Dr. Danish Saleheen, a Pakistani-American professor at Columbia University, and his fellow researchers have published a comprehensive analysis of 173,303 genomes from Pakistan, one of the largest genomic studies ever conducted in South Asia. This landmark work is upending how scientists understand human genetics and drug development. "South Asians have been severely underrepresented in genome studies—comprising just 2% of global genomic databases despite representing 25% of the world's population," study leader Dr. Saleheen explained. The study is sponsored by Novartis, Columbia University Irving Medical Center, and the Center for Non-Communicable Diseases, Karachi, Pakistan. Its results could fundamentally transform drug discovery. 

The study, published in the journal Nature, has identified knockouts of nearly 6,500 genes—about one third of all protein-coding genes (exomes)—in 34,000 individuals. Cousin marriages are quite prevalent in Pakistan, with half of all marriages occurring between close relatives. Landmark research, including the Pakistan Genomic Resource, highlights how these genetic traits act as both a medical challenge and a massive opportunity for scientific discovery.  

Study of Knockout Genes in Humans vs Mice

What are "knockout genes"? In Pakistan, the study has identified thousands of individuals with naturally missing or "knocked out" or "deleted" genes. Researchers use mice for studying diseases and "knock out" or delete specific genes to study how the deletions impact health and contribute to disease. The problem is that translation of such findings to humans has been difficult, "because mouse genes often have different functions than their human counterparts," Saleheen says. “What’s unique about our Pakistan study is we can go back to participants and conduct comprehensive medical exams to see what kind of effects the gene deletion may have on the individual,” he adds.