Abstract
BACKGROUND: Leishmaniasis is a major public health concern, with a high annual incidence and extensive geographical distribution. This parasitic disease is transmitted through the bite of specific species of sand flies and is caused by flagellated protozoa. Leishmania major is one of the main causes of cutaneous leishmaniasis (CL) in Iran, with diverse clinical manifestations. This research seeks to explore the impact of genetic diversity on clinical differences by investigating variations in chromosomal count and analyzing single nucleotide polymorphisms (SNPs) and insertions/deletions (Indels). MATERIALS AND METHODS: The whole genome of the Iranian Leishmania major strain MRHO/IR/75/ER has been sequenced using next-generation sequencing. Data alignment to the reference genome, variant calling, and SNP, Indel, and chromosomal variation identification were carried out using bioinformatics tools. RESULTS: The findings indicated notable karyotypic variations in the Iranian Leishmania major strain, specifically demonstrating monosomy on chromosome 2 and trisomy on chromosomes 5, 13, 28, and 31. The analysis of SNPs and INDELs revealed 144,509 genetic variants, with 99% situated within coding regions. Significant changes were observed in MRPA, HSP70.4, GP63, and CPA, which may affect drug resistance and pathogenicity. CONCLUSION: This research clarifies the genetic diversity of L. major and its consequences for disease development and resistance to treatment. Further functional studies are essential to validate these genetic discoveries and their implications for clinical practice.