Array informatics to understand ploidy concordance

阵列信息学以了解倍性一致性

基本信息

批准号：
7782362
负责人：
Matthew Rabinowitz
金额：
$ 80.07万
依托单位：
NATERA, INC.
依托单位国家：
美国
项目类别：
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/7782362
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 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 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 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 preimplantation public health relevance reproductive response standard of care trend

项目摘要

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.

描述（由申请人提供）：在每个 IVF 周期中，必须决定选择哪个胚胎进行移植。这一决定对试管婴儿周期的结果产生深远的影响，即胚胎是否会发育成健康的孩子。据估计，至少 50% 的人类胚胎受到非整倍体等染色体异常的影响，此类胚胎的植入可能会导致不良结果，例如植入失败、自然流产或三体后代的诞生。生殖专家越来越多地转向植入前遗传学诊断（PGD），以努力识别最有可能发育成健康儿童的胚胎。然而，当前的技术昂贵、不可靠，并且通常仅测试一小部分染色体。 GSN 开发了一种名为 Parental SupportTM (PS) 的创新技术，其输出是对数千个位点的胚胎 DNA 进行计算机重建，置信度超过 99%。这项技术将首次允许 IVF 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 技术与基于 Infinium 的新型高度并行定制基因分型平台集成，以大幅降低成本，从而使 GSN 能够以卓越的准确性、范围和成本提供 PGD 服务相当于当前不太可靠的 FISH 方法。然后，新的定制平台将应用于第二阶段，我们建议评估第 5 天的新滋养外胚层活检技术、第 3 天的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活检技术的价值，评估第 3 天到第 5 天之间胚胎自我修正的大部分未经研究的现象，并为 IVF 医生提供有关发育潜力的强大而深远的知识每个胚胎。