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March 6, 2015
Advancements in medical science have literally created miracles for women with fertility issues. One of the most successful conception procedures is in vitro fertilization (IVF), in which egg and sperm are joined in laboratory conditions and then implanted into the mother or surrogate. But despite IVF successes, the procedure still comes with some limitations – for example, it has not yet been possible to systematically scan the entire genome of the pre-implanted IVF embryo, which could be critical in detecting mutations associated with conditions such as Down syndrome or autism. But according to a study conducted by researchers at Complete Genomics, Reprogenetics and the New York University Fertility Center, and published in the journal Genome Research, whole-genome sequencing (WGS) of IVF embryos may now be possible.
De novo mutations
Given parents' medical histories, physicians can predict the likelihood that children will inherit genetic conditions. However, Brock Peters, Ph.D., director of research at Complete Genomics and lead author of the study, told Genetic Engineering & Biotechnology News (GEN) that de novo mutations – those that spontaneously occur in eggs or sperm without genetic antecedents from the parents' cells – have traditionally been much harder to detect. To detect these, whole-genome sequencing of the embryo is necessary and the findings of this study show that researchers may have found a way to do this.
The researchers performed whole-genome sequencing on three biopsies from two IVF embryos. Each biopsy contained between 5 and 10 cells, and traditional attempts at WGS would amplify the cell DNA before sequencing. However, the amplification process can introduce thousands of errors that can improperly be identified as spontaneous mutations, so in this study a different method was used.
Peters and his colleagues used long fragment read technology which reduces errors 100-fold compared to traditional methods. Using this new technique, more than 100,000 sequencing errors were removed from the process, and the researchers were able to identify 82 percent of de novo mutations in the IVF embryos.
Peters told GEN that accurately diagnosing de novo mutations in IVF births with whole-genome sequencing is such a difficult process that even a slight margin of error can throw off an entire experiment. As such it was more important than ever to minimize the chance of false positives.
"Because each individual carries on average less than 100 de novo mutations, being able to detect and assign parent of origin for these mutations, which are the cause of many diseases, required this extremely low error rate," Peters told the source. "The biggest hurdle now is one of how to analyze the medical impact of detected mutations and make decisions based on those results."
Further to this specific study, the methods used have applications in other clinical scenarios. For situations in which obtaining cells is a challenge – such as securing circulating tumor cells – the procedure these researchers used has direct application potential.