Females may have “Protection Model” for Neurodevelopmental Disorders

Two weeks ago, a large cohort study including researchers from all over the world provides evidence that females may have a “protection model” requiring more genetic mutations than males to be diagnosed with neurodevelopmental disorders.

Previously it has been shown that there is a gender bias for neurodevelopmental disorders (such as Autism Spectrum Disorder (ASD) and ADHD).  More males are currently diagnosed, but until now no conclusive evidence has surfaced as to why this is true.   The study proposes that females require more extreme genetic mutations than males to be diagnosed with the disorders.

To explore the gender bias, the researchers joined forces and analyzed over 15,000 individuals with disorders and about 750 individuals with ASD.  Using modern molecular techniques, the DNA from each individual was sequenced and then looked at for mutations.  The mutations examined were copy-number variants (CNV) and single-nucleotide variants (SNV), which are changes in the numbers of gene or a change in just one nucleotide base respectively.

Interestingly enough, the results showed that females who were diagnosed with a disorder or ASD had a greater number of CNVs and SNVs than males diagnosed with the same.  This suggests that for the same diagnosis, females require more genetic mutations, which in turn supports the theory that females have a “protection model.”  This is also interesting because the X chromosome was often thought to be a main component in the gender bias, but the results suggest that the source may be genome wide.

To read the article: https://www.cell.com/AJHG/abstract/S0002-9297(14)00059-7

Jacquemont, Sé, et al. “A Higher Mutational Burden in Females Supports a Female Protective Model in Neurodevelopmental Disorders.” The American Journal of Human Genetics, Volume 94, Issue 3, 415-425. doi:10.1016/j.ajhg.2014.02.001


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