News Release

Mutation detection in human in vitro fertilized embryos using whole-genome sequencing

Peer-Reviewed Publication

Cold Spring Harbor Laboratory

February 11, 2015 - Pre-implantation genetic diagnosis (PGD) is used in fertility clinics to detect large chromosomal abnormalities or genetic mutations passed on by parents to their in vitro fertilized (IVF) embryos. However, it is not possible to comprehensively scan the embryo's genome to detect spontaneous mutations. In a study published online today in Genome Research, scientists developed a whole-genome sequencing approach using 5- to 10-cell biopsies from human embryos to detect potential disease-causing mutations.

Researchers from Complete Genomics, Reprogenetics, and the NYU Fertility Center sequenced three biopsies from two IVF embryos in attempt to detect de novo mutations, those that arise spontaneously in the egg or sperm and are not inherited from either parent. These types of mutations are thought to account for a large fraction of severe intellectual disability, autism, epileptic encephalopathies, and other congenital disorders.

Since only 5 to 10 cells can be biopsied from a blastocyst embryo, the DNA is amplified before sequencing. This amplification process introduces thousands of errors that appear to be de novo mutations. Until now, it has been difficult to disentangle the sequencing errors from true de novo mutations. Using their previously published method Long Fragment Read (LFR) technology, the researchers assigned DNA fragments to the maternal or paternal genome using DNA barcodes and were able to remove over 100,000 sequencing errors, reducing the error rate approximately 100-fold over previous studies.

"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," said co-corresponding authors Brock Peters and Radoje Drmanac from Complete Genomics. Overall, the researchers detected 82% of all de novo changes in the IVF embryos; this is the first demonstration that a large majority of single base de novo mutations could be detected in a PGD test.

In one embryo, the researchers did not find any de novo mutations in protein-coding regions of the genome. However, in another other embryo from the same couple, the researchers found two coding mutations in the ZNF266 and SLC26A10 genes that may be potentially damaging. The authors point out, however, that it is currently unknown if there would be any health consequences for a child born with these mutations.

"The biggest hurdle now is one of how to analyze the medical impact of detected mutations and make decisions based on those results," said Peters and Drmanac.

In addition to PGD, this new methodology could be useful for other applications in which cells are limited, such as sequencing circulating tumor cells (CTCs) or circulating fetal cells (CFCs), each of which are present in rare subpopulations in the blood.


Media contacts:

The authors are available for more information by contacting: Caren Begun, Green Room Communications (, +1-856-424-2023).

Prior to the embargo date, interested reporters may obtain copies of the manuscript via email from Peggy Calicchia, Administrative Assistant, Genome Research (, +1-516-422-4012).

About the article:

The manuscript will be published online ahead of print on 11 February 2015. Its full citation is as follows: Peters BA, Kermani BG, Alferov O, Agarwal MR, McElwain MA, Gulbahce N, Hayden DM Tang YT, Zhang RY, Terle R, Crain B, Prates R, Berkeley A, Munné S, Drmanac R. 2015. Detection and phasing of single base de novo mutations in biopsies from human in vitro fertilized embryos by advanced whole-genome sequencing. Genome Res doi: 10.1101/gr.181255.114

About Genome Research:

Launched in 1995, Genome Research is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.

About Cold Spring Harbor Laboratory Press:

Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. The Press is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit our website at

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