Association of toll-like receptor 4 polymorphisms with somatic cell score and lactation persistency in Holstein bulls.
Mastitis, an inflammatory disease of the mammary gland generally caused by intramammary infections, is the most frequently occurring disease in the North American dairy industry. Reduced milk yield, milk quality, and lactation persistency as well as early culling contribute to the economic losses associated with this disease. During intramammary infections, cells of the innate immune system become activated through pattern recognition receptors that recognize conserved molecular signatures associated with the invading pathogen. The quality, timing, and intensity of the host inflammatory and subsequent immune response determine the fate of this disease. Toll-like receptor 4 (TLR4) is an important pattern recognition receptor that recognizes endotoxins associated with gram-negative bacterial infections. Its role in pathogen recognition and subsequent initiation of the inflammatory and immune response makes it a suitable candidate gene for enhancing disease resistance in Canadian Holsteins. In this study, polymorphisms in the TLR4 gene were identified in the Canadian Holstein bull population. Genotypes and haplotypes were constructed, and their associations with somatic cell score and lactation persistency were determined. Sequencing of selective DNA pools was used to reveal polymorphisms in TLR4. Two DNA pools were constituted based on high and low estimated breeding values for somatic cell scores. A total of 3 single nucleotide polymorphisms (SNP), including 1 SNP in a putative promoter region (P-226) and 2 SNP in exon3 (E3+1656 and E3+2021) of TLR4 were detected. A total of 388 bulls were genotyped for the SNP, haplotypes were reconstructed, and their frequencies were obtained. Polymorphisms in these regions were found to be associated with estimated breeding values for lactation persistency, and somatic cell scores in the Canadian Holstein bull population. The unfavorable alleles at P-226 and E3+1656 were found at a frequency of 40 and 37%, respectively; hence, selection against these alleles is promising in Canadian Holsteins. Selection against the unfavorable allele, T at E3+2021, is limited because of its low frequency (7%). Two frequently occurring haplotypes (GCC and CTC) occurred in 86% of the Canadian Holstein bull population chosen for genotyping. The most frequent haplotype (GCC; 54%) was found to be associated with higher lactation persistency and lower somatic cell scores. The transversion SNP in the putative promoter region (P-226) was in a potential DNA binding site.
Sharma
B S
BS
Centre for Genetic Improvement of Livestock, Department of Animal and Poultry Science, University of Guelph, Guelph, N1G 2W1, Canada.
Leyva
I
I
Schenkel
F
F
Karrow
N A
NA
D000818:Animals; D001483:Base Sequence; D001947:Breeding; D002417:Cattle / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D007774:Lactation / Q000235:genetics*; D008297:Male; D008414:Mastitis, Bovine / Q000235:genetics*; D008892:Milk / Q000166:cytology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods / Q000662:veterinary; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D017931:DNA Primers; D051197:Toll-Like Receptor 4