Preimplantation Genetic Diagnosis for Aneuploidy and Translocations Using Array Comparative Genomic Hybridization
Preimplantation Genetic Diagnosis for Aneuploidy and Translocations Using Array Comparative Genomic Hybridization
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DOI：
10.2174/138920212802510457
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发表时间：
2012-09-01
期刊：
影响因子：
2.6
通讯作者：
Munne, Santiago
中科院分区：
文献类型：
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作者：
Munne, Santiago
至少50%的人类胚胎是异常的，而在40岁以上的女性中，这一比例增加到80%。这些异常导致体外受精过程中移植的胚胎着床率较低，35岁以下妇女的着床率为30%，40岁或以上妇女的着床率为6%。因此，选择正常胚胎进行移植可以改善妊娠结果。胚胎的遗传分析称为胚胎植入前遗传学诊断（PGD），染色体分析首先使用FISH进行，最多可同时分析单个细胞上的12个探针。然而，该技术的次优利用和固定单个细胞的复杂性产生了相互矛盾的结果。微阵列测试的引入使PGD得到了振兴，微阵列测试允许在一次测试中分析所有24种染色体类型，而不需要细胞固定，并且具有惊人的冗余性，使测试更加健壮和可靠。最近在科学会议上发表和展示的数据表明，微阵列测试后植入率和妊娠率增加，结果的改善已经预测了很长一段时间。通过使用覆盖大部分基因组的标记，不仅可以在单细胞中检测到非整倍体，还可以检测到易位。我们的验证结果表明，阵列CGH在单个细胞中具有6Mb的分辨率，因此可以分析大多数易位，因为这也是核型的限制。即使对于交换片段较小的易位，只要4个片段中有3个大于6Mb，就可以检测到易位。
At least 50% of human embryos are abnormal, and that increases to 80% in women 40 years or older. These abnormalities result in low implantation rates in embryos transferred during in vitro fertilization procedures, from 30% in women < 35 years to 6% in women 40 years or older. Thus selecting normal embryos for transfer should improve pregnancy results. The genetic analysis of embryos is called Preimplantation Genetic Diagnosis (PGD) and for chromosome analysis it was first performed using FISH with up to 12 probes analyzed simultaneously on single cells. However, suboptimal utilization of the technique and the complexity of fixing single cells produced conflicting results. PGD has been invigorated by the introduction of microarray testing which allows for the analysis of all 24 chromosome types in one test, without the need of cell fixation, and with staggering redundancy, making the test much more robust and reliable. Recent data published and presented at scientific meetings has been suggestive of increased implantation rates and pregnancy rates following microarray testing, improvements in outcome that have been predicted for quite some time. By using markers that cover most of the genome, not only aneuploidy can be detected in single cells but also translocations. Our validation results indicate that array CGH has a 6Mb resolution in single cells, and thus the majority of translocations can be analyzed since this is also the limit of karyotyping. Even for translocations with smaller exchanged fragments, provided that three out of the four fragments are above 6Mb, the translocation can be detected.