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PLXNC1 and RDH13 associated with bilateral convergent strabismus with exophthalmus in German Brown cattle.

ABSTRACT: PURPOSE: We performed an association study for bilateral convergent strabismus with exophthalmus (BCSE) in German Brown cattle using single nucleotide polymorphisms (SNPs) located within six positional candidate genes and additional SNPs from bovine SNP databases surrounding these candidate genes. Mutation analyses included synaptotagmin 3 and 5 (SYT3, SYT5), carnitine palmitoyl-transferase 1C (CPT1C) on bovine chromosome 18 (BTA18), and plexin C1 (PLXNC1), intracellular suppressor of cytokine signaling-2 (SOCS2), and kinesin family member 21A (KIF21A) on BTA5. METHODS: For all six candidate genes, we performed cDNA analyses using eye tissues of three BCSE-affected and three unaffected controls and searched the sequences for polymorphisms. Furthermore, we screened a total of 213 SNPs on BTA5 and 136 SNPs on BTA18 from the bovine SNP databases in 29 BCSE-affected German Brown cattle and 23 breed and sex matched controls for association with BCSE. All SNPs detected within the open reading frame (ORF) of the candidate genes and all SNPs from bovine databases putatively associated with BCSE in the detection sample were genotyped in a random sample of 179 BCSE-affected German Brown cows and 161 breed and sex matched controls and tested for association with BCSE. RESULTS: In total, we detected five novel SNPs within the coding sequence of the candidate genes PLXNC1 and KIF21A. The association analyses for single SNPs and haplotypes in 340 German Brown cattle revealed significant associations for five SNPs with BCSE. Four of these five SNPs were located within PLXNC1 and RDH13 and one SNP in the neighborhood of PLXNC1. Each one SNP within PLXNC1 (DN825458:c.168G>T) and RDH13 (AM930553:c.703C>A) were significantly associated with BCSE after correcting for multiple testing whereas all other SNPs failed this significance threshold. The marker-trait associations for haplotypes confirmed the significant associations with BCSE for both genes, PLXNC1 and RDH13. CONCLUSIONS: The association analyses for single SNPs and haplotypes corroborated the results of the linkage study that the centromeric region of BTA5 and the telomeric end of BTA8 harbor genes responsible for BCSE. Intragenic SNPs of the genes PLXNC1 and RDH13 were experiment-wide significantly associated with BCSE and seem to play an important role in the pathogenesis of BCSE.

SUBMITTER: Fink S

PROVIDER: S-EPMC3429361 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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PLXNC1 and RDH13 associated with bilateral convergent strabismus with exophthalmus in German Brown cattle.

Fink Steffen S Mömke Stefanie S Distl Ottmar O

Molecular vision 20120809

<h4>Purpose</h4>We performed an association study for bilateral convergent strabismus with exophthalmus (BCSE) in German Brown cattle using single nucleotide polymorphisms (SNPs) located within six positional candidate genes and additional SNPs from bovine SNP databases surrounding these candidate genes. Mutation analyses included synaptotagmin 3 and 5 (SYT3, SYT5), carnitine palmitoyl-transferase 1C (CPT1C) on bovine chromosome 18 (BTA18), and plexin C1 (PLXNC1), intracellular suppressor of cyt ...[more]

PMID: 22933835

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Project description:PURPOSE: Bilateral convergent strabismus with exophthalmos (BCSE) is a widespread inherited eye defect in several cattle populations. Its progressive condition often leads to blindness in affected cattle and shortens their length of productive life. Furthermore, breeding with BCSE-affected animals is forbidden by the German animal welfare laws. We performed a mutation and association analysis for three candidate genes (troponin T type 1 [TNNT1], retinol dehydrogenase 13 [RDH13], and TCF3 fusion partner [TFPT]), which are located within the previously identified BCSE-linked region on the telomeric end of bovine chromosome 18 (BTA18). In addition, we developed single nucleotide polymorphisms (SNPs) within these three candidate genes and nine other genes that are contained in this genomic BCSE-region to perform association analyses with BCSE in German Brown cattle. METHODS: We performed cDNA analyses of all three candidate genes using eye tissues of three affected German Brown cows and three unaffected controls. Furthermore, we screened the exonic and the adjacent genomic sequences of RDH13, TNNT1, and TFPT using four BCSE-affected and four controls of German Brown cattle. Here, we included all exons of RDH13 and those exons of TNNT1 and TFPT for which SNPs were detected by cDNA analyses. In addition, we developed 21 polymerase chain reaction (PCR) products for 17 more genes in the BCSE region and searched them for polymorphisms. All markers detected were genotyped in 48 BCSE-affected German Brown cows and 48 breed and sex matched controls and tested for association with BCSE. RESULTS: In total, we detected 29 SNPs in 12 genes. In the coding sequence of the three candidate genes, we identified 10 exonic SNPs and a new splice variant of TNNT1. Four SNPs were associated with the BCSE phenotype in single marker-trait analyses. These SNPs were located within DHDH (dihydrodiol dehydrogenase dimeric), CPT1C (carnitine palmitoyltransferase 1C), TNNT1, and NALP7. The marker-trait association for haplotypes including five SNPs of CPT1C, SYT5 (synaptotagmin V), RDH13, and NALP7 (NLR family, pyrin domain containing 7) revealed a significant association with BCSE. We identified three individual haplotypes that were significantly associated with BCSE. These haplotypes spanned the region from 56.05 Mb to 62.87 Mb on BTA18. CONCLUSIONS: The haplotype association analysis corroborated the results of the linkage study that the telomeric end of BTA18 harbors a gene responsible for BCSE and further refines the BCSE region to a 6.82 Mb interval ranging from 56.05 Mb to 62.87 Mb on BTA18.

Dataset Information

PLXNC1 and RDH13 associated with bilateral convergent strabismus with exophthalmus in German Brown cattle.

Publications

PLXNC1 and RDH13 associated with bilateral convergent strabismus with exophthalmus in German Brown cattle.

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