|MA, LI - University Of Maryland|
|SONSTEGARD, TAD - Recombinetics, Inc|
|Van Tassell, Curtis - Curt|
|CROOKER, BRIAN - University Of Minnesota|
|TAN, CHENG - South China Agricultural University|
|PRAKAPENKA, DZIANIS - University Of Minnesota|
|Liu, Ge - George|
|DA, YANG - University Of Minnesota|
Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/17/2019
Publication Date: 2/11/2019
Citation: Ma, L., Sonstegard, T.S., Cole, J.B., Van Tassell, C.P., Wiggans, G.R., Crooker, B.A., Tan, C., Prakapenka, D., Liu, G., Da, Y. 2019. Genome changes due to artificial selection in U.S. Holstein cattle. BMC Genomics. 20:128. https://doi.org/10.1186/s12864-019-5459-x.
Interpretive Summary: We present results from two unique and complementary analyses to understand how the genome of Holstein cattle has changed in response to genetic selection over more than 40 years. The selection signature analysis compared a unique Holstein line unselected since 1964 with Holsteins that did undergo genetic selection. The observed genome-wide changes affected genomic regions containing genes with known fertility and immunity functions. Several selection signatures involved large clusters of microRNA genes, olfactory receptors, zinc fingers, cationic amino acid transporters, sialic acid-binding Ig-like genes, vomeronasal receptors, keratin genes, EMR2 receptors, and transfer RNA’s. An accompanying genome-wide association study included almost 300,000 genotyped Holstein cows and identified new additive and dominance genetic effects on nine Holstein traits. The integrated analysis of selection signatures and individual cow genotypes identified selection for positive effects and against negative effects, the overlap between dominance effects and selection signatures due to heterozygosity changes, and the lack of genetic selection for the most-significant gene on milk production due to extreme antagonistic effects with other important traits, such as fat and protein yields. The results of this study show that the integrated analysis of selection signature and GWAS is a powerful approach to discover and understand genetic variants associated with quantitative traits in dairy cattle.
Technical Abstract: We conducted an integrated analysis of selection signature and large-sample genome-wide association study (GWAS) using nearly 294,079 cows to identify genomic changes associated with the phenotypic changes since 1964 and the relationship between QTL effects and genetic selection. The direct comparison between the selected and unselected Holstein genomes showed that the forty years of genetic selection since 1964 affected 40% of the Holstein genome. Many selection signatures contained genes with documented fertility functions, leading to the hypothesis that hitchhiking of negative effects of fertility genes due to genetic selection for improving milk production contributed to the unintended declines in fertility since 1964. The bovine MHC region of Chr23 had a strong selection signature and significantly decreased heterozygosity in contemporary relative to the unselected Holsteins. This region also had significant SNP effects on milk production. A large 28 Mb region in the center of Chr20 was covered by long haplotypes with high frequencies and high values of extended haplotype homozygosity, and had highly significant SNP effects on milk yield particularly in the GHR-PRLR region. The large-scale GWAS confirmed DGAT1 to have the most significant effects for milk production but revealed that DGAT1 had extreme antagonistic pleiotropy effects on milk production with the largest positive effect on fat yield and the largest negative effects on milk and protein yields. The selection signature analysis revealed that the DGAT1 allele frequencies remained relatively unchanged since the mid-1980’s. A Chr05 region with the most significant dominance effects overlapped with a selection signature due to increased long-range heterozygosity in an elite group of Holsteins. The GC gene of Chr06 was highly significant for milk production, daughter pregnancy rate and somatic cell score, and the GC region was close to a selection signature due to recent genetic selection.