04 April 2015
By Darren Logan
A family tree showing the incidence of anosmia in five generations of the same family.
We generally do not think about our sense of smell too often. Yet it contributes hugely to the multi-sensory perception of our world.
For example, approximately 80 per cent of the flavour of our food relies entirely on smell; without it we are restricted to just five basic tastes.
Most of us will have experienced this when suffering a heavy cold, when our noses are completely blocked, meals are bland and unappetizing.
In addition, we routinely use smell to warn of danger and signal safety, to attract partners and customers (think ‘new car smell’) and to evoke memories.
In fact, olfaction, the technical term for our sense of smell, is sufficiently important to us that the molecular odour receptors in our nose are encoded by the largest single family of genes in our genomes.
So, what happens if you lose your sense of smell or if you were born without it? Having had a research interest in sensory genetics for a number of years, I knew that such a condition, called anosmia, existed. However, like most of us, I had never really considered the profound and disconcerting affect the absence of smell may have on everyday life.
I recently visited Fifth Sense, a charity supporting people with smell and taste disorders. One member, Sarah Kathleen Page, a photographer who was born with anosmia, summed up life without smell:
"We cannot smell the gas leak slowly filling up our home, we cannot smell our newly born daughter, we cannot fully enjoy the sensory pleasures most people take for granted. We hope for a doctor that believes us when we say we cannot smell and long for a friend that never forgets. Without someone to say, ‘I understand, I believe you and I will do my best to help’ we live in a very lonely world."
To better understand this disorder, my laboratory has begun a study to find the genetic basis of being born without the ability to smell. Along with colleagues at the Monell Chemical Senses Center in Philadelphia, we launched a social media campaign to find families with people who can and cannot smell across multiple generations. We received responses from across the world.
In one case, we found a family with anosmia across five generations; each time, the condition was inherited from parent to child. After carefully mapping out the family trees, we carried out a standardized smell test on each family member to confirm the diagnosis. We then collected saliva and are now sequencing their genomes.
Using a strategy developed at the Wellcome Trust Sanger Institute to successfully identify the genes involved in other rare diseases, we will compare the genetic variation from those within the same family who can and cannot smell. This approach helps narrow down the search for the precise gene responsible.
Identifying the genetic causes of anosmia is only the first step in a long journey. Like many rare genetic conditions, it is unrealistic to expect that new treatments or cures will automatically follow. However, we aim to press on and investigate how these genes contribute to the complex neural circuits that connect our noses and brains. Only then can we evaluate them as potential targets for clinical intervention.
Darren Logan joined the Wellcome Trust Sanger Institute faculty in 2010. His team – Genetics of Behaviour – combines comparative genomics, reverse genetics, behavioural testing, and neural activation studies to identify and investigate genes involved in the signalling, sensing and processing of olfactory cues that influence behaviour. They aim to understand the role of these genes in instructing normal perception and behaviours and their dysfunction in neurological disorders.