Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci.

Objective: This study aims to develop a noninvasive prenatal test on the basis of the analysis of cell-free DNA in maternal blood to detect fetal aneuploidy at chromosomes 13, 18, 21, X, and Y.

Methods: A total of 166 samples from pregnant women, including 11 trisomy 21, three trisomy 18, two trisomy 13, two 45,X, and two 47,XXY samples, were analyzed using an informatics-based method. Cell-free DNA from maternal blood was isolated, amplified using a multiplex polymerase chain reaction (PCR) assay targeting 11,000 single nucleotide polymorphisms on chromosomes 13, 18, 21, X, and Y in a single reaction, and sequenced.

Informatics enhanced SNP microarray analysis of 30 miscarriage samples compared to routine cytogenetics.

Purpose: The metaphase karyotype is often used as a diagnostic tool in the setting of early miscarriage; however this technique has several limitations. We evaluate a new technique for karyotyping that uses single nucleotide polymorphism microarrays (SNP). This technique was compared in a blinded, prospective fashion, to the traditional metaphase karyotype.

Origins and rates of aneuploidy in human blastomeres.

Objective: To characterize chromosomal error types and parental origin of aneuploidy in cleavage-stage embryos using an informatics-based technique that enables the elucidation of aneuploidy-causing mechanisms.

Design: Analysis of blastomeres biopsied from cleavage-stage embryos for preimplantation genetic screening during IVF.

Setting: Laboratory.

Comprehensive analysis of karyotypic mosaicism between trophectoderm and inner cell mass.

Aneuploidy has been well-documented in blastocyst embryos, but prior studies have been limited in scale and/or lack mechanistic data. We previously reported preclinical validation of microarray 24-chromosome preimplantation genetic screening in a 24-h protocol. The method diagnoses chromosome copy number, structural chromosome aberrations, parental source of aneuploidy and distinguishes certain meiotic from mitotic errors.

Preclinical validation of a microarray method for full molecular karyotyping of blastomeres in a 24-h protocol.

Background: Preimplantation genetic screening (PGS) has been used in an attempt to determine embryonic aneuploidy. Techniques that use new molecular methods to determine the karyotype of an embryo are expanding the scope of PGS.

Methods: We introduce a new method for PGS, termed 'parental support', which leverages microarray measurements from parental DNA to 'clean' single-cell microarray measurements on embryonic cells and explicitly computes confidence in each copy number call.