Maternal plasma sequencing: a powerful tool towards fetal whole genome recovery

Elisavet A Papageorgiou, Philippos C Patsalis

Noninvasive prenatal diagnosis of chromosomal aneuploidies, although challenging, has been achieved through the implementation of novel methodologies such as methylated DNA immunoprecipitation and next generation sequencing technologies. Nevertheless, additional developments are required towards the interpretation of other fetal abnormalities of higher complexity, such as de novo mutations including microdeletion and microduplication syndromes as well as complex diseases. The application of next generation sequencing technologies towards fetal whole genome recovery has demonstrated great potential to achieve the above goal. In a research article published in Genome Medicine, Chen et al. presented a novel approach that allowed more robust and accurate characterization of parental alleles compared with previous studies. This was achieved through a revolutionary strategy based on the use of trios and unrelated individuals that simultaneously targets the interpretation of the fetal haplotype and phenotype in one step. It is hereby shown that the implementation of a more accurate experimental design in combination with proper analytical tools can provide robust noninvasive fetal whole genome recovery with the potential for further developments beyond the DNA level.