vary even amongst males of the same family. Patients can die suddenly in infancy or suffer further developmental impairment du ....Opitz syndrome is a debilitating genetic disorder which affects the normal development of many organs and tissues of the human embryo. Patients with Opitz syndrome commonly present with facial deformities (such as cleft lip and palate) as well as both genital and heart defects. Males are usually more severely affected than females although the severity of the disease can vary even amongst males of the same family. Patients can die suddenly in infancy or suffer further developmental impairment due to respiratory complications and swallowing difficulties that result from the significant facial deformities. A brighter outlook for patients is expected if early and often repeated surgical repair is undertaken to correct not only the facial deformities but also any heart and genital abnormalities. Our research laboratory has recently identified the gene that, when mutated, causes one form of Opitz syndrome. Defects in this gene account for around half the cases with the disorder. Evidence suggests that there may be a number of other genes involved in causing the remaining cases of the disease. The proposed research is aimed at investigating the molecular and developmental mechanisms that go awry as a result of the gene mutation. It is anticipated that these studies will provide valuable scientific knowledge about why some patients are more severely affected than others as well as offering clues to the identity of the genes that cause the remaining cases of Opitz syndrome. The results also have potentially important implications for the understanding of other diseases that show similar deformities. The knowledge gained from this research is expected to provide a valuable aid for effective genetic counselling (as well as the option of prenatal diagnosis) for families at risk of further affected pregnancies. This will also ultimately lead to more effective disease management and correction in the affected child.Read moreRead less
Normal embryonic and foetal devlopment depends on the ability of cells to move from one place to another. This behaviour enables cells to be produced at one site and transported to one or a number of other sites. Although the face appears to us as a single seamless unit it originates as a number of blocks of tissue which begin development separately and must grow in a coordinated way that enables them to meet at precisely the correct time, in the correct place and in the correct order. The basis ....Normal embryonic and foetal devlopment depends on the ability of cells to move from one place to another. This behaviour enables cells to be produced at one site and transported to one or a number of other sites. Although the face appears to us as a single seamless unit it originates as a number of blocks of tissue which begin development separately and must grow in a coordinated way that enables them to meet at precisely the correct time, in the correct place and in the correct order. The basis of this growth and fusion is the ability of individual cells to move around the embryo to supply the raw materials for this construction process when and where they are needed. The combined activities of the cells in constructing the various parts of the embryo is known as morphogenesis which literally means creating shape. We are trying to gain insight into the basis of morphogenesis that produces the face. This is important because the face and other structures that are closely associated with it are particularly prone to errors. Despite this, surprisingly little is known about the mechansims that control development of the face. We know a great deal about which cells are involved in constructing the face but very little about what triggers the initial steps of development or maintains ordered growth. Our research is aimed at defining genes that are important in controlling development of the face through the study of normal development and birth defects. We are defining the function of genes that appear to be important in controlling the behaviour of cells during early development of the face. This knowledge will assist in understanding the control mechanism for facial devlopment and will eventually lead to improvements in the treatment and prevention of birth defects affecting these structures.Read moreRead less