Doctoral defence: Hindrek Teder "Developing and introducing targeted and whole-genome sequencing based non-invasive prenatal testing in Estonia“

On 10 June at 13:00 Hindrek Teder will defend his doctoral thesis "Developing and introducing targeted and whole-genome sequencing based non-invasive prenatal testing in Estonia“.

Supervisors:
Associate Professor Priit Palta, University of Tartu
Professor Andres Salumets, University of Tartu
Associate Professor Kaarel Krjutškov, University of Tartu

Opponent:
Associate Professor Erik Sistermans, Vrije Universiteit Amsterdam (Netherlands)

Summary
Fetal screening allows to detect congenital anomalies and more frequent chromosomal abnormalities, such as Down, Edwards and Patau syndrome. Early information about a fetus’s possible health problem allows to make an informed decision about the continuation of the pregnancy and better prepare the future parents.

Conventional screening includes an ultrasound and blood serum analysis by way of which most of the fetal chromosomal abnormalities are detected. For a final diagnosis, the patients who are deemed to have a high risk for fetal chromosomal aberrations are referred to an invasive procedure. The disadvantage of the aforementioned screening method is a considerable number of false positive results, which is why most of the patients who receive a positive result are actually carrying a fully healthy fetus. The invasive procedure that follows the screening is unnecessary for those patients, causes them undue stress and this may also lead to a higher risk of miscarriage. 

The focal point of this doctoral thesis is non-invasive prenatal testing (NIPT), which is based on the analysis of cell-free DNA (cfDNA) of fetal origin that is found in maternal blood. In comparison to the above-mentioned conventional screening methods, NIPT is considerably more sensitive and specific for detecting the most common chromosomal abnormalities.

In the framework of the thesis, TAC-seq based analysis workflow was developed and used to detect chromosome 21 trisomy. In addition, NIPT analysis framework, which uses different machine learning methods, was developed for determining fetal trisomies from cfDNA sample. Also, a validation study of NIPT was carried out on pregnant women in Estonian cohort using a whole-genome sequencing based workflow.