“Goldilocks” CNV Genes That Tell the Tale of Human Evolution Hold Clues to Variety of Diseases

Geneticists from Trinity College Dublin in Ireland have used our evolutionary history to shine light on a plethora of neurodevelopmental disorders and diseases. Their findings isolate a relatively short list of genes as candidates for many diverse conditions including autism spectrum disorders, schizophrenia, ADHD, intellectual disability, developmental delay, and epilepsy. The geneticists' findings were published in February 8, 2017 in Nature Communications. The open-access article is titled “Dosage Sensitivity Is a Major Determinant of Human Copy Number Variant Pathogenicity.” There are over 20,000 genes in the human genome that contain the all-important codes used to produce specific proteins in the body. In their study, the Trinity geneticists focused on regions of the genome that are duplicated or deleted in some individuals. These regions, termed “copy number variants” (CNVs), are abundant in humans. Not all CNVs result in noticeable differences between individuals -- sometimes the genes within them function similarly regardless of the number of copies present. However, variations in other CNVs are implicated in a variety of debilitating disorders and diseases. These disease CNVs are large, and a major challenge is to identify which genes within the regions are causing the problems. Professor in Genetics at Trinity, Aoife McLysaght, Ph.D., said: "Our idea was that there must be some genes within these regions with 'Goldilocks' properties: too much or too little duplication, and things don't work properly. The number of copies must be just right." The Trinity team looked back over our evolutionary history to discover which genes don't tolerate increases or decreases over evolutionary time. This segment of their work suggested that the key is in the presence of these Goldilocks genes within the disease-causing CNVs.
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