Array informatics to understand ploidy concordance

阵列信息学以了解倍性一致性

• 批准号: 7941702
• 负责人: Matthew Rabinowitz
• 金额: $ 79.9万
• 依托单位: NATERA, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-14 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7941702
• 关键词: Address; Affect; Algorithms; Alleles; Aneuploid Cells; Aneuploidy; Bioinformatics; Biological; Biological Assay; Biopsy; Birth; Cell Line; Cells; Characteristics; Child; Childhood; Chromosome Deletion; Chromosome Pairing; Chromosome Positioning; Chromosome abnormality; Chromosomes; Clinic; Communities; Computer Simulation; Congenital chromosomal disease; Couples; Custom; DNA; DNA Microarray Chip; DNA analysis; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic Services; Down Syndrome; Dropout; Drops; Embryo; Enrollment; Evaluation; Excision; Face; Fathers; Fertilization in Vitro; Fetus; Fluorescent in Situ Hybridization; Frequencies; Funding; Gene Frequency; Genes; Genetic; Genome; Genotype; Goals; Grant; Health; Healthcare; Hour; Human; Human Genetics; Human Genome Project; Implant; Individual; Informatics; Inner Cell Mass; Kinetics; Knowledge; Lead; Letters; Life; Live Birth; Manufacturer Name; Measurement; Measures; Medical; Meiosis; Methods; Minor; Mission; Modeling; Molecular; Morbidity - disease rate; Mothers; Outcome; Output; Parents; Performance; Phase; Physicians; Placenta; Ploidies; Population; Precipitation; Preimplantation Diagnosis; Procedures; Process; Protocols documentation; Proxy; Quality of life; Reagent; Reporting; Research Infrastructure; Risk; Running; Sampling; Screening Result; Screening procedure; Security; Services; Single Nucleotide Polymorphism; Source; Specialist; Spontaneous abortion; Staging; Statistical Methods; Swab; System; Techniques; Technology; Testing; Time; Triad Acrylic Resin; Uterus; Variant; base; blastocyst; cost; design; disease phenotype; embryo stage 2; fetal; follow-up; genetic analysis; genotyping technology; implantation; improved; innovation; innovative technologies; insertion/deletion mutation; interest; mortality; natural Blastocyst Implantation; new technology; novel; offspring; preimplantation; reconstruction; reproductive; response; standard of care; trend

DESCRIPTION (provided by applicant): In each IVF cycle, a decision must be made as to which embryo(s) will be selected for transfer. This decision has a far reaching impact on the outcome of an IVF cycle, namely whether the embryo will develop into a healthy child. It is estimated that at least 50% of human embryos are affected by chromosomal abnormalities such as aneuploidy, and implantation of such embryos can lead to undesired outcomes such as failed implantation, spontaneous abortion, or birth of a trisomic offspring. Reproductive specialists have been increasingly turning to pre-implantation genetic diagnosis (PGD) in efforts to identify embryos with the best chance of developing into healthy children. However, current techniques are expensive, unreliable and typically test only a small selection of chromosomes. GSN has developed an innovative technology termed Parental SupportTM (PS) whose output is an in silico reconstruction of the embryonic DNA at thousands of loci with confidence exceeding 99%. This technology will, for the first time, allow IVF physicians to screen embryos for chromosomal abnormalities including aneuploidy, translocations and deletions across all 23 pairs of chromosomes with an error rate below 0.1%. The Phase I objective of this application is to integrate our PS technology with a new, highly parallelized custom Infinium-based genotyping platform to dramatically reduce costs that will, in turn, enable GSN to offer PGD service with superior accuracy, scope and at a cost equivalent to current, less reliable FISH methods. The new customized platform will then be applied in Phase II where we propose to evaluate the concordance between a new trophectoderm biopsy technique on day 5, traditional blastomere biopsy on day 3, and the actual child. The results from these studies will allow us to assess the value of the new biopsy technique, evaluate the largely unstudied phenomenon of embryo self-correction between day 3 and day 5, and provide IVF physicians with powerful and far-reaching knowledge about the developmental potential of each embryo.

说明（由申请人提供）：在每个试管婴儿周期中，必须决定选择哪些胚胎进行移植。这一决定对体外受精周期的结果，即胚胎是否会发育成健康的孩子，有着深远的影响。据估计，至少50%的人类胚胎受到染色体异常的影响，如非整倍体，植入这种胚胎可能导致不希望的结果，如植入失败、自然流产或生出三体后代。生殖专家越来越多地转向胚胎植入前遗传学诊断（PGD），以努力确定最有可能发育成健康儿童的胚胎。然而，目前的技术既昂贵又不可靠，而且通常只能检测一小部分染色体。GSN开发了一种称为亲代支持tm （parents SupportTM， PS）的创新技术，其输出是在数千个位点上对胚胎DNA进行计算机重建，置信度超过99%。这项技术将首次允许试管婴儿医生筛查胚胎的染色体异常，包括所有23对染色体的非整倍体、易位和缺失，错误率低于0.1%。该应用程序的第一阶段目标是将我们的PS技术与一个新的，高度并行的定制的基于infinium的基因分型平台集成在一起，以显着降低成本，从而使GSN能够提供具有卓越准确性，范围和成本的PGD服务，相当于目前不太可靠的FISH方法。然后，新的定制平台将应用于II期，我们建议在第5天评估新的滋养外胚层活检技术，第3天传统卵裂球活检技术与实际儿童之间的一致性。这些研究的结果将使我们能够评估新的活检技术的价值，评估在第3天到第5天之间胚胎自我纠正的大部分未被研究的现象，并为试管婴儿医生提供关于每个胚胎发育潜力的强大而深远的知识。