Genome-wide association study and functional analyses for clinical and subclinical ketosis in Holstein cattle

Abstract

Ketosis is one of the most frequent metabolic diseases in high-yielding dairy cows and is characterized by high concentrations of ketone bodies in blood, urine, and milk, causing high economic losses. The search for polymorphic genes, whose alleles have different effects on resistance to developing the disease, is of extreme importance to help select less susceptible animals. The aims of this study were to identify genomic regions associated with clinical and subclinical ketosis (β-hydroxybutyrate concentration) in North American Holstein dairy cattle and to investigate these regions to identify candidate genes and metabolic pathways associated with these traits. To achieve this, a GWAS was performed for 4 traits: clinical ketosis lactation 1, clinical ketosis lactation 2 to 5, subclinical ketosis lactation 1, and subclinical ketosis lactation 2 to 5. The estimated breeding values from 77,277 cows and 7,704 bulls were deregressed and used as pseudophenotypes in the GWAS. The top-20 genomic regions explaining the largest proportion of the genetic variance were investigated for putative genes associated with the traits through functional analyses. Regions of interest were identified on chromosomes 2, 5, and 6 for clinical ketosis lactation 1; 3, 6, and 7 for clinical ketosis lactation 2 to 5; 1, 2, and 12 for subclinical ketosis lactation 1; and 20, 11, and 25 for subclinical ketosis lactation 2 to 5. The highlighted genes potentially related to clinical and subclinical ketosis included ACAT2 and IGF1. Enrichment analysis of the list of candidate genes for clinical and subclinical ketosis showed molecular functions and biological processes involved in fatty acid metabolism, lipid metabolism, and inflammatory response in dairy cattle. Several genomic regions and SNPs related to susceptibility to ketosis in dairy cattle that were previously described in other studies were confirmed. The novel genomic regions identified in this study aid to characterize the most important genes and pathways that explain the susceptibility to clinical and subclinical ketosis in dairy cattle.

Genomic characterization of autozygosity and recent inbreeding trends in all major breeds of US dairy cattle

“…The 3.44 Mb overlapped region on BTA6 between AY and BS contained several genes with known functions associated with traits selected for in dairy cattle; these were ADAMTS3, ANKRD17, GC, and NPFFR2. These genes have been associated with productive life (ADAMTS3 and NPFFR2; Mészáros et al, 2014;Zhang et al, 2016), milk and milk component yield (ADAMTS3, ANKRD17, GC, and NPFFR2; Costa et al, 2019;Jiang et al, 2019), clinical mastitis (GC and NPFFR2; Sahana et al, 2014;Freebern et al, 2020), and subclinical ketosis (ANKRD17; Soares et al, 2021). Trait enrichment based on QTL annotated in this chromosome corroborated the high selective pressure for loci on BTA6 affecting health, milk and milk component yield, and productive life in AY and BS.…”

Unraveling Admixture, Inbreeding, and Recent Selection Signatures in West African Indigenous Cattle Populations in Benin

“…In addition, the segment BTA 2:70–71 Mb covered various candidate genes such as EN1 , involved in growth traits in cattle ( Buroker, 2014 ). Further regions under selection in BO_cur host candidate genes, significantly associated with different traits, including ADAM32 , ADAM9 , HTRA4 , and KLHL21 with residual feed intake and immune responses, PLEKHA2 and TNFRSF25 with growth and carcass performances, HTRA4 with milk, and HOOK1 with heat stress ( Fan et al, 2015 ; Tizioto et al, 2015 ; Seong et al, 2016 ; Blanco et al, 2017 ; Hardie et al, 2017 ; Hay and Roberts, 2018 ; Sengar et al, 2018 ; Skibiel et al, 2018 ; Oliveira et al, 2019 ; Braz et al, 2020 ; Brunes et al, 2021 ; Soares et al, 2021 ).…”

Genomewide Association Analyses of Lactation Persistency and Milk Production Traits in Holstein Cattle Based on Imputed Whole-Genome Sequence Data

“…They are central genes controlling many proteolytic cascades, including important mammalian coagulation pathways [69]. Both genes were formerly associated with milk production traits in buffaloes [70] and somatic cell count in Jersey cows and clinical ketosis lactation in Holstein cattle [71,72], but this is the first time that SERPINB6 and SERPINB9 have been associated with LP. Due to its relationship with other dairy cattle traits, its molecular role in the expression of LP should be further investigated.…”