Resolving genome fractions using polymorphism counts

Abstract

Methods of reliably estimating genomic fraction (e.g., fetal fraction) from polymorphisms such as small base variations or insertions-deletions are disclosed. Sequenced data from a multigenomic source is used to determine allele counts for one or more of the polymorphisms. For one or more of the polymorphisms, zygosity is assigned, and genomic fraction is determined from the zygosity and allele counts. Certain embodiments employ SNPs as the relevant polymorphism. The disclosed methods can be applied as part of an intentional, pre-designed re-sequencing study targeted against known polymorphisms or can be used in a retrospective analysis of variations found by coincidence in overlapping sequences generated from maternal plasma (or any other setting where a mixture of DNA from several people are present).

Description

[0001] Cross References to Related Applications

[0002] This application claims priority to US Provisional Application Serial No. 61 / 474362, filed April 12, 2011, the contents of which are hereby incorporated by reference in their entirety for all purposes. Background technique

[0003] The discovery of free-floating fetal DNA (sometimes referred to as "cell free DNA" or "cfDNA") in maternal blood allows the possibility of detection of chromosomal abnormalities, aneuploidy and aberrations from blood samples. The fractional abundance of fetal DNA in maternal plasma is not constant and varies with several factors, including sample processing and gestational age.

[0004] When using DNA sequencing to identify chromosomal aberrations or genetic defects, it is important to know the relative abundance of fetal DNA in the total population of DNA. For example, when the fetal fraction is known, statistical power (probability of identifying anomalies, or sensitivity) can be calculate...

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