It is a technical challenge to generate sufficient amounts of whole genome

It is a technical challenge to generate sufficient

This preview shows page 4 - 6 out of 7 pages.

It is a technical challenge to generate sufficient amounts of whole-genome amplified DNA with high fidelity for complete genome sequencing from a single human cell [46] , since commercial MDA kits are optimized for greater than 10 ng input genomic DNA. Our laboratory has, however, developed a WGA protocol by MDA that generated approximately 100 ng template-dependent am- plified DNA (equivalent to about 15 000 genomes) with high fidelity from a single human blastomere in 4 h [19] . Excessive WGA by current MDA technology generates amplified DNA of low fidelity. In order to generate complete genome sequences from a single human cell, the analytical sensitivity of sequencing method needs to be improved. Alternatively, PGD by targeted sequencing of the disease gene may re- quire less amount of amplified DNA template. For PGD, larger amounts of whole-genome amplified DNA can be generated from several trophectoderm cells biopsied from blastocysts on day 5 after fertilization [47,48] . By genotyping multiple cells, the ADO rates are also 11 April 27, 2012 | Volume 2 | Issue 2 | WJMG | Lau EC. Preimplantation genetic diagnosis
Image of page 4
lower and the accuracy of SNP genotyping increases [49,50] . A drawback of blastocyst testing, however, is that it al- lows less time for PGD, and thus the embryos may need to be frozen for transfer in the next fertilization cycle if test results are not obtained within a day [48] . ETHICAL CONCERNS OF PREIMPLANTATION TESTING Confidentiality of genomic data Genomic technologies acquire the nucleotide sequence and SNPs of the entire genome rather than distinct parts of an individual genome, and thus obtain increased knowledge about genotypes and diseases. The scientific benefits of whole genome analysis are, however, accom - panied by legal and ethical concerns. Informed consent and legislation are needed to protect these genomic data, as well as the privacy and confidentiality of patients’ families [51,52] . Non-medical use of preimplantation testing While preimplantation testing was initiated to help patient families at risk for severe genetic diseases avoid the trans- mission of these medical conditions [1,2] , non-medical use of PGD presents some ethical concerns [53] . For instance, non-medical use of PGD for gender selection for family balancing is a controversial issue. Although there is no broad cultural preference for male or female offspring in the U.S., there is a preference of males in some countries. In fact, non-medical use of PGD for family balancing is prohibited in many countries [54] , mainly because it could disrupt the sex ratio of the population. FUTURE PROSPECTS FOR PREIMPLANTATION TESTING Universal access to preimplantation testing Since the majority of fertility centers in the United States do not have the facilities and expertise for PGD, preim- plantation testing is often conducted via “mail order” ser- vice by sending biopsied blastomeres to a few nationwide preimplantation testing providers (Strawn EY, MD, Medi- cal College of Wisconsin, Milwaukee, Wisconsin, unpub- lished data). That would obviate the high cost of setting
Image of page 5
Image of page 6

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture