April 25, 2017 Credit: martha sexton/public domain

Researchers from the Wellcome Trust Sanger Institute and their collaborators have shown that receptors in the noses of mice exposed to certain smells during life are different to genetically similar mice that lived without those smells. Published today in eLife, the study found it is this combination of genetics and experience that gives each individual a unique sense of smell.

Our sense of smell comes from the olfactory organ in the nose, which is made up of sensory neurons containing receptors that can detect odours. There are about one thousand types of olfactory receptors in the nose, compared with only three types of visual receptors in the eye, and 49 types of taste receptors on the tongue. Of our senses, the olfactory system is the most complex, and combinations of signals from different olfactory receptors allow people to smell an enormously large repertoire of odours. However, how different people vary in their smelling abilities is not well understood.

To investigate the sense of smell the researchers used laboratory mice as a model, comparing the olfactory neurons from genetically identical animals that grew up in different environments. They also compared animals that grew up in the same environment but were genetically different.

The team used RNA sequencing to see which receptor genes were active. The researchers found that genetics controlled which receptors were present in the mice. Crucially however, they found that the environment that the individual had lived in had a significant effect on the number of cells able to identify each smell.

Professor Fabio Papes, an author on the paper from the University of Campinas in Brazil, said: "It became clear that the role of genes, especially those that encode olfactory receptors in the genome, is very important in the construction of nasal tissue, but there was a very remarkable contribution of the environment, something that has not been previously described to this extent. We found the cellular and molecular construction of the olfactory tissue at a given moment is prepared not only by the organism's genes but also by its life history."

Olfactory neurons are formed throughout an individual's lifetime, and the study showed the olfactory system adapted to the environment, leading to more cells capable of detecting scents to which there has been greater exposure. As a consequence, different individuals, even if genetically similar, may have completely different olfactory abilities. This could contribute to the individuality of the sense of smell, even in humans.

The knowledge that an individual's history can affect the structure of olfactory tissue neurons may have implications for personalised medicine as different people's sense organs could be constructed differently and respond in different ways. Studying olfactory neurons can also provide information about how the neurons in the brain are organised and function.

Dr Darren Logan, the lead author on the study from the Wellcome Trust Sanger Institute, said: "The neurons in the olfactory system are highly connected to the neurons in the brain and studying these can help us understand neuronal development. We have shown that each individual has a very different combination of possible olfactory neurons, driven by genetics. In this study we also show that, with experience of different smells, these combinations of neurons change, so both genetics and environment interplay to give every individual a unique sense of smell."

Explore further: New PET imaging technique may help monitor neurological disease progression

More information: Ximena Ibarra-Soria et al, Variation in olfactory neuron repertoires is genetically controlled and environmentally modulated, eLife (2017). DOI: 10.7554/eLife.21476

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Genetics and environment combine to give everyone a unique sense of smell - Phys.Org

A couple sits close, intently studying a dossier. On the dossier is a list starting with Embryo #1.

According to the description, Embryo #1 is female, has a high risk of Type II Diabetes, will have blue eyes and blond hair, and has a 20% chance of being in the 90th percentile for math ability.

Alternatively, Embryo #100 is male, will have blue eyes and dark hair, has a 60% chance of being in the top 10% for musical ability, and is at a high risk for depression.

Between Embryo #1 and #100 lie similarly detailed descriptions.

While this may sound like science fiction, according to Hank Greely, Dean F. and Kate Edelman Johnson Professor of Law at Stanford University, this scenario is the soon-to-be future of human reproduction.

I predict in [my] book [The End of Sex and the Future of Human Reproduction] that in 20 to 40 years the majority of babies born to people with good health coverage anywhere in the world will not be conceived in a bed or in the back of a car or under a keep off grass sign, but will be conceived in a lab so that parents can then do whole genome sequencing and pick the embryo that they want, Greely said during his Gladstone GO Graduate Student Organization sponsored bioethics seminar on April 14.

Greely went on to share several stories about advances in human reproduction that will make this future he envisions possible, starting with preimplantation genetic diagnosis (PGD).

A three day embryo is like eight grapes inside a water balloon thats filled with jello, Greely explained. The grapes really arent attached to each other, so what you [do is] make a little hole in the water balloon--the membrane holding the embryo together and suck out one of those cells. And the other seven cells [do] fine, they [do] not fail at any higher rate than embryos regularly fail, and you take that cell and do genetic testing on it.

According to Greely, PGD has been clinically available for 25 years, but recently scientists have been using five- or six-day-old embryos from which they can take five, 10, or even 15 cells, thus allowing for more confidence in the genetic testing results.

This procedure, however, is currently limited by the expense of sequencing, the short time frame between taking cells from the embryo for genetic testing and implanting the embryo, and our understanding of genetics.

As sequencing becomes cheaper and allows our knowledge of genetics to grow, Greely predicts that PGD will advance to what he calls enhanced PGD, in which cells taken from embryos will have their entire genome sequenced.

Another huge limitation to PGD is that before you can run genetic tests you first must harvest eggs from the female.

Normally women ripen one or at most two eggs a month, Greely said. If youre going to go in [for] this invasive procedure you want as many ripe eggs as possible. Very expensive hormones [are used] in order to convince more eggs to ripen than normal. This causes cramping, bloating, mood swings, unpleasantness as well as the fact that [the woman] has to give herself a shot every day for 30 days in a row which people, understandingly, find a little bit disconcerting.

Furthermore, although a small percentage, some women who go through egg harvesting end up hospitalized or may even die.

Nobody goes through IVF [in vitro fertilization] just for the heck of it, Greely said. They do it because they have to.

Importantly, Greely also stresses that this unpleasantness and risk all falls on the female.

So what can we do to move away from current methods of egg retrieval? Greely believes the answer is induced pluripotent stem cells (iPSCs).

iPSCs are generated by reprogramming adult cells in a way which induces a loss of their defined cellular identity. In this state the cell now has the the potential to differentiate into any cell type, whether it be an epithelial cell, a cardiomyocyte, or an oocyte.

Greely thus envisions a world in which an individual would give a skin biopsy that would be reprogrammed to become iPSCs which would then be used to make oocyte precursors and finally an oocyte that could be fertilized.

This method, known as in vitro gametogenesis (IVG), could also be used on skin biopsies from males to generate oocytes or skin biopsies from females to generate sperm, thus making it possible for same sex couples to have children who are biologically related to both parents.

Additionally, instead of harvesting only a few eggs, IVG could potentially generate hundreds of eggs non-invasively.

Taking it a step further, whole genome sequencing (WGS) could be performed on all fertilized eggs to generate genetic profiles of each embryo. Parents could know whether the embryo is at high risk for early onset disease or other diseases and medical conditions. They could also learn about the cosmetic make up, behaviors, and sex, and use all this information to help them choose the embryo they want implanted.

One important caveat to this scenario, however, is that rarely do traits adhere to simple Mendelian genetics with one gene coding for one trait.

Its all going to be really complicated, Greely stated. Probably involving hundreds or thousands of different genetic loci and with a big dollop of environment and chance.

Another issue is how parents will parse through all this information.

Even if youre only looking at 20 different things of significance how do you weigh 50% higher risk of Type II Diabetes versus 50% lower risk of schizophrenia versus 50% chance of being in the top 10% for music ability versus [being] very, very tall? Greely asks. Its going to be a real hard decision.

Thus, an important aspect of this future Greely envisions will be educating parents to help them make informed decisions that they will ultimately feel comfortable with.

Despite this being a bioethics seminar, Greely only discussed a few ethical quandaries.

For instance, if you can take anyone's cells and make them into eggs and sperm, then anyone can be a genetic parent. A 50-year-old woman could become a mother, but an eight-month old baby or a woman who died and whose cells were frozen could both also become genetic parents.

While Greelys point seemed to be that this would change family structures, I think the real issue at the crux of this is legal regulation, which Greely didnt touch too much on in his talk.

One of the most challenging moral dilemmas associated with this future of human reproduction was, surprisingly, not brought up until the question was posed by an audience member.

As technology like PGD becomes more available and more powerful, will we lose populations of people?

For example, if you knew that an embryo would give rise to a child who was deaf, autistic, or achondroplastic would you chose against that embryo? And if you and others choose against that embryo how will that impact our society?

For one, it will decrease the number of individuals who make up that community thus decreasing research, social, and political support for this community.

Additionally, if parents tend to select against these traits it may send the message that these traits are bad and that individuals who do have these traits are leading lives that arent worth living.

But how does one determine what is and isnt a life worth living?

While society as a whole might label certain traits like those listed above as disabilities, members of these communities dont all hold that view, instead seeing it as a different way of being. For example, autism is sometimes thought of as neurodiversity.

How will beliefs like this affect a parents choice? Will an individual who is deaf select to have a deaf child?

This leads to a whole new set of issues Greely also did not cover.

In the future, will parents be discriminated against for choosing certain traits for their children or for choosing to procreate the old fashion way instead of selecting their child based on traits that society sees as favorable? What new power dynamics will these technologies create?

Greely also failed to talk about issues surrounding availability of this technology.

While he hypothesizes that health care programs will fully pay for IVG and WGS--as in the long run it will ultimately reduce healthcare spending--this coverage isnt going to happen instantly. In the beginning, these processes will still be expensive and likely only available to those with enough money.

If wealthy individuals are screening their embryos to ensure the healthiest embryo is implanted, what will this mean for populations who cant afford this service? It seems very possible that the burden of health care expenses could fall entirely on them.

Additionally, this could impact the amount of money funneled into biomedical research whether it be because individuals feel they no longer need to donate to a cause that doesnt affect them or because research in that field no longer seems like a priority due to a shrinking community of affected individuals.

All of this, however, is dependent on how much information we will actually be able to glean from an embryos genetics alone.

Greely believes that cheap sequencing changes everything and while it will definitely lead to advancements, it may not be as comprehensive as Greely predicts.

Despite what I believe to be Greelys slightly over-optimistic vision, his last point rings true.

If we understand the issues better in advance we are less likely to screw up.

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The Future of Genetics - Synapse