Hardy-Weinberg Research Articles

Patterns of KIR-genotypes in women with preimplantation losses after assisted reproductive technologies

Aim. To analyze the frequency and distribution of KIR genotypes in women with repeated preimplantation losses during ARTs compared to women with control group. Methods. DNA isolation from leukocytes by the salting method, PCR-SSP, agarose gel electrophoresis; methods of statistical analysis. Results. The molecular genetic determination of KIR genes in the group of women with recurrent implantation failures and in the control group of women was performed. The frequency and distribution of KIR genotypes in the study groups were determined. In women with RIF, a slightly shifted distribution of the frequency of KIR genotypes was found, towards the homozygous genotype by haplotype "A", the frequency of which was almost half of all identified genotypes (42.86 %). The distribution and frequency of KIR genotypes in the control group was normal and described by the Hardy-Weinberg principle. A comparative analysis of the study groups using statistical methods showed a significantly higher frequency of the KIR-AA genotype (χ2=8.875; p<0.005) in the group of women with RIF compared to the control group of women. The calculation of the odds ratio indicates a 2-fold increase of risk for recurrent implantation failures after ARTs (OR=1.94; CI 95 %: 1.25–3.00) in women with the KIR-AA genotype. Conclusions. We regard the KIR-AA genotype as a significant risk factor for preimplantation loss. KIR genotyping is considered an important molecular genetic test for determining the risk of fetal rejection by the maternal immune system, which will help to correctly direct treatment interventions to keep the pregnancy alive.

Genetic differentiation and heavy metal pollution influence on horseshoe crab Tachypleus gigas populations in Peninsular Malaysia: A comprehensive allozyme analysis

This study aimed study the genetic diversity and differentiation of Asian horseshoe crab Tachypleus gigas (Müller, 1785) populations across three distinct locations in Peninsular Malaysia: Kampung Pasir Puteh (KPPuteh), Kuala Sungai Ayam (KSAyam), and Kampung Pulau Sayak (KPSayak). A total of 28 individuals were collected, and their genetic structure was analyzed using starch gel electrophoresis. The study employed multiple buffer systems optimized for separating 20 different enzymes, each contributing to understanding the genetic variability within and between populations. The findings of this study, which revealed significant genetic differentiation, particularly between populations in polluted and less impacted environments, as reflected by high FST values and distinct clustering in the UPGMA dendrogram, are of paramount importance. The results indicate that environmental factors, especially metal-polluted sites at KPPuteh and KSAyam, have played a critical role in shaping the genetic structure of these populations. Populations from the two polluted sites, exhibited higher genetic diversity and greater deviations from Hardy–Weinberg equilibrium, suggesting localized selection pressures. Conversely, from a less polluted site, the unpolluted site at KPSayak population showed lower genetic variability and was genetically distinct from the others. These findings underscore the importance of considering environmental influences in conservation strategies for T. gigas, highlighting the need for site-specific management to preserve genetic diversity and ensure long-term survival of the species.

Accessing the genetic diversity of natural populations of Acrocomia aculeata (Arecaceae) through microsatellites

Acrocomia aculeata holds cultural and economic importance as the second-largest producer of oleaginous fruits in arid and semi-arid regions, with potential for exploitation as an agricultural crop. It is a tropical arborescent species distributed throughout tropical and subtropical Americas, with a significant occurrence of natural populations in the Cerrado biome. Its broad distribution across various landscapes is supported by a mixed reproductive system, diverse pollination strategies, and resilience to environmental stressors. Despite its resilience in fragmented habitats, anthropogenic habitat fragmentation generally harms populations, affecting gene flow and genetic diversity. In this context, this study aimed to assess genetic diversity and structure of natural populations of A. aculeata from northern Minas Gerais using microsatellites. The five natural populations were named according to the municipality where they were collected, being them Espinosa, Mirabela, Claro dos Poções, Grão Mogol, and Itacambira. The results revealed that four SSR loci amplified 46 different alleles, totaling 1352 alleles. The loci showed significant deviations from Hardy-Weinberg Equilibrium, with a mean f of 0.288. Among the populations analyzed, ITA was the most genetically diverse, while ESP was the least diverse. As subpopulations, they displayed high genetic structure, with a mean FST of 0.329 and FIT of 0.484. The study suggests the natural populations of Macaw palm in northern Minas Gerais that can be used for germplasm banks, and the ones that requires human intervention to restore genetic diversity.

Association of HOTAIR rs7958904 Polymorphism with Cervical Cancer Risk.

Cervical cancer (CC) has been the prominent cause of cancer-associated fatalities among women in developing countries. In terms of occurrence and mortality, it is ranked second in Bangladesh. Although different genetic polymorphisms linked with this cancer have been investigated over time, the association between the HOTAIR rs7958904 variant and cervical cancer is being reported for the first time in Bangladeshi women. RT-PCR-based TaqMan assay was employed to perform this case-control study on 200 cervical cancer patients and 148 healthy volunteers. Both cases and controls had average ages of 57.5 and 52.5years, respectively. According to Hardy-Weinberg equilibrium, the rs7958904 allele of HOTAIR gene pretended no deviation for both cases and control groups. The genotyping results showed that rs7958904 has a significant correlation to the development of cervical cancer in different genetic association models, such as co-dominant 1 (CC vs. GG: OR = 1.67, p = 0.0435), co-dominant 2 (CC vs. GG: OR = 3.13, p = 0.0006), co-dominant 3 (CC vs. CG: OR = 1.88, p = 0.0384), dominant (CG + CC vs. GG: OR = 1.98, p = 0.004), recessive (CC vs. GG + CG: OR = 2.25, p = 0.005), and allele model (C vs. G: OR = 1.70, p = 0.0006). In conclusion, the HOTAIR rs7958904 variant has a substantial role in cervical cancer development in Bangladeshi women. Further functional studies with a larger population size are required to support our findings.

Study on Single Nucleotide Polymorphism of LAP3 Gene and Its Correlation with Dairy Quality Traits of Gannan Yak.

This study explored the polymorphism of the leucine aminopeptidase (LAP3) gene and its relationship with milk quality characteristics in Gannan yak. A cohort of 162 Gannan yak was genotyped utilizing the Illumina Yak cGPS 7K BeadChip, and the identified single nucleotide polymorphisms (SNPs) were evaluated for their association with milk protein, casein, lactose, and fat concentrations. The results showed that four SNPs (g.4494G > A, g.5919A > G, g.8033G > C, and g.15,615A > G) in the LAP3 gene exhibited polymorphism with information content values of 0.267, 0.267, 0.293, and 0.114, respectively. All four SNPs were in Hardy-Weinberg equilibrium (p > 0.05). The g.4494G > A and g.5919A > G SNPs were significantly associated with protein content (p < 0.05), with homozygous genotypes showing significantly higher protein content than heterozygous genotypes (p < 0.05). The g.8033G > C SNP was significantly associated with casein content, protein content, non-fat solids, and acidity (p < 0.05), with the CC genotype having significantly higher casein, protein, and non-fat solids content than the GG and GC genotypes (p < 0.05). The g.15,615A > G SNP was significantly associated with average fat globule diameter (p < 0.05). In general, the mutations within the LAP3 gene demonstrated a positive impact on milk quality traits in Gannan yak, with mutated genotypes correlating with enhanced milk quality. These results indicate that the LAP3 gene could be a significant or candidate gene affecting milk quality traits in Gannan yak and offer potential genetic markers for molecular breeding programs in this species.

Candidate SNPs associated with anxiety and depression in children and adolescents in the USH1C gene

Introduction: Anxiety and depression in children and adolescents are growing concerns globally, with significant rates of diagnosis across diverse populations. According to the Centers for Disease Control and Prevention (CDC), approximately 7.1% of children aged 3 to 17 years in the United States have been diagnosed with anxiety, and 3.2% with depression. The aim of this study is to analyze the correlation between SNPs in the USH1C gene and predisposition to anxiety and depression in children and adolescents from specific populations.Methods: Genotypes from the 1000 Genomes Project were used to evaluate SNPs in Southeast Asian and European populations. Linkage disequilibrium (LD) analysis was performed using VcfTools and the biological effects of the SNPs were assessed using the Variant Effect Predictor (VEP).Results: Two SNPs, rs4757538 and rs16934376, were identified, which showed strong LD with SNP rs79878474 in South Asian populations (r² &gt; 0.7), suggesting their possible association with anxiety and depression. Allele frequencies varied significantly between populations. Hardy-Weinberg equilibrium analysis showed significant imbalance at the global level, but not within individual populationsConclusions: The analyzed SNPs might be related to predisposition to anxiety and depression in specific populations. These findings underline the importance of considering genetic diversity in future studies and developing personalized interventions to address these disorders in children and adolescents

PSX-7 Heritability estimates for longevity-related traits in U.S. Katahdin ewes

Abstract Genetic selection for increased ewe longevity can directly contribute to improved flock profitability and welfare. Therefore, this study aimed to estimate heritabilities for eight longevity-related traits in 12,149 Katahdin ewes. The ewes were daughters of 1,157 sires and 6,147 dams and were born between 1989 and 2020 in 58 flocks located across the U.S. The National Sheep Improvement Program provided the data. Age at last lambing (ALL); productive life (PL; number of days between the first and last lambing), total number of litters (TLI), lambs born (TNB), and lambs weaned (TNW) over the lifetime of the ewe; total litter weight at lambing (TLB) and weaning (TLW) over the lifetime of the ewe, and TLW divided by the weight of the ewe adjusted for 120 d (TLWadj) were evaluated (Table 1). Body weights (BW) at lambing and weaning (WW) were adjusted for sex effect, while WW was also adjusted for 60 d old. Ewes with lambing interval and age at the first lambing greater than 720 d and 1,095 d, respectively, were excluded. Moreover, only flocks that reported lambing records across at least 7 consecutive years and an average of 20 or more lambing records over the yr were evaluated. Fixed effects of contemporary group (flock, year, and season of birth of the ewe), the combined effect of the birth type and rearing type of the ewe, and age class at first lambing, as well as the animal random effect, were included in the animal model fitted. Contemporary groups with less than three ewes were excluded. Moreover, we excluded records deviating ± ± 3.0 SD from the mean. Variance components were estimated by restricted maximum likelihood based on pedigree (by fitting the A matrix) and genomic information [by fitting an H matrix including pedigree and genomic relationships from 10,032 animals genotyped with a 50K single nucleotide polymorphisms (SNP) chip]. The criteria used to exclude SNP were MAF &amp;lt; 0.05, call rate &amp;lt; 0.95 (for both SNP and animals), and a maximum difference of 0.15 between the observed and expected heterozygosity (Hardy-Weinberg equilibrium). After quality control, 31,182 SNP were used for the analyses. The analyses were performed using the BLUPF90+ programs. The pedigree-based heritability estimates were: ALL (0.10 ± 0.017), PL (0.11 ± 0.023), TLI (0.10 ± 0.017), TNA (0.11 ± 0.017), TNW (0.11 ± 0.018), TLB (0.12 ± 0.020), TLW (0.10 ± 0.024), and TLWadj (0.07 ± 0.031). The genomic-based heritability estimates were: ALL (0.13 ± 0.018), PL (0.14 ± 0.024), TLI (0.13 ± 0.018), TNB (0.13 ± 0.018), TNW (0.14 ± 0.018), TLB (0.15 ± 0.021), TLW (0.11 ± 0.024), and TLWadj (0.07 ± 0.032). The relative standard error (RSE) of the estimates obtained with the A matrix ranged from 15.5% (TNB) to 44.3% (TLWadj) and from 12.9% (TNW) to 45.7% (TLWadj) when fitting the H matrix. In conclusion, longevity-related traits in U.S. Katahdin ewes are heritable, and estimates are slightly greater (with reduced RSE) when incorporating genomic information to estimate variance components.

Prevalence Estimates and Genetic Diversity for Autosomal Dominant Retinitis Pigmentosa Due to RHO, c.68C>A (p.P23H) Variant

ObjectiveTo provide the most up-to-date clinical prevalence estimate for autosomal dominant retinitis pigmentosa (adRP) patients due to RHO c.68C>A, (p.P23H) in the United States, supported by two independent approaches; literature based meta-analysis of reported patients and population genetics modeling. DesignSystematic review and meta-analysis plus population genetics modeling. MethodsSystematic review of the literature describing RP patients attributed to RHO variants was conducted to support a meta-analysis used to estimate the clinical prevalence of the RHO P23H patients diagnosed in the US. In parallel, large-scale genetic diversity studies describing the US population and non-European cohorts of the Americas (PAGE II), were evaluated to ascertain the allele frequencies of variant RHO c.68C>A, (p.P23H). The genetic prevalence for variant RHO c.68C>A, (p.P23H) was calculated using Hardy-Weinberg equilibrium. Further demographic data, including age and average age of onset for visual impairment were incorporated into a basic distribution model to estimate clinical prevalence of genetically predisposed persons. ResultsThe estimated clinical prevalence of adRP due to RHO P23H based on literature review was approximately 2000-3000 patients. In comparison the genetic prevalence of persons with RHO c.68C>A, (p.P23H) in the United States was an estimated 6176 (90% CI: 3333-11398) and only half of them are expected to cluster with European genetic ancestry. This variant was found enriched in subgroups of African American or other non-European biogeographic ancestries. Of the estimated 6200 persons carrying this variant in the US, ∼3500 (estimate range: 1900-6500) are expected to show clinical signs of visual impairment as modeled by average age of onset previously reported for patients with this variant. ConclusionsWe utilized two independent approaches to estimate the total number of adRP patients due to RHO c.68C>A, (p.P23H) in the United States; systematic literature review based meta-analysis and population genetics modeling. Both approaches yielded similar, overlapping estimates of adRP patients due to RHO P23H. However, comparison of these estimates provides some indication for a diagnosis gap. Unexpectedly, this variant is present at relatively higher frequency in some predominantly non-European genetic ancestries in the US. While this genetic analysis supports our estimates of clinical prevalence of adRP due to RHO P23H in the United States, it also has implications for diagnosing potential adRP patients due to this variant, raising questions of genotype-phenotype correlation and access to genetic testing.

Association of VDR Polymorphisms with Muscle Mass Development in Elite Young Soccer Players: A Pilot Study.

The vitamin D receptor (VDR) is an important candidate gene in musculoskeletal phenotypes. Polymorphisms in the VDR have been previously associated with several pathologies and muscular strength in athletes and elderly people; however, the literature reported contradictory results. The object of this research was to verify the association between the most studied VDR variants (rs2228570, rs7975232, and rs1544410) and the increase in muscle mass in elite young soccer players. A sample of 55 soccer players (15-18 years old) from a professional team were selected for this study. DNA was extracted by the salting-out method, and polymorphisms were genotyped by PCR-RFLP, followed by 2% agarose gel electrophoresis. To test the effect of the three SNPs (single nucleotide polymorphisms), a logistic regression analysis was applied. The body composition determination was carried out through the skinfold thickness method, and the muscular area of the arm and lower limb were calculated using the Frisancho formula. All three polymorphisms met the Hardy-Weinberg equilibrium (p > 0.05) and their frequencies fell within the worldwide variability. A significant correlation between rs1544410 and the increase in calf muscle mass was observed. Individuals carrying the A allele showed higher calf muscular mass than those carrying the G allele (p = 0.034). Moreover, a haplotype analysis applied to the two SNPs in linkage disequilibrium (rs7975232 and rs1544410) showed that the AG haplotype appeared negatively correlated to the calf muscle area. In conclusion, we confirm an association between VDR polymorphisms and muscular mass that could encourage the genetic screening of the VDR gene to identify a potential risk of injury and for individual nutritional interventions.

Semi-supervised machine learning method for predicting homogeneous ancestry groups to assess Hardy-Weinberg equilibrium in diverse whole-genome sequencing studies

Large-scale, multi-ethnic whole-genome sequencing (WGS) studies, such as the National Human Genome Research Institute Genome Sequencing Program's Centers for Common Disease Genomics (CCDG), play an important role in increasing diversity for genetic research. Before performing association analyses, assessing Hardy-Weinberg equilibrium (HWE) is a crucial step in quality control procedures to remove low quality variants and ensure valid downstream analyses. Diverse WGS studies contain ancestrally heterogeneous samples; however, commonly used HWE methods assume that the samples are homogeneous. Therefore, directly applying these to the whole dataset can yield statistically invalid results. To account for this heterogeneity, HWE can be tested on subsets of samples that have genetically homogeneous ancestries and the results aggregated at each variant. To facilitate valid HWE subset testing, we developed a semi-supervised learning approach that predicts homogeneous ancestries based on the genotype. This method provides a convenient tool for estimating HWE in the presence of population structure and missing self-reported race and ethnicities in diverse WGS studies. In addition, assessing HWE within the homogeneous ancestries provides reliable HWE estimates that will directly benefit downstream analyses, including association analyses in WGS studies. We applied our proposed method on the CCDG dataset, predicting homogeneous genetic ancestry groups for 60,545 multi-ethnic WGS samples to assess HWE within each group.

Estimating carrier rates and prevalence of porphyria-associated gene variants in the Chinese population based on genetic databases

Porphyria is a group of rare metabolic disorders caused by mutations in the genes encoding crucial enzymes in the heme biosynthetic pathway. However, the lack of comprehensive genetic analysis of porphyria patients in the Chinese population makes identifying and diagnosing carriers of the condition challenging. Using the ChinaMAP database, we determined the frequencies of P/LP porphyria-associated gene variants according to the ACMG guidelines. We also calculated the carrier rates and prevalence of each type of porphyria in the Chinese population under Hardy–Weinberg equilibrium. Compared with the variants in the gnomAD database, the genetic spectrum of porphyria-related P/LP variants in the Chinese population is distinct. In the ChinaMAP database, we identified 23 variants. We estimated the carrier rates for autosomal dominant porphyrias (AIP, HCP, VP, PCT) in the Chinese population to be 1/1059, 1/1513, 1/10588, and 1/1765, respectively. For autosomal recessive porphyrias (ADP, EPP, HEP, CEP), the estimated carrier rates were 1/5294, 1/2117, 1/1765, and 1/2647, respectively, with predicted prevalence rates of 8.92 × 10−9, 7.51 × 10−5, 8.02 × 10−8, and 3.57 × 10−8, respectively. Notably, 12 of the variants we identified were unique to the Chinese population. The predicted prevalence rate of EPP was the highest among the various types of porphyria in the Chinese population, while the others were moderate to low. This is the first comprehensive genetic study on porphyria in the Chinese population. Clarifying the genetic characteristics of various porphyria types among the Chinese population provides scientifically sound reference data for both research and genetic screening to identify porphyria carriers.

Concurrent detection of the mitochondrial DNA copy number and the +35G/C polymorphism in the mitochondrial transcription factor A gene in endometriosis

Background and aimEndometriosis is a chronic gynecological inflammatory disease. The mitochondrial DNA copy number (mtDNA CN) and mitochondrial transcription factor A (TFAM) are known to contribute to human pathologies and cancer. Therefore, this study aims to reveal the association of mtDNA CN and TFAM+35G/C (rs1937) polymorphism with the risk of endometriosis in Egyptian females. Materials and methodsThis case-control study involved 160 Egyptian females divided into two groups: 80 endometriosis cases and 80 controls. The mtDNA CN was quantified using a real-time quantitative PCR (qPCR), and the TFAM +35G/C SNP (rs1937) was genotyped using the TaqMan allelic discrimination assay technique. ResultsThe mtDNA CN was markedly decreased in endometriosis cases compared to controls (P < 0. 001). TFAM rs1937 genotypes and allele distributions were all in Hardy-Weinberg equilibrium. The GC genotype and the ‘C’ allele frequency (P = 0.015 and P = 0.017, respectively) were substantially greater in endometriosis cases. ConclusionDecreased mtDNA CN and the GC genotype of TFAM +35G/C polymorphism were significantly associated with the risk of endometriosis in Egyptian females.

The prognostic difference study on the individualized clopidogrel administration in Hmong and Dong patients based on the CYP2C19 gene polymorphism after percutaneous coronary intervention.

This study explored the distribution characteristics of CYP2C19 gene polymorphism among Hmong and Dong patients in the Qiandongnan region of Guizhou province after percutaneous coronary intervention (PCI). The aim was to assess the clinical impact of individualized clopidogrel administration based on CYP2C19 genotypes. A total of 208 patients were classified into ultra-fast, fast, intermediate, and slow metabolic groups. They were randomly assigned to clopidogrel individualized administration (IA) or conventional treatment (CA) groups. Patients were followed for 6 months to evaluate major adverse cardiovascular events (MACE) and adverse reactions. The CYP2C19 genotype distribution was in Hardy-Weinberg equilibrium, showing consistency in the population. While no significant ethnic differences were found in genotype and metabolic distribution, allele distribution varied, with Hmong patients exhibiting a higher proportion of CYP2C19*1 alleles than Dong patients. Following individualized administration, the IA group demonstrated lower incidences of non-fatal myocardial infarction and emergency revascularization compared to the CA group. Bleeding events were higher in the IA group, but the total MACE incidence was lower. No statistical difference in MACE and adverse drug reactions (ADR) was observed in the CA group across metabolic types, but MACE incidence was higher in intermediate and slow metabolic groups. In the IA group, no significant difference in MACE was noted among metabolic types, but ADR incidence varied significantly, particularly in dyspnea. The study highlighted significant CYP2C19 allele distribution differences between Hmong and Dong patients post-PCI in Qiandongnan. Patients with slow metabolic profiles demonstrated higher MACE incidence with conventional clopidogrel dosage, whereas CYP2C19-guided therapy reduced MACE without increasing bleeding risk. These findings supported clinical individualized clopidogrel administration in post-PCI patients in the Qiandongnan region, contributing to rational clopidogrel use.

High Resolution Class I HLA -A, -B, and -C Diversity in Eastern and Southern African Populations.

Africa remains significantly underrepresented in high-resolution Human Leukocyte Antigen (HLA) data, despite being one of the most genetically diverse regions in the world. This critical gap in genetic information poses a substantial barrier to HLA-based research on the continent. In this study, Class I HLA data from Eastern and Southern African populations were analysed to assess genetic diversity across the region. We examined allele and haplotype frequency distributions, deviations from Hardy-Weinberg Equilibrium (HWE), linkage disequilibrium (LD), and conducted neutrality tests of homozygosity across various populations. Additionally, the African HLA data were compared to those of Caucasian and African American populations using the Jaccard index and multidimensional scaling (MDS) methods. The study revealed that South African populations exhibited 50.4% more genetic diversity within the Class I HLA region compared to other African populations. Zambia showed an estimated 36.5% genetic diversity, with Kenya, Rwanda and Uganda showing 35.7%, 34.2%, and 31.1%, respectively. Furthermore, an analysis of in-country diversity among different tribes indicated an average Class I HLA diversity of 25.7% in Kenya, 17% in Rwanda, 2.8% in South Africa, 13.6% in Uganda, and 6.5% in Zambia. The study also highlighted the genetic distinctness of Caucasian and African American populations compared to African populations. Notably, the differential frequencies of disease-promoting and disease-preventing HLA alleles across these populations emphasize the urgent need to generate high-quality HLA data for all regions of Africa and its major ethnic groups. Such efforts will be crucial in enhancing healthcare outcomes across the continent.

Investigating the impact of a novel GHRHR gene variant on growth traits in Damascus goats

This study investigates the genotype and allele frequencies of three novel SNP loci (c.4218 T>G, c.2203 T>C, and c.7966 A>C) in the GHRHR gene within the Damascus goat breed and their associations with growth traits. The genotype frequencies for c.4218 T>G were 0.65 (TT), 0.15 (TG), and 0.20 (GG), with allele frequencies of 0.73 (T) and 0.27 (G), showing a significant deviation from Hardy-Weinberg equilibrium (HWE). The c.2203 T>C locus had genotype frequencies of 0.75 (TT) and 0.25 (CC), and the c.7966 A>C locus had 0.81 (AA) and 0.19 (CC), both consistent with HWE. Association analysis revealed significant correlations between the c.4218 T>G SNP and body weight and rump width, with the TT genotype showing the highest averages for both traits. The c.2203 T>C SNP was significantly associated with body weight and chest width, with the TT genotype again showing higher averages. The c.7966 A>C SNP was associated with chest depth and body length, with the AA genotype displaying lower averages for these traits. In silico predictions using multiple computational tools indicated that the identified missense SNP (p.31Ile>Ser) is novel and likely deleterious to the GHRHR protein's function and stability. Molecular docking demonstrated that the wild-type GHRHR binds more effectively with G protein alpha compared to the mutated form, predicting a mechanism through which this variant reduces the interactions of GHRHR with its cognate proteins. These findings provide valuable insights into the genetic factors influencing growth traits in Damascus goats and highlight the potential impact of the p.31Ile>Ser SNP on GHRHR functionality. This research underscores the importance of incorporating genetic markers in breeding programs to enhance growth traits and overall productivity.

Bone Mineral Density and the Risk of Type-2 Diabetes in Postmenopausal Women: rs4988235 Polymorphism Associated with Lactose Intolerance Effects.

The study was conducted among 607 female patients in the postmenopausal period in whom bone densitometry and vitamin-D3 levels were assayed and genotyping of the rs4988235 polymorphism of MCM6 gene was performed. The obtained results were analysed for the presence of T2DM, obesity surrogates, medical data, and past medical history. The distribution of genotype frequencies was consistent with the Hardy-Weinberg equilibrium (p > 0.050). Postmenopausal women with the GG homozygote of rs4988235 polymorphism consumed significantly less calcium (dairy), which was probably related to the observed lactose intolerance. The GG homozygote of women with rs4988235 polymorphism was significantly more likely to have T2DM relative to the A allele carriers (p = 0.023). GG homozygotes had significantly lower femoral-vertebral mineral density despite the significantly more frequent supplementation with calcium preparations (p = 0.010), vitamin D (p = 0.01), and anti-osteoporotic drugs (p = 0.040). The obtained results indicate a stronger loss of femoral-neck mineral density with age in the GG homozygotes relative to the A allele carriers (p = 0.038). In the population of women after menopause, the carriage of the G allele of rs4988235 polymorphism of the MCM6 gene, i.e., among the patients with lactose intolerance, significantly increased the risk of developing T2DM and the loss of BMD.

Individual Identification and Assessment of Genetic Diversity Using Microsatellite Markers in Racing Pigeons Raised in Turkiye

The implementation of a swift and economical molecular genetic approach, ensuring both efficacy and cost-effectiveness and facilitating population certification, is of utmost significance for breeders and the conservation of Turkiye's native pigeon biodiversity. In this study, we aimed to examine the genetic structure of racing pigeons (Columba livia domestica) raised in Turkiye using a genetic marker panel consisting of eight short tandem repeat (STR) loci. For this purpose, DNA was isolated from the shed feathers of 216 pigeons. Genomic DNA was amplified using the multiplex allele-specific PCR and subsequent capillary electrophoresis with ABI PRISM 3130XL Genetic Analyzer. Next, PCR products were analyzed in the GeneMapper Software program (Applied Biosystems). For parent testing, paternity index (PI), combined paternity index (CPI), and cumulative probability of paternity (CPP) were calculated. Furthermore, population genetic diversity was evaluated using heterozygosity (He), polymorphism information content (PIC), and Hardy–Weinberg equilibrium (HWE) testing. Results revealed that the total number of alleles is 81 and the number of alleles per locus varies between 4 and 19. The similarity rate between parent and offspring was calculated as 99.99% and above. Since no pedigree information was given when the samples were analyzed, obtaining this similarity ratio demonstrates the reliability of the panel. He values range from 0.362 to 0.919, and the PIC values range from 0.295 to 0.909. Loci PG-1, PG-2, and PG-3 show significant genetic diversity, with moderate to high PIC values reflecting varied allele frequencies in the population. Consequently, the set of seven STR markers (+ one sex marker) can be applied to identify and confirm parentage on a regular basis, thereby facilitating efficient breeding programs and ensuring genetic diversity conservation. This panel enables efficient pedigree analysis and gender determination, optimizing cost-effectiveness. The methodology presented in this study is ideal for pedigree analysis and breed certification in the Turkish pigeon breeding industry. Consequently, we affirm that the study data carries considerable national importance.

AGTR1 A1166C gene polymorphism is associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension: A retrospective analysis

Objective: To investigate whether angiotensin II type 1 receptor (AGTR1 A1166C) gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension. Methods: This retrospective analysis included 198 patients (⩾18 years of age) who received valsartan monotherapy (80 mg/day) for newly developed essential hypertension at the authors’ center between January 1, 2020 and December 31, 2023. Genotyping for AGTR1 A1166C gene polymorphism was done by polymerase chain reaction (PCR)-melting curve analysis of genomic DNA from peripheral blood samples. A dominant genetic model for AGTR1 A1166C (AA genotype versus AC + CC genotype) was used. Multivariate regression analysis of baseline variables and AGTR1 polymorphism was conducted to identify predictors of target blood pressure attainment (&lt;140/90 mmHg) at the 4-week follow-up. Results: The median age of the 198 patients was (53.7±13.5) years, and 58% were men. Genotyping assays showed that 164 patients had the AA genotype, and 34 patients were of the AC/CC genotype, including 30 with the AC genotype and 4 with the CC genotype. Allele distribution was consistent with Hardy Weinberg equilibrium. 109 Patients (55.1%) attained the blood pressure target. Multivariate analysis showed that smoking (versus no smoking, HR 0.314, 95% CI 0.159-0.619, P=0.001) and AGTR1 A1166C AA genotype (versus AC/CC, HR 2.927, 95% CI 1.296-6.611, P=0.023) were significant and independent predictors of target attainment. 25 Patients (73.5%) with AGTR1 A1166C AC/CC genotype attained the target versus 51.2% (51/164) of patients with AGTR1 A1166C AA genotype (P=0.017). Patients with AGTR1 A1166C AC/CC genotype had a significantly greater reduction in systolic blood pressure [(33.1±10.8) mmHg versus (29.2±11.7) mmHg in AA carriers; P=0.029)]. Conclusions: Hypertensive patients carrying one or two C alleles of the AGTR1 A1166C gene were more responsive to valsartan treatment.

Association between IL-6 -174 G/C (rs1800795) and IL-1A -889 C/T (rs1800587) cytokine variants with polycystic ovary syndrome in Iranian women: A case-control study

Background and AimInfertility in women has various causes, one of which is ovulation disorders. Polycystic ovary syndrome (PCOS) affecting ovulation is a complex idiopathic disease in which genetic polymorphisms may be involved. This study aimed to investigate the relationship between IL-6 -174 G/C and IL-1A -889 G/A cytokine polymorphisms with polycystic ovary syndrome in a population of Iranian women. Materials and MethodsIn this case-control pilot study, 120 PCOS patients (60 infertile, LPI, and 60 women with recurrent pregnancy abortion, LPA) and 60 controls, CTRLs) participated. After genomic DNA extraction from peripheral blood, we investigated for the polymorphisms rs1800795 of the IL-6 -174 and rs1800587 of the IL-1A-889 using specific primers and PCR-RFLP followed by NlaIII enzyme digestion and PCR-ARMS techniques. ResultsThere was a significant difference in the studied groups in terms of clinical characteristics (p-value < 0.05) except for the levels of HDL and LDL. Regarding demographic and clinical characteristics of patients, a significant correlation was observed between C/G and G/G genotypes of rs1800795 and FBS level (p value = 0.002). Also, rs1800587 showed a substantial relationship between CC and CT genotypes with the level of LH in LPI and the level of FBS in the LPAs (p value = 0.04). There was no significant difference between the frequencies of rs1800795 and frequencies of rs1800587 genotypes in the three studied groups (p value > 0.05).The studied variants were in Hardy-Weinberg equilibrium. ConclusionThe present work showed that rs1800795 and rs1800587 were not directly associated with PCOS in Iranian patients while the SNPs showed an indirect relationship with some factors affecting the disease.However, using genome-wide association analysis is a proper suggestion to obtain more reliable information about the disease’s genetic view. To our knowledge, this is the first report that implicates the role of the examined SNPs in an Iranian PCOS population.

The role of double heterozygotes of SLC3A1 and SLC7A9 in the prevalence of cystine stones

PurposeCystine stones, an autosomal recessive disorder caused by cystinuria, result from pathogenic variants of SLC3A1 and SLC7A9. Previous publications revealed that clinical prevalence is higher than genetically predicted prevalence. Heterozygous carriers in either gene are not stone formers. However, double heterozygotes (DH), individuals with 2 heterozygous pathogenic variants in both genes, were never evaluated and may explain the gap between clinical and genetic prevalence. MethodsBecause of the rarity of the condition, direct clinical observation is impractical. We perform this population study as a surrogate by identifying the observed DH, deriving the theoretical/expected DH, and testing the null hypothesis (NH) that the observed DH frequency is equal or greater than expected. These NH biologically correlate to DH and are asymptomatic and without cystine stone. ResultsUsing the 1000 Genome Database, we identified 0 DH. We derived the theoretical/expected DH with Hardy-Weinberg Equilibrium and Mendel’s law of independent assortment as 4.94 × 10−s. Population proportion test revealed z = −0.353, and P = .362, the NH cannot be rejected. ConclusionStatistical testing does not support that DH are symptomatic, ie, DH of SLC3A1 and SLC7A9 may not present with cystine stone, and other factors responsible for the gap that current genetics knowledge cannot explain.