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DYS464 and Male Infertility

Dr. Mark A. Jobling at the University of Leicester published a study in 2005 that examined DYS464, a Y-DNA marker commonly sequenced for genetic genealogical purposes. As it turns out, sequencing DYS464 can inadvertently detect an AZFc deletion. Deletion of AZFc (azoospermia factor c) causes spermatogenic failure and subsequently, male infertility. This marker is tested by at least 6 firms.

Dr. Jobling pointed out that a previous study had concluded that an AZFc deletion could be found in 1 in every 4000 males. In Dr. Jobling’s study there were 3 cases in 3255 males tested, which he states is “not significantly different from 1 in 4000.” A story in the New Scientist stated that “a study by Jobling’s team suggests that 1 in 1000 men has the deletion,” but I think that is an overstatement by the media. I haven’t seen anywhere that Dr. Jobling made such a statement – he was merely listing some of his data. Elsewhere, Ann Turner has suggested that at FTDNA, the number is around 1 in 8,000. Although the exact frequency has not yet been determined, it appears that it is rather low.

The number of markers tested will undoubtedly continue to rise before we cross The Barrier, the move from individual STRs to full-genome sequencing. As a result, the probability that a tested marker could reveal more than just genealogical information will become more and more likely. It is, and always will be, important that individuals be aware of the possible consequences of DNA testing BEFORE they undergo DNA testing. Naturally, this awareness is the responsibility of both the DNA testing firm and the individual.

HT: Hsien, and thank you to the Journal of Medical Genetics for making this paper open access.

Blaine Bettinger

Intellectual property attorney, genealogist, and author of The Genetic Genealogist since 2007

18 Comments

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  3. It bears repeating that this could cause problems in two ways:

    1) Men who don’t have biological children may suddenly find they’re not able to.

    2) Men who already have children may find that they’re not the biological father.

    I haven’t seen any testing company explain let alone mention this possibility. Seems like it might be time to replace this marker with another?

  4. this year in our lab there were 2 male inferetility cases with Y microdeletion (AZFc) detected – the first cases when this test is performed (c.a. 3 years). EMQN has very good guidelines for this simple multiplex PCR test with primers listed – you can virtually perform it at home if you have PCR machine – its very easy test:)
    http://www.emqn.org/emqn/BestPractice/mainColumnParagraphs/011/document/AZF_Guidelines_2004.pdf
    To my knowledge Y microdeletions are the cause around 7,3% of all male infertility, and even 66% for azospermia cases).

  5. Hsien – The problem is that DYS464 is such a valuable marker. Unfortunately, I think that the secrets revealed by DNA are only going to get much, much worse. All sequencing companies are going to have to make iron-tight releases to survive. I wonder what the releases for paternity testing firms are like?

    RamÅ«nas – Thank you for stopping by! I think it would be very interesting to see a study of the actual frequency, but the sample size would have to be pretty big.
    Do you think there will be a day when everyone has a PCR machine at home? I can picture it: “Mom, what kind of bug is this?” “I don’t know, mash it up and stick it in the sequencer!”

  6. Yeah, I don’t know if the problem is as bad for paternity tests because they typically only examine around 16 markers. But when you have companies that are offering 67 Y-DNA markers a pop, then there’s definitely more chances of there being some unexpected results!

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