Neurological disorders are complex in various ways. A simple limitation is that brain tissue is difficult to study and research questions often have to be answered by other study designs. Another more important complexity is the often multifactorial nature of these disorders. Human Prion protein (PRNP) and Endothelin Receptor B (EDNRB) genes isolated from healthy and diseased Pakistani individuals (suffering from neurological disorders) have been investigated for genetic association of the polymorphism with these neurological disorders. Novel mutations in EDNRB gene were identified from Pakistani population. Phylogentics was performed to know the relatedness of the PRPN genes of different species. The transfer of prion proteins causes the prion protein diseases. The phylogensis of PRPN genes will help the scientists to investigate the probability of zoonosis of the disease from different species to humans.