Abstract: Described herein are methods directed to determining the carrier status or genotype of a subject. Described herein is a method that combines experimental and computational approaches to resolve the structure of genomic loci (i.e., the genotype) whose sequences are highly homologous to other sequences in the genome. In particular, the determination of carrier status and/or copy number of a gene in a subject, wherein the gene has a corresponding highly homologous homolog, e.g., gene or pseudogene, utilizes Next Generation Sequencing. Also described herein is a computer-assisted method for such determinations.

Abstract: A computer-implemented method for optimizing performance of a DNA-based noninvasive prenatal screen includes generating a plurality of synthetic sequencing datasets by, for each of the plurality of synthetic sequencing datasets, (i) generating at least one of a plurality of synthetic copy number variants comprising a synthetic number of copies of at least a portion of a region of interest represented by a synthetic number of sequencing reads from one or more segments within the region of interest, and (ii) modifying a real sequencing dataset, which includes genetic sequencing data from a real test sample comprising maternal and fetal cfDNA, by replacing a number of real sequencing reads from the one or more segments within the region of interest in the real test sample with the synthetic number of sequencing reads. Various other methods and systems are also disclosed.

Abstract: Described herein are methods directed to determining the carrier status or genotype of a subject. Described herein is a method that combines experimental and computational approaches to resolve the structure of genomic loci (i.e., the genotype) whose sequences are highly homologous to other sequences in the genome. In particular, the determination of carrier status and/or copy number of a gene in a subject, wherein the gene has a corresponding highly homologous homolog, e.g., gene or pseudogene, utilizes Next Generation Sequencing. Also described herein is a computer-assisted method for such determinations.