Thu 12 Jun. 2014, 13:00
Title: A Novel Method for Detecting Genetic Anomalies through Non-Invasive Prenatal Testing
Speaker: Ladislav Rampášek, University of Toronto
Traditionally, tests of genetic abnormalities in a fetus require a sample of either the amniotic fluid or of chorionic tissue from placenta. Both these procedures are invasive and carry a small but non negligible risk of procedure-related miscarriage. However, the past several years have seen the development of non-invasive methodologies based on DNA sequencing of maternal blood samples. These methods are based on the observation that maternal blood plasma contains a fraction of DNA (typically 5-15%) originating from the fetus, and such methodologies have already been used for the detection of anomalies affecting whole chromosomes (aneuploidies), and to a more limited extent for smaller (typically several megabases long) Copy Number Variants (CNVs). In this talk, I will briefly present overview of the current state of non-invasive prenatal testing, the central ideas of computational and statistical methods published so far, and their application in clinical practice. In the second half, I will present our novel method for detecting CNVs, which can detect much shorter variants than previous methods. Our method combines three types of information within a unified Hidden Markov Model: the imbalance of allelic ratios at SNP positions, the use of parental genotypes to phase nearby SNPs, and depth of sequencing coverage to better differentiate between various types of CNVs and improve precision. This work has been accepted for ISMB 2014 as “Probabilistic method for detecting copy number variation in a fetal genome using maternal plasma sequencing” (Ladislav Rampášek, Aryan Arbabi, and Michael Brudno).