Reproductive genetic carrier screening aims to offer couples information about their chance of having children with certain autosomal recessive and X-linked genetic conditions. We developed a gene list for use in “Mackenzie’s Mission”, a research project in which 10,000 couples will undergo screening. Criteria for selecting genes were: the condition should be life-limiting or disabling, with childhood onset, such that couples would be likely to take steps to avoid having an affected child; and/or be one for which early diagnosis and intervention would substantially change outcome. Strong evidence for gene-phenotype relationship was required. Candidate genes were identified from OMIM and via review of 23 commercial and published gene lists. Genes were reviewed by 16 clinical geneticists using a standard operating procedure, in a process overseen by a multidisciplinary committee which included clinical geneticists, genetic counselors, an ethicist, a parent of a child with a genetic condition and scientists from diagnostic and research backgrounds. 1300 genes met criteria. Genes associated with non-syndromic deafness and non-syndromic differences of sex development were not included. Our experience has highlighted that gene selection for a carrier screening panel needs to be a dynamic process with ongoing review and refinement.
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We thank the following clinicians for advice on genes in their area of expertise; Stephen Alexander, Janice Fletcher, Paul Gray, Lilian Johnstone, Ian Kerridge, Andrew Mallett, John Massie, Hugh McCarthy, Vanessa Morgan, Philip Robinson, Monique Ryan, Peter Trnka, Jan Walker, Bridget Wilcken. We thank Morgan Carpenter for a submission on genes involved in differences of sex development. We thank Richard Allcock, Michael Fietz and Georgina Hollingsworth for helpful comments. We thank members of the NHMRC Centre for Research Excellence in Genetic Eye Diseases (APP1116360) for comment on ocular genes under consideration.
The Australian Reproductive Genetic Carrier Screening Project is funded by Australian Government’s Medical Research Future Fund as part of the Australian Genomics Health Futures Mission (GHFM73390 (MRFF- G-MM)). NGL is supported by Australian National Health and Medical Research Council Fellowship APP1117510.
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The authors declare that they have no conflict of interest.
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Kirk, E.P., Ong, R., Boggs, K. et al. Gene selection for the Australian Reproductive Genetic Carrier Screening Project (“Mackenzie’s Mission”). Eur J Hum Genet (2020). https://doi.org/10.1038/s41431-020-0685-x