Gene Mapping and Gene-Set Analysis for Milk Fever Incidence in Holstein Dairy Cattle

Hendyel A Pacheco,Simone Da Silva,Anil Sigdel,Klibs N Galvão,Rodrigo A Texeira,Francisco Peñagaricano,Chun Kuen Mak,Laila T Dias

doi:10.3389/fgene.2018.00465

Hendyel A Pacheco, Simone Da Silva + Show 6 more

Open Access

https://doi.org/10.3389/fgene.2018.00465

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Abstract

Milk fever is an important metabolic disorder that affects dairy cows around parturition. It is associated with a breakdown in the mechanisms of calcium homeostasis, resulting in very low blood calcium levels (hypocalcemia). The main objective of this study was to dissect the genetic basis underlying milk fever incidence in Holstein cattle. Data consisted of 31.6 k producer-recorded lactation incidence records from 15.3 k cows. The analysis included a whole-genome scan and a subsequent gene-set analysis in order to reveal individual genes, genetic mechanisms and biological pathways implicated in the incidence of periparturient hypocalcemia. The association analysis identified at least eight different genomic regions that explain considerable amounts of additive genetic variance for milk fever incidence. Notably, some of these regions harbor genes, such as CYP27A1, CYP2J2, GC, SNAI2, and PIM1, that are directly involved in vitamin D metabolic pathway. Moreover, the gene-set analysis revealed several functional terms, such as calcium ion binding, calcium ion transportation, T cell differentiation, B cell activation, protein phosphorylation, apoptosis, and protein kinase activity, among others, that could be implicated in the development of periparturient hypocalcemia. Overall, this comprehensive study contributes to a better understanding of the genetic control of this complex disease. In addition, these findings may contribute to the development of novel breeding strategies for reducing the incidence of milk fever in dairy cattle.

Highlights

Periparturient hypocalcemia or periparturient paresis, commonly known as milk fever, is a metabolic disorder that affects dairy cows around parturition
Milk fever is considered a gateway disease because the occurrence of periparturient hypocalcemia is related to increased incidence rates of other transition disorders, such as retained placenta, metritis and mastitis
We performed an integrative genomic analysis in order to reveal the genetic basis of periparturient hypocalcemia, commonly known as milk fever, in Holstein dairy cattle

Summary

Introduction

Periparturient hypocalcemia or periparturient paresis, commonly known as milk fever, is a metabolic disorder that affects dairy cows around parturition. The onset of lactation demands a huge amount of calcium for colostrum and milk synthesis, and some cows are unable to adapt to this demand and succumb to clinical hypocalcemia (Horst et al, 1997, 2005). Milk fever arises when the homeostatic mechanisms fail to maintain normal blood calcium concentrations in early lactation. Clinical symptoms include partial to complete paralysis (downer cows) and reduced feed intake. The occurrence of milk fever predisposes the cow to other metabolic and infectious. Genetic Dissection of Milk Fever disorders, such as retained placenta, uterine prolapse, endometritis, displaced abomasum, ketosis, and mastitis (Mulligan et al, 2006). Economic losses are substantial and include losses due to on-farm death, premature culling, reduced milk production, and increased veterinary and treatment costs (Liang et al, 2017)

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