Author : IAIVF | 04 August 2017

E-NEWS "ESHRE HIGHLIGHT" Keynote Lecture -Non-invasive prenatal testing (NIPT) - state of the art

Y. Lo 1 . 

1The Chinese University of Hong Kong, Li Ka Shing Institute of Health Sciences Prince of Wales Hospital, Shatin- New Territories, Hong Kong. 


We explored the limit of noninvasive prenatal testing (NIPT) by sequencing the plasma DNA of a pregnant woman to 270X haploid genome coverage. This sequencing depth represents the deepest that any case has been sequenced to date. By using such a depth of sequencing and a custom-built bioinformatics pipeline, we were able to detect fetal de novo mutations on a genomewide level at a sensitivity of 85% and a positive predictive value of 74%. These results indicate that we have solved a hitherto unsolved challenge in NIPT. Furthermore, we have shown that at such a depth of sequencing, we were also able to elucidate the maternal inheritance of the fetus without using haplotype-based approaches. This development has allowed us to increase the resolution of determining the maternal inheritance of the fetus by 90-fold. Furthermore, we have observed that there are recurrent DNA sites that plasma DNA molecules tend to preferentially end on. We called such positions "preferred DNA ends". Interestingly, circulating DNA fragments derived from the fetus and those derived from the pregnant woman have sets of different preferred ends. This development allows one to predict the likelihood that a plasma DNA fragment is of fetal or maternal origin without using DNA polymorphisms. This approach also allows one to estimate the fetal DNA fraction without using DNA polymorphisms or size analysis. We believe that such 'second generation noninvasive fetal genomics' would have many exciting diagnostic applications and may facilitate an increased understanding of the biology of circulating DNA.