Gene Submission

Submit a disease variant to establish a connection

CONNECTION APPLICATION
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Who can submit a gene?

Australian clinicians and diagnostic labs (including research diagnostic groups) discovering genes or variants of unknown significance (VUS/GUS) in patients, who want to connect with functional genomics researchers who can investigate the functions of those genes and/or the functional attributes of the gene variants.

Which genes/variants should be submitted?

The Network welcomes the submission of functional genomics studies in the following categories:

Stream 1: Assessing the impact of variants in known or novel disease genes

This will support the investigation of variants that change the coding sequence of a gene or variations that encompass genomic alternations likely to alter gene expression or splicing.

Projects may include:

Investigating genetic changes in individuals with clinically diagnosed disease who lack mutations in known disease genes.
Genetic lesions in known disease genes which do not reach the necessary threshold to provide diagnostic certainty but for which a compelling case for causation can be made. This might include a pattern of familial inheritance, de novo appearance and/or bioinformatic or other analyses that establish the potential impact on protein function or gene expression.
Investigation of novel oligogenic mechanisms of disease in which pathology arises through cumulative effects of mutations in more than one disease gene in an affected individual.

Stream 2: Analysis of multiple variants in a single gene

For many known disease genes there are often significant numbers of potentially disease-causing variants which do not reach the current threshold for definitive genetic diagnosis.

The Network will mobilise the entire Australian biomedical community of clinicians and scientists to communicate, integrate their resources, and work collaboratively to gain insights into the clinical and functional attributes of rare disease genes and cancer genes. Through the database capturing the resources and expertise existing in the Australian research community, connections will be fostered between teams with matching research interest to deliver a better understanding of the genetic and cellular disease mechanisms, develop prevention guidelines and diagnostic tests, and investigate potential therapies. The goal of the Australian Functional Genomics Network is to improve the lives of patients and their families through the coordination of functional genomics research in Australia.

The specific objectives of the Network are to:

provide functional validation of human genetic variants that cause disease;
develop insights into an evidence-based rationale for treatment (e.g. identification of candidate drug targets) via knowledge of disease gene function and molecular pathway;
complement clinical disease gene discoveries by functional genomics investigation that lead to significant and impact research output, such as publications, health policy and practice of clinical management; and
establish sustainable collaborations between clinical teams and model system research teams to conduct outstanding research that will attract further competitive funding support.

Clinical Review Committee

The committee is composed of clinical geneticists and genetic pathology experts from around Australia, who will review the submitted clinical and genetic evidence. Committee members will consider the likelihood that a given variant causes the patient phenotype and the likelihood that subsequent variant modelling would provide diagnostic certainty and improve the clinical management of the affected individual/s. Application will be scored against the following:

Quality of the genetic data as disease-causing
Disease severity, progression and medical need
Potential therapeutic tractability / therapeutic need to lack of existing therapies
The novelty of the implicated biological pathway
Counselling impact

Those with scores of 3 or higher will progress to the Scientific Review Committee.

Scientific Review Committee

The Scientific Review Committee will identify the best candidate model system investigators registered in the AFGN database. The best candidate/s will then be invited to apply for funding. Proposals will consist of a summary of the potential studies to be undertaken and a proposed budget to be considered for funding. Applications will be ranked based primarily on the suitability of the proposed research to resolve the variant/s under consideration. The committee will also consider the approaches used, the timeline to success, and the cost/value for money.

Funding Allocations

Projects will be funded in “quanta” based on the scope of the project, the number of variants to be modelled and the organism or cellular system in which modelling will take place. Each quantum equates to $15,000 and a maximum of 4 quanta (total of $60,000) can be applied for any given project submission.

The Network has no formal requirement for prior partnership. Applications are welcomed from pre-existing or newly formed teams of clinicians and model system investigators who share an interest in pursuing disease gene discovery or validating variants of unknown significance. The Network also welcomes proposals from other organizations such as rare disease foundations who are interested in funding Catalyst Grants in targeted areas. [contact us at: functional.genomics@mcri.edu.au]

Frequently Asked Questions

The most usual reason for the Clinical Review Committee to decline an application is the lack of adequate genetic data to support causality. Applications will also be declined if it is deemed that the proposing study is on a relatively common variant in the population. If a variant phenotype in a known gene is proposed, an appropriate justification that this is a distinct phenotype is likely to be underpinned by a different pathogenic mechanism (e.g. gain-of-function versus previously known hypomorphic mutations) may be provided.

A key objective of the Network is to expedite collaborations on model-based studies of rare disease genes. Although applications from clinical teams are encouraged, we recognise that there could be situations where there is insufficient detailed analysis of genetic data. Such applications will be put “on hold” whereupon additional input from molecular geneticist studies can help build the case for further consideration.

The review committee will call the different groups to consider a multi-team collaboration. Applicants may recognize that a collaborative project is more likely to lead to significant research output, given the fierce competition for publishing research findings in journals of high repute.