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Gene selection for the Australian Reproductive Genetic Carrier Screening Project (“Mackenzie’s Mission”)

European Journal of Human Genetics volume 29, pages 79–87 (2021)Cite this article

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Abstract

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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Fig. 1: The Mackenzie’s Mission gene list selection process.

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Acknowledgements

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.

Funding

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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Author notes

  1. These authors contributed equally: Nigel G. Laing, Martin B. Delatycki

Authors and Affiliations

  1. Centre for Clinical Genetics, Sydney Children’s Hospital Randwick, Randwick, NSW, Australia

    Edwin P. Kirk, Kirsten Boggs, Sarah Righetti & Tony Roscioli

  2. School of Women’s and Children’s Health, University of New South Wales, Randwick, NSW, Australia

    Edwin P. Kirk, Sarah Righetti & Clara W. T. Chung

  3. NSW Health Pathology East Genomics Laboratory, Randwick, NSW, Australia

    Edwin P. Kirk & Tony Roscioli

  4. Centre for Medical Research, The University of Western Australia, Nedlands, WA, Australia

    Royston Ong, Samantha Edwards & Nigel G. Laing

  5. Harry Perkins Institute for Medical Research, Nedlands, WA, Australia

    Royston Ong, Samantha Edwards & Nigel G. Laing

  6. Australian Genomics Health Alliance, Melbourne, VIC, Australia

    Kirsten Boggs & Jade Caruana

  7. Department of Clinical Genetics, Children’s Hospital Westmead, Westmead, NSW, Australia

    Kirsten Boggs, Robyn V. Jamieson, Alan Ma & Meredith Wilson

  8. SA Pathology, Adelaide, SA, Australia

    Tristan Hardy

  9. Repromed, Dulwich, SA, Australia

    Tristan Hardy

  10. Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia

    Tristan Hardy

  11. Genetic Services of Western Australia, Perth, WA, Australia

    Ben Kamien & Nicholas Pachter

  12. Neuroscience Research Australia, Randwick, NSW, Australia

    Tony Roscioli

  13. Murdoch Children’s Research Institute, Parkville, VIC, Australia

    David J. Amor, Jade Caruana, Alison Archibald & Martin B. Delatycki

  14. Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia

    David J. Amor & Alison Archibald

  15. Department of Clinical Genetics, Liverpool Hospital, Liverpool, NSW, Australia

    Madhura Bakshi, Clara W. T. Chung, Alison Colley & Sulekha Rajagopalan

  16. Eye Genetics Research Unit, Children’s Medical Research Institute, Children’s Hospital Westmead, Save Sight Institute, University of Sydney, Sydney, NSW, Australia

    Robyn V. Jamieson

  17. Disciplines of Genomic Medicine, and Child and Adolescent Health, University of Sydney, Sydney, NSW, Australia

    Robyn V. Jamieson

  18. South Australian Clinical Genetics Service, Royal Adelaide Hospital, Adelaide, SA, Australia

    Jan Liebelt

  19. Women’s and Children’s Hospital, Adelaide, SA, Australia

    Jan Liebelt

  20. Discipline of Genomic Medicine, University of Sydney, Sydney, NSW, Australia

    Alan Ma & Meredith Wilson

  21. School of Medicine, The University of Western Australia, Perth, WA, Australia

    Nicholas Pachter

  22. PathWest Laboratory Medicine, Perth, WA, Australia

    Anja Ravine & Mark Davis

  23. http://orcid.org/0000-0000-0000-0000

    Rachael Casella

  24. Victorian Clinical Genetics Services, Parkville, VIC, Australia

    Alison Archibald & Martin B. Delatycki

  25. Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia

    Julie McGaughran

  26. School of Medicine, University of Queensland, Brisbane, QLD, Australia

    Julie McGaughran

  27. The University of Sydney, Faculty of Medicine & Health, Sydney School of Public Health, Sydney Health Ethics, Sydney, Australia

    Ainsley J. Newson

Authors
  1. Edwin P. Kirk
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  20. Rachael Casella
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  26. Nigel G. Laing
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Correspondence to Edwin P. Kirk.

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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 29, 79–87 (2021). https://doi.org/10.1038/s41431-020-0685-x

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