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 lifelimiting 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 genephenotype 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.

While noninvasive prenatal testing based on cell‐free fetal DNA has recently revolutionized the field of aneuploidy screening in pregnancy, it remains limited to aneuploidy and microdeletion screening, and is unable to reliably detect single gene disorders. A number of recent studies have demonstrated the potential of circulating trophoblastic cells in providing cell‐based noninvasive diagnosis with sequencing or array‐based assays. However, considering the extreme rarity of these cells in blood, efficient, high‐throughput, and clinically applicable enrichment technologies are yet to be developed. This study demonstrates for the first time the utility of inertial microfluidics for efficient isolation of trophoblastic cells from maternal peripheral blood. Under optimal operating conditions, high‐recovery yields (79%) are obtained using a trophoblastic cell‐line, which is subsequently confirmed with analysis of maternal blood. Feasibility of obtaining a diagnosis from cells isolated from a maternal sample is demonstrated in a case of confirmed fetal trisomy 21 in which six fetal cells are found in a 7 mL blood sample using fluorescence in situ hybridization. Finally, it is demonstrated that trophoblastic cells isolated using inertial microfluidics could be picked and subjected to a clinically validated sequencing assay, paving the way for further validation of this technology and larger clinical studies.