Scientists map genetic constraints to pinpoint disease-causing mutations
Researchers developed a new method to distinguish harmful genetic variations from benign ones by analyzing which DNA regions have remained unchanged across mammalian evolution. The breakthrough could accelerate drug development and genetic testing by helping companies and clinicians identify mutations that actually cause disease rather than wading through thousands of genetic variants.
Originaltitel: Leveraging base-pair mammalian constraint to understand genetic variation and human disease
<p>Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.</p>