Genetic dissection of milk yield traits and mastitis resistance QTL on chromosome 20 in dairy cattle

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Genetic dissection of milk yield traits and mastitis resistance QTL on chromosome 20 in dairy cattle. / Kadri, Naveen Kumar; Guldbrandtsen, Bernt; Lund, Mogens Sandø; Sahana, Goutam.

In: Journal of Dairy Science, Vol. 98, No. 12, 12.2015, p. 9015-9025.

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Kadri, Naveen Kumar ; Guldbrandtsen, Bernt ; Lund, Mogens Sandø ; Sahana, Goutam. / Genetic dissection of milk yield traits and mastitis resistance QTL on chromosome 20 in dairy cattle. In: Journal of Dairy Science. 2015 ; Vol. 98, No. 12. pp. 9015-9025.

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@article{54f3364137a84754827bbe5682e2d5eb,
title = "Genetic dissection of milk yield traits and mastitis resistance QTL on chromosome 20 in dairy cattle",
abstract = "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 (CM) and milk yield (MY) 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), which identifies 1,568 single nucleotide polymorphisms (SNP) 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 CM and MY 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, there was indication on differences in the causal factor(s) across breeds. A previously reported F279Y mutation (rs385640152) within the growth hormone receptor (GHR) gene showed strong association with milk, fat, 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 SNP 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 (CARD6) and 35,969,994 bp (rs133596506) in an intronic region of the leukemia inhibitory factor receptor gene (LIFR). These findings suggest that it may be possible to separate these beneficial and detrimental genetic factors through targeted selective breeding",
author = "Kadri, {Naveen Kumar} and Bernt Guldbrandtsen and Lund, {Mogens Sand{\o}} and Goutam Sahana",
note = "Selected as Editors Choice",
year = "2015",
month = dec,
doi = "10.3168/jds.2015-9599",
language = "English",
volume = "98",
pages = "9015--9025",
journal = "Journal of Dairy Science",
issn = "0022-0302",
publisher = "Elsevier Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - Genetic dissection of milk yield traits and mastitis resistance QTL on chromosome 20 in dairy cattle

AU - Kadri, Naveen Kumar

AU - Guldbrandtsen, Bernt

AU - Lund, Mogens Sandø

AU - Sahana, Goutam

N1 - Selected as Editors Choice

PY - 2015/12

Y1 - 2015/12

N2 - 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 (CM) and milk yield (MY) 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), which identifies 1,568 single nucleotide polymorphisms (SNP) 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 CM and MY 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, there was indication on differences in the causal factor(s) across breeds. A previously reported F279Y mutation (rs385640152) within the growth hormone receptor (GHR) gene showed strong association with milk, fat, 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 SNP 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 (CARD6) and 35,969,994 bp (rs133596506) in an intronic region of the leukemia inhibitory factor receptor gene (LIFR). These findings suggest that it may be possible to separate these beneficial and detrimental genetic factors through targeted selective breeding

AB - 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 (CM) and milk yield (MY) 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), which identifies 1,568 single nucleotide polymorphisms (SNP) 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 CM and MY 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, there was indication on differences in the causal factor(s) across breeds. A previously reported F279Y mutation (rs385640152) within the growth hormone receptor (GHR) gene showed strong association with milk, fat, 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 SNP 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 (CARD6) and 35,969,994 bp (rs133596506) in an intronic region of the leukemia inhibitory factor receptor gene (LIFR). These findings suggest that it may be possible to separate these beneficial and detrimental genetic factors through targeted selective breeding

U2 - 10.3168/jds.2015-9599

DO - 10.3168/jds.2015-9599

M3 - Journal article

C2 - 26409972

VL - 98

SP - 9015

EP - 9025

JO - Journal of Dairy Science

JF - Journal of Dairy Science

SN - 0022-0302

IS - 12

ER -