Genome assemblies of Indian <i>desi</i> cattle reveal hotspots of rearrangements and immune-related genetic diversity

India, home to the world's largest cattle population, hosts native dairy breeds essential to its agricultural economy because of their adaptability and resilience. This study characterizes the genomes of five prominent breeds-Gir, Kankrej, Red Sindhi, Sahiwal, and Tharparkar-highlighting their unique genomic characteristics. The <i>de novo</i> assemblies ranged from 2.70 to 2.78 Gb in size, with 90% of the genomes assembled in just 56 to 1663 scaffolds. The use of reference-guided scaffolding further enhanced these genomes, resulting in 93.3%-96.7% pseudomolecule coverage with strong BUSCO scores (94.1%-95.5%). Comparative analyses revealed 87%-95% synteny with the Brahman genome and identified 19.84-153.16 Mb of structural rearrangements per genome, including inversions, translocations, and duplications. Synteny diversity analysis uncovered 10 643 perfectly collinear regions spanning 87.3 Mb and 6622 hotspots of rearrangement (HOT regions) covering 55.18 Mb. These HOT regions, characterized by high synteny diversity, were significantly enriched with immune-related genes. Moreover, immune-related gene clusters, including major histocompatibility complex, natural killer complex, and leukocyte receptor complex, were identified within HOT regions in the <i>desi</i> reference genome. Our findings provide valuable insights into the genetic diversity of <i>desi</i> cattle breeds. The high-quality genome assemblies generated in this study will serve as valuable resources for future research in genetic improvement, disease resistance, and environmental adaptation.