Prediction of fetal DNA allows diagnosing known/passed mutations before child’s birth. Public health significance of such early testing is that it can reassure parents who have negative results and offers timely information for those with abnormal results.
My dissertation work presents a new approach of reconstructing fetal DNA from maternal plasma. The method works because plasma from pregnant women, which contains “cell-free DNA”, has been noted to contain fetal DNA as well as maternal DNA. I developed and tested a workflow that implements my suggested approach. The workflow was broken into several parts, each fully documented in this dissertation. Each step we have taken was supported with explanation of the logic driving the step. The approach works through the examination of sequencing data sets generated by short-read sequencing (also known as next-generation sequencing), by calling variation (single nucleotide polymorphisms, or SNPs) within those samples vis-à-vis a reference sequence. I developed and introduced a series of quality control criteria applied to SNPs to improve overall prediction. A novel single individual haplotyping method was developed and applied to haplotype the parental samples. The obtained parental haplotypes were incorporated into the workflow and along with parental genotypes were used to find transmitted haplotypes in the maternal plasma. The predicted haplotypes were then aligned to each other to obtain phased SNPs. For evaluation, I compared fetal SNPs predicted by my method against control fetal SNPs (from sequencing of fetal DNA). Overall prediction power is discussed. Possible ways of improvements that should affect the overall prediction are also described
