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Identification of genomic loci associated with Rhodococcus equi susceptibility in foals.

McQueen CM, Doan R, Dindot SV, Bourquin JR, Zlatev ZZ, Chaffin MK, Blodgett GP, Ivanov I, Cohen ND - PLoS ONE (2014)

Bottom Line: A joint analysis including all study foals revealed a 3- to 4-fold increase in odds of disease for a homozygous SNP within the associated region when comparing the clinical group with either of the other 2 groups of foals or their combination.The region contains the transient receptor potential cation channel, subfamily M, member 2 (TRPM2) gene, which is involved in neutrophil function.No associations were identified in the CNV-based GWAS.

View Article: PubMed Central - PubMed

Affiliation: Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, United States of America.

ABSTRACT
Pneumonia caused by Rhodococcus equi is a common cause of disease and death in foals. Although agent and environmental factors contribute to the incidence of this disease, the genetic factors influencing the clinical outcomes of R. equi pneumonia are ill-defined. Here, we performed independent single nucleotide polymorphism (SNP)- and copy number variant (CNV)-based genome-wide association studies to identify genomic loci associated with R. equi pneumonia in foals. Foals at a large Quarter Horse breeding farm were categorized into 3 groups: 1) foals with R. equi pneumonia (clinical group [N = 43]); 2) foals with ultrasonographic evidence of pulmonary lesions that never developed clinical signs of pneumonia (subclinical group [N = 156]); and, 3) foals without clinical signs or ultrasonographic evidence of pneumonia (unaffected group [N = 49]). From each group, 24 foals were randomly selected and used for independent SNP- and CNV-based genome-wide association studies (GWAS). The SNP-based GWAS identified a region on chromosome 26 that had moderate evidence of association with R. equi pneumonia when comparing clinical and subclinical foals. A joint analysis including all study foals revealed a 3- to 4-fold increase in odds of disease for a homozygous SNP within the associated region when comparing the clinical group with either of the other 2 groups of foals or their combination. The region contains the transient receptor potential cation channel, subfamily M, member 2 (TRPM2) gene, which is involved in neutrophil function. No associations were identified in the CNV-based GWAS. Collectively, these data identify a region on chromosome 26 associated with R. equi pneumonia in foals, providing evidence that genetic factors may indeed contribute to this important disease of foals.

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Related in: MedlinePlus

Schematic diagram representing the distribution of the total population into the 3 subgroups (R. equi pneumonia foals [clinical], subclinical foals, and unaffected foals), and by genome-wide association studies versus PCR genotyping for TRPM2 SNP.The 3 comparisons among groups are also summarized.
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pone-0098710-g001: Schematic diagram representing the distribution of the total population into the 3 subgroups (R. equi pneumonia foals [clinical], subclinical foals, and unaffected foals), and by genome-wide association studies versus PCR genotyping for TRPM2 SNP.The 3 comparisons among groups are also summarized.

Mentions: Three case-control GWAS were performed among the 24 randomly selected foals representing each group (clinical group, subclinical group, and unaffected group; Figure 1). The number of SNPs excluded on the basis of missingness per individual, missingness per SNP, and minor allele frequency were 0, 1,292, and 11,157, respectively (12,449 total SNPs). For comparisons 1, 2, and 3 (Figure 1), the number of SNPs excluded on the basis of Hardy-Weinberg equilibrium were 0, 83, and 54, respectively. After filtering, the total genotyping rate of the foals was estimated at 99.4%. Comparison 1 (clinical [N = 24] vs. subclinical + unaffected [N = 48]; λ = 1.16) identified 7 regions showing evidence of moderate association with clinical pneumonia (P<1×10−5) (Figure 2A and Table 1). Comparison 2 (clinical [N = 24] vs. subclinical [N = 24]; λ = 1.00 [Figure S1A]) identified 10 regions with moderate association (Figure 2B and Table 1). The region associated with clinical pneumonia had a (point-wise) value of EMP1 ≤0.0002. Comparison 3 (clinical [N = 24] vs. unaffected [N = 24]; λ = 1.44 [Figure S1B]) identified 2 regions with moderate association (Figure 2C and Table 1). Results from each GWAS comparison are provided in Table S1.


Identification of genomic loci associated with Rhodococcus equi susceptibility in foals.

McQueen CM, Doan R, Dindot SV, Bourquin JR, Zlatev ZZ, Chaffin MK, Blodgett GP, Ivanov I, Cohen ND - PLoS ONE (2014)

Schematic diagram representing the distribution of the total population into the 3 subgroups (R. equi pneumonia foals [clinical], subclinical foals, and unaffected foals), and by genome-wide association studies versus PCR genotyping for TRPM2 SNP.The 3 comparisons among groups are also summarized.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043894&req=5

pone-0098710-g001: Schematic diagram representing the distribution of the total population into the 3 subgroups (R. equi pneumonia foals [clinical], subclinical foals, and unaffected foals), and by genome-wide association studies versus PCR genotyping for TRPM2 SNP.The 3 comparisons among groups are also summarized.
Mentions: Three case-control GWAS were performed among the 24 randomly selected foals representing each group (clinical group, subclinical group, and unaffected group; Figure 1). The number of SNPs excluded on the basis of missingness per individual, missingness per SNP, and minor allele frequency were 0, 1,292, and 11,157, respectively (12,449 total SNPs). For comparisons 1, 2, and 3 (Figure 1), the number of SNPs excluded on the basis of Hardy-Weinberg equilibrium were 0, 83, and 54, respectively. After filtering, the total genotyping rate of the foals was estimated at 99.4%. Comparison 1 (clinical [N = 24] vs. subclinical + unaffected [N = 48]; λ = 1.16) identified 7 regions showing evidence of moderate association with clinical pneumonia (P<1×10−5) (Figure 2A and Table 1). Comparison 2 (clinical [N = 24] vs. subclinical [N = 24]; λ = 1.00 [Figure S1A]) identified 10 regions with moderate association (Figure 2B and Table 1). The region associated with clinical pneumonia had a (point-wise) value of EMP1 ≤0.0002. Comparison 3 (clinical [N = 24] vs. unaffected [N = 24]; λ = 1.44 [Figure S1B]) identified 2 regions with moderate association (Figure 2C and Table 1). Results from each GWAS comparison are provided in Table S1.

Bottom Line: A joint analysis including all study foals revealed a 3- to 4-fold increase in odds of disease for a homozygous SNP within the associated region when comparing the clinical group with either of the other 2 groups of foals or their combination.The region contains the transient receptor potential cation channel, subfamily M, member 2 (TRPM2) gene, which is involved in neutrophil function.No associations were identified in the CNV-based GWAS.

View Article: PubMed Central - PubMed

Affiliation: Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, United States of America.

ABSTRACT
Pneumonia caused by Rhodococcus equi is a common cause of disease and death in foals. Although agent and environmental factors contribute to the incidence of this disease, the genetic factors influencing the clinical outcomes of R. equi pneumonia are ill-defined. Here, we performed independent single nucleotide polymorphism (SNP)- and copy number variant (CNV)-based genome-wide association studies to identify genomic loci associated with R. equi pneumonia in foals. Foals at a large Quarter Horse breeding farm were categorized into 3 groups: 1) foals with R. equi pneumonia (clinical group [N = 43]); 2) foals with ultrasonographic evidence of pulmonary lesions that never developed clinical signs of pneumonia (subclinical group [N = 156]); and, 3) foals without clinical signs or ultrasonographic evidence of pneumonia (unaffected group [N = 49]). From each group, 24 foals were randomly selected and used for independent SNP- and CNV-based genome-wide association studies (GWAS). The SNP-based GWAS identified a region on chromosome 26 that had moderate evidence of association with R. equi pneumonia when comparing clinical and subclinical foals. A joint analysis including all study foals revealed a 3- to 4-fold increase in odds of disease for a homozygous SNP within the associated region when comparing the clinical group with either of the other 2 groups of foals or their combination. The region contains the transient receptor potential cation channel, subfamily M, member 2 (TRPM2) gene, which is involved in neutrophil function. No associations were identified in the CNV-based GWAS. Collectively, these data identify a region on chromosome 26 associated with R. equi pneumonia in foals, providing evidence that genetic factors may indeed contribute to this important disease of foals.

Show MeSH
Related in: MedlinePlus