Industry Odisha Bureau, Aug 14: Researchers have identified naturally occurring human gene knockouts at an unprecedented scale. A study involving 1,73,303 participants discovered significant loss-of-function variants across approximately 6,476 genes. About one in five carried at least one gene with both copies stopped. These individuals essentially provide nature-performed experiments for understanding actual human gene function.
The Pakistan Genome Resource analysed 1,66,625 exomes and 6,678 whole genomes across 23 cities. Researchers identified 6.6 million coding variants, with 47 percent absent from non-South Asian genetic databases. About 30 percent were absent from South Asian data, highlighting under representation in global knowledge.
People with naturally inactive genes allow researchers to ask three fundamental questions about function. Does a gene’s absence cause disease, produce little obvious effect, or sometimes confer benefit? The answers can guide drug discovery by identifying promising therapeutic targets for development.
APOC3 provides one clear example of genetic evidence supporting potential drug targets. Participants lacking functional APOC3 copies showed substantially lower triglyceride concentrations and smaller post-meal increases. This human evidence led to olezarsen’s approval in December 2024 for chylomicronaemia syndrome treatment.
Human genetic data can also warn researchers away from ineffective therapeutic approaches. PLA2G7 loss reduced Lp-PLA2 substantially but did not reduce coronary disease occurrence. Darapladib, targeting the same enzyme, had previously failed in large cardiovascular clinical trials.
However, genetic evidence requires careful interpretation before translating into actual clinical applications. LRRK2 represents an important Parkinson’s disease target, yet Pakistani data suggested kidney impairment concerns. A naturally inactive gene differs fundamentally from a drug partially inhibiting a protein.
Mice lacking PRDM9 are infertile, yet Pakistani individuals with the same genetic loss had children. This demonstrates that animal laboratory findings cannot always predict human biological outcomes accurately.
India’s population-specific genetic diversity similarly justifies investment in comprehensive genomic research programmes. GenomeIndia has already sequenced 10,000 genomes from 83 distinct population groups, providing reference maps. Future genomic research should link genetic data with medical records and laboratory measurements.
For medical science and drug discovery, human genetic variation offers powerful research clues. Studied carefully and ethically, population diversity can reveal what individual genes actually do.
