Laboratory Considerations for Reproductive Genetic Carrier Screening: Experiences from Mackenzie's Mission
- Author(s)
- Cliffe, CC; Allcock, RJN; Laing, NG; Zhang, F; Lee, C; Archibald, AD; Chow, MTM; Davis, MR; Delatycki, MB; Marum, JE; Monaco, A; Ong, R; Righetti, S; Rodrigues, B; Roscioli, T; Zhu, Y; Mackenzie’s Mission Laboratory Team; Lunke, S; Kirk, EP;
- Journal Title
- Journal of Molecular Diagnostics
- Publication Type
- Online publication before print
- Abstract
- The Australian Reproductive Genetic Carrier Screening Project, "Mackenzie's Mission", performed couple-based screening for 9107 reproductive couples for over 1280 genes associated with severe autosomal and X-linked recessive disorders. It identified close to 1:50 participating couples as having a previously unknown increased risk of having children with a condition screened. Here we describe the processes, successes and challenges of the laboratory testing undertaken during Mackenzie's Mission. Samples were mouth swabs, self-collected and posted to one of three testing laboratories. Two laboratories used exome sequencing; the other a targeted gene panel. Both were equally effective in identifying increased risk couples for small sequence variants. FMR1 and SMN1 testing were performed separately. A Variant Review Committee met weekly to discuss reportable variants and variants difficult to classify. This promoted consistent reporting. Exclusion of variants previously classified by a laboratory as Benign, Likely Benign and/or Variant of Uncertain Significance, significantly reduced the analysis required for each reproductive couple. The pan-ancestral screening approach was suitable for data from people of various ancestries despite the increased analysis time required for data from couples of African, Middle Eastern and Asian ancestry. For consanguineous couples there was a significant increase in the number of variants requiring review and ∼10-fold more increased risk reports issued. We demonstrated large-scale, pan-ancestral reproductive genetic carrier screening is feasible across Australia's diverse population.
- Department(s)
- Pathology
- Publisher's Version
- https://doi.org/10.1016/j.jmoldx.2026.06.009
- Open Access at Publisher's Site
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Creation Date: 2026-08-11 02:01:21
Last Modified: 2026-08-11 02:01:47