Hardy-Weinberg Research Articles

Genetic Diversity of Prussian Carp, Carassius Gibelio (Bloch 1782), Populations in Euphrates River Based on mtDNA and Microsatellites

Population genetic studies can be useful in understanding invasion scenarios of non-native species. Carassius gibelio is an invasive species that can be found in various river and lake systems around the world. In this study, species identification was made by mtDNA COI sequence analysis for C. gibelio populations along the Euphrates River system and the genetic diversity of the populations was revealed using mtDNA D-loop and microsatellite markers. A total of 19 alleles were detected as a result of four microsatellite markers. It has been determined that fish populations are not in Hardy-Weinberg equilibrium because they show inbreeding reproduction and gynogenetics. According to microsatellite data, there is no genetic structure that coincides with the geographical distribution of the populations. The Euphrates River ecosystem is exposed to the effects of invasive species as well as anthropogenic activities and the survival and diversity of natural fish populations in the rivers are endangered. If necessary precautions are not taken, natural and endemic species will not be able to compete and there will be a high probability that they will be replaced by the invasive species C. gibelio in the future.

Population genetics assessment of two pocilloporid coral species from the northern red sea: Implications for urbanized reef sustainability

Understanding the genetic makeup of key coral species is vital for effective coral reef management, as heightened genetic diversity directly influences long-term survival and resilience against environmental changes. This study focused on two widespread Indo-Pacific branching corals, Pocillopora damicornis (referred as Pocillopora cf. damicornis (as identified only morphologically) and Seriatopora hystrix, by genotyping 222 and 195 colonies, respectively, from 10 sites in the northern Gulf of Eilat, Red Sea, using six and five microsatellite markers, respectively. Both species exhibited low observed heterozygosity (0.47 for P. cf. damicornis, 0.32 for S. hystrix) and similar expected heterozygosity (0.576 for P. cf. damicornis, 0.578 for S. hystrix). Pocillopora cf. damicornis showed minimal deviations from Hardy-Weinberg equilibrium (HWE) and low but positive F values, indicating high gene flow, while S. hystrix exhibited higher diversion from HWE and positive F values, suggesting isolation by distance and possible non-random mating or genetic drift. As the Gulf of Eilat undergoes rapid urbanization, this study highlights the anthropogenic impacts on the population genetics of key ecosystem engineering species and emphasizes the importance of managing genetics of Marine Protected Areas while implementing active coral reef restoration. The differences in reproductive traits between the two species (S. hystrix being a brooder, while P. cf. damicornis a broadcast spawner), underscore the need for sustainable population genetics management of the coral reefs for the future and resilience of the coral reef ecosystem of the northern Red Sea region.

Unveiling the genetic structure of pig population in a Himalayan state Uttarakhand through microsatellite and mitochondrial DNA analyses.

This study traced the maternal lineage of the domestic swine populations using mitochondrial DNA control region markers and genetic diversity using microsatellite markers in Uttarakhand, an Indian state situated at the foothills of the world's youngest (geo-dynamically sensitive) mountain system, "the Himalayas". Analysis of 68 maternally unrelated individuals revealed 20 haplotypes. The maternal signature of the Pacific, Southeast Asian, European, and ubiquitously distributed Chinese haplotypes was present in Uttarakhand's domestic pig population. The D3 haplotype reported in wild pigs from North India was also identified in 47 domestic samples. A unique gene pool, UKD (Uttarakhand Domestic), as another lineage specific to this region has been proposed. Genotypes were analyzed, using 13 sets of microsatellite markers. The observed (Ho) and expected (He) heterozygosities were 0.83 ± 0.02 and 0.84 ± 0.01, respectively. The average polymorphic information content value of 0.83 ± 0.01 indicated the high informativeness of the marker. The overall mean FIS value for all the microsatellite markers was low (F = 0.04, P < 0.01). Seven loci deviated from Hardy-Weinberg equilibrium (HWE) at a significant level (p < 0.05). Two clusters were identified, indicating overlapping populations. These results suggested that though belonging to different maternal lineages, the traditional management practices in Uttarakhand have allowed for genetic mixing and the sharing of genetic material among pig populations. It could contribute to increased genetic diversity but might also result in the loss of distinct genetic characteristics or breed purity of the local breeds if not carefully managed.

Association of polymorphisms in the TNFA, TNFRSF1A and TNFRSF1B genes with lepromatous leprosy in Western Mexican patients.

Studies in different populations have shown that single-nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and TNF receptors 1 and 2 (TNFR1 and TNFR2) may be involved in the pathogenesis of lepromatous leprosy (LL). To further explore the results in a Mexican population, we compared the frequencies of the polymorphisms in - 308 G>A TNFA (rs1800629), - 383 A>C TNFRS1A (rs2234649), and + 196 T >G TNFSR1B (rs1061622) genes in LL patients (n = 133) and healthy subjects (n = 198). The genotyping was performed with the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique. Statistical analysis was performed using the χ2 test, within the 95% confidence interval. Odds ratios (OR) were calculated and Hardy-Weinberg equilibrium was verified for all control subjects and patients. We found an association between the TNFSR1 -383 A>C genotype and the risk of lepromatous leprosy when leprosy patients were compared to controls (OR = 1.71, CI: 1.08-2.69, p = 0.02). Furthermore, it was also associated with the risk of LL in a dominant model (AC + CC vs AA, OR: 1.65, 95% CI: 1.05-2.057, p = 0.02). Similar genotype and allele frequencies for the SNPs TNFA - 308 G>A and TNFSR2 + 196 T>G were observed between leprosy patients and healthy subjects. The TNFSR1 -383 A>C could be a potential marker for the identification of high-risk populations. However, additional studies, using larger samples of different ethnic populations, are required.

Single-Base Gene Variants in MIR-146A and SCN1A Genes Related to the Epileptogenic Process in Drug-Responsive and Drug-Resistant Temporal Lobe Epilepsy-A Preliminary Study in a Brazilian Cohort Sample.

The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy-Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06-3.37); OR = 1.38 (95%CI = 1.04-1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25-5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01-2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08-5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04-17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.

#2709 Genome wide association study regarding disturbed AVF patency

Abstract Background and Aims Veins are frequently exposed to arterial circulation, as coronary artery bypass grafts (CABG) and as a peripheral venous bypass to treat atherosclerotic disease, or in the case of arterio-venous fistulas (AVF) to provide a vascular access for hemodialysis. Therapeutic success is dependent on proficient venous remodeling after introduction in the arterial circulation to sustain the increased hemodynamic pressure. Frequently observed adverse outcomes after the aforementioned procedures include the stenosis or total occlusion of the vein, requiring surgical or interventional treatment or leading to bypass/ AVF failure. Hereditary factors associated with disturbed venous patency have been previously investigated in all three conditions. For example, distinct VEGF-A as well as TGF-beta polymorphisms have been identified to correlate with AVF failure. In the present analysis we aimed at investigating whether genetic polymorphisms associated with disturbed venous patency after AVF creation are similar to findings in CABG and peripheral bypass patients in a genome wide association study. Method The analyses were conducted in White Europeans (N= 425,406) in the UK Biobank using regenie software. This software employs a linear mixed model that accounts for the impact of population structure and individual relatedness. Out of approximately 805,000 variants, we selected 606,201 high-quality variants to construct a relatedness model for regenie. These selected variants were identified by a genotyping rate exceeding 80%, minor allele frequencies greater than 1%, and Hardy-Weinberg equilibrium p-values below 10^-8. We adjusted for age, sex, BMI, smoking, and history venous thromboembolism. We assessed the association of 9,757,417 imputed SNPs, each having a minimum allele count of 12 and a minimum info score of 0.3. Results In total, 768 patients underwent at least 1 surgery for AVF creation. Out of those, 341 (44.4%) had a recorded procedure or diagnosis associated with disturbed fistula patency. The controls included 6067 CABGs and 384 peripheral bypasses with 76 (1.3%) and 67 (17.4%) recorded events, respectively. We found no genome wide significant associations for the tested SNPs and patency-related AVF complications (Fig. 1). Additionally, we also found no genome wide significant associations after combining the phenotypes (Fig. 2). Conclusion Multiple studies have evaluated genetic associations and adverse clinical outcomes after AVF creation. Nevertheless, the generalizability of these findings might be limited at least partially due to small sample sizes. While the sample size of the present analysis is similar to previous research efforts and therefore also comparably low, the lack of consistency in results might be suggestive of the difficulties research in this field faces. Additionally, we found no indication that impaired venous patency after AVF creation is related to complications after coronary or peripheral bypass surgery regarding genetic patient profiles. However, whether this is due to differences in pathophysiology and related genetic predispositions or due to the limited sample size and incidence rates of the present study remains to be determined in follow-up investigations.

Identification of FASN Gene Polymorphisms, Expression and Their Relationship with Body Size Traits in Guizhou White Goat (Capra hircus) with Different Genders.

To investigate the nucleotide variation sites (SNPs) and expression differences of the fatty acid synthase gene (FASN) in Guizhou white goats, the relationship between the variation and body size traits was investigated. In this study, DNA was extracted from the blood of 100 samples of white goats from different regions in Guizhou province, China, and the variation sites were screened using pooled sequencing by mixing DNA samples, and 242 blood samples with body size traits were used for association analysis. The allele frequency, genotype frequency, homozygosity, heterozygosity and effective gene number were calculated by using PopGene 32.0 software, the population polymorphism information content was calculated by using PIC software (Version 0.6), and the state of genetic balance of the genes was analyzed by using the chi-square test. The mRNA of FASN gene expression levels in male and female goats were investigated by using real-time fluorescence quantitative PCR (RT-qPCR). The general linear mixed model of MINTAB software (Version 16.0) was used to analyze the association between FASN gene nucleotide mutation sites and body size traits. The results showed that there was one nucleotide mutation site g.141 C/T in the target fragment of FASN gene amplification, and revealed two alleles, C and T, and three genotypes CC, CT and TT. The genotype frequencies for CC, CT and TT were 0.4308, 0.4205 and 0.1487, respectively. The allele frequencies for C and T were 0.6410 and 0.3590, respectively. The genetic homozygosity (Ho) was higher than the heterozygosity (He). The χ2 test showed that the mutation site was in the Hardy-Weinberg equilibrium state (p > 0.05). The RT-qPCR results showed that the FASN gene had different expression levels in the longissimus dorsi muscle of male and female goats, and its expression was significantly higher in male goats than in female goats. The association analysis results showed that the mutation of the FASN gene had different effects on body size traits of male and female goats, and the presence of the populations of the T allele and the TT genotype recorded higher body size traits (body weight, heart girth and wither height) in female populations. Therefore, the site of the FASN gene can be used as a candidate marker for the early selection of growth traits in Guizhou white goats.

HER2/neu 655 polymorphism, trastuzumab-induced cardiotoxicity, and survival in HER2-positive breast cancer patients

PurposeHER2 overexpression in breast cancer correlates with poor outcomes. The incorporation of Trastuzumab into the treatment regimen has notably improved patient prognoses. However, cardiotoxicity emerges in approximately 20% of patients treated with the drug. This study aims to investigate the association between the HER2 655 A > G polymorphism, Trastuzumab-induced cardiotoxicity, and patient survival.MethodsThe study involved 88 patients treated with Trastuzumab. Cardiotoxicity, defined as a reduction in left ventricular ejection fraction (LVEF) from baseline or the emergence of clinical signs of congestive heart failure, was identified during treatment follow-up. Genotyping of HER2 655 A > G employed TaqMan SNP technology.ResultsGenotype frequencies of HER2/neu 655 (53 AA, 32 AG, and 3 GG) were consistent with Hardy–Weinberg equilibrium. No significant differences were observed in mean baseline LVEF between patients who developed cardiotoxicity and those who did not. Within these groups, neither AA nor AG genotypes showed an association with changes in mean baseline or reduced LVEF levels. Logistic regression analysis, adjusted for hormonal status and anthracycline treatment, revealed that AG genotype carriers face a significantly higher risk of cardiotoxicity compared to AA carriers (OR = 4.42; p = 0.037). No association was found between the HER2/neu 655 A > G polymorphism and disease-free or overall survival, regardless of whether the data was adjusted for stage or not.ConclusionHER2 655 A > G polymorphism is significantly linked to an increased risk of Trastuzumab-induced cardiotoxicity but does not correlate with variations in disease-free survival or overall survival rates.

Detection and Analysis of Antidiarrheal Genes and Immune Factors in Various Shanghai Pig Breeds

The aim of this study was to identify effective genetic markers for the Antigen Processing Associated Transporter 1 (TAP1), α (1,2) Fucosyltransferase 1 (FUT1), Natural Resistance Associated Macrophage Protein 1 (NRAMP1), Mucin 4 (MUC4) and Mucin 13 (MUC13) diarrhea-resistance genes in the local pig breeds, namely Shanghai white pigs, Fengjing pigs, Shawutou pigs, Meishan pigs and Pudong white pigs, to provide a reference for the characterization of local pig breed resources in Shanghai. Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLR) and sequence sequencing were applied to analyze the polymorphisms of the above genes and to explore the effects on the immunity of Shanghai local pig breeds in conjunction with some immunity factors. The results showed that both TAP1 and MUC4 genes had antidiarrheal genotype GG in the five pig breeds, AG and GG genotypes of the FUT1 gene were detected in Pudong white pigs, AA antidiarrheal genes of the NRAMP1 gene were detected in Meishan pigs, the AB type of the NRAMP1 gene was detected in Pudong white pigs, and antidiarrheal genotype GG of the MUC13 gene was only detected in Shanghai white pigs. The MUC13 antidiarrhea genotype GG was only detected in Shanghai white pigs. The TAP1 gene was moderately polymorphic in Shanghai white pigs, Fengjing pigs, Shawutou pigs, Meishan pigs and Pudong white pigs, among which TAP1 in Shanghai white pigs and Shawutou pigs did not satisfy the Hardy–Weinberg equilibrium. The FUT1 gene of Pudong white pigs was in a state of low polymorphism. NRAMP1 of Meishan pigs and Pudong white pigs was in a state of moderate polymorphism, which did not satisfy the Hardy–Weinberg equilibrium. The MUC4 genes of Shanghai white pigs and Pudong white pigs were in a state of low polymorphism, and the MUC4 genes of Fengjing pigs and Shawutou pigs were in a state of moderate polymorphism, and the MUC4 genes of Fengjing pigs and Pudong white pigs did not satisfy the Hardy–Weinberg equilibrium. The MUC13 gene of Shanghai white pigs and Pudong white pigs was in a state of moderate polymorphism. Meishan pigs had higher levels of IL-2, IL-10, IgG and TNF-α, and Pudong white pigs had higher levels of IL-12 than the other pigs. The level of interleukin 12 (IL-12) was significantly higher in the AA genotype of the MUC13 gene of Shanghai white pigs than in the AG genotype. The indicator of tumor necrosis factor alpha (TNF-α) in the AA genotype of the TAP1 gene of Fengjing pigs was significantly higher than that of the GG and AG genotypes. The indicator of IL-12 in the AG genotype of the Shawutou pig TAP1 gene was significantly higher than that of the GG genotype. The level of TNF-α in the AA genotype of the NRAMP1 gene of Meishan pigs was markedly higher than that of the AB genotype. The IL-2 level of the AG type of the FUT1 gene was obviously higher than that of the GG type of Pudong white pigs, the IL-2 level of the AA type of the MUC4 gene was dramatically higher than that of the AG type, and the IgG level of the GG type of the MUC13 gene was apparently higher than that of the AG type. The results of this study are of great significance in guiding the antidiarrhea breeding and molecular selection of Shanghai white pigs, Fengjing pigs, Shawutou pigs, Meishan pigs and Pudong white pigs and laying the foundation for future antidiarrhea breeding of various local pig breeds in Shanghai.

Reassessing the association: Evaluation of a polyalanine deletion variant of RUNX2 in non-syndromic sagittal and metopic craniosynostosis.

The RUNT-related transcription factor RUNX2 plays a critical role in osteoblast differentiation, and alterations to gene dosage cause distinct craniofacial anomalies. Uniquely amongst the RUNT-related family, vertebrate RUNX2 encodes a polyglutamine/polyalanine repeat (Gln23-Glu-Ala17 in humans), with the length of the polyalanine component completely conserved in great apes. Surprisingly, a frequent 6-amino acid deletion polymorphism, p.(Ala84_Ala89)del, occurs in humans (termed 11A allele), and a previous association study (Cuellar etal. Bone 137:115395;2020) reported that the 11A variant was significantly more frequent in non-syndromic sagittal craniosynostosis (nsSag; allele frequency [AF] = 0.156; 95% confidence interval [CI] 0.126-0.189) compared to non-syndromic metopic craniosynostosis (nsMet; AF = 0.068; 95% CI 0.045-0.098). However, the gnomAD v.2.1.1 control population used by Cuellar etal. did not display Hardy-Weinberg equilibrium, hampering interpretation. To re-examine this association, we genotyped the RUNX2 11A polymorphism in 225 individuals with sporadic nsSag as parent-child trios and 164 singletons with sporadic nsMet, restricting our analysis to individuals of European ancestry. We compared observed allele frequencies to the non-transmitted alleles in the parent-child trios, and to the genome sequencing data from gnomAD v.4, which display Hardy-Weinberg equilibrium. Observed AFs (and 95% CI) were 0.076 (0.053-0.104) in nsSag and 0.082 (0.055-0.118) in nsMet, compared with 0.062 (0.042-0.089) in non-transmitted parental alleles and 0.065 (0.063-0.067) in gnomAD v.4.0.0 non-Finnish European control genomes. In summary, we observed a non-significant excess, compared to gnomAD data, of 11A alleles in both nsSag (relative risk 1.18, 95% CI 0.83-1.67) and nsMet (relative risk 1.29, 95% CI 0.87-1.92), but we did not replicate the much higher excess of RUNX2 11A alleles in nsSag previously reported (p = 0.0001).

Genetic Polymorphism of g.3768T&gt;C loci of NRAMP1 gene in Kampung and KUB Chickens

Natural Resistance-Associated Macrophage Protein 1 (NRAMP1) is a gene that regulates the body's resistance to illness. The genetic diversity of Kampung and KUB chicken population in Lombok island West Nusa Tenggara province was investigated based on g.3768T&gt;C loci of NRAMP1 gene. Experimental animal consisted of 105 KUB and 67 Kampung chickens. The NRAMP1 gene polymorphisms in both population were identified using PCR-RFLP method. Genetic parameters of g.3768T&gt;C loci were calculated using PopGene32. In this study, the locus g.3768T&gt;C of the NRAMP1gene found three genotypes (TT, CT, CC) with the frequency of the C allele was higher than the T allele, respectively 0.709 and 0.210 in Kampung chicken, and 0.738 and 0.262 in KUB chicken. The mean value of observed heterozygosity (Ho) and expected heterozygosity (He) of g.3768T&gt;C loci in both populations revealed low to medium genetic diversity, with the values 0.222 and 0.400, respectively. The mean value of observed heterozygosity is lower than expected, indicating that the population is heading towards a heterozygosity deficit and proving that the two populations are not in Hardy-Weinberg equilibrium. The mean PIC value of the NRAMP1 gene (g.3768T&gt;C) in both chicken population was 0.319 and classified as fairly informative (0.50 &gt; PIC &gt; 0.25). Meanwhile, the value of the genetic differentiation index (Fst) for Kampung and KUB chicken population were 0.385 and 0.433, indicating that there is differentiation between two chicken population at the observed loci.

Association of Polymorphism with Periodontitis and Salivary Levels of Hypoxia-Inducible Factor-1α.

This investigation aims to investigate the association between HIF-1α genetic polymorphism and periodontitis and examine and contrast the levels of HIF-1α present in the saliva of subjects afflicted with periodontitis and in the control group. Additionally, this study aims to establish diagnostic proficiency of this biomarker in distinguishing between periodontal health and disease. This study entailed the collection of venous blood samples and unstimulated saliva samples from a total of 160 participants, encompassing 80 individuals diagnosed with periodontitis and 80 periodontitis-free individuals. The periodontal parameters were evaluated, involving the measurement of clinical attachment loss, the probing pocket depth, and the bleeding on probing percentage. Subsequently, genetic analysis of HIF-1α using polymerase chain reaction (PCR) technique, DNA sequencing, and enzyme-linked immunosorbent assays was conducted. The genetic analysis of 352 bp of the HIF-1α gene revealed the presence of 66 single-nucleotide polymorphisms (SNPs) in control samples, whereas 78 SNPs were found in periodontitis sample. The nucleotide A was replaced with a C nucleotide at position 207 of the amplified PCR fragments. The homozygous AA pattern was predominant in the control group, with significant differences between the two groups. In contrast, the homozygous CC pattern was more dominant in the periodontitis group, with significant differences between the two groups. The analysis of Hardy-Weinberg equilibrium for the comparison between the observed and the expected genotypes showed significant differences between the observed and the expected values in the control and periodontitis groups, as well as the total sample. The highest mean values of the measured periodontal parameters were found in the periodontitis group (clinical attachment loss = 4.759, probing pocket depth = 4.050, and bleeding on probing = 30.950) with statistically significant differences between the groups. The periodontitis group showed significantly higher salivary HIF-1α levels compared to control group (p < 0.001). Besides, HIF-1α is a good biomarker in distinguishing between periodontal health and periodontitis. rs1951795 SNP of HIF-1α has no significant impact on the progression of periodontitis and the salivary level HIF-1α. Periodontitis results in a notable elevation in HIF-1α salivary levels, with an outstanding diagnostic ability to distinguish between periodontitis and periodontal health.

Consanguinité et son impact sur la santé et la dynamique du génome : Un exemple de la Tunisie

The genetic disease spectrum in Tunisia arises from the founder effect, genetic drift, selection, and consanguinity. The latter represents a deviation from panmixia, characterized by a non-random matrimonial choice that may be subject to several rules, such as socio-cultural, economic, or other factors. This shifts the genetic structure away from the Hardy-Weinberg equilibrium, increasing homozygous genotypes and decreasing heterozygotes, thus raising the frequency of autosomal recessive diseases. Similar to other Arab populations, Tunisia displays high consanguinity rates that vary geographically. Approximately 60% of reported diseases in Tunisia are autosomal recessive, with consanguinity possibly occurring in 80% of families for a specific disease. In inbred populations, consanguinity amplifies autosomal recessive disease risk, yet it does not influence autosomal dominant disease likelihood but rather impacts its phenotype. Consanguinity is also suggested to be a major factor in the homozygosity of deleterious variants leading to comorbid expression. At the genome level, inbred individuals inherit homozygous mutations and adjacent genomic regions known as runs of homozygosity (ROHs). Short ROHs indicate distant inbreeding, while long ROHs refer to recent inbreeding. ROHs are distributed rather irregularly across the genome, with certain short regions featuring an excess of ROH, known as ROH islands. In this review, we discuss consanguinity's impact on population health and genome dynamics, using Tunisia as a model.

Effect of PEAR1, PTGS1 gene polymorphisms on the recurrence of aspirin-treated patients with ischemic stroke in the Han population of China: A 4-year follow-up study.

Platelet endothelial aggregation receptor 1 (PEAR1) and prostaglandin endoperoxide synthase 1 (PTGS1) polymorphisms can affect laboratory aspirin resistance. However, the impact of genetic polymorphisms on the recurrence of ischemic stroke (IS) patients treated with aspirin is not fully understood. This study aimed to examine the relationship between gene polymorphisms of PEAR1 and PTGS1 and IS recurrence in patients treated with aspirin. Peripheral blood samples were collected from 174 patients with nonrecurrent IS and 34 with recurrent IS after aspirin treatment. Follow-up was performed on all patients. PEAR1 rs12041331 and PTGS1 rs10306114 polymorphisms were determined using the PCR fluorescence probe method. And the correlations of them with the clinical characteristics were examined by multivariable logistic regression analysis. The distribution frequencies of PEAR1 rs12041331 and PTGS1 rs10306114 genotypes were in Hardy-Weinberg equilibrium, and there was no significant difference in the distribution of PEAR1 rs12041331 polymorphism. Compared to the nonrecurrent group, the AA genotype of the PTGS1 polymorphism was more frequent in the recurrent group (59.77% vs 35.29%, P = .003), and the A allele also showed a higher frequency than the G allele in the recurrent group (P = .001). Multivariable logistic regression analysis showed that smoking (OR = 5.228, 95% CI: 1.938-14.102, P = .001), coronary heart disease (OR = 4.754, 95% CI: 1.498-15.089, P = .008), and the polymorphism at PTGS1(A>G) AA/AG + GG (OR = 2.955, 95% CI: 1.320-6.616, P = .008) were independently associated with IS recurrence in Chinese patients. Our findings suggested that PTGS rs10306114 polymorphisms should receive more attention in the use of aspirin in patients with IS.

Genetic Analysis of TPM1 Gene Polymorphism (rs11071720) in Patients with Non-Syndromic Cleft Lip/Palate in the South Indian Population. A Case Control Study

The aim of this study was to find out if there was an association between TPM1 gene polymorphism (rs11071720) and non-syndromic cleft lip and palate in humans. Twenty five patients with non-syndromic cleft lip and palate (NSCL/P) and twenty five healthy patients as controls were enrolled in the study. Whole blood drawn from the participants was used to obtain genomic DNA. Sequence specific primers were used to amplify the region spanning the polymorphic site of the TPM1 gene using polymerase chain reaction (PCR). The genotype of the subjects was identified employing the RFLP technique. The genotype and allele frequency distributions in the non-syndromic cleft lip and cleft palate patients and control groups were compared using Chi-square test. In the NSCL/P, the genotype in the order from highest to lowest frequency was TC (48%), followed by CC (32%) and TT (20%). Although the genotype frequency of the case and the control groups were found to be in agreement with Hardy Weinberg Equilibrium, the genotype frequencies TC, CC and TT of the polymorphism (rs11071720) among the two groups were not statistically significant which was evident from the p-value 0.8472. No significant association was found between TPM1 gene (rs11071720) polymorphism and NSCL/P.

Vascular endothelial growth factor I/D variant and postmenopausal osteoporosis risk in the Turkish population

Introduction Postmenopausal osteoporosis (PMOP) is a common metabolic bone disorder manifested by low bone mineral density and increased fracture risks in postmenopausal women. Vascular endothelial growth factor (VEGF) has been shown to play an important role in bone formation. In this study, we investigated the potential association between the VEGF insertion/deletion (I/D) variant (rs35569394) and PMOP in a cohort of postmenopausal Turkish women. Methods This study included 300 women, including 150 PMOP patients and 150 healthy postmenopausal women. A T score was used in the diagnosis of OP. DNA was extracted from all subjects. The VEGF I/D polymorphism was analyzed by the PCR method. The Hardy-Weinberg equilibrium (HWE) test and odds ratio (OR) were analyzed, considering CI 95% and p ≤ 0.05. Results The mean age of patients aged between 40 and 74 was 60.32 ± 8.65. The frequency of the I/I, I/D, and D/D genotypes was 7.34% versus 6.66%; 67.33% versus 65.34%; and 25.33% versus 28%, in patients and the control group, respectively. The allele frequencies were I: 41% (patients) and 39.4% (controls); D: 59% (patients) and 60.66% (controls). There was no statistically significant difference in the VEGF − 2549 I/D allele and genotype distribution between patients with PMOP and control subjects (p = 0.349, p = 0.864, respectively). Conclusion Our results showed that the VEGF I/D variant was not a significant factor in the development of PMOP in a Turkish population sample. These findings need confirmation in other ethnic populations.

Genetic variation in two candidate genes against gastrointestinal parasites in Colombian Hair Sheep

Objective. To characterize two SNP-type genetic polymorphisms in the GLI1 (rs411868094) and IL20RA (rs419463995) genes, candidates for resistance against gastrointestinal parasites in two biotypes of Colombian hair sheep. Materials and methods. From the DNA bank of the Animal Genetics Laboratory of the University of Sucre, 167 samples, belonging to the Ethiopian (n=94) and Sudan (n=73) biotypes, were analyzed by PCR and subsequent bidirectional sequencing of two SNPs in the GLI1 (T&gt;G) and IL20RA (G&gt;A) genes. Allelic and genotypic frequencies, observed (Ho) and expected (He) heterozygosity, F index, and Hardy-Weinberg equilibrium deviations (EHW) were calculated using the GENALEX version 6.5 program. Results. For the GLI1 locus, the mean genotypic frequencies were 0.155±0.07, 0.370±0.07, and 0.475±0.07 for GG, GT, and TT, respectively. In the Ethiopian biotype, the highest frequencies of the genotype of interest (GG) were found. For the IL20RA locus, the AA and AG genotypes had similar and the highest frequency (0.465±0.03) compared to the GG genotype (0.110±0.01). The genotype of interest at this locus (AA) was the most frequent in both OPC biotypes. Conclusions. The alleles of interest associated with low FEC had a low frequency for the GLI1 gene, but a high frequency for IL20RA. The Ethiopian OPC biotype showed the highest frequencies of the genotypes of interest.

Association analysis between Acetyl-Coenzyme A Acyltransferase-1 gene polymorphism and growth traits in Xiangsu pigs.

Acetyl-Coenzyme A Acyltransferase-1 (ACAA1) is a peroxisomal acyltransferase involved in fatty acid metabolism. Current evidence does not precisely reveal the effect of the ACAA1 gene on pig growth performance. The present study assessed the mRNA expression levels of the ACAA1 gene in the heart, liver, spleen, lung, kidney of 6-month-old Xiangsu pigs and in the longissimus dorsi muscle at different growth stages (newborn, 6months and 12months of age) using RT-qPCR. The relationship between single-nucleotide polymorphisms (SNPs) of ACAA1 gene and growth traits in 6-month-old and 12-month-old Xiangsu pigs was investigated on 184 healthy Xiangsu pigs using Sanger sequencing. The ACAA1 gene was expressed in heart, liver, spleen, lung, kidney, and longissimus dorsi muscle of 6-month-old pigs, with the highest level of expression in the liver. ACAA1 gene expression in the longissimus dorsi muscle decreased with age (p < 0.01). In addition, four SNPs were identified in the ACAA1 gene, including exon g.48810 A>G (rs343060194), intron g.51546 T>C (rs319197012), exon g.55035 T>C (rs333279910), and exon g.55088 C>T (rs322138947). Hardy-Weinberg equilibrium (p > 0.05) was found for the four SNPs, and linkage disequilibrium (LD) analysis revealed a strong LD between g.55035 T>C (rs333279910) and g.55088 C>T (rs322138947) (r 2 = 1.000). Association analysis showed that g.48810 A>G (rs343060194), g.51546 T>C (rs319197012), g.55035 T>C (rs333279910), and g.55088 C>T (rs322138947) varied in body weight, body length, body height, abdominal circumference, leg and hip circumference and living backfat thickness between 6-month-old and 12-month-old Xiangsu pigs. These findings strongly demonstrate that the ACAA1 gene can be exploited for marker-assisted selection to improve growth-related phenotypes in Xiangsu pigs and present new candidate genes for molecular pig breeding.

A Pilot Study for Drug-Resistant Tuberculosis Disease Patients Suggests that A964G (rs153109)—Interleukin 27 may be Protective

Abstract Context: Variation in the transcription of host genes of inflammatory cytokines may underscore variation in their production. Thus, the host-immune status plays a vital role in determining the fate of the invading bacilli. Materials and Methods: Two hundred consenting volunteers and drug-resistant tuberculosis (DR-TB) patients had their blood samples amplified for the A964G (rs153109) gene. The amplicons were digested using the Xhol enzyme for genotyping purpose. Results: Among the cases: AA (homozygous wild type; n = 33), AG (heterozygous wild type; n = 36), GG (homozygous mutant, n = 10), A (wild allele, n = 102), and T (mutant allele; n = 66); while among the healthy volunteers: AA (homozygous wild type; n = 20), AG (heterozygous wild type; n = 40), GG (homozygous mutant, n = 4) A (wild allele, n = 80), and T (mutant allele; n = 48). The Hardy Weinberg Equilibrium (HWE) assessment of the samples from the control participants was statistically significant (P = 0.015). Nevertheless, the assessment of the association between the genotypes and the phenotypes assessed revealed that the healthy volunteers had more (twice) heterozygous genotype (AG) (crude statistics: P =0.045, OR = 1.99 (1.02–3.90)) when compared to the DR-TB patients. Conclusion: Although the AG genotype of A964G (rs153109)—Interleukin 27 gene may have a protective role against the development of MTB/XPERT positive DR-TB disease, the significant HWE finding among the genotype from the samples of the healthy volunteers suggests that this current result may be a false positive finding.

Prolactin gene (C576A) polymorphism is associated with milk production performance in crossbred Anglo-Nubian dairy goats

Crossbred Anglo-Nubian goats (Anglo-Nubian × native goat breeds), are valued for exceptional milk production and adaptability. In-depth research on these goats is imperative to propel advancements in dairy goat breeds and enhance milk production efficiency within the region. The present study aims to assess polymorphism in prolactin (C576A) gene and determine the influence of different prolactin (PRL) genotypes to milk yield performance in crossbred Anglo-Nubian dairy goats raised from Awang, Opol, Misamis Oriental and Talay, Dumaguete City, Negros Oriental. Genomic DNA was extracted from hair follicles using commercial DNA extraction kit and PCR-RFLP was performed for the genotyping of the C576A polymorphism located in exon 5 of goats’ prolactin gene using Eco241 restriction enzyme. Genotypic frequencies of 0.56 for AA, 0.44 for AB, while allelic frequencies of 0.78 for A, and 0.22 for B were recorded. All populations followed the Hardy–Weinberg principle, except for dairy goats from Farm A located in Opol, Misamis Oriental. A two-way factorial (2 × 4) in a Randomized Complete Block Design was used to evaluate the relationship between genotypes and milk yield performance. AB genotype goats produced significantly higher milk yield traits (average daily milk yield and total milk production) than AA genotype, an indication that the polymorphism in the caprine PRL (C576A) gene influenced milk yield performance in the population of studied crossbred Anglo-Nubian goats. These results have to be validated in other dairy goat breeds.