Associations between polymorphisms of LAP3 and SIRT1 genes with clinical mastitis and milk production traits in Sahiwal and Karan Fries dairy cattle.

Bovine mastitis continues to remain as the most challenging disease in dairy cattle, as a result improvement of selection methods has great economic relevance while a deeper understanding of the genetic mechanisms regulating milk production traits and mastitis is of general scientific interest. This study aimed to evaluate the association of SNPs of the LAP3 and SIRT1 genes with estimated breeding values (EBVs) of milk production traits and clinical mastitis in dairy cattle of Indian origin. DNA samples from 263 animals (Sahiwal and Karan Fries cattle) were genotyped by PCR-RFLP to assess their pattern of genetic variation. EBVs of milk production traits and phenotypic records of incidences of clinical mastitis were used for association analysis. A total of 9 SNPs were identified, including three (rs110932626: A>G, rs716493845: C>T and rs43702363: C>T) in intron 12, four (g.24904G>C, rs110839532: G>T, rs43702361: T>C and rs41255599: C>T) in exon 13 and within 3'UTR of LAP3 gene and two (rs110250233: G>A and rs42140046: C>G) in the promoter region of SIRT1 gene. Eight of these identified SNPs were chosen for subsequent genotyping and association analyses. Association analysis revealed that SNP rs41255599: C>T was significantly associated with lactation milk yield, 305-day milk yield, 305-day fat yield, 305-day solid not fat yield, lactation length and incidence of clinical mastitis (p < 0.05) in Sahiwal cattle. For Karan Fries cattle, two SNPs including rs110932626: A>G and rs43702363: C>T showed significant association with 305-day milk yield. Overall, these findings provide evidence for association of the LAP3 gene with milk production traits and clinical mastitis in dairy cattle, indicating the potential role of LAP3 variants in these traits.

Worku D ，Gowane GR ，Mukherjee A ，Alex R ，Joshi P ，Verma A ... -  《Veterinary Medicine and Science》

Inputs for optimizing selection platform for milk production traits of dairy Sahiwal cattle.

The premises for the potential success of molecular breeding is the ability to identify major genes associated with important dairy related traits. The present study was taken up with the objectives to identify single nucleotide polymorphism (SNP) of bovine MASP2 and SIRT1 genes and its effect on estimated breeding values (EBVs) and to estimate genetic parameters for lactation milk yield (LMY), 305-day milk yield (305dMY), 305-day fat yield (305dFY), 305-day solid not fat yield (305dSNFY) and lactation length (LL) in Sahiwal dairy cattle to devise a promising improvement strategy. Genetic parameters and breeding values of milk production traits were estimated from 935 Sahiwal cattle population (1979-2019) reared at National Dairy Research Institute at Karnal, India. A total of 7 SNPs, where one SNP (g.499C>T) in exon 2 and four SNPs (g.576G>A, g.609T>C, g.684G>T and g.845A>G) in exon 3 region of MASP2 gene and 2 SNPs (g.-306T>C and g.-274G>C) in the promoter region of SIRT1 gene were identified in Sahiwal cattle population. Five of these identified SNPs were chosen for further genotyping by PCR-RFLP and association analysis. Association analysis was performed using estimated breeding values (n = 150) to test the effect of SNPs on LMY, 305dMY, 305dFY, 305dSNFY and LL. Association analysis revealed that, three SNP markers (g.499C>T, g.609T>C and g.-306T>C) were significantly associated with all milk yield traits. The estimates for heritability using repeatability model for LMY, 305dMY, 305dFY, 305dSNFY and LL were low, however the corresponding estimates from first parity were 0.20±0.08, 0.17±0.08, 0.13±0.09, 0.13±0.09 and 0.24, respectively. The repeatability estimates were moderate to high indicating consistency of performance over the parities and hence reliability of first lactation traits. Genetic correlations among the traits of first parity were high (0.55 to 0.99). From the results we could conclude that optimum strategy to improve the Sahiwal cattle further would be selecting the animals based on their first lactation 305dMY. Option top include the significant SNP in selection criteria can be explored. Taken together, a 2-stage selection approach, select Sahiwal animals early for the SNP and then on the basis of first lactation 305dMY will help to save resources.

Worku D ，Gowane G ，Alex R ，Joshi P ，Verma A ... -  《PLoS One》

Candidate SNP of CACNA2D1 Gene Associated with Clinical Mastitis and Production Traits in Sahiwal (Bos taurus indicus) and Karan Fries (Bos taurus taurus × Bos taurus indicus).

The present study was conducted to identify polymorphisms in CACNA2D1 gene and their association with clinical mastitis and production traits. Exon 18 and its flanking regions were screened for the presence of SNPs. Statistical analysis was performed to identify association of period of birth, breed, and genotype with mastitis incidence on randomly selected 103 Sahiwal and 102 Karan Fries cattle. PCR-RFLP analysis revealed that g.38819398G > A mutation in exon 18 (269 bp amplicon) of CACNA2D1 gene resolved into AA, AG, and GG genotypes in Sahiwal and Karan Fries cattle. Wald chi-square analysis revealed that the period of birth, breed, and genotype were significantly associated with mastitis incidence. GG genotyped cattle were found to be less susceptible to mastitis. Least square analysis revealed that GG and AG genotype animals of G38819398A SNP of CACNA2D1 gene in Sahiwal as well as in Karan Fries cattle were associated with higher average milk yields during 1st, 2nd, and 3rd lactations (P < 0.01). These observations and their differential association with the incidence of mastitis and production traits can be utilized as an aid to selection for simultaneous improvement of both antagonistic traits; however, validation of results on large number of animals is warranted.

Magotra A ，Gupta ID ，Verma A ，Alex R ，Mr V ，Ahmad T ... -  《-》

Polymorphism in DNA repair gene BRCA1 associated with clinical mastitis and production traits in indigenous dairy cattle.

The present study was conducted on Karan Fries cows to identify SNPs in breast cancer 1 (BRCA1) gene and their association with inflammation of mammary gland and production traits. Chi square analysis showed significant association of both SNPs i.e. G43737229T (P < 0.01) and G43761121A (P < 0.05) with incidence of clinical mastitis. Logistic modeling showed that GG genotype cows of G43737229T SNP was less susceptible to mastitis in comparison to TT genotype cows as the odds ratio of TT against GG for the non-incidence of mastitis was less i.e. 0.23. Whereas, cows with genotype AA of G43761121A SNP were less prone to clinical mastitis in comparison to GG genotype cows. G-T haplotype and GGTT combined genotype exhibited maximum mastitis incidences. Least squares analysis revealed significant association of G43737229T SNP with total milk yield (P < 0.01), 305 days milk yield (P < 0.01) and lactation length (P < 0.05). The TT and GT genotyped Karan Fries cows were associated with higher milk yields during first and second lactation, as well as with first lactation length. These observations on SNPs, genotypes and combined genotypes of BRCA1 gene and their differential association with the incidence of mastitis and production traits can be utilized as an aid to selection for simultaneous improvement of both antagonistic traits.

Magotra A ，Gupta ID ，Ahmad T ，Alex R ... -  《-》

Genetic dissection of milk yield traits and mastitis resistance quantitative trait loci on chromosome 20 in dairy cattle.

Intense selection to increase milk yield has had negative consequences for mastitis incidence in dairy cattle. Due to low heritability of mastitis resistance and an unfavorable genetic correlation with milk yield, a reduction in mastitis through traditional breeding has been difficult to achieve. Here, we examined quantitative trait loci (QTL) that segregate for clinical mastitis and milk yield on Bos taurus autosome 20 (BTA20) to determine whether both traits are affected by a single polymorphism (pleiotropy) or by multiple closely linked polymorphisms. In the latter but not the former situation, undesirable genetic correlation could potentially be broken by selecting animals that have favorable variants for both traits. First, we performed a within-breed association study using a haplotype-based method in Danish Holstein cattle (HOL). Next, we analyzed Nordic Red dairy cattle (RDC) and Danish Jersey cattle (JER) with the goal of determining whether these QTL identified in Holsteins were segregating across breeds. Genotypes for 12,566 animals (5,966 HOL, 5,458 RDC, and 1,142 JER) were determined by using the Illumina Bovine SNP50 BeadChip (50K; Illumina, San Diego, CA), which identifies 1,568 single nucleotide polymorphisms on BTA20. Data were combined, phased, and clustered into haplotype states, followed by within- and across-breed haplotype-based association analyses using a linear mixed model. Association signals for both clinical mastitis and milk yield peaked in the 26- to 40-Mb region on BTA20 in HOL. Single-variant association analyses were carried out in the QTL region using whole sequence level variants imputed from references of 2,036 HD genotypes (BovineHD BeadChip; Illumina) and 242 whole-genome sequences. The milk QTL were also segregating in RDC and JER on the BTA20-targeted region; however, an indication of differences in the causal factor(s) was observed across breeds. A previously reported F279Y mutation (rs385640152) within the growth hormone receptor gene showed strong association with milk, fat, and protein yields. In HOL, the highest peaks for milk yield and susceptibility to mastitis were separated by over 3.5 Mb (3.8 Mb by haplotype analysis, 3.6 Mb by single nucleotide polymorphism analysis), suggesting separate genetic variants for the traits. Further analysis yielded 2 candidate mutations for the mastitis QTL, at 33,642,072 bp (rs378947583) in an intronic region of the caspase recruitment domain protein 6 gene and 35,969,994 bp (rs133596506) in an intronic region of the leukemia-inhibitory factor receptor gene. These findings suggest that it may be possible to separate these beneficial and detrimental genetic factors through targeted selective breeding.

Kadri NK ，Guldbrandtsen B ，Lund MS ，Sahana G ... -  《-》