A system-based analysis of the genetic determinism of udder conformation and health phenotypes across three French dairy cattle breeds

Marete, Andrew; Lund, Mogens Sandø; Boichard, Didier; Ramayo-Caldas, Yuliaxis

doi:10.1371/journal.pone.0199931

Cited by 25 publications

(24 citation statements)

References 43 publications

(51 reference statements)

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“…Large portion of genes detected in this study was associated with immune system functioning or antimicrobial resistance and included several members of interleukins and β-defensins family. We also detected some genes responsible for mammary gland development ( SOSTDC1 , PYGO2 , MED1 , CCND1 , FGF2 ), which may be of high importance for the improved population and its milking abilities (Gu et al 2009 ; Närhi et al 2012 ; Casimiro et al 2013 ; Marete et al 2018 ). A revision of the gene functions showed that SOSTDC1 ( Sclerostin Domain Containing 1 ) controls the size and shape of mammary buds in mice (Närhi et al 2012 ), while PYGO2 ( Pygopus Family PHD Finger 2 ) ablation results in defective mammary morphogenesis and regeneration (Gu et al 2009 ).…”

Section: Discussionmentioning

confidence: 87%

“…A revision of the gene functions showed that SOSTDC1 ( Sclerostin Domain Containing 1 ) controls the size and shape of mammary buds in mice (Närhi et al 2012 ), while PYGO2 ( Pygopus Family PHD Finger 2 ) ablation results in defective mammary morphogenesis and regeneration (Gu et al 2009 ). Moreover, the FGF2 gene (in addition to its effect on fat yield) was shown to play a role in development and reorganization of the mammary gland (Marete et al 2018 ).…”

Section: Discussionmentioning

confidence: 99%

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Diversifying selection signatures among divergently selected subpopulations of Polish Red cattle

et al. 2019

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Polish Red cattle is one of the few indigenous breeds of European red cattle which is characterized by several desired features, such as high disease resistance, good health, longevity, good fertility, and high nutritional value of milk. Currently, Polish Red cattle population is a subject of two independent breeding programs: (i) improvement program and (ii) genetic resources conservation program. The aim of the improvement program is the genetic progress in terms of milk production and body conformation traits, while the conservation program mainly focuses on protection of the genetic resources of Polish Red cattle and preservation of the existing, original gene pool. By the analysis of F ST genetic distances across genome-wide SNP panel, we detected diversifying selection signatures among these two subpopulations and indicated (among others) the significance of DGAT1 and FGF2 genes for milk production traits in these cattle. We also found that among genes being presumably under selection in terms of milk production, there are genes responsible, for example, for mammary gland development (e.g., SOSTDC1 , PYGO2 , MED1 , and CCND1 ) and immune system response (e.g., IL10RA , IL12B , and IL21 ). The most important finding of this study is that the most pronounced genetic differences between the analyzed populations were associated with β-defensin genes (e.g., DEFB1 , DEFB4A , DEFB5 , DEFB7 , DEFB10 , DEFB13 , EBD , BNBD-6 , and LAP ) located within so-called bovine cluster D on BTA27. The β-defensins are expressed mainly in the mammary gland and are antimicrobial peptides against the Gram-negative and Gram-positive bacteria, viruses, and other unicellular parasites. This suggests that antimicrobial resistance of mammary gland is of high importance during selection towards increased milk production and that genes responsible for this process are selected together with increasing levels of productivity. Electronic supplementary material The online version of this article (10.1007/s13353-019-00484-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Diversifying selection signatures among divergently selected subpopulations of Polish Red cattle

et al. 2019

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“…(2) Whole genome sequence variants-a custom part of up to 7,232 SNP selected from sequence data as part of 1,000 Bull Genomes Project Run 4 (Daetwyler et al, 2014 ) based on their functional annotation. The full description of the EuroG10k chip and quality control procedure was previously described by Marete et al ( 2018a ) and Boichard et al ( 2018 ). Cows with phenotypes were rather old animals and were genotyped with the 50 k chip.…”

Section: Methodsmentioning

confidence: 99%

A Meta-Analysis Including Pre-selected Sequence Variants Associated With Seven Traits in Three French Dairy Cattle Populations

et al. 2018

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A within-breed genome-wide association study (GWAS) is useful when identifying the QTL that segregates in a breed. However, an across-breed meta-analysis can be used to increase the power of identification and precise localization of QTL that segregate in multiple breeds. Precise localization will allow including QTL information from other breeds in genomic prediction due to the persistence of the linkage phase between the causal variant and the marker. This study aimed to identify and confirm QTL detected in within-breed GWAS through a meta-analysis in three French dairy cattle breeds. A set of sequence variants selected based on their functional annotations were imputed into 50 k genotypes for 46,732 Holstein, 20,096 Montbeliarde, and 11,944 Normande cows to identify QTL for milk production, the success rate at insemination of cows (fertility) and stature. We conducted within-breed GWAS followed by across-breed meta-analysis using a weighted Z-scores model on the GWAS summary data (i.e., P-values, effect direction, and sample size). After Bonferroni correction, the GWAS result identified 21,956 significantly associated SNP (PFWER < 0.05), while meta-analysis result identified 9,604 significant SNP (PFWER < 0.05) associated with the phenotypes. The meta-analysis identified 36 QTL for milk yield, 48 QTL for fat yield and percentage, 29 QTL for protein yield and percentage, 13 QTL for fertility, and 16 QTL for stature. Some of these QTL were not significant in the within-breed GWAS. Some previously identified causal variants were confirmed, e.g., BTA14:1802265 (fat percentage, P = 1.5 × 10−760; protein percentage, P = 7.61 × 10−348) both mapping the DGAT1-K232A mutation and BTA14:25006125 (P = 8.58 × 10−140) mapping PLAG1 gene was confirmed for stature in Montbeliarde. New QTL lead SNP shared between breeds included the intronic variant rs109205829 (NFIB gene), and the intergenic variant rs41592357 (1.38 Mb upstream of the CNTN6 gene and 0.65 Mb downstream of the CNTN4 gene). Rs110425867 (ZFAT gene) was the top variant associated with fertility, and new QTL lead SNP included rs109483390 (0.1 Mb upstream of the TNFAIP3 gene and 0.07 Mb downstream of PERP gene), and rs42412333 (0.45 Mb downstream of the RPL10L gene). An across-breed meta-analysis had greater power to detect QTL as opposed to a within breed GWAS. The QTL detected here can be incorporated in routine genomic predictions.

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“…We did not find significant difference between daughter yield deviations of heterozygous and wild-type homozygous bulls ( Figure 6). In addition, no udder-related QTL have been reported in Normande cattle, either within the NH7 interval or on chromosome 11 (Boichard et al, 2003;Marete et al, 2018). This is in line with a possible recessive effect of the mutation on udder morphology in surviving homozygotes, although more live homozygous cows are needed to confirm this assumption.…”

Section: Surviving Cad Homozygotes Exhibit Broad Range Of Symptoms Dementioning

confidence: 64%

A missense mutation (p.Tyr452Cys) in the CAD gene compromises reproductive success in French Normande cattle

Uddin¹,

Hozé²,

Michot³

et al. 2019

Journal of Dairy Science

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We scanned the genome of 77,815 Normande cattle with different Illumina SNP chips (Illumina Inc., San Diego, CA) to map recessive embryonic lethal mutations using homozygous haplotype deficiency. We detected 2 novel haplotypes on chromosomes 11 and 24 but did not confirm 6 previously reported haplotypes. The one on chromosome 11 showed a marked reduction in conception rates and moderate decrease in nonreturn rate in at-risk versus control mating, supporting late embryonic mortality. After fine mapping and analyzing whole-genome sequences, we prioritized a missense mutation in CAD (g.72399397T>C; p.Tyr452Cys)-a gene encoding a protein (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase) essential for de novo pyrimidine biosynthesis-as a candidate causal variant. This transition mutation replaces a tyrosine residue, which is perfectly conserved among living organisms, with a cysteine residue in the carbamoyl-phosphate synthetase 2 domain of the protein. A single animal was confirmed to be homozygous for the mutation based on Sanger sequencing. However, large-scale genotyping of the candidate variant with the Illumina EuroG10k BeadChip revealed an absence of live homozygotes in a panel of 33,323 Normande animals and an absence of carriers in 348,593 animals from 19 other cattle breeds. These results support recessive embryonic lethality with nearly complete penetrance, as was previously reported in CAD mutants in several eukaryote species. The only homozygous cow had extremely poor udder conformation, suggesting a potential role of CAD in udder development, but no effect was detected when comparing daughter yield deviations of 250 heterozygous bulls with that of 2,912 homozygotes for the ancestral allele. Together, our results showed the importance of large-scale screening for homozygous haplotype deficiency with hundreds of thousands of animals, validating results with an independent data set, and considering unexpected live homozygotes, to avoid both false-positive and false-negative discoveries. These discoveries will be used primarily in mating decisions to avoid at-risk mating. In addition, we recommend including CAD in the breeding objectives of Normande cattle.

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A system-based analysis of the genetic determinism of udder conformation and health phenotypes across three French dairy cattle breeds

Cited by 25 publications

References 43 publications

Diversifying selection signatures among divergently selected subpopulations of Polish Red cattle

Diversifying selection signatures among divergently selected subpopulations of Polish Red cattle

A Meta-Analysis Including Pre-selected Sequence Variants Associated With Seven Traits in Three French Dairy Cattle Populations

A missense mutation (p.Tyr452Cys) in the CAD gene compromises reproductive success in French Normande cattle

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