Methods of quality control using single-nucleotide polymorphisms in pre-implantation genetic screening
AssigneeLaboratory Corporation of America Holdings
InventorsMark Umbarger, Athurva Gore, Gregory Porreca
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Abstract
The present invention provides methods for validating results of a pre-implantation genetic screen. Methods of the invention increase the efficacy of the common PGS assay FAST-SeqS by taking advantage of single-nucleotide polymorphisms (SNPs) generated from the assay to confirm copy number calls, detect errors, identify samples, and recognize and identify sources of contamination. Methods of the invention increase the reliability of a PGS result, thereby making embryo selection more precise and improving outcomes of in vitro fertilization.
Claims19
A method for pre-implantation genetic screening of an embryo, the method comprising:
- obtaining a genomic sample from an embryo pre-implantation, wherein a plurality of single nucleotide polymorphisms (SNPs) are distributed throughout the genomic sample;
- performing FAST-SeqS on the genomic sample to produce sequencing reads;
- identifying, using the sequencing reads, a set of SNPs from the plurality of SNPs in a region of the genomic sample covered by the sequencing reads;
- determining, using the set of SNPs, a plurality of allele fractions for the set of SNPs in the region of the genomic sample covered by the sequencing reads, wherein each allele fraction of the plurality of allele fractions is a proportion of an allele at a particular locus within the region;
- enumerating read counts from the sequencing reads;
- determining a putative chromosome copy number of a chromosome of the genomic sample according to the read counts;
- screening out the embryo from implantation when the putative chromosome copy number indicates diploidy and the plurality of allele fractions indicate aneuploidy or unexpected integral multiples of a haploid chromosome.
A method for confirming or refuting a putative chromosome copy number of a genomic sample of an embryo pre-implantation, the method comprising:
- obtaining a genomic sample from an embryo pre-implantation, wherein a plurality of single nucleotide polymorphisms (SNPs) are distributed throughout the genomic sample;
- performing FAST-SeqS on the genomic sample to produce sequencing reads;
- obtaining a putative chromosome copy number for the genomic sample, the putative chromosome copy number calculated from counts of the sequencing reads;
- identifying, using the sequencing reads, a set of SNPs from the plurality of SNPs in a region of interest of the genomic sample covered by the sequencing reads;
- determining, using the set of SNPs, a plurality of allele fractions of the set of SNPs in the region of interest in the genomic sample, wherein each allele fraction of the plurality of allele fractions is a proportion of an allele of one SNP of the set of SNPs;
- and
- confirming the putative chromosome copy number when the putative chromosome copy number is consistent with the plurality of allele fractions;
- or
- refuting the putative chromosome copy number when the putative chromosome copy number is inconsistent with the plurality of allele fractions.
Dependencies are inferred from the claim text.