Genetic And Phenotype Studies Of Partial Epilepsy In Gypsies
Funder
National Health and Medical Research Council
Funding Amount
$646,136.00
Summary
Epilepsy is one of the most common serious neurological disorders, which affects more than 50 million people worldwide. Genetic research, with a major contribution from Australian researchers, has led to the discovery of many rare forms of the disease caused by mutations in single genes of large effect. However, the vast majority of cases worldwide belong to the so-called genetically complex forms, involving multiple interacting genes and environmental factors. The genetically complex epilepsies ....Epilepsy is one of the most common serious neurological disorders, which affects more than 50 million people worldwide. Genetic research, with a major contribution from Australian researchers, has led to the discovery of many rare forms of the disease caused by mutations in single genes of large effect. However, the vast majority of cases worldwide belong to the so-called genetically complex forms, involving multiple interacting genes and environmental factors. The genetically complex epilepsies have proved particularly difficult to understand and the numerous genetic studies conducted so far have failed to produce important and replicable results. It is becoming increasingly clear that enormous genetic heterogeneity, with many rare mutations occurring in different affected subjects, will be a major obstacle to understanding the molecular basis of complex epilepsies. In this context, genetically isolated populations, which stem from a small number of ancestors, can be particularly helpful and revealing, since their limited genetic diversity means that the number of genes involved in causing complex epilepsies may be smaller and shared between individuals and families. In this study, we will analyze affected families, as well as non-familial cases of epilepsy, from a genetically isolated population - the European Roma-Gypsies. We will determine the number of potential susceptibility genes involved in familial forms, the overlap and differences between families, as well as the contribution of the genes identified in families to the development of sporadic epilepsy.Read moreRead less
High Resolution Mapping Of Genomic Regions Implicated In Migraine
Funder
National Health and Medical Research Council
Funding Amount
$392,545.00
Summary
Migraine is a frequent, debilitating and painful disorder that affects a significant proportion of the population. Using the diagnostic criteria of the international Headache Society, the prevalence of migraine has been estimated to be approximately 12%, with a recent study in the United States showing that migraine affects 4% of children, 6% of men and 18% of women. The aetiology of migraine is unknown and there are no laboratory based diagnostic tests to identify those who suffer from the diso ....Migraine is a frequent, debilitating and painful disorder that affects a significant proportion of the population. Using the diagnostic criteria of the international Headache Society, the prevalence of migraine has been estimated to be approximately 12%, with a recent study in the United States showing that migraine affects 4% of children, 6% of men and 18% of women. The aetiology of migraine is unknown and there are no laboratory based diagnostic tests to identify those who suffer from the disorder. Clinical diagnosis is currently based on patient symptom descriptions, with individual symptoms being shown to vary with age. Migraine is believed to have a genetic basis with specific environmental factors, such as particular foods, hormonal levels and fatigue, being capable of inducing attacks in predisposed individuals. Migraine shows strong familial aggregation with about 50% of those affected, having another close relative also affected with the disorder. At present the number of genes involved in the disorder is unknown and have not been identified. Recent studies in our laboratory have localised two migraine genes, one to chromosome 19 and the other to the X chromosome. More recently we have also found evidence for a third gene on chromosome 1. This study is aimed at fine scale mapping analysis of these three chromosomal regions in order to pinpoint the location of migraine genes. Our ultimate aim is to identify the molecular causes of this disorder. This would have important implications to both the diagnosis and treatment of migraine.Read moreRead less
Genome-wide Association Study Of Migraine In Women With Endometriosis
Funder
National Health and Medical Research Council
Funding Amount
$320,036.00
Summary
Typical migraine, is a frequent, debilitating and painful disorder that affects people during their most productive years (25% of females and 7.5% of males). Women suffering endometriosis (a painful gynecologic disorder affecting up to 10% of women) are at an increased risk of suffering migraine headaches. Our proposed collection of migraine phenotype data on our endometriosis cohort will facilitate identification of genes underlying both disorders.
The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
Identifying Rare Genetic Variants Conferring Susceptibility To Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$293,898.00
Summary
Recently there has been success in identifying common genetic variants that confer susceptibility to multiple sclerosis. The variants that have been discovered so far have modest effects on risk of disease, and only explain a small proportion of familial aggregation of disease. In this study we aim to identify rarer genetic variants that have stronger effects on risk of disease, using new statistical methods and new methods to sequence very large amounts of DNA.
A Zebrafish Model Of Facioscapulohumeral Dystrophy For Therapy Development And Functional Studies
Funder
National Health and Medical Research Council
Funding Amount
$390,601.00
Summary
This project seeks to develop a zebrafish model for a genetic muscle-wasting disease called facioscapulohumeral dystrophy (FSHD). Our zebrafish model will enable us to better understand the biological mechanisms underlying the disease, as well as provide a platform for therapeutic testing and discovery.
Uncovering The Function Of Susceptibility Variants In Alzheimer's Disease: From GWAS To Cell-Type Specific EQTLs And MQTLs
Funder
National Health and Medical Research Council
Funding Amount
$647,804.00
Summary
This project will investigate some of the genetic and epigenetic changes that occur inside certain brain cells that make them selectively vulnerable to Alzheimer's disease, in order to better understand the mechsnisms that give origin to the disease and identify possible targets for precision therapies.