Conservation & local programs

Signatures of selection revealed by SNPs and structural variants in unselected and contemporary Holstein cattle

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Abstract

Since the 1960s, intensive selection in US dairy cattle has considerably increased milk yield; however, these gains have coincided with more health problems such as mastitis, metabolic disorders, and infertility. Immune system functions are particularly affected by the reduction in genomic diversity in Holsteins. In 1964, a Holstein breeding experiment at the University of Minnesota established a selected line, Contemporary Holsteins (CH), and an unselected control line, Unselected Holsteins (UH). The UH line was maintained to represent U.S. Holsteins from the mid-1960s. UH cows produce less milk but exhibit superior overall health compared with CH cows. This study aimed to detect SNPs and structural variants (SVs) from long-read sequencing data and assess selection's impact in UH and CH cows. Thirty-four UH and 25 CH cows were sequenced on an Oxford Nanopore platform at ~20à— coverage. Reads were mapped to the ARS-UCD2.0 cattle reference genome with Minimap2; and SNPs and SVs were called using Clair3 and Sniffles2, respectively. Variants were filtered for quality ≥ 20, depth ≥ 5, and SVs ≥ 50 bp. Selection signatures were identified using Fixation Index (Fst) estimates from VCFtools with a 50 kb window and a step size of 20 kb. Top 1% Fst windows (SNPs) and Fst > 0.25 windows (SVs) were considered significant selection signatures. Selection signatures were further examined by overlapping them with cattle annotated genes and quantitative trait loci (QTLs). The average N50 read length for the 59 samples was ~25.6 Kb. After filtering, UH cows retained ~5.50 M SNPs and 23,196 SVs, while CH cows retained 4.74 M SNPs and 22,324 SVs. Approximately 12 M SNPs and 41,407 SVs were common to both groups. From SNP data, 810 regions (top 1% Fst) were identified as candidate selection regions, overlapping 685 genes and 3,199 QTLs from 176 traits. Genes within these regions were linked to immune functions (ITGA4, LUZP2, RCAN3, TNFAIP2, TRAF3), reproduction (AMH, PRLR, WEE2, ZP4), and milk production (IGF1R, MAP2K6, PRLR, STAT4). SV-based Fst analysis identified 2,374 selection signatures (Fst > 0.25), encompassing 350 genes and 8,247 QTLs representing 558 traits. Key genes identified were linked to immunity (FCRL6, IGF2BP1, IL13, PRF1, SLAMF8), lipid metabolism (ABCA6, ACOT2, DHCR24), reproduction (GHR, POU5F1, SPATA22), and feed intake (GFRAL, HCRTR2). Both datasets revealed several olfactory receptor genes, suggesting selection related to behavioral traits. Twenty-nine genes were included in both SNP and SV regions and included ATG2B, CD226, CPNE4, CSMD1, HTR4, TDRD9, and TRAPPC9. These results demonstrate that long-term selection in Holsteins has shaped genomic regions associated with immunity, fertility, and metabolism. Combined SNP-SV analysis using long-read data offers new insights into the genetic basis of health and productivity in Holstein cows under selection.

Keywords: 2026

How to Cite:

Boschiero, C., Rosen, B., Liu, G., Weber, W., Seykora, A., Lippolis, J., Cole, J. & Crooker, B., (2026) “Signatures of selection revealed by SNPs and structural variants in unselected and contemporary Holstein cattle”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2283971. doi: https://doi.org/10.31274/wcgalp.23542

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