Whole genome resequencing reveals the genetic basis of stature in short-statured Indian cattle.

India possesses a rich diversity of indigenous cattle that are well adapted to varied agro-climatic regions. These populations exhibit remarkable variation in stature (height at withers), ranging from short-statured types such as Vechur, Punganur, Malnad Gidda, and Khariar to tall and heavy breeds like Kankrej, Ongole and other milch breeds (Sahiwal, Gir, etc.). The short-statured breeds offer potential advantages in feed efficiency, disease resilience, and cultural value besides being economical to maintain. However, their genetic basis for stature remains underexplored. This study leverages whole-genome resequencing (WGS) data on short-statured (n = 19) and tall (Kankrej as representative; n = 19) Indian cattle to delineate the copy number variation (CNV) landscape and selection signatures underpinning stature divergence. Post-quality control, CNVs were detected from duplicate-marked bam files using CNVnator with read-depth methodology, filtered (q0 < 0.5, p < 0.01, size 1 kb-5 Mb), and concatenated into CNV regions (CNVRs). Selection signatures were identified using cross population extended haplotype homozygosity (XP-EHH) methodology for inter-population comparison of short-statured cattle with tall cohort. Genes harboured under CNVRs and sweep windows were annotated using GALLO, with functional mining from literature databases. In short-statured cattle, 41,913 CNVs were concatenated into 10,075 CNVRs, with 8.01% genomic coverage. A total of 25 genes were found to be common across two analyses i.e., unique (non-overlapping) CN regions in 70% short-statured individuals and scan of selection signature. Key genes across the analyses included IGF1R (cell proliferation), FGFR3 (skeletal growth), SOX6 (body size), EXT2/LGR4 (bone density), PRKCD (developmental regulation), ADAMTSL2 (extracellular matrix integrity), SLC25A6 (glucose metabolism), and SDHA (energy supply). Unique non-overlapping copy number regions (e.g., 78 regions found in 100% of dwarf individuals) harbored several genes, including ARL13B (osteogenesis), AXIN2 (bone remodeling), CCND2 (myogenesis), and TNNT1 (muscle contraction). This comprehensive CNV map and scan for signatures of selection unveil stature-associated genomic variants, informing conservation strategies for threatened short-statured breeds by enhancing their socio-economic value through targeted breeding. The findings underscore CNVs as pivotal drivers of phenotypic diversity in cattle populations, with implications for livestock genomics and sustainable agriculture.