Dataset Information

Investigation of single-nucleotide polymorphisms in the NR3C1a glucocorticoid receptor gene in Cocker Spaniels with primary immune thrombocytopenia.

ABSTRACT:

Background

In dogs, 6 single-nucleotide polymorphisms (SNPs) have been described in the glucocorticoid receptor gene NR3C1a, 2 of which were nonsynonymous SNPs in exons 2 and 8. The clinical importance of these SNPs is unknown.

Objectives

To investigate whether SNPs in NR3C1a are associated with clinical outcome in Cocker Spaniels with primary immune thrombocytopenia (pITP).

Animals

Twenty-four Cocker Spaniels with pITP presented to a referral center. Dogs were classified as slow (n = 11) or fast responders (n = 12) based on time required after initiating glucocorticoid treatment to achieve a platelet count >70 000/μL.

Methods

Deoxyribonucleic acid was extracted from stored blood samples before amplification by PCR and sequencing of exons 2 and 8 of NR3C1a. Associations between genotype and clinical response variables were investigated.

Results

Neither previously identified nonsynonymous SNPs were identified. The synonymous SNP NR3C1a:c.798C>T in exon 2 was found at an increased prevalence compared to a previous report. No difference was found in prevalence of any genotype at NR3C1a:c.798C>T between fast and slow responders (P = .70).

Conclusions and clinical importance

None of the previously reported nonsynonymous SNPs in exons 2 and 8 of the NR3C1a gene were detected in our cohort of Cocker Spaniels with pITP. The synonymous SNP NR3C1a:c.798C>T in exon 2 was reported at a higher frequency than previously, but was not associated with outcome measures that estimated responsiveness to glucocorticoids.

SUBMITTER: Tayler S

PROVIDER: S-EPMC9308442 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Investigation of single-nucleotide polymorphisms in the NR3C1a glucocorticoid receptor gene in Cocker Spaniels with primary immune thrombocytopenia.

Tayler Sarah S Hazuchova Katarina K Riddle Anna A Swann James W JW Glanemann Barbara B

Journal of veterinary internal medicine 20220610 4

<h4>Background</h4>In dogs, 6 single-nucleotide polymorphisms (SNPs) have been described in the glucocorticoid receptor gene NR3C1a, 2 of which were nonsynonymous SNPs in exons 2 and 8. The clinical importance of these SNPs is unknown.<h4>Objectives</h4>To investigate whether SNPs in NR3C1a are associated with clinical outcome in Cocker Spaniels with primary immune thrombocytopenia (pITP).<h4>Animals</h4>Twenty-four Cocker Spaniels with pITP presented to a referral center. Dogs were classified a ...[more]

PMID: 35689373

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Project description:BACKGROUND:Cocker spaniels are predisposed to immune-mediated haemolytic anaemia (IMHA), suggesting that genetic factors influence disease susceptibility. Dog leukocyte antigen (DLA) class II genes encode major histocompatibility complex (MHC) molecules that are involved in antigen presentation to CD4(+) T cells. Several DLA haplotypes have been associated with autoimmune disease, including IMHA, in dogs, and breed specific differences have been identified. Cytotoxic T lymphocyte antigen 4 (CTLA4) is a critical molecule involved in the regulation of T-cell responses. Single nucleotide polymorphisms (SNPs) in the CTLA4 promoter have been shown to be associated with several autoimmune diseases in humans and more recently with diabetes mellitus and hypoadrenocorticism in dogs. The aim of the present study was to investigate whether DLA-DQB1 alleles or CTLA4 promoter variability are associated with risk of IMHA in Cocker spaniels. RESULTS:There were a restricted number of DLA-DQB1 alleles identified, with a high prevalence of DLA-DQB1*007:01 in both groups. A high prevalence of DLA-DQB1 homozygosity was identified, although there was no significant difference between IMHA cases and controls. CTLA4 promoter haplotype diversity was limited in Cocker spaniels, with all dogs expressing at least one copy of haplotype 8. There was no significant difference comparing haplotypes in the IMHA affected group versus control group (p?=?0.23). Homozygosity for haplotype 8 was common in Cocker spaniels with IMHA (27/29; 93 %) and in controls (52/63; 83 %), with no statistically significant difference in prevalence between the two groups (p?=?0.22). CONCLUSIONS:DLA-DQB1 allele and CTLA4 promoter haplotype were not found to be significantly associated with IMHA in Cocker spaniels. Homozygosity for DLA-DQB1*007:01 and the presence of CTLA4 haplotype 8 in Cocker spaniels might increase overall susceptibility to IMHA in this breed, with other genetic and environmental factors involved in disease expression and progression.

Project description:Single-nucleotide polymorphisms (SNPs) provide an abundant source of DNA polymorphisms in a number of eukaryotic species. Information on the frequency, nature, and distribution of SNPs in plant genomes is limited. Thus, our objectives were (1) to determine SNP frequency in coding and noncoding soybean (Glycine max L. Merr.) DNA sequence amplified from genomic DNA using PCR primers designed to complete genes, cDNAs, and random genomic sequence; (2) to characterize haplotype variation in these sequences; and (3) to provide initial estimates of linkage disequilibrium (LD) in soybean. Approximately 28.7 kbp of coding sequence, 37.9 kbp of noncoding perigenic DNA, and 9.7 kbp of random noncoding genomic DNA were sequenced in each of 25 diverse soybean genotypes. Over the >76 kbp, mean nucleotide diversity expressed as Watterson's theta was 0.00097. Nucleotide diversity was 0.00053 and 0.00111 in coding and in noncoding perigenic DNA, respectively, lower than estimates in the autogamous model species Arabidopsis thaliana. Haplotype analysis of SNP-containing fragments revealed a deficiency of haplotypes vs. the number that would be anticipated at linkage equilibrium. In 49 fragments with three or more SNPs, five haplotypes were present in one fragment while four or less were present in the remaining 48, thereby supporting the suggestion of relatively limited genetic variation in cultivated soybean. Squared allele-frequency correlations (r(2)) among haplotypes at 54 loci with two or more SNPs indicated low genome-wide LD. The low level of LD and the limited haplotype diversity suggested that the genome of any given soybean accession is a mosaic of three or four haplotypes. To facilitate SNP discovery and the development of a transcript map, subsets of four to six diverse genotypes, whose sequence analysis would permit the discovery of at least 75% of all SNPs present in the 25 genotypes as well as 90% of the common (frequency >0.10) SNPs, were identified.

Dataset Information

Investigation of single-nucleotide polymorphisms in the NR3C1a glucocorticoid receptor gene in Cocker Spaniels with primary immune thrombocytopenia.

Background

Objectives

Animals

Methods

Results

Conclusions and clinical importance

Publications

Investigation of single-nucleotide polymorphisms in the NR3C1a glucocorticoid receptor gene in Cocker Spaniels with primary immune thrombocytopenia.

Similar Datasets

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