The collection of faults (mutations) in genes causing inherited disease and making this data available is essential for genetic health care and research in all areas of human disease. Collection of such data has been occurring for decades in approximately 10% of the 20,000 human genes, but in a manner that is incomplete and inconsistent around the globe. These collections have been compiled on either a gene by gene basis by experts into so called locus specific databases (LSDBs) (see list of LSDBs), or into large aggregated collections across all genes, e.g. OMIM and HGMD. However, the presence of clinical information in these databases is often non-existent, due in large part to differences in privacy legislation across different countries. Furthermore, OMIM does not collect all possible mutations deliberately, and HGMD, whilst it is more comprehensive, is commercial and relies solely upon published data.

Diagnostic laboratories on the other hand, which usually continue on screening specific genes well after the first number of publications on patient cohorts, have a wealth of data with linked clinical information that is not in the public domain. The Human Variome Project was initiated to ensure collection of all mutations and associated clinical data in all genes worldwide and to ensure free and open access to this important data.

To further the aims of the Human Variome Project two HVP pilot projects have been developed:

1. The initiation of country specific collection in individual countries. This HVP Pilot seeks to establish systems to systematically collect every mutation that is characterised by a diagnostic laboratory, clinic or research laboratory in an individual country. To date, this HVP Pilot includes activities in the Kuwait, Korea, China, Argentina and Australia. Such initiatives will ensure complete collection of mutations and their effect worldwide. It is intended that the information from these individual databases will be shared globally through systems put in place by the Human Variome Project.
2. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT; www.insight-group.org), noting their need in treating and advising patients and at risk family members, have in collaboration with the HVP initiated an HVP Pilot to collect all data worldwide on their four genes of interest. This will be a model for the collection of mutations in all genes worldwide.

Objective

To create a data repository called the Australian Human Variome Database to provide access to information on all genetic variants characterised by Australian laboratories and clinics in a single location. Additionally, to provide a service that streamlines the reporting of genetic variants from Australian diagnostic laboratories and integrates these reports with appropriate clinical data, to facilitate the flow of data into the Australian Human Variome Database. Together, these two services will comprise the Australian Node of the Human Variome Project, the ultimate goal of which, is to create linkages between similar nodes in all countries and will act as a pilot system for other countries.

Progress/ Plans

The HVP Australian Node aims to provide medical scientists and clinicians a facility to share and review interpretations of genetic variants, thereby improving the diagnositic process.

Data Collected

In it's first phase, the Australian node will collect genetic data and a small compliment of phenotype data to help build context around the interpretation. For example; gene and variant names, the methods sued to identify the variant, disease if diagnosed, and age of diagnosis.

No identifying information about the patient will be stored in the Australian Node.

Collection Process Summary

Where possible, most of the data will be extracted from the laboratory LiMS (Laboratory information Management System) or via a compatible system such as MAWSON to reduce the effort of data entry.  A non-reversible hashing algorithm is used to de-identify the patient at the laboratory before the data is transported to the Australian Node.

The MAWSON project is a project to collect all genetic variants found by participating diagnostic laboratories in Australia, and to store this information along with the laboratory's assessment of clinical significance. At this stage, the project is restricted to collecting variants identified during testing of the BRCA1 and BRCA2 genes. The main goals of the project are to increase quality of clinical interpretation of variants, support collaboration between the laboratories to achieve more reliable assessment of pathogenity, and toimprove the consistency, efficiency, and quality of test reporting. The MAWSON project collaborates with the Australian node of the Human Variome Project (HVP) to avoid duplication of effort in data collection (uploadingdata on MAWSON and onto HVP; cleansing the raw data etc.). The project is funded by the Commonwealth Department of Health and Aging Quality Use of Pathology Program.

De-identified linkage with other clinical data sets using BioGrid Australia may provide a rich source of information for research projects.

Click on image to enlarge diagram of HVP dataflow

Usage Summary

Registered users of the Australian Node may search the Australian Node portal for variants.  Further query or research will require approval from HVP administration to ensure and validate ethical usage.