1. NIPD for trisomy 21
NIPD for trisomy 21 (A) Foetal cell-free DNA (cfDNA) from the foetal circulation crosses the placenta into the maternal circulation, which thus contains both maternal and foetal cfDNA. (B) cfDNA is collected from maternal blood samples. The maternal cfDNA tends to be longer fragments than foetal cfDNA so that separation is possible but not straightforward. In general, however, there is no separation stage. In cases where the foetus is affected by trisomy 21, there will be more foetal cfDNA fragments derived from chromosome 21 (coloured red and indicated by asterisks) in comparison with a case where the foetus is unaffected. (C) The total cfDNA is analysed by DNA sequencing using NGS, allowing a count of how many reads have been obtained from each chromosome. If there was an over-representation of chromosome 21 fragments in the cfDNA sample then there will be increased representation of NGS sequence reads that match chromosome 21 (asterisked). The analysis is often quantified by calculating ratios of (for example) chromosome 21 reads to chromosome 1 reads. If only foetal cfDNA was present the chr 21:chr 1ratio would be expected to be 1:1 from an unaffected foetus, and 1.5:1 from an affected foetus, but the additional presence of disomic maternal cfDNA in the sample means that the ratio will be lower.
Maria Jackson et al. Essays Biochem. 2018;62:
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