scholarly journals Association Between Temperament Related Traits and SNPs in the Serotonin and Oxytocin Systems in Merino Sheep

2020 ◽  
Author(s):  
Luoyang Ding ◽  
Shane K Maloney ◽  
Mengzhi Wang ◽  
Jennifer Rodger ◽  
Lianmin Chen ◽  
...  
Keyword(s):  
Serotonin Receptor ◽  
Emotional Reactivity ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Behavioural Phenotype ◽  
Single Nucleotide ◽  
Gene Markers ◽  
Merino Sheep ◽  
The Central Nervous System ◽  
Arena Test

Abstract Background: Animal temperament is defined as the consistent behavioural and physiological differences that are seen between individuals in response to the same stressor. Neurotransmitter systems, like serotonin and oxytocin in the central nervous system, underlie the variation in temperament in humans. The variations like single nucleotide polymorphisms (SNPs) in the genes for tryptophan 5-hydroxylase (TPH2), the serotonin transporter (SLC6A4), the serotonin receptor (HTR2A), or the oxytocin receptor (OXTR) are associated with the behavior phenotypes in human. Thus, the objective of this study was to identify SNPs in TPH2, SLC6A4, HTR2A and OXTR and to test if those variations predict the temperament of Merino sheep. Results: Using ewes from the UWA temperament flock, that has been selected on emotional reactivity for more than 20 generations, eight SNPs (rs107856757, rs107856818, rs107856856 and rs107857156 in TPH2, rs20917091 in SLC6A4, rs17196799 and rs17193181 in HTR2A, and rs17664565 in OXTR) were found to be distributed differently between calm and nervous sheep. These eight SNPs were then genotyped in 260 sheep from a non-selected flock that has never been selected on emotion reactivity, followed by the estimation of the behavioural traits of those 260 sheep using an arena test and an isolation box test. We found that several SNPs in TPH2 (rs107856757, rs107856818, rs107856856 and rs107857156) were in strong linkage disequilibrium, and all were associated with behavioural phenotype in the non-selected sheep. Similarly, rs17196799 in HTR2A was also associated with the behavioural phenotype. Conclusions: We thus conclude that, rs107856856 and rs17196799 could be used as gene markers for the temperament of Merino sheep, with allele C of rs107856856 and allele A of rs17196799 being associated with calm temperament.

scholarly journals Association of TRAF1/C5 Locus Polymorphisms with Epilepsy and Clinical Traits in Mexican Patients with Neurocysticercosis

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Marcela Villegas ◽  
Edda Sciutto ◽  
Marcos Rosetti ◽  
Agnes Fleury ◽  
Gladis Fragoso
Keyword(s):  
Severe Disease ◽  
Taenia Solium ◽  
Parasite Load ◽  
Mexican Population ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Content Type ◽  
Infection Resistance ◽  
The Central Nervous System

ABSTRACT Neurocysticercosis is caused by the establishment of Taenia solium cysts in the central nervous system. Murine cysticercosis by Taenia crassiceps is a useful model of cysticercosis in which the complement component 5 (C5) has been linked to infection resistance/permissiveness. This work aimed to study the possible relevance for human neurocysticercosis of single nucleotide polymorphisms (SNPs) in the C5-TRAF1 region (rs17611 C/T, rs992670 G/A, rs25681 G/A, rs10818488 A/G, and rs3761847 G/A) in a Mexican population and associated with clinical and radiological traits related to neurocysticercosis severity (cell count in the cerebrospinal fluid [CSF cellularity], parasite location and parasite load in the brain, parasite degenerating stage, and epilepsy). The AG genotype of the rs3761847 SNP showed a tendency to associate with multiple brain parasites, while the CT and GG genotypes of the rs17611 and rs3761847 SNPs, respectively, showed a tendency to associate with low CSF cellularity. The rs3761847 SNP was associated with epilepsy under a dominant model, whereas rs10818488 was associated with CSF cellularity and parasite load under dominant and recessive models, respectively. For haplotypes, C5- and the TRAF1-associated SNPs were, respectively, in strong linkage disequilibrium with each other; thus, these haplotypes were studied independently. For C5 SNPs, carrying the CAA haplotype increases the risk of showing high CSF cellularity 3-fold and the risk of having extraparenchymal parasites 4-fold, two conditions that are related to severe disease. For TRAF1 SNPs, the GA and AG haplotypes were associated with CSF cellularity, and the AG haplotype was associated with epilepsy. Overall, these findings support the clear participation of C5 and TRAF1 in the risk of developing severe neurocysticercosis in the Mexican population.

scholarly journals Association of non-synonymous SNPs of <i>OPN</i> gene with litter size traits in pigs

2015 ◽  
Vol 58 (2) ◽  
pp. 317-323 ◽  
Author(s):  
T. Kumchoo ◽  
S. Mekchay
Keyword(s):  
Litter Size ◽  
Reproductive Traits ◽  
Snp Markers ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Large White ◽  
Single Nucleotide ◽  
Pcr Rflp ◽  
Polymerase Chain ◽  
Acid Exchange

Abstract. Osteopontin (OPN) gene is a secreted phosphoprotein which appears to play a key function in the conceptus implantation, placentation and maintenance of pregnancy in pigs. The objectives of this study were to verify the non-synonymous single nucleotide polymorphisms (SNPs) and their association with litter size traits in commercial Thai Large White pigs. A total of 320 Thai Large White sows were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Three SNPs at c.425G> A, c.573T> C and c.881C> T revealed amino acid exchange rates of p.110Ala> Thr, p.159Val> Ala and p.262Pro> Ser, respectively, and were then segregated. These three SNPs were significantly associated with total number born (TNB) and number born alive (NBA) traits. No polymorphisms of the two SNP markers (c.278A> G and c.452T> G) were observed in this study. Moreover, the SNPs at c.425G> A and c.573T> C were found to be in strong linkage disequilibrium. The association of OPN with litter size emphasizes the importance of porcine OPN as a candidate gene for reproductive traits in pig breeding.

Polymorphisms of IRAK1 Gene on X Chromosome Is Associated with Hashimoto Thyroiditis in Korean Children

Endocrinology ◽  
2020 ◽  
Vol 161 (8) ◽  
Author(s):  
Hye-Ri Shin ◽  
Won Kyoung Cho ◽  
In-Cheol Baek ◽  
Na Yeong Lee ◽  
Yoon Ji Lee ◽  
...  
Keyword(s):  
X Chromosome ◽  
Hashimoto Thyroiditis ◽  
Categorical Variables ◽  
Graves Disease ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Korean Children ◽  
Autoimmune Thyroid ◽  
Thyroid Associated Ophthalmopathy

Abstract Autoimmune thyroid disease (AITD) is predominant in females and has been focused on the sexual diploid in immune response. The IL-1 receptor-associated kinase 1 (IRAK1) gene on the X chromosome was recently suggested as strong autoimmune disease-susceptible loci, second to the major histocompatibility complex region. We investigated the frequency of IRAK1 single-nucleotide polymorphisms (SNPs) in children with AITD. In this study, we observed that SNPs of IRAK1 including rs3027898, rs1059703, and rs1059702 in 115 Korean AITD pediatric patients (Graves’ disease = 74 [females = 52/males = 22]; Hashimoto disease [HD] = 41 [females = 38/males = 3]; thyroid-associated ophthalmopathy [TAO] = 40 (females = 27/males = 13); without TAO = 75 (females = 63/males = 12); total males = 25, total females = 90; mean age = 11.9 years) and 204 healthy Korean individuals (males = 104/females = 100). The data from cases and controls were analyzed from separate sex-stratified or all combined by χ 2 test for categorical variables and Student t test for numerical variables. Our study revealed that SNPs of IRAK1-associated HD and without TAO but Graves’ disease and TAO were not found significant. When cases and controls were analyzed by separate sex, we found that rs3027898 AA, rs1059703 AA, and rs1059702 GG showed disease susceptibility in female AITD, HD, and without TAO. Also, all rs3027898, rs1059703, and rs1059702 were found to be in strong linkage disequilibrium (D′ = 0.96-0.98, r2 = 0.83–0.97). The haplotype of 3 SNPs was higher in AITD than in controls (CGA, r2 = 5.42, P = 0.019). Our results suggest that IRAK1 polymorphisms may contribute to the pathogenesis of HD, AITD, and without thyroid-associated ophthalmopathy for females.

Variation at the von Willebrand Factor (vWF) Gene Locus Is Associated With Plasma vWF:Ag Levels: Identification of Three Novel Single Nucleotide Polymorphisms in the vWF Gene Promoter

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4277-4283 ◽  
Author(s):  
Angela M. Keightley ◽  
Y. Miu Lam ◽  
Jolene N. Brady ◽  
Cherie L. Cameron ◽  
David Lillicrap
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Von Willebrand Factor ◽  
Gene Locus ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Polymorphic Variation ◽  
Single Nucleotide ◽  
Haplotype 1 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Both genetic and environmental factors contribute to the normal population variability of plasma von Willebrand Factor (vWF) levels, however, regulatory mechanisms at the vWF gene locus itself have not yet been identified. We have investigated the association between polymorphic variation in the 5′-regulatory region of the vWF gene and levels of plasma vWF:Ag in a study of 261 group O blood donors. Three novel single nucleotide polymorphisms (SNPs) were identified in the vWF promoter: C/T at -1234, A/G at -1185, and G/A at -1051. These SNPs had identical allele frequencies of 0.36 for the -1234C, -1185A, and -1051G alleles and 0.64 for the -1234T, -1185G, and -1051A alleles and were in strong linkage disequilibrium. In fact, these polymorphisms segregated as two distinct haplotypes: -1234C/-1185A/-1051G (haplotype 1) and -1234T/-1185G/-1051A (haplotype 2) with 12.6% of subjects homozygous for haplotype 1, 40.6% homozygous for haplotype 2, and 42.5% of subjects heterozygous for both haplotypes. Only 4.3% of individuals had other genotypes. A significant association between promoter genotype and level of plasma vWF:Ag was established (analysis of covariance [ANCOVA], P = .008; Kruskal-Wallis test,P = .006); individuals with the CC/AA/GG genotype had the highest mean vWF:Ag levels (0.962 U/mL), intermediate values of vWF:Ag (0.867 U/mL) were observed for heterozygotes (CT/AG/GA), and those with the TT/GG/AA genotype had the lowest mean plasma vWF:Ag levels (0.776 U/mL). Interestingly, when the sample was subgrouped according to age, the significant association between promoter genotype and plasma vWF:Ag level was accentuated in subjects &gt; 40 years of age (analysis of variance [ANOVA], P = .003; Kruskal-Wallis test, P= .001), but was not maintained for subjects ≤ 40 years of age (ANOVA, P &gt; .4; Kruskal-Wallis test, P &gt; .4). In the former subgroup, mean levels of plasma vWF:Ag for subjects with the CC/AA/GG, CT/AG/GA, and TT/GG/AA genotypes were 1.075, 0.954, and 0.794 U/mL, respectively. By searching a transcription factor binding site profile database, these polymorphic sequences were predicted to interact with several transcription factors expressed in endothelial cells, including Sp1, GATA-2, c-Ets, and NFκB. Furthermore, the binding sites at the -1234 and -1051 SNPs appeared to indicate allelic preferences for some of these proteins. Electrophoretic mobility shift assays (EMSAs) performed with recombinant human NFκB p50 showed preferential binding of the -1234T allele (confirmed by supershift EMSAs), and EMSAs using bovine aortic endothelial cell (BAEC) nuclear extracts produced specific binding of a nuclear protein to the -1051A allele, but not the -1051G allele. These findings suggest that circulating levels of vWF:Ag may be determined, at least in part, by polymorphic variation in the promoter region of the vWF gene, and that this association may be mediated by differential binding of nuclear proteins involved in the regulation of vWF gene expression.

scholarly journals Variations in MHC-DRB1 exon2 and associations with Brucellosis susceptibility in Chinese Merino sheep

2016 ◽  
Author(s):  
Yue’e Chen ◽  
Wanyun Xu ◽  
Chuangfu Chen ◽  
Hugh T Blair ◽  
Jianfeng Gao
Keyword(s):  
Haplotype Analysis ◽  
Nucleotide Polymorphisms ◽  
Control Groups ◽  
Single Nucleotide ◽  
Merino Sheep ◽  
Pcr Products ◽  
Polymerase Chain ◽  
And Control ◽  
Control Samples ◽  
Online Software

MHC-DRB1 exon2 was amplified by polymerase chain reaction (PCR) from 126 healthy and 67 Brucellosis-infected Chinese Merino sheep. PCR products were analyzed using the SSCP technique, and then cloned to allow sequencing of the different alleles. For each SNP, allelic and genotypic frequencies were compared between case and control samples, in addition the association with Brucellosis susceptibility was determined. Haplotypes and their frequencies were established and analyzed by SHEsis online software. There were forty-one single nucleotide polymorphisms (SNPs) in the 270 bp DNA sequence. The distribution of C>T alleles at locus 109 was significantly different between case and control samples. The linkage disequilibrium (LD) analysis showed that there were nine LD blocks in MHC-DRB1 exon2 and strong LD between SNPs existed in every Block. Haplotype analysis identified nine haplotypes with strong LD, but only Hap8 and Hap9 in case-control groups were significantly different (P<0.05); neither haplotype contained the C>T allele at locus 109. In conclusion, genetic variants of MHC-DRB1 gene exon2 demonstrated associations with Brucellosis susceptibility, indicating that further research is warranted.

Variation at the von Willebrand Factor (vWF) Gene Locus Is Associated With Plasma vWF:Ag Levels: Identification of Three Novel Single Nucleotide Polymorphisms in the vWF Gene Promoter

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4277-4283 ◽  
Author(s):  
Angela M. Keightley ◽  
Y. Miu Lam ◽  
Jolene N. Brady ◽  
Cherie L. Cameron ◽  
David Lillicrap
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Von Willebrand Factor ◽  
Gene Locus ◽  
Strong Linkage Disequilibrium ◽  
Nucleotide Polymorphisms ◽  
Polymorphic Variation ◽  
Single Nucleotide ◽  
Haplotype 1 ◽  
Von Willebrand ◽  
Willebrand Factor

Both genetic and environmental factors contribute to the normal population variability of plasma von Willebrand Factor (vWF) levels, however, regulatory mechanisms at the vWF gene locus itself have not yet been identified. We have investigated the association between polymorphic variation in the 5′-regulatory region of the vWF gene and levels of plasma vWF:Ag in a study of 261 group O blood donors. Three novel single nucleotide polymorphisms (SNPs) were identified in the vWF promoter: C/T at -1234, A/G at -1185, and G/A at -1051. These SNPs had identical allele frequencies of 0.36 for the -1234C, -1185A, and -1051G alleles and 0.64 for the -1234T, -1185G, and -1051A alleles and were in strong linkage disequilibrium. In fact, these polymorphisms segregated as two distinct haplotypes: -1234C/-1185A/-1051G (haplotype 1) and -1234T/-1185G/-1051A (haplotype 2) with 12.6% of subjects homozygous for haplotype 1, 40.6% homozygous for haplotype 2, and 42.5% of subjects heterozygous for both haplotypes. Only 4.3% of individuals had other genotypes. A significant association between promoter genotype and level of plasma vWF:Ag was established (analysis of covariance [ANCOVA], P = .008; Kruskal-Wallis test,P = .006); individuals with the CC/AA/GG genotype had the highest mean vWF:Ag levels (0.962 U/mL), intermediate values of vWF:Ag (0.867 U/mL) were observed for heterozygotes (CT/AG/GA), and those with the TT/GG/AA genotype had the lowest mean plasma vWF:Ag levels (0.776 U/mL). Interestingly, when the sample was subgrouped according to age, the significant association between promoter genotype and plasma vWF:Ag level was accentuated in subjects > 40 years of age (analysis of variance [ANOVA], P = .003; Kruskal-Wallis test, P= .001), but was not maintained for subjects ≤ 40 years of age (ANOVA, P > .4; Kruskal-Wallis test, P > .4). In the former subgroup, mean levels of plasma vWF:Ag for subjects with the CC/AA/GG, CT/AG/GA, and TT/GG/AA genotypes were 1.075, 0.954, and 0.794 U/mL, respectively. By searching a transcription factor binding site profile database, these polymorphic sequences were predicted to interact with several transcription factors expressed in endothelial cells, including Sp1, GATA-2, c-Ets, and NFκB. Furthermore, the binding sites at the -1234 and -1051 SNPs appeared to indicate allelic preferences for some of these proteins. Electrophoretic mobility shift assays (EMSAs) performed with recombinant human NFκB p50 showed preferential binding of the -1234T allele (confirmed by supershift EMSAs), and EMSAs using bovine aortic endothelial cell (BAEC) nuclear extracts produced specific binding of a nuclear protein to the -1051A allele, but not the -1051G allele. These findings suggest that circulating levels of vWF:Ag may be determined, at least in part, by polymorphic variation in the promoter region of the vWF gene, and that this association may be mediated by differential binding of nuclear proteins involved in the regulation of vWF gene expression.

scholarly journals Pharmacogenetics of antipsychotic-induced side effects

2009 ◽  
Vol 11 (4) ◽  
pp. 405-415 ◽  
Keyword(s):  
Weight Gain ◽  
Side Effects ◽  
Serotonin Receptor ◽  
Antipsychotic Drugs ◽  
Receptor Gene ◽  
Effect Sizes ◽  
Patient Specific ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Primary Focus

Currently available antipsychotic drugs (APDs) carry significant though highly variable, liability to neurologic and metabolic side effects. Pharmacogenetics approaches offer the possibility of identifying patient-specific biomarkers for predicting risk of these side effects. To date, a few single nucleotide polymorphisms (SNPs) in a handful of genes have received convergent support across multiple studies. The primary focus has been on SNPs in dopamine and serotonin receptor genes: persuasive meta-analytic evidence exists for an effect of the dopamine D2 and D3 receptor genes (DRD2 and DRD3) in risk for tardive dyskinesia (TD) and for an effect of variation at the 5-HT2C receptor gene (HTR2C) for liability to APD-induced weight gain. However, effect sizes appear to be modest, and pharmacoeconomic considerations have not been sufficiently studied, thereby limiting clinical applicability at this time. Effects of these genes and others on risk for TD, extrapyramidal side effects, hyperprolactinemia, and weight gain are reviewed in this article.

New single nucleotide polymorphisms of androgen receptor gene (AR) in the Russian breed of Dzhalginsky Merino sheep

2016 ◽  
Vol 52 (10) ◽  
pp. 1056-1061
Author(s):  
V. I. Trukhachev ◽  
A. Yu. Krivoruchko ◽  
V. S. Skripkin ◽  
A. N. Kvochko ◽  
A. N. Kulichenko ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Single Nucleotide Polymorphisms ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Merino Sheep

scholarly journals Molecular mechanism for the multiple sclerosis risk variant rs17594362

2019 ◽  
Vol 28 (21) ◽  
pp. 3600-3609
Author(s):  
Dongkyeong Kim ◽  
Yungki Park
Keyword(s):  
Multiple Sclerosis ◽  
Molecular Mechanism ◽  
Demyelinating Disease ◽  
Nucleotide Polymorphisms ◽  
Enhancer Activity ◽  
Single Nucleotide ◽  
Risk Variant ◽  
Epigenome Editing ◽  
Multiple Sclerosis Risk ◽  
The Central Nervous System

Abstract Multiple sclerosis (MS) is known as an autoimmune demyelinating disease of the central nervous system. However, its cause remains elusive. Given previous studies suggesting that dysfunctional oligodendrocytes (OLs) may trigger MS, we tested whether single nucleotide polymorphisms (SNPs) associated with MS affect OL enhancers, potentially increasing MS risk by dysregulating gene expression of OL lineage cells. We found that two closely spaced OL enhancers, which are 3 Kb apart on chromosome 13, overlap two MS SNPs in linkage disequilibrium—rs17594362 and rs12429256. Our data revealed that the two MS SNPs significantly up-regulate the associated OL enhancers, which we have named as Rgcc-E1 and Rgcc-E2. Analysis of Hi-C data and epigenome editing experiments shows that Rgcc is the primary target of Rgcc-E1 and Rgcc-E2. Collectively, these data indicate that the molecular mechanism of rs17594362 and rs12429256 is to induce Rgcc overexpression by potentiating the enhancer activity of Rgcc-E1 and Rgcc-E2. Importantly, the dosage of the rs17594362/rs12429256 risk allele is positively correlated with the expression level of Rgcc in the human population, confirming our molecular mechanism. Our study also suggests that Rgcc overexpression in OL lineage cells may be a key cellular mechanism of rs17594362 and rs12429256 for MS.

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