A landmark study of more than 173,000 genomes from Pakistan has identified a large number of individuals carrying completely non-functional genes, offering new insights that could reshape global drug development and human genetics research.
A genome is the complete set of genetic instructions found within an organism. It serves as a master blueprint containing all the DNA (or RNA in some viruses) required to build, grow, and sustain life.
Published in Nature, the research based on the Pakistan Genome Resource found that around 20% of participants are “human knockouts,” meaning they possess at least one gene that does not function at all. Scientists say the dataset reveals loss-of-function variants in nearly 6,500 genes, around one-third of all human protein-coding genes.
The study identified approximately 34,000 individuals with at least one fully inactivated gene, providing researchers with a rare opportunity to observe what happens in humans when specific genes are switched off naturally.
Experts say this could help uncover gene functions that remain unknown decades after the Human Genome Project.
Researchers noted that many genes considered essential based on mouse studies appear to be variable in humans, raising concerns about the reliability of animal models in predicting drug responses. The findings may also help explain why many experimental drugs succeed in animals but fail in human clinical trials.
