Posted By: HGG Advances
Each month, the editors of Human Genetics and Genomics Advances interview an early-career researcher who has published work in the journal. This month we check in with Sara Azidane Chenlo to discuss her paper “Identification of novel driver risk genes in CNV loci associated with neurodevelopmental disorders.”
HGGA: What motivated you to start working on this project?
SAC: I’ve always been fascinated by the human brain, its intricate functioning, the emotional patterns that regulate it, and its ways of encoding reality. I am particularly intrigued by the challenges and limitations faced by individuals who don’t fit within neuronormativity. Understanding these complexities in neurodivergence is crucial, especially considering that an estimated 7-15% of the population suffers from some form of neurodevelopmental disorders (NDD), such as Autism Spectrum Disorder (ASD), ADHD, schizophrenia or intellectual disabilities.
My interest in copy number variants (CNVs) in NDDs was driven by the desire to address this challenge. It’s estimated that up to 15% of neurodevelopmental disorders are caused by CNVs. However, the mechanisms through which these complex genetic structures influence such diseases remain largely unknown. Why is the deletion of the same region associated with different disorders? What gene causes the phenotype? Is there more than one gene responsible? How might the disruption of different genes contribute to various aspects of the broad phenotypic framework?
I found it fascinating to identify genetic risk patterns, especially the large unknown CNVs, that can inform better diagnosis and treatment of NDDs. This could lead to less biased and more accurate standards and improve the quality of life for individuals suffering from these disorders.
HGGA: What about this paper/project most excites you?
SAC: The most exciting part of this project is the discovery and validation of novel NDD risk genes. We identified 22 NDD-risk genes that had never been associated with NDDs before and found that many of them are involved in critical pathways in neural development.
Additionally, we discovered new significant associations, linking some of these genes to clinical signs and symptoms often reported in patients with syndromic forms of NDDs. For instance, we found ANGPT2 to be associated with micrognathia, cryptorchidism, and hypertelorism.
HGGA: What do you hope is the impact of this work for the human genetics community?
SAC: Given the heterogeneity of these disorders and the fact that most risk genes have yet to be identified, I believe that validating new risk genes for NDDs is a significant breakthrough. This advancement could not only improve diagnostics for patients with NDDs but also enable the characterization of new syndromes and expand our understanding of the molecular processes and pathways involved in these conditions.
HGGA: What are some of the biggest challenges you’ve faced as a young scientist?
SAC: The hardest part for me as a young researcher is managing the fear of making mistakes and the frustration that comes with it. However, science advances through trial and error. Making mistakes and communicating them can be painful, but spotting and solving these errors is what helps me grow and improve every day.
This fear is also probably also accentuated by the fact that as female scientists, we tend to integrate unconscious bias. I am lucky as my current environment is specifically encouraging of female scientists, fostering a supportive atmosphere that promotes diversity in research and innovation.
HGGA: And for fun, what is one of the most fascinating things in genetics you’ve learned about in the past year or so?
SAC: Recently, I discovered the strong genetic correlation between NDDs and substance use disorders (including cocaine, opiates, and even natural rewards like food). This genetic overlap may explain the frequent comorbidity between NDDs and substance abuse disorders, and why individuals with ASD, ADHD, or intellectual disabilities are at a higher risk for developing substance abuse problems compared to the general population. For example, mTOR inhibition has been shown to rescue the synaptic surplus and functional hyperconnectivity seen in some patients with autism and also helps attenuate addictive behavior patterns in situations of drug abuse.
Whether this higher risk of substance abuse is due to a predisposition to repetitive behaviors or a coping mechanism for self-regulation, the underlying genetic risk factors present an interesting research avenue. This broadens our understanding of neurodevelopmental and psychiatric disorders significantly.
Sara Azidane Chenlo is a data analyst at STALICIA, a biopharmaceutical company in Barcelona, Spain.