Hardy-Weinberg Equilibrium Test Research Articles

Genetic Diversity in Katchaikatty Sheep based on Microsatellites Polymorphism

Background: Sheep is one of the important species of livestock in India contributing to meat production. India has 44 distinct breeds of sheep, out of which 10 are found in Tamil Nadu. The present study describes the molecular characterization of recently registered breed of sheep - Katchaikatty sheep, genetic variability and genetic structure of the population by microsatellite marker analyses. Methods: DNA from 50 unrelated Katchaikatty sheep was amplified with 25 FAO recommended fluorescent tagged ovine-specific microsatellite markers and genotyped on an automated Genetic Analyzer. In each locus, observed (no) and effective number of microsatellite alleles (ne), allele frequencies, observed (Ho) and expected (He) heterozygosity and heterozygosity deficit estimate (FIS), polymorphism information content (PIC) and Chi-square (χ2) test for Hardy-Weinberg equilibrium (HWE) were assessed. Mode-shift analyses were performed. Result: The study revealed a total of 144 alleles across all the loci. The number of alleles at each locus varied from one to 10 with a mean of 5.76 alleles. The PIC values in the microsatellite loci ranged from 0.34 (OarAE129) to 0.83 (OarFCB48) with an average of 0.59, which showed a high genetic polymorphism. Six out of 25 microsatellite loci studied were in Hardy-Weinberg equilibrium and 19/25 loci showed positive FIS values. The overall mean observed and expected heterozygosity were 0.50 and 0.65 respectively and the estimates elucidated a substantial genetic variability in Katchaikatty sheep population. Mode shift analysis revealed a normal L-shaped curve, describing that the Katchaikatty population had not experienced any genetic bottleneck and remained in mutation-drift equilibrium.

Forensic autosomal and gonosomal short tandem repeat marker reference database for populations in Burkina Faso

Tandem repeat genetic profiles used in forensic applications varies between populations. Despite the diversity and security issues in the Sahel that require the identification of victims (soldiers and civilians), Burkina Faso (BF) remains understudied. To fill this information gap, 396 unrelated individuals from BF were genotyped using a MICROREADER 21 ID System kit. All 20 short tandem repeat (STR) loci tested passed the Hardy–Weinberg equilibrium (HWE) test. The combined powers of exclusion for duos (CPE duos) and trios (CPE trios) for the 20 tested loci were 0.9999998 and 0.9999307, respectively. The probability that two individuals would share the same DNA profiles among the BF population was 9.80898 × 10–26. For the X-chromosome STR analysis, 292 individuals were included in this study using a MICROREADER 19X Direct ID System kit. Among the 19 loci, no significant deviations from HWE test were observed in female samples after Bonferroni correction (p < 0.05/19 = 0.0026), except for loci GATA165B12 and DXS7423. The results showed that the combined power of exclusion (CPE) and the combined power of discrimination in females (CPDF) and males (CPDM) were 0.999999760893, 0.999999999992, and 1, respectively. Comparison with other African sub-populations showed that geographical proximity is a reliable indicator of genetic relatedness.

Investigation of cosmopolitan and local Italian beef cattle breeds uncover common patterns of heterozygosity

The analysis of livestock heterozygosity is less common compared to the study of homozygous patterns. Heterozygous-Rich Regions (HRRs) may harbor significant loci for functional traits such as immune response, survival rate, and fertility. For this reason, this study was conducted to investigate and characterize the heterozygosity patterns of four beef cattle breeds, which included two cosmopolitan breeds (Limousine and Charolaise) and two local breeds (Sarda and Sardo Bruna). Our analysis identified regions with a high degree of heterozygosity using a consecutive runs approach, the Tajima D test, nucleotide diversity estimation, and Hardy Weinberg equilibrium test. These regions exhibited recurrent heterozygosity peaks and were consistently found on specific chromosomes across all breeds, specifically autosomes 15, 16, 20, and 23. The cosmopolitan and Sardo Bruna breeds also displayed peaks on autosomes 2 and 21, respectively. Thirty-five top runs shared by more than 25% of the populations were identified. These genomic fragments encompassed 18 genes, two of which are directly linked to male fertility, while four are associated with lactation. Two other genes play roles in survival and immune response. Our study also detected a region related to growth and carcass traits in Limousine breed. Our analysis of heterozygosity-rich regions revealed particular segments of the cattle genome linked to various functional traits. It appears that balancing selection is occurring in specific regions within the four examined breeds, and unexpectedly, they are common across cosmopolitan and local breeds. The genes identified hold potential for applications in breeding programs and conservation studies to investigate the phenotypes associated with these heterozygous genotypes. In addition, Tajima D test, Nucleotide diversity, and Hardy Weinberg equilibrium test confirmed the presence of heterozygous fragments found with Heterozygous-Rich Regions analysis.

Implications of the Co-Dominance Model for Hardy-Weinberg Testing in Genetic Association Studies.

The standard way of using tests for compatibility of genetic markers with the Hardy-Weinberg equilibrium (HWE) assumptionvas a means of quality control in genetic association studies (GAS) is to vcarry out this step of preliminary data analysis with the sample of non-diseased vindividuals only. We show that this strategy has no rational basis whenever the genotype--phenotype relation for avmarker under consideration satisfies the assumption of co-dominance. The justification of this statement is the fact rigorously shown here that under co-dominance, the genotype distribution of a diallelic marker is in HWE among the controls if and only if the same holds true for the cases. The major practical consequence of that theoretical result is that under the co-dominance model, testing for HWE should be done both for cases and controls aiming to establish the combined (intersection) hypothesis of compatibility of both underlying genotype distributions with the HWE assumption. A particularly useful procedure serving this purpose is obtained through applying the confidence-interval inclusion rule derived by Wellek, Goddard and Ziegler (Biom J. 2010; 52:253-270) to both samples separately and combining these two tests by means of the intersection-union principle.

Polymorphism of the Forkhead box-O3 (FOXO3) Longevity Gene rs2802292 and senescence-associated secretory phenotype (SASP) in Indonesian Elderly Population

BACKGROUND: Forkhead box O3 (FOXO3) is a transcription factor that regulates stress resistance, metabolism, cell cycle, and apoptosis. Several studies exhibited the association of the FOXO3 polymorphism rs2802292 with human longevity and protects individuals from degenerative diseases. The emergence of degenerative diseases in the elderly is associated with the accumulation of senescent cells that secrete a secretome known as a senescence-associated secretory phenotype (SASP) consists of several cytokines, chemokines, growth factors, proteases. OBJECTIVE: The aim of this research was to analysis polymorphism of FOXO3 gene rs2802292 G-allele and its impact to the SASP by measuring IL-1α, IL-6, IL-8, and IL-10 in Indonesian elderly populations. METHODS: This study was conducted on 92 elderly subjects living at Jakarta. DNA was isolated from the whole blood then continued with PCR and sequencing for FOXO3 rs2802292 analysis. SASP was analyzed from the plasma using Luminex. Statistical analysis was performed using ANOVA and Kruskal Wallis. RESULTS: The results showed that FOXO3 rs2802292 was detected in Indonesian elderly population as follows GG, GT, TT genotype frequencies were 17.4 %, 42.4 % and 40.2 % respectively. Meanwhile, G and T allele frequencies based on the Hardy-Weinberg equilibrium test were 0.385 and 0.615 respectively. GG genotype was significantly found in subjects with longevity. Nevertheless, SASP analysis was found no significant differences both among GG, GT, TT genotypes. CONCLUSION: The frequency of FOXO3 rs2802292 G-allele in Indonesian elderly population was 0.385 and significantly detected in subjects with longevity. However, the FOXO3 rs2802292 polymorphism did not affect cytokines level as the component of SASP.

Towards pharmacogenomics-guided tuberculosis (TB) therapy: N-acetyltransferase-2 genotypes among TB-infected Kenyans of mixed ethnicity

BackgroundThough persons of African descent have one of the widest genetic variability, genetic polymorphisms of drug-metabolising enzymes such as N-Acetyltransferase-2 (NAT2) are understudied. This study aimed to identify prevalent NAT2 single nucleotide polymorphisms (SNPs) and infer their potential effects on enzyme function among Kenyan volunteers with tuberculosis (TB) infection. Genotypic distribution at each SNP and non-random association of alleles were evaluated by testing for Hardy-Weinberg Equilibrium (HWE) and Linkage Disequilibrium (LD).MethodsWe isolated genomic DNA from cryopreserved Peripheral Blood Mononuclear Cells of 79 volunteers. We amplified the protein-coding region of the NAT2 gene by polymerase chain reaction (PCR) and sequenced PCR products using the Sanger sequencing method. Sequencing reads were mapped and aligned to the NAT2 reference using the Geneious software (Auckland, New Zealand). Statistical analyses were performed using RStudio version 4.3.2 (2023.09.1 + 494).ResultsThe most frequent haplotype was the wild type NAT2*4 (37%). Five genetic variants: 282C > T (NAT2*13), 341 T > C (NAT2*5), 803A > G (NAT2*12), 590G > A (NAT2*6) and 481C > T (NAT2*11) were observed with allele frequencies of 29%, 18%, 6%, 6%, and 4% respectively. According to the bimodal distribution of acetylation activity, the predicted phenotype was 76% rapid (mainly consisting of the wildtype NAT2*4 and the NAT2*13A variant). A higher proportion of rapid acetylators were female, 72% vs 28% male (p = 0.022, odds ratio [OR] 3.48, 95% confidence interval [CI] 1.21 to 10.48). All variants were in HWE. NAT2 341 T > C was in strong complete LD with the 590G > A variant (D′ = 1.0, r2 = − 0.39) but not complete LD with the 282C > T variant (D′ = 0.94, r2 = − 0.54).ConclusionThe rapid acetylation haplotypes predominated. Despite the LD observed, none of the SNPs could be termed tag SNP. This study adds to the genetic characterisation data of African populations at NAT2, which may be useful for developing relevant pharmacogenomic tools for TB therapy. To support optimised, pharmacogenomics-guided TB therapy, we recommend genotype-phenotype studies, including studies designed to explore gender-associated differences.

DGAT1 Gene Polymorphism in Morkaraman and Tushin

This study aims to investigate the polymorphism of the Diacylglycerol acyltransferase1 (DGAT1) gene locus in 105 Morkaraman and 65 Tushin lambs to determine the distribution of genotype and allele frequencies of lambs in terms of related genes. DGAT1/Alu1 gene polymorphism was defined by using the PCR-RFLP method in the DNAs isolated from hair samples taken from Morkaraman and Tushin lambs used in this study. PCR- RFLP products were run in an electrophoresis medium and the results were visualized on an ultraviolet (UV) transluminator. When the population was examined in terms of allele frequencies, it was defined that the C allele and the T allele were 0.72% and 0.28% for the Morkaraman, and 0.71% and 0.29% for Tushin, respectively. The CC, CT, and TT genotype frequencies of the DGAT1 gene in the population were found to be 53.3%, 38.1%, and 8.6% for the Morkaraman and 50.8%, 40.0%, and 9.2% for the Tushin, respectively. In the Hardy-Weinberg genetic equilibrium test, it was observed that the distribution of genotype frequencies was in balance (P&gt;0.05) in the population. It has been defined that the genotype and allele frequencies determined in terms of DGAT1 gene polymorphism may be found to be sufficient to reveal the genotype diversity of the breeds. The genotype and allele frequencies determined in terms of DGAT1 gene polymorphism were sufficient to reveal the genotype diversity of the breed, the sheep with CC genotype are economically advantageous in the herd, and therefore DGAT1 gene can be used for marker-assisted selection (MAS).

PSXII-1 Genetic Regions Associated with Cryptorchidism in Related Wagyu Cattle

Abstract Wagyu cattle have gained popularity in recent years due to their increased amounts of intramuscular marbling and their calving ease in crossbred cattle. The small effective population size of Wagyu cattle outside of Japan has led to inbreeding and an increased presentation of autosomal recessive traits. Cryptorchidism, the absence of at least one testicle from the scrotum, is the most common genital defect in males and is seen more commonly in inbred populations suggesting an autosomal recessive inheritance. The objective of this study was to identify genetic regions associated with unilateral cryptorchidism in related Wagyu cattle. All individuals in the study shared a common cow ancestor in their pedigree. Fourteen individuals, three cases and eleven controls, were genotyped using the Illumina BovineHD BeadChip (San Diego, CA). There were 450,083 SNPs that remained for the haplotype analysis after SNPs were removed for quality control parameters of genotyping call rate (&amp;lt; 90%), minor allele frequency (&amp;lt; 1%) and failure to meet Hardy Weinberg equilibrium testing (P &amp;lt; 1 x 10-5). No animals were removed due to low call rate (&amp;lt; 90%). Haplotypes were detected within the SNP and Variation Suite v8.2 (Golden Helix, Bozeman, MT) for an association with cryptorchidism using a chi-square test (P &amp;lt; 0.05) and false discovery rate (FDR &amp;lt; 0.05). There were 107,439 different SNP haplotype combinations among 49,627 haplotypes identified in the Wagyu cattle. The average haplotype size was 21.7 kb in Wagyu cattle. Prior to multiple testing correction, 1,233 haplotypes were associated (P &amp;lt; 0.05), with 6 haplotypes on BTA7 (P = 0.001 to P = 0.002) being of particular interest as the SNPs for those haplotypes were identical and homozygous, whereas none of the controls were homozygous for the SNPs. The SNP haplotype pattern observed on BTA7 was consistent with an autosomal recessive trait. When applying multiple testing corrections (FDR &amp;lt; 0.05), none of the haplotypes were significant. Additional unilateral cryptorchid bulls that share the same common cow ancestor have been identified and will be tested to see if the haplotypes on BTA7 are segregating with the phenotype. Identifying genetic regions associated with cryptorchidism will allow the identification of carriers for this trait that can then be used for choosing mates that are not carrying this trait. Reducing the number of cryptorchid males in a breed with a small effective population size would allow breeders to utilize the genetics of carriers without increasing the frequency of cryptorchidism.

Genetic Association Between ICAM-1 Gene Variants and Susceptibility to Ischemic Cardiomyopathy.

The current work was aimed at exploring the association between single nucleotide polymorphisms (SNPs) in the ICAM-1 gene, along with the identification of additional haplotypes and their potential role in the susceptibility to ischemic cardiomyopathy (ICM). The control group underwent a Hardy-Weinberg equilibrium test. The associations of genotypes and alleles with susceptibility to ICM were then analyzed using logistic regression analysis. Subsequently odds ratios (ORs) along with 95% confidence intervals (95% CI) were calculated. Interaction analysis was conducted between these SNPs. Furthermore, linkage disequilibrium analysis and haplotype analysis were performed on SNPs that showed interactions with each other. The incidence of ICM was significantly higher among individuals carrying the T allele of rs3093032 (OR = 2.032, 95% CI, 1.275-3.241, P = 0.003) relative to those with the C allele. In addition, CT genotype carriers had a higher susceptibility to ICM than CC genotype carriers (OR = 2.490, 95% CI, 1.445-4.29, P = 0.001). Furthermore, 3 SNPs (rs3093032, rs923366, rs3093030) exhibited a strong interaction with each other, whereas rs281437 showed no interaction with the other 3 SNPs. Individuals carrying the C rs3093032 -T rs923366 -C rs3093030 haplotype had an elevated risk of ICM compared with those carrying the C rs3093032 -C rs923366 -C rs3093030 haplotype (OR = 2.280, 95% CI, 1.568-3.315, P < 0.001). Moreover, individuals carrying the T rs3093032 -C rs923366 -C rs3093030 haplotype were more susceptible to ICM than those carrying the C rs3093032 -C rs923366 -C rs3093030 haplotype (OR = 2.388, 95% CI, 1.469-3.880, P < 0.001). Regarding rs3093032, the minor alleles and haplotypes are associated with an increased ICM risk: 3 SNPs (rs3093032, rs923366, rs3093030) in ICAM-1 have strong interaction with each other.

Genetic diversity and population structure of Mastacembelus armatus in the river systems of southern China revealed by microsatellites

The Zig-zag eel (Mastacembelus armatus) is an economically important species in southern China. Its natural resources have declined year by year due to overfishing. Understanding its genetic diversity and population structure is very important for resource conservations. Here, we first successfully developed 28 polymorphic microsatellite markers for zig-zag eels and ten of them were used to examine the genetic diversity and differentiation of 7 populations collected from the major river systems of south China. In total, 224 alleles were found with the 10 microsatellite loci in 7 populations, ranging from 4.6 (Nandujiang: NDJ) to 11.1 (Xijiang, XJ), with an average of 8.871 alleles. The average observed and expected heterozygosity ranged from 0.550 (NDJ) to 0.964 (Yuangjiang, YJ) and from 0.537 (NDJ) to 0.775 (Tanjiang, TJ), respectively. The average polymorphism-information content ranged from 0.472 (NDJ) to 0.757 (TJ). Hardy–Weinberg equilibrium test results revealed the loci showed differing deviation in different populations. In total, low level of genetic diversity was only found in HJ (Hanjiang) and NDJ populations. Besides, evidence of recent bottleneck was found in the HJ populations. Analysis of molecular variation showed that the percent variation within individuals (75.00%) was higher than that among populations (25%). In addition, population structure and the pairwise FST revealed that there was low differentiation among XJ, TJ and YJ populations. These data provide important genetic resources for understanding the population differentiation and facilitating genetic conservation and utilization of this species.

Potential role of glutathione S‑transferase M1 gene polymorphism in kidney calcium oxalate stone formation.

The purpose of this study was to look into the effects of glutathione S-transferase M1 (GSTM1) gene polymorphism on the formation of kidney calcium oxalate stones. A total of 159 patients with kidney calcium oxalate stones were included in this study as a case group. One hundred and three healthy individuals were included in the control group. The age, gender, and levels of calcium (Ca), uric acid (UA), creatinine (Cr), and urinary creatinine (Ucr) are tracked. Peripheral blood samples are used to perform a polymerase chain reaction to identify the glutathione S-transferase (GST) gene polymorphism (PCR). A commercial kit was used in this study to measure the levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (T-AOC), and 8-hydroxydeoxyguanosine (8-OHdG) in peripheral blood. There was no difference in age or gender distribution between the case and control groups (P > 0.05). The Cr, Ucr, Ca, UA, 8-OHdG, MDA, NO, and T-AOC in the case group were significantly higher than those in the control group (P < 0.001). The Hardy-Weinberg genetic equilibrium test showed no difference between the case group (P = 0.23) and the control group (P = 0.09). In the case group, the 8-OHdG and NO in GSTM1 null genotype were significantly higher than those in GSTM1 genotype(P < 0.05), but there was no significant difference in MDA and T-AOC (P > 0.05). Multivariate regression analysis showed that the GSTM1 null genotype was positively correlated with 8-OHdG (P < 0.001) and NO (P < 0.001). GSTM1 gene polymorphism might be a detecting risk factor for kidney calcium oxalate stone formation. ChiCTR2100051300.

Effect of vitamin D binding protein gene polymorphism on susceptibility and prognosis of severe acute pancreatitis

To investigate the effect of vitamin D binding protein (DBP) gene polymorphism on susceptibility and prognosis of severe acute pancreatitis (SAP). A prospective study was conducted. Eighty-three patients with SAP who were admitted to the department of general surgery of Tianjin Fifth Central Hospital from March 2018 to March 2021 were selected as the research objects, and 83 healthy people in the same period were selected as controls. Peripheral blood RNA was extracted and reverse transcribed into cDNA, and the genotype and allele frequency of DBP gene rs7041 locus were detected by fluorescence quantitative analyzer. Hardy-Weinberg equilibrium was used to test the genetic balance. On the day of admission, serum C-reactive protein (CRP) level was detected by scattering immunoturbidimetry, serum procalcitonin (PCT) level was detected by electrochemiluminescence, serum DBP level was detected by enzyme-linked immunosorbent assay (ELISA), and neutrophil to lymphocyte ratio (NLR) was calculated automatically by the instrument. The length of intensive care unit (ICU) stay, the length of hospital stay and prognosis during hospitalization of patients were statistically analyzed. Multivariate Logistic regression analysis was used to screen the influencing factors of SAP occurrence. The results of Hardy-Weinberg equilibrium test showed that the distribution of gene polymorphisms in the two groups of subjects conformed to the law of genetic equilibrium. The frequencies of TT genotype and T allele of DBP gene rs7041 locus in the patients of SAP group were significantly higher than those in the healthy control group [TT genotype: 34.94% (29/83) vs. 9.64% (8/83), T allele: 55.42% (92/166) vs. 38.55% (64/166), both P < 0.01], and the frequency of GT genotype was significantly lower than that in the healthy control group [40.96% (34/83) vs. 57.83% (48/83), P < 0.05]. There was no significant difference in the frequency of GG genotype between the healthy control group and SAP group [32.53% (27/83) vs. 24.10% (20/83), P > 0.05]. Further multivariate Logistic regression analysis showed that TT genotype [odds ratio (OR) = 2.831, 95% confidence interval (95%CI) was 1.582-5.067, P < 0.001] and T allele (OR = 2.533, 95%CI was 1.435-4.472, P < 0.001) of DBP gene rs7041 locus were independent risk factors for SAP in healthy people, while GT genotype was a protective factor for SAP (OR = 0.353, 95%CI was 0.143-0.868, P = 0.041). The levels of CRP, PCT, NLR and DBP in patients with TT genotype of DBP gene rs7041 locus were significantly higher than those in patients with GG/GT genotype on the day of admission in SAP group [CRP (mg/L): 43.25±13.25 vs. 31.86±12.83, PCT (μg/L): 1.53±0.24 vs. 1.21±0.20, NLR: 3.15±0.53 vs. 2.71±0.48, DBP (μg/L): 87.78±19.64 vs. 70.58±18.67, all P < 0.01]. The length of ICU stay in patients with TT genotype of DBP gene rs7041 locus in SAP group was significantly longer than that in patients with GG/GT genotype (days: 11.35±1.58 vs. 9.71±1.35, P < 0.01). The length of hospital stay of patients with TT genotype was longer than that of patients with GG/GT genotype (days: 23.41±3.64 vs. 23.17±3.57), and the in-hospital mortality was higher than that of patients with GG/GT genotype [34.48% (10/29) vs. 29.63% (16/54)], but the difference was not statistically significant (both P > 0.05). The risk of SAP was significantly increased in patients with TT genotype of rs7041 locus of DBP gene, and the mechanism may be related to the increase of DBP expression. And carrying the TT genotype will prolong the ICU hospitalization time of SAP patients, but the effect on prognosis is not obvious.

Molecular characterization of guava Psidium guajava in Cereté, Córdoba, Colombia

Guava (Psidium guajava L.) is the most cherished cultivated fruit species in the Myrtaceae family, and it is a perennial tree native to tropical America. The objective of this study was to determine the genetic variability of Psidium guajava in Cereté (Colombia) using SSR markers. DNA extraction was performed using the Mini-prep method with modifications. Nine microsatellites were amplified using the PCR Touchdown technique. Genetic-population parameters such as the number of alleles, effective number of alleles, observed heterozygosity, expected heterozygosity, fixation index, Hardy-Weinberg equilibrium, and polymorphic information content were calculated using PopGene 1.31 software. The number of alleles varied between 4 for markers mPgCIR13, mPgCIR20, mPgCIR23, and 8 for marker mPgCIR19, respectively. The average value of effective number of alleles was 3.722, observed heterozygosity was 0.217, and expected heterozygosity was 0.254. The average fixation index was 0.101. Hardy-Weinberg equilibrium tests revealed significant differences in the markers. The FIS coefficient had an average value of 0.385, the FIT coefficient showed an average of 0.490, and the FST coefficient had a value of 0.178. Genetic distance analysis showed that Mateo Gómez was closely related to Retiro de los Indios, while Rabolargo appeared to be the most distant population. The study revealed low genetic variability within and between the populations studied, possibly, reflecting the type of asexual propagation applied in guava crops.

Associations between polymorphisms in the cannabinoid receptor 1 gene, cognitive impairments and tardive dyskinesia in a Chinese population with schizophrenia

ObjectiveTardive dyskinesia (TD) is a medically induced movement disorder that occurs as a result of long-term use of antipsychotic medications, commonly seen in patients with schizophrenia (SCZ). The study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) of the CNR1 gene, TD and cognitive impairments in a Chinese population with SCZ. MethodsA total of 216 SCZ patients were recruited. The participants were divided into TD and without TD (WTD) groups using the Schooler-Kane International Diagnostic Criteria. The severity of TD was assessed using the Abnormal Involuntary Movement Scale (AIMS). Cognitive function was assessed using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) scale. Hardy-Weinberg equilibrium tests, chained disequilibrium analyses and haplotype analyses were performed using SHE-sis software. To explore the main effects of TD diagnosis, genotype and cognitive function, as well as interaction effects, analysis of covariance (ANCOVA) was employed. ResultsThe prevalence of TD was approximately 27.3%. Significant differences were observed in the rs806368 CT genotype and rs806370 TC genotype within the hypercongenic pattern between the male TD and WTD groups (OR = 2.508, 95% CI: 1.055–5.961, p = 0.037; OR = 2.552, 95% CI: 1.073–6.069, p = 0.034). Among TD patients, those carrying the rs806368 CC genotype exhibited higher limb trunk scores (p < 0.05). Moreover, there was a statistically significant difference in visuospatial/construction between the TD and WTD groups (p = 0.04), and a borderline significant difference in visuospatial/construction when considering the interaction between TD diagnosis and genotype at the rs806368 locus (p = 0.05). ConclusionCNR1 rs806368 and rs806370 polymorphisms may play a role in TD susceptibility. Additionally, CNR1 gene polymorphisms were associated with the severity of involuntary movements and cognitive impairments in TD patients.

Correlation of SV2C rs1423099 single nucleotide polymorphism with sporadic Parkinson's disease in Han population in Southern China

BackgroundThe synaptic vesicle glycoprotein 2 (SV2) has been implicated in synaptic function throughout the brain. Accumulating evidence investigated that SV2C contributed to dopamine release and the disrupted expression of SV2C was considered to be a unique feature of PD that may facilitate dopaminergic neuron dysfunction. ObjectiveThis study aimed to examine the relationship between the SV2C rs1423099 single nucleotide polymorphism and sporadic Parkinson's disease (PD) in the Chinese Han population. Materials and methodsThis study enrolled 351 patients with sporadic PD and 240 normal controls in Chinese Han population. Peripheral blood DNA was extracted by DNA extraction kits and the rs1423099 genotype was analyzed by Agena MassARRAY DNA mass spectrometry. The differences in genotype and allele distribution frequencies between PD patients and control groups were compared using chi-squared tests or Fisher's exact tests. ResultsNo statistical difference was revealed in age and sex distribution between the cases and control groups, and the distribution of genotype and allele frequencies was consistent with the Hardy-Weinberg equilibrium test. In SV2C rs1423099 dominant model, the frequency of the CC/CT genotype was significantly higher in the PD group compared to the control group (OR = 4.065,95% CI: 2.801–10.870, p = 0.002). Nevertheless, in the recessive model, CC or CT/TT genotypes have no statistical difference in the two groups (p = 0.09). Additionally, in allelic analysis, the C allele was investigated to increase the risk of PD (OR = 1.346, 95% CI: 1.036–1.745, p = 0.026); Furthermore, subgroup analysis suggested that those carrying the C allele in the male subgroup were at a higher risk to afflicted with PD (OR = 1.637, 95% CI: 1.147–2.336, p = 0.006). ConclusionSV2C rs1423099 single nucleotide polymorphism was associated with sporadic Parkinson's disease in the Chinese Han population, particularly in males.

Association between Maternal FUT2 204A&gt;G (rs492602) Genetic Polymorphism and Congenital Heart Disease in the Indian Population: A Study in Maternal-fetal Dyads

Background: FUT2 secretor genetic variants are strongly associated with absorption and circulatory levels of vitamin B12, thereby affecting folate metabolism pathway. The aim of this study was to evaluate the association between maternal FUT2 204A&gt;G (rs492602) genetic polymorphism and CHD in the Indian population.Materials and method: One hundred and ten pregnant women who were vitamin B12 deficient with fetuses diagnosed with CHD were included in the case group and an equal number of healthy pregnant women with normal fetuses were selected as the control group. DNA was extracted from blood and umbilical cord tissue samples, and genotyped for FUT2 rs492602 polymorphism using allele-specific polymerase chain reaction. Hardy–Weinberg equilibrium test was used to calculate allele and genotype frequencies.Results: Significant increase in the frequency of AG (odds ratio=2.25; 95% CI: 1.25–4.05; p=0.009) and GG (odds ratio=3.51; 95% CI: 1.47-8.43; p=0.006) genotypes as well as G allele of FUT2 rs492602 were observed in the maternal case group. Furthermore, in the fetus case group, there was a significantly higher incidence of GG genotype (odds ratio=2.87; 95% CI: 1.26–6.57; p=0.018) and G allele (odds ratio=1.70; 95% CI: 1.15–2.53; p=0.009).Conclusion: FUT2 rs492602 are associated with CHD in the Indian population. Maternal genetic polymorphism that regulates vitamin B12 metabolic pathway might influence fetal cardiac development, thus serving as a predictor for CHD.Keywords: congenital heart disease, FUT2, single nucleotide polymorphism (SNP), vitamin B12

BHMT polymorphism and susceptibility to PTE in Chinese patients.

Pulmonary thromboembolism (PTE) is as a common form of venous thrombosis and a potentially fatal cardiovascular disorder, which has become a severe clinical problem with high incidence and mortality. The PTE has a strong genetic basis, which contributes up to half of the variance in PTE incidence and susceptibility single-nucleotide polymorphisms (SNPs) is associated with PTE. Betaine homocysteine methyltransferase (BHMT) is an essential enzyme that catalyzes the remethylating reaction from homocysteine to methionine and participates in conserving methionine and detoxifying homocysteine. In this work, we aimed to explore BHMT polymorphism and susceptibility to PTE in Chinese patients. Variant loci of the BHMT gene were screened in serum samples of PTE patients, followed by verification using Sanger sequencing. These polymorphic loci were validated in 16 PTE patients and 16 matched normal patients. The frequency differences between the allele and genotypes were compared using the Hardy-Weinberg equilibrium test and Chi-square test. A SNP was identified in PTE patients and a heterozygous transition of G>A (Arg239Gln) in rs3733890 was found. The variance difference at rs3733890 between normal patients (2/16, 0.125) and PTE patients (9/16, 0.5625) was significant (p<0.01). Therefore, we concluded that the BHMT polymorphism, rs3733890 may be a susceptibility SNP for PTE.

Documentation of Genetic Diversity by Insulin-Like Growth Factor1 Receptor (Exon2) Gene for Fallow Deer (Dama dama) in Iraq.

Insulin-Like Growth Factor1 Receptor (Exon2) (IGF1R) gene plays a vital role in physiological impacts, such as growth, development, reproduction, and metabolism. A significant difference was noted between the IGR1R (exon 2) gene and the body weight of Dama dama. In addition, the heterozygosity pattern (AB) was significantly higher than the other pattern (AA). There are three single nucleotide polymorphisms (SNPs; 144G>C, 147A>G, and 210A>C) within the IGF-1R (exon 2) locus. The statistical analyses indicated the presence of three different haplotypes (GAA, CAA, and GGC). The analysis of relative frequencies indicated that the most frequent haplotype in the studied Dama dama population was Hap3 (GGC) (43.4782%) out of the three observed haplotypes. The results of SSCP-PCR revealed the variability of the target gene between the genotype frequencies in Fallow deer (Dama dama) with a high level of significance (P≤0.01) with two patterns (AA and AB) and an absence of BB pattern. The allele frequency of AA record a high level (71.74%) than the other genotype (AB) (28.26%), with a high-frequency level of the A allele (0.86) than the B allele (0.14). In current findings, SSCP genotyped in the Dama dama DNA observed an estimated 72% monomorphic loci and 28% polymorphic loci approximately. Hardy Weinberg equilibrium test (HW) was applied to the SSCP-PCR data matrix, and the statistical test was based on a chi-square (χ2) test. Chi-square was (55.928%) with a highly significant level (P≤0.01) recorded in the present study. As related to AA and AB genotypes mean, a significant difference (P≤0.05) was noted between IGF1R (exon 2) gene with a body weight of Dama dama, as well as the heterozygosity pattern (AB), was significantly (P≤0.05) higher than the other pattern (AA) (30.34±3.01kg versus 24.85±1.94kg), respectively. A significant impact (P≤0.05) between IGF1R (exon2) polymorphism and heart girth was founded to be related to the AB pattern (heterozygous) (76.92 ± 3.20 cm), whereas the lower value was related to the AA pattern (71.33 ± 2.49 cm). No significant differences in effects were shown in relation to body length and height at the shoulder. The present study is also interested in genetic characterization by calculating (Ne) as a tool for genetic diversity. Therefore, the number of alleles detected (Na) indicates that two alleles only were unique in the population of the study, with (1.3204) being the number of efficient alleles (Ne). Moreover, Shannon's Information index was recorded at 0.4073. The observed homozygosity (O.Hom.) and heterozygosity (HO) were (0.7174 and 0.2826), respectively. The values of expected homozygosity (E.Hom.) and heterozygosity (HE) were 0.7547 and 0.2453, respectively. The genetic diversity of Nei was 0.2427. The results showed an unexpected influx of IGF1R diversity measured by Fis and recorded the value (- 0.1646). In this sense, the results of the current study may be considered an approximation to the total genetic diversity of the population of Dama dama in Iraq, but the information obtained is relevant to proposing the strategies of conservation for the genetic diversity observed.

Comprehensive investigating of MMR gene in hepatocellular carcinoma with chronic hepatitis B virus infection in Han Chinese population.

Hepatocellular carcinoma associated with chronic hepatitis B virus infection seriously affects human health. Present studies suggest that genetic susceptibility plays an important role in the mechanism of cancer development. Therefore, this study focused on single nucleotide polymorphisms (SNPs) of MMR genes associated with HBV-HCC. Five groups of participants were included in this study, which were healthy control group (HC), spontaneous clearance (SC), chronic hepatitis B group (CHB), HBV-related liver cirrhosis group (LC) and HBV-related hepatocellular carcinoma group (HBV-HCC). A total of 3128 participants met the inclusion and exclusion criteria for this study. 20 polymorphic loci on MSH2, MSH3 and MSH6 were selected for genotyping. There were four case-control studies, which were HC vs. HCC, SC vs. HCC, CHB vs. HCC and LC vs. HCC. We used Hardy-Weinberg equilibrium test, unconditional logistic regression, haplotype analysis, and gene-gene interaction for genetic analysis. Ultimately, after excluding confounding factors such as age, gender, smoking and drinking, 12 polymorphisms were found to be associated with genetic susceptibility to HCC. Haplotype analysis showed the risk haplotype GTTT (rs1805355_G, rs3776968_T, rs1428030_C, rs181747_C) was more frequent in the HCC group compared with the HC group. The GMDR analysis showed that the best interaction model was the three-factor model of MSH2-rs1981928, MSH3-rs26779 and MSH6-rs2348244 in SC vs. HCC group (P=0.001). In addition, we found multiplicative or additive interactions between genes in our selected SNPs. These findings provide new ideas to further explore the etiology and pathogenesis of HCC. We have attempted to explain the molecular mechanisms by which certain SNPs (MSH2-rs4952887, MSH3-rs26779, MSH3-rs181747 and MSH3-rs32950) affect genetic susceptibility to HCC from the perspectives of eQTL, TFBS, cell cycle and so on. We also explained the results of haplotypes and gene-gene interactions. These findings provide new ideas to further explore the etiology and pathogenesis of HCC.

Single-nucleotide polymorphisms of matrix metalloproteinase genes are associated with graft fibrosis after kidney transplantation.

Further research needs to be conducted on the role of genetic variables in kidney transplantation fibrosis. In this study, we used next-generation sequencing (NGS) to examine the relationship between matrix metalloproteinase (MMP) genes and single-nucleotide polymorphisms (SNPs) in renal allograft fibrosis. This study comprised 200 patients, whose complete DNA samples were taken. The SNPs in MMP genes were identified using targeted NGS. Hardy-Weinberg equilibrium (HWE) and minor allele frequency (MAF) tests were conducted, followed by a linkage disequilibrium (LD) analysis. Finally, the SNPs and severity of kidney allograft fibrosis were evaluated using different inheritance models. In total, 41 MMP gene-related SNPs were identified using targeted sequencing, and 20 tagger SNPs were retained for further study. The general linear models (GLMs) revealed that sirolimus treatment had a substantial effect on kidney graft fibrosis. The multiple inheritance model analyses revealed that SNP rs9059 of the MMP9 gene was strongly associated with kidney graft fibrosis. The in-vitro experiments showed the MMP9 rs9509 mutation promotes the process of epithelial-mesenchymal transition (EMT) in the human kidney 2 (HK2) cells. The SNP rs9059 is associated with significant kidney allograft pathological changes by promoting EMT progression. Our findings provide insights into the etiology of renal allograft interstitial fibrosis and the MMP9 could be used as a potential treatment target in the future.