Thursday, July 17, 2014

The DNA of The Price of Darkness

If you could study the DNA of anyone on Earth to learn what made him or her tick, who would you choose? Noam Chomsky, Bill Gates, Serena Williams, Madonna? It is probably safe to say that not many people would have chosen Ozzy Osbourne, the founder of the heavy metal pioneers, Black Sabbath. But scientists couldn’t wait to put Ozzy under the microscope…and for good reason.

I only have black genes!

Also known as The Prince of Darkness, Ozzy is a remarkable human specimen. It is no secret that he has constantly struggled with addiction, toured for nearly half a century, bit off the head of a bat, survived reality television, and, on top of all that, has kids. His wife and manager, Sharon, once compared his resilience to that of a cockroach. Ah, love and marriage.

What powerful forces were finally able to put the Prince of Darkness in his place? Wife and kids.

When scientists sequence a genome, they basically get to read the DNA of that organism, which is analogous to learning the ingredients of a recipe. In heavy metal parlance, Ozzy’s genome is the biological version of “Diary of a Madman”. Doctors, and even Ozzy himself, have long been bewildered at his continued existence…most people who climb aboard a crazy train and live the Ozzy lifestyle would have been dead long ago!

Ozzy once considered that he was like a cat with nine lives, but there were no feline genes detected in his genome. In fact, like most scientific results, more questions were raised than answered. Among some of the more intriguing things spotted in his DNA was a never-before-seen mutation in his ADH4 gene. ADH4 encodes a protein called alcohol dehydrogenase 4 that processes alcohol and has been linked to alcohol and drug dependence. However, we need to learn a lot more about ADH4 and other metabolic genes if we are to make sense of the results.

Researchers also found traces of Neanderthal genes in Ozzy’s DNA. However, this probably has nothing to do with his wild life or ability to howl all night long since a large number of people also possess Neanderthal DNA. Recent research indicates that ~20% of the Neanderthal genome still exists in modern humans of non-African ancestry.

So what does all of this tell us and should we be knocking on Bob Dylan’s door for a DNA sample? Frankly, the data is just a ‘Blizzard of Ozz’ at the moment. There is no “Ozzy Osbourne” gene, nor anything concrete that explains why he is who he is. There is nothing that will be of immediate benefit to substance abusers or help Justin Bieber write better songs. We still have a lot to learn about the complexities of gene expression regulation. For example, you can’t make a cake if you only know the ingredients. We need to know how and when those ingredients are used and in what proportions. Similarly, we can’t understand Ozzy Osbourne just from a list of his genes.

Genes are kind of like different musical instruments, but other factors that are “epigenetic” in nature (epigenetic meaning “above the gene”) control the level of each instrument, tell it when to play, or when to rest. Scientists are discovering that many factors from our environment can influence epigenetic factors, which in turn regulate the amount of a gene’s activity. Nevertheless, Ozzy’s genome has provided some clues into what genes we might want to explore further, and that kind of knowledge is power. The more genomes that are sequenced, the more confidence we can have in the correlations that arise between gene and phenotype.

For more, check out this TEDMED talk where the Ozzman and Sharon discuss his genome.

You can also read more about Ozzy’s genome results, and his hilarious medical advice (which has greater credibility than that discharged by another “Dr. Oz” we know!), in his book, “Trust Me, I’m Dr. Ozzy”.

Contributed by: Bill Sullivan
Follow Bill on Twitter: @wjsullivan

Sankararaman, S., Mallick, S., Dannemann, M., Prüfer, K., Kelso, J., Pääbo, S., Patterson, N., & Reich, D. (2014). The genomic landscape of Neanderthal ancestry in present-day humans Nature, 507 (7492), 354-357 DOI: 10.1038/nature12961

Luo X, Kranzler HR, Zuo L, Lappalainen J, Yang BZ, & Gelernter J (2006). ADH4 gene variation is associated with alcohol dependence and drug dependence in European Americans: results from HWD tests and case-control association studies. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 31 (5), 1085-95 PMID: 16237392

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