DonoSafe® : genomics for safe gamete donation

The DonoSafe^® genomic test analyzes, through massive parallel sequencing, the DNA of more than 200 genes in a gamete donor and the recipient. The test uncovers several thousands of pathogenic mutations in genes involved in more than 300 severe genetic diseases occurring with a combined frequency of at least 1 in 300 births.

A positive test result for a gamete donor (egg or sperm donor) in any single gene (or multiple genes) provides valuable information about the reproductive risks, depending on the corresponding carrier status of the recipient, and prevents the birth of an affected child.

As gamete donation, for a number of reasons, is becoming now more frequent, the DonoSafe^® genomic test may be applied in a gamete bank, providing extremely useful clinical information by avoiding genetically ‘incompatible’ donations, which may otherwise result in a 25% risk of giving birth to an affected child or the unwilling transmission of other genetic disorders.

Therefore, the ultimate purpose of this genomic test is to determine whether the gamete donor and possibly the recipient (depending on disease inheritance) are unsuspecting carriers of any one of these 340 genetic disorders, through the detection of pathogenic gene mutations. The current list of genes and the associated disorders may be expanded in the future.

DONOSAFE_DISEASE GENE LIST.pdf

This type of carrier testing for single-gene disorders is not something new. For example, carrier testing for cystic fibrosis (incidence ~1 in 2,500 births) has been a common practice in most countries-populations, while carrier testing for Tay-Sach’s disease, Canavan disease, Nieman Pick Disease Type A, Bloom syndrome and Gaucher’s disease is also common among individuals of Ashkenazi Jewish descent.

Typically, carriers for any of the 340 severe diseases included in the Donosafe^® pan-ethnic genomic panel are asymptomatic and usually present without any prior family history of the disorder.

Therefore, they cannot be identified by any other way and this is the main reason why children affected by these genetic diseases are born and diagnosed after birth.

Prior knowledge of a gamete donor’s carrier status, by identification of the corresponding pathogenic gene mutations for any of these disorders through the Donosafe^® test, permits, among others, proper genetic ‘matching’ of the prospective recipient by avoiding combinations where both donor and recipient are unsuspecting carriers of the same recessive genetic disorder, which may otherwise have resulted in the birth of a severely affected child (1 in 4 risk).

Testing requires a biological sample (blood or saliva) from the gamete donor and recipient (a sample collection and shipment kit will be provided). Prior to testing, both individuals must complete and sign the Test Information and Consent Form, with the option of receiving online pre-test genetic counseling.

The samples are shipped to our laboratory where genomic DNA is extracted, followed by massive parallel sequencing (NGS) of the 285 genes. Sequence reads are then aligned and mapped to the human genome reference sequence and all variants and putative mutations are prioritized through a proprietary specially developed in-house bioinformatics pipeline.

Only known pathogenic or obligatory pathogenic (nonsense, frameshift, consensus splice-site) mutations will be reported, together with a full clinical assessment and clinical genetic evaluation.

Please note that in special circumstances where the IVF cycle is imminent, the DonoSafe^® test should be performed concurrently for both gamete donor and recipient in order to avoid unnecessary delays.

A final clinical report is released, containing all the relevant findings and recommendations for further actions, where applicable. Positive findings and reproductive options are discussed in the context of a personalized genetic counseling session.

Results are evaluated and reported based on current knowledge.

The sensitivity of the DonoSafe^® test is ~95% and it will not detect numerical or structural chromosomal abnormalities as well as deletions or duplications >15-20 base-pairs.

A negative result does not exclude totally the presence of a pathogenic mutation in the offspring, which may result from rare events such as, for example, a de novo mutation or the presence of germline mosaicism for a mutation in the gamete donor.