Thu 12 Jun. 2014, 13:00
M 213

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).