Allele Frequency Distribution Research Articles

Collagen Gene Variants and Anterior Cruciate Ligament Rupture in Italian Athletes: A Preliminary Report.

Several studies have investigated the role of genetics in anterior cruciate ligament (ACL) rupture, often returning conflicting results. The present pilot study aimed to analyze the association between six Single Nucleotide Polymorphisms (SNPs) (rs1800012; rs12722; rs13946; rs240736; rs970547; and rs4870723, located on the COL1A1, COL5A1, COL12A1, and COL14A1 genes), and ACL rupture, among Italian athletes. A hypothesis-driven association study was conducted. In total, 181 male and female athletes (n = 86 injured; n = 96 non-injured) were genotyped for the prioritized variants. All polymorphisms were genotyped using PCR RFLP, with the only exception being the rs1800012 on the COL1A1 gene, which was detected using MTPA PCR. The allele frequency distribution fell within the worldwide range. Despite the evident population variability, no selective pressure signals were recorded using PBS analysis. No significant difference was detected between the cases and controls for any of the SNPs (rs1800012; rs13946; rs240736; rs970547, and rs4870723) included in the analyses (p > 0.008, Bonferroni-adjusted for multiple comparisons). Moreover, no significant differences were found when males and females were assessed separately. Further investigations based on a larger sample size are needed, in order to draw solid conclusions for the influence between collagen genes and ACL rupture.

Human Leukocyte Antigen Polymorphism HLA-A*24:02 is Associated with Acute Liver Disease in HBV-Infected Han Chinese Adults

ABSTRACT Background Whether polymorphic Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-DRB1 alleles were associated with acute liver disease after hepatitis B virus (HBV) infections was investigated. Methods In this study, from initially 100 participants in each group, HLA-A, HLA-B and HLA-DRB1 sequences were available from 86 acute hepatitis B (AHB) patients and from 84 HBV-resistant individuals (controls), using sequencing-based typing allele groups and alleles that exhibited differences in distribution between the case and control groups were subjected to chi-squared and logistic regression analyses to identify those associated with AHB. A dose response analysis was also performed on the effect of HLA-A*24:02 allele number on acute liver disease following HBV infection. Results The frequency distribution of HLA-B and HLA-DRB1 alleles in the control group were in Hardy-Weinberg Equilibrium (P > .05). HLA-A*24:02 (χ2 = 6.949, P = .008) occurred most frequently in the AHB and HLA-DRB1*12:02 (χ2 = 7.768, P = .005) in the control group. With adjustment for sex, the logistic regression model showed that the HLA-A*24:02 allele was significantly associated with AHB liver injury (P = .0326, OR = 2.270, 95% CI: 1.070–4.816), whereas the other HLA-A, HLA-B, and HLA-DRB1 alleles were not (P > .05). A linear response was observed for the association between HLA-A*24:02 allele number and acute liver disease after HBV infections (χ2 = 4.428, P = .025). Conclusion The HLA-A*24:02 allele may influence the severity of the cellular response to HBV infection, increasing the elimination of HBV-infected hepatocytes. The HLA-A*24:02 allele may be a potential screening marker for identifying people or regional populations in China at higher risk of acute liver disease following HBV infection.

COMPARATIVE ANALYSIS OF THE GENETIC STRUCTURE OF SCALED AND FRAMED CARP CHERNIGIVRYBHOSP PJSC

Aim. This study aimed to analyze the genetic structure of Ukrainian scaled and framed carp, by examining the frequencies of allelic variants and genotypes of protein polymorphic systems. Methods of research. The research was conducted using electrophoresis in polyacrylamide and starch gels, followed by histochemical staining. The genetic structure of the carp groups was assessed by analyzing the distribution of allele and genotype frequencies of loci encoding various proteins and enzymes: transferrin (TF), albumin (ALB), esterase (EST), hemoglobin (HB), ceruloplasmin (С), amylase (AM) and purine nucleoside phosphorylase (PN). The obtained data were mathematically processed using the "BIOSYS" software. Research results. In the scaled and framed studied carp groups, the spectra of hemoglobin, ceruloplasmin, amylase and purine nucleoside phosphorylase, which encode the corresponding enzymes were found to be monomorphic under the given conditions of electrophoretic investigation. This finding was confirmed by the data of other authors. The genetic structure of scaled and framed carp. was analyzed using the transferrin, albumin, and esterase loci. Four allelic forms of the transferrin locus were found in the investigated stock of scaled carp: Tf A, Tf B, Tf C1 and Tf C2. The highest frequency was observed for the Tf B allelic variant (0.400), while the lowest frequency was observed for Tf A (0.050). Four allelic forms of the transferrin locus have been established in the framed carp group: Tf B, Tf C1, Tf C2 and Tf D. The allelic variant B occurred with the highest frequency (0.739), while the Tf C2 allele occurred with the lowest frequency (0.043). The analysis of the genotypes of the stock of scaled carp showed that only 5 of the 15 possible genotypes were present, among which the homozygous genotype BB occurred with the highest frequency, and it was 40%. The genotypes AA, AB, AC2, AD, BC1, BC2, BD, C1D, C2D and DD were absent. In this group of framed carp, three genotypes out of the fifteen possible variations were found namely Tf BВ, Tf С1С2 and Tf С1D. The homozygous BB genotype occurred with the highest frequency, accounting for 73.9%. According to the esterase locus, a specific feature of both scaled and framed carp studied stocks on this farm was the absence of the SS homozygous genotype. In the studied scaled carp group, the FS heterozygous genotype had the highest frequency (65%). The Est F allele had a frequency of 0.675, while the Est S allele had a frequency of 0.261. In the electrophoretic analysis of blood plasma in framed carp, the Est F allelic variant occurred with a frequency of 0.739, while the Est S allele occurred with a frequency of 0.261. The FS heterozygous genotype in the framed carp stock had a predominant frequency of 52.2%. At the albumin locus in both scaled and framed carp groups, two alleles, A and B, were identified, with the frequencies 0.600 and 0.400 in scaled and 0.848 and 0.152 in framed carp, respectively. Three possible genotypes of the albumin locus were identified. According to the analysis of the correspondence of the distribution of genotypes of scaled and framed carp to the ratio according to the Hardy-Weinberg law at a significance level of 5%, it was shown that there are no deviations at the EST and ALB loci. According to the locus of transferrin in both studied scaled and framed carp stocks, the presence of a statistically significant difference in the observed distribution of the number of genotypes compared to the expected according to the Hardy-Weinberg law was established. In the scaled carp group, the observed level of heterozygosity at the transferrin locus was lower (0.300) than expected (0.692). The level of observed heterozygosity was observed for the esterase and albumin loci, which exceeded the expected values in both cases. In the framed carp of the studied group, the highest level of observed heterozygosity was found at the EST locus (0.522), while the lowest was observed at the TF locus (0.261). According to the ALB locus, the level of observed heterozygosity was 0.304. In contrast to the transferrin locus, the observed heterozygosity values for the esterase and albumin loci in this group exceeded the expected values. The average values of heterozygosity for the three loci were higher in the scaled carp group (Ho = 0.517 and He = 0.545) compared to the framed group (Ho = 0.362 and He = 0.365). Conclusions. The studied protein and enzyme systems allowed for the demonstration of the genetic structure features of scaled and framed carp farmed by Chernihivrybhosp PJSC, which were expressed in a specific set of TF allelic variants. Another peculiarity of individuals from this farm was the absence of the SS genotype at the esterase locus.

Association of Interleukin-2 Gene Polymorphism with Henoch-schönlein Purpura Nephritis.

Henoch-Schönlein purpura nephritis (HSPN) is a common vasculitis that mostly affects children, and previous studies have indicated that genetic factors may influence disease susceptibility. The aim of this study was to evaluate a possible association of three interleukin-2(IL-2) gene polymorphisms (rs3136534, rs2069776, and rs2069762) with HSPN in the Chinese population. A total of 81 patients with HSPN and 200 healthy children were enrolled. The distribution of genotypes, allelic frequencies, and haplotype frequencies among the three IL-2 polymorphisms were analyzed using the Sequenom MassARRAY system by means of matrix-assisted laser desorption ionization-time of flight mass spectrometry method. Compared to the healthy controls, genotyping analysis demonstrated rs3136534 was associated with a decreased HSPN risk in the dominant inheritance model (G/T+T/T vs. G/G; OR, 0.54; 95% CI, 0.31-0.93). However, the frequency of the T allele and haplotypes of rs3136534 showed no statistical significance. For the frequency of genotype, allele, and haplotype of the rs2069776 and rs20697622 polymorphisms, no significant differences were observed between HSPN patients and controls. Our results suggest that the rs3136534 polymorphism of the IL-2 gene is associated with susceptibility to HSPN in Chinese children.

The study of Associations between TNFα GENE G308A polymorphism and clinical-neurological, neuroimaging, hemodynamic characteristics and cognitive dysfunction in patients with post-infectious encephalopathy

Introduction. Infectious diseases can affect brain function and cause the development of encephalopathy, even if the pathogen does not directly affect the central nervous system. Infections caused by viruses, bacteria, or parasites can lead to a secondary inflammatory response in the brain, commonly known as neuroinflammation, through the action of inflammatory mediators that affect the brain endothelium and parenchyma, and the response of brain cells to these mediators. Neurological consequences associated with infectious diseases are poorly understood. Nowadays, there is no established strategy for the treatment or prevention of neurological damage associated with peripheral infections. Aim of study was: to establish probable associations of the G308A polymorphic variant of the TNFα gene with clinical-neurological, neuroimaging, hemodynamic characteristics and cognitive dysfunction in patients with post-infectious encephalopathy. Material and methods. 128 patients with PIE who were undergoing treatment in the neurological departments of the communal non-profit enterprise "Ternopil Regional Clinical Psychoneurological Hospital" during 2021-2022 were examined. 26 patients underwent molecular genetic analysis. The control group consisted of 12 practically healthy persons, representative in terms of age and sex. All patients met the inclusion criteria for the study. Neuroimaging was performed using multispiral computed tomography (CT) or magnetic resonance imaging (MRI). The state of cerebral blood flow was studied using transcranial duplex scanning (TCI) of intracranial vessels and extracranial brachiocephalic vessels on a Philips HDI device. Research in the cognitive sphere was carried out using the Montreal Cognitive Test (The Montreal Cognitive Assessment, MoCA). The molecular genetic study of the G308A polymorphic variant of the TNFα gene was carried out according to standard protocols developed in the molecular genetic laboratory of the state institution "Reference Center for Molecular Diagnostics of the Ministry of Health of Ukraine". The results. Analyzing the dependence of clinical-neurological syndromes, neuroimaging, hemodynamic characteristics, and cognitive dysfunction on the polymorphic variant G308A of the TNFα gene in patients with PIE, probable differences in the distribution of genotype frequencies were established only for clinical-neurological syndromes (cephalic syndrome, p=0.005 and movement disorder syndrome, p =0.038) and neuroimaging changes (gliosis phenomenon, p=0.026). Regarding the frequency distribution of alleles of the G308A polymorphic variant of the TNFα gene in patients with PIE, a probable predominance of carriers of the A allele among persons with cephalic syndrome compared to persons without cephalic syndrome was found (91.67% vs. 8.33%). Conclusions. Thus, the allelic polymorphism of the TNFα gene affects the course of PIE, which determines the expediency of further research.

Prevalence and Frequency Distribution of HLA-A, HLA-B and HLA-C Alleles in the Punjab, Pakistan

The Human Leukocyte Antigen (HLA) system, a set of highly polymorphic genes, has been found to play an effective role in the disease resistance and disease susceptibility. In this study, prevalence of class-I alleles of HLA was characterized at HLAA,- B and -C loci in the 216 individuals randomly selected population at different regions of Punjab province of Pakistan. The study revealed that at HLA-A locus the allele 11 was most prevalent with 16.7 % frequency. Similarly, at HLA-B locus the allele 51 was found abundant with 15% frequency and at HLA-C locus the allele 7 was prevalent with 24% frequency. Among the two-locus HLA class I haplotypes, B*08/C*07 was found to be the most prevalent followed by B*35/C*04. Surprisingly, HLA-B*29 and HLA-B*36 alleles were found in the Punjabi population which is contrary to the previous reports.

Association of interleukin-8 polymorphism (+ 781 C/T) with the risk of oral Lichen Planus disease

BackgroundOral Lichen Planus (OLP) is a chronic inflammatory mucosal disease. The pathogenesis of OLP is unknown. The Single Nucleotide Polymorphism (SNP) that occurs in the regulatory position + 781 could affect the expression of interleukin-8. This polymorphism is probably associated with increased serum levels of IL-8. The current study aimed to investigate the genotype and allele frequencies of IL-8( + 781 C/T) in OLP patients and whether it is associated with the severity of OLP disease in an Iranian population.MethodsThree milliliters of saliva were taken from 100 patients with OLP and 100 healthy individuals who were matched in age and gender. After DNA extraction from saliva samples of patients and healthy individuals, the genotype of IL-8 at position + 781 is detected using the PCR-RFLP method. The results were analyzed using SPSS software.ResultsFrequency of C/C, T/C, and T/T genotypes at position IL-8 + 781 gene in the patient group were 47%, 41%, and 12%, respectively, and in the control group, were 37%, 42%, and 21%. The difference between the two groups regarding allele frequency distribution was statistically significant (χ2 = 3.86, p = 0.049, 95% CI = 0.44-1, OR = 0.66). Our results indicated the significantly higher frequency of the TT genotype in the erosive OLP compared to the nonerosive group (p = 0.03, OR = 0.89, 95% CI = 0.49–1.6).ConclusionThis study depicted the difference in the frequency of SNP IL-8 + 781 C/T allele in the patient and control groups had a significant association with the risk of OLP. In addition, our data revealed that IL-8 + 781 C/T polymorphisms might be associated with the severity of OLP in the Iranian population.

Intratumor heterogeneity in colorectal cancer: Distribution of tumor suppressor gene variants with regard to patient lymph node status.

Intratumor heterogeneity (ITH) results from accumulation of somatic mutations in the fractions of successive cancer cell generations. We aimed to use deep sequencing to investigate ITH in colorectal tumors with particular emphasis on variants in oncogenes (ONC) and tumor suppressor genes (TSG). Samples were collected from 16 patients with colorectal cancer and negative or positive lymph node status (n = 8 each). We deep-sequenced a panel of 56 cancer-related genes in the central and peripheral locations of T3 size primary tumors and healthy mucosa. The central region of T3 tumors has a different frequency profile and composition of genetic variants. This mutation profile is capable of independently discriminating patients with different lymph node status (p = 0.028) in the central region. We noted an increasing number of mutations outside of the central region of the tumor and a higher number of mutations in tumors from node-positive patients. Unexpectedly, in the healthy mucosa, we identified somatic mutations with variant allele frequencies, characteristic not only of heterozygotes and homozygotes but also of other discrete peaks (e.g., around 10%, 20%), suggestive of clonal expansion of certain mutant alleles. We found differences in the distribution of variant allele frequencies in TSGs when comparing node-negative and node-positive tumors (p = 0.029), as well as central and peripheral regions (p = 0.00399). TSGs may play an important role in the escape of the tumor toward metastatic colonization.

Vitamin D status, vitamin D receptor gene polymorphism, and haplotype in patients with cutaneous leishmaniasis: Correlation with susceptibility and parasite load index.

CL endemicity was reported worldwide including in Saudi Arabia, imposing a major challenge on the health authorities. Vitamin D and its receptor (VDR) are key modulators of the immune response where the VDR is expressed. A remarkable lack of data exists in humans about the contribution of vitamin D and polymorphisms of the VDR gene in protozoan infections, especially cutaneous leishmaniasis (CL). This is the first work conducted to assess the relationship between vitamin D status, polymorphisms of the VDR gene (BsmI, ApaI, TaqI, and FokI), and VDR haplotype with parasite tissue load and susceptibility to CL. Fifty-two patients with confirmed CL (21 patients receiving vitamin D medication and 31 patients not receiving it) and 46 control subjects participated in this cross-sectional investigation. VDR genotyping was determined by restriction fragment length polymorphism analysis. Serum levels of 25-OH vitamin D were assessed using the ELISA method in all participants. The skin biopsy quantified the parasite load based on the Ridley parasitic index. The mean serum level of 25-OH vitamin D in CL patients who were not receiving vitamin D therapy was significantly lower compared to CL patients on vitamin D therapy and controls (p <0.001 for both) and CL patients with no history of vitamin D therapy had a significantly higher frequency of vitamin D deficiency compared to CL patients on vitamin D therapy and controls (p < 0.05). Compared to CL patients with no history of vitamin D therapy, CL patients receiving vitamin D therapy had a significantly lower mean size of the lesion and RPI (p = 0.02, .03 respectively). The frequency of genotype "aa" and its "a" allele in ApaI SNP of VDR was significantly lower in CL patients compared to controls (p = 0.006 and 0.03 respectively). However, patients with CL had a considerably greater frequency of the "A" allele than the controls (p = 0.03), suggesting its role in CL susceptibility. There was no statistically significant difference between the two groups in the genotype and allele frequency distributions of BsmI, TaqI, and FokI (p > 0.05). When compared to controls, CL cases had a considerably greater frequency of the "B-A-T-F" haplotype (p = 0.04), and a significantly lower frequency of the "B-a-T-F" haplotype (p = 0.01) suggesting that these haplotypes may have the potential susceptibility or protection against CL respectively. The "Aa" genotype in ApaI SNP of VDR had considerably lower levels of vitamin D with higher parasite load compared to the "AA" and: aa" genotypes (p = 0.02,0.02 respectively). A significant negative correlation was found between the parasite load and 25-OH vitamin D levels (r2 = -0.53, p< 0.001). According to these findings, vitamin D levels and "ApaI" VDR gene polymorphisms could affect the parasite load and susceptibility to infection, whereas BsmI, FokI, and TaqI polymorphisms did not. Correction of vitamin D levels may aid in CL management.

Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations

BackgroundYungui Plateau in Southwest China is characterized by multi-language and multi-ethnic communities and is one of the regions with the wealthiest ethnolinguistic, cultural and genetic diversity in East Asia. There are numerous Tai-Kadai (TK)-speaking populations, but their detailed evolutionary history and biological adaptations are still unclear.ResultsHere, we genotyped genome-wide SNP data of 77 unrelated TK-speaking Zhuang and Dong individuals from the Yungui Plateau and explored their detailed admixture history and adaptive features using clustering patterns, allele frequency differentiation and sharing haplotype patterns. TK-speaking Zhuang and Dong people in Guizhou are closely related to geographically close TK and Hmong-Mien (HM)-speaking populations. Besides, we identified that Guizhou TK-speaking people have a close genetic relationship with Austronesian (AN)-speaking Atayal and Paiwan people, which is supported by the common origin of the ancient Baiyue tribe. We additionally found subtle genetic differences among the newly studied TK people and previously reported Dais via the fine-scale genetic substructure analysis based on the shared haplotype chunks. Finally, we identified specific selection candidate signatures associated with several essential human immune systems and neurological disorders, which could provide evolutionary evidence for the allele frequency distribution pattern of genetic risk loci.ConclusionsOur comprehensive genetic characterization of TK people suggested the strong genetic affinity within TK groups and extensive gene flow with geographically close HM and Han people. We also provided genetic evidence that supported the common origin hypothesis of TK and AN people. The best-fitted admixture models further suggested that ancestral sources from northern millet farmers and southern inland and coastal people contributed to the formation of the gene pool of the Zhuang and Dong people.

Where the wild things are: genetic associations of environmental adaptation in the Oryza rufipogon species complex.

Crop wild relatives host unique adaptation strategies that enable them to thrive across a wide range of habitats. As pressures from a changing climate mount, a more complete understanding of the genetic variation that underlies this adaptation could enable broader utilization of wild materials for crop improvement. Here, we carry out environmental association analyses (EAA) in the Oryza rufipogon species complex (ORSC), the wild progenitor of cultivated Asian rice, to identify genomic regions associated with environmental adaptation characterized by variation in bioclimatic and soil variables. We further examine regions for colocalizations with phenotypic associations within the same collection. EAA results indicate that significant regions tend to associate with single environmental variables, although 2 significant loci on chromosomes 3 and 5 are detected as common across multiple variable types (i.e. precipitation, temperature, and/or soil). Distributions of allele frequencies at significant loci across subpopulations of cultivated Oryza sativa indicate that, in some cases, adaptive variation may already be present among cultivars, although evaluation in cultivated populations is needed to empirically test this. This work has implications for the potential utility of wild genetic resources in pre-breeding efforts for rice improvement.

Genetic Variations in IL-1β, TNF-α, and TGF-β Associated with the Severity of Chronic Cervical Spondylitis in Patients.

Chronic cervical spondylitis (CCS), a degenerative disorder of the spine, is known for causing disability among old and young people. Single-nucleotide polymorphisms (SNPs) in various cytokine genes have demonstrated an impactful association with several inflammatory disorders. In the present study, we have investigated the SNPs and allelic distribution of the three most prevalent cytokines genes, IL-1β (-511C/T), TNF-α (-308G/A), and TGF-β (-509C/T), along with serum levels of these cytokines in 252 subjects. SNPs were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and digested fragments were separated and visualized using agarose gel electrophoresis and Native Polyacrylamide gel electrophoresis (PAGE). The serum cytokine levels were analyzed with a flow cytometer using a customized multiplex bead-based assay. It was observed that these SNPs did not reflect the susceptibility to CCS but were associated with susceptibility to CCS. We found a significant association between the C/C and G/G genotypes and the C and G alleles of IL-1β and TNF-α, respectively, suggesting a lower risk of CCS. The frequency distribution of risk alleles (-511T) and (-308A) were simultaneously higher in CCS compared to the control, reflecting the susceptibility to CCS. TGF-β showed a significant association with disease susceptibility, along with a significant correlation between age and the chronicity of CCS. The serum cytokine levels were significantly different in CCS and controls.

Allele Frequencies and Forensic Data of 25 STR Markers for Individuals in Northeast Brazil.

Identifying DNA markers such as Short Tandem Repeats (STR) can be used to investigate genetic diversity based on levels of heterozygosity within and between populations. Allele frequencies and forensic data for STRs were obtained from a sample of 384 unrelated individuals living in Bahia, Northeastern Brazil. Thus, the present study aimed to identify the allele frequency distribution, in addition to the forensic and genetic data, of 25 STR loci in the population of Bahia. Buccal swabs or fingertip punctures were utilized to amplify and detect 25 DNA markers. The most polymorphic loci were SE33 (43), D21S11, and FGA (21). The least polymorphic were TH01 (6), TPOX, and D3S1358 (7). Forensic and statistical data were obtained through data analysis, which revealed a large genetic diversity, with an average value of 0.813 for the analyzed population. The present study was more robust than previous STR marker studies and will contribute to future research on population genetics in Brazil and worldwide. The results of this study allowed the establishment of haplotypes found in the forensic samples of Bahia State to serve as a reference in the elucidation of criminal cases and paternity tests, as well as population and evolutionary investigations.

An Expiration Date for Pharmacogenetic Test Results and Prescribing Guidance?

The mother of Bob, an 18-year-old student headed to college, calls the clinical laboratory requesting pharmacogenetics test results and the “traffic-light” drug guidance table from 12 years ago. As a boy, Bob had been treated by a child psychiatrist for autism spectrum disorder and anxiety. She was told these results were good for life. Now a young adult, Bob has a new psychiatrist who wishes to have this information for personalized treatment. How should the clinical laboratory respond to the request? In this real-world situation, a fundamental question arises: Should pharmacogenetic test results and decision support bear an expiration date? Advances in molecular diagnostics, deeper sampling of diverse populations, new drugs, and evolving guidance from learned societies all point to the need for a term of use. The default “Normal” or “Functional” status in pharmacogenetic testing is defined as the absence of variants, and such default status is potentially iatrogenic. The omission of rare/ethnic-specific genetic variants with different effect sizes and allele frequency distribution across different populations can exacerbate the problem. At the same time, the resolution of pharmacogenetic tests has improved with advances in diagnostics technology (e.g., next-generation sequencing, sampling longer tracks of a given locus).

Self-contained Beta-with-Spikes Approximation for Inference Under a Wright-Fisher Model.

We construct a reliable estimation method for evolutionary parameters within the Wright-Fisher model, which describes changes in allele frequencies due to selection and genetic drift, from time-series data. Such data exist for biological populations, for example via artificial evolution experiments, and for the cultural evolution of behavior, such as linguistic corpora that document historical usage of different words with similar meanings. Our method of analysis builds on a Beta-with-Spikes approximation to the distribution of allele frequencies predicted by the Wright-Fisher model. We introduce a self-contained scheme for estimating parameters in the approximation, and demonstrate its robustness with synthetic data, especially in the strong-selection and near-extinction regimes where previous approaches fail. We further apply the method to allele frequency data for baker's yeast (Saccharomyces cerevisiae), finding a significant signal of selection in cases where independent evidence supports such a conclusion. We further demonstrate the possibility of detecting time-points at which evolutionary parameters change in the context of a historical spelling reform in the Spanish language.

Can gray whale management units be assessed using mitochondrial DNA?

Although most eastern North Pacific gray whales (Eschrichtius robustus) feed in Alaskan waters north of the Aleutian peninsula, some have been reported as long-term feeding residents in more southern waters ranging from northern California to southeast Alaska. The population history of this smaller putative southern feeding population is unknown. Recently, native Americans of the Makah tribe attained permits to harvest up to five whales per year in Washington State waters. Managers need to know whether southern summer residents could be potentially depleted through low-level harvesting. This paper investigates the feasibility of using genetic data to assess the plausibility of two possible population histories for the southern feeding group: panmixia with the northern feeding group and a single colonisation event less that a century ago. We find that a genetic study would most probably result in an unambiguous answer to the question of whether the southern feeding group is a separate population founded by a single colonisation event. Simulations show that a single founding event in the last century would result in genetic differentiation 97.8% of the time (a = 0.05) between the two feeding groups. Further, sensitivity analyses of uncertain parameters used in the model show that the results do not depend on the values of growth rate, mitochondrial allele frequency distribution or population size of the eastern North Pacific gray whale after commercial harvest.

High carrier frequency of pathogenic PATL2 gene mutations predicted in population: a bioinformatics-based approach.

Topoisomerase II homologue 2 (PATL2) has been confirmed to be a key gene that contributes to oocyte maturation. However, the allele distribution and carrier frequency of these mutations remain uncharacterized. So a bioinformatics subcategory analysis of PATL2 mutations from outcome data and Single Nucleotide Polymorphism (SNP) databases was conducted. Altogether, the causative PATL2 mutation number detected in patients with oocyte maturation defects in the clinical studies and pathogenic PATL2 mutation sites predicted by software based on the database was approximately 53. The estimated carrier frequency of pathogenic mutation sites was at least 1.14‰ based on the gnomAD and ExAC database, which was approximately 1/877. The highest frequency of mutations detected in the independent patients was c.223-14_223-2del13. The carrier frequency of this mutation in the population was 0.25‰, which may be a potential threat to fertility. Estimated allele and carrier frequency are relatively higher than those predicted previously based on clinical ascertainment. A review of PATL2 mutation lineage identified in 34 patients showed that 53.81%, 9.22% and 14.72% of the oocytes with PATL2 mutations were arrested at the germinal vesicle (GV) stage, metaphase I (MI) stage and first polar body stage, respectively. Oocytes that could develop to the first polar body stage were extremely rare to fertilise, and their ultimate fate was early embryonic arrest. Phenotypic variability is related to the function of the regions and degree of loss of function of PATL2 protein. A 3D protein structure changes predicted by online tools, AlphaFold, showed aberrations at the mutation sites, which may explain partially the function loss. When the mutated and wild-type proteins are not in the same amino acid category, the protein structure will be considerably unstable. The integration of additional mutation sites with phenotypes is helpful in drawing a complete picture of the disease. Bioinformatics analysis of PATL2 mutations will help reveal molecular epidemiological characteristics and provide an important reference for new mutation assessment, genetic counselling and drug research.

Genome-wide association studies combined with k-fold cross-validation identify rs17822931 as an ancestry-informative marker in Han Chinese population.

DNA-based ancestry inference has long been a research hot spot in forensic science. The differentiation of Han Chinese population, such as the northern-to-southern substructure, would benefit forensic practice. In the present study, we enrolled participants from northern and southern China, each participant was genotyped at ∼400K single-nucleotide polymorphisms (SNPs) and data of CHB and CHS from 1000 Genomes Project were used to perform genome-wide association analyses. Meanwhile, a new method combining genome-wide association study (GWAS) analyses with k-fold cross-validation in a small sample size was introduced. As a result, one SNP rs17822931 emerged with a p-value of 7.51E-6. We also simulated a huge dataset to verify whether k-fold cross-validation could reduce the false-negative rate of GWAS. The identified ABCC11 rs17822931 has been reported to have allele frequencies varied with the geographical gradient distribution in humans. We also found a great difference in the allele frequency distributions of rs17822931 among five different cohorts of the Chinese population. In conclusion, our study demonstrated that even small-scale GWAS can also have potential to identify effective loci with implemented k-fold cross-validation method and shed light on the potential maker of rs17822931 in differentiating the north-to-south substructure of the Han Chinese population.

Genetic polymorphism of IL-17F rs763780 contributes to the susceptibility to bipolar disorder but not to schizophrenia in the Turkish population

This study aims to investigate the genetic polymorphism in the interleukin-17F (IL-17F) (rs763780, 7488 A/G) gene in bipolar disorder (BD) and schizophrenia (SCZ) patients by comparing it with healthy controls considering clinical parameters. A sample of 107 patients with BD, 129 patients with SCZ, and 100 healthy volunteers were included. SCID-I was used to confirm the diagnosis according to DSM-IV-TR criteria. The Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HAM-D) were administered to BD patients. The Positive and Negative Symptoms Scale (PANSS) was applied to the patients with SCZ. PCR-RFLP was used to determine IL-17F gene polymorphism. Our results demonstrated that the distributions of the IL-17F genotype and the allele frequencies of BD patients were statistically significantly different from the control group. The AA genotype (OR: 0.283; 95% Cl: 0.140–0.573; p<.001) and A allele (OR: 0.333; 95% Cl: 0.171–0.646; p=.001) frequencies were significantly higher in the control group than in the BD group. The IL-17F genotype and the allele frequency distributions of SCZ patients were not statistically significantly different from the control group. When comparing scale scores due to the IL-17F genotype distributions in patients with BD or SCZ, there was no statistically significant difference between the groups of IL-17F genotypes. In summary, whereas the IL-17F polymorphism may be associated with BD, this polymorphism was not related to SCZ.

СВЯЗЬ ПОЛИМОРФНОГО ВАРИАНТА RS989692 ГЕНА НЕПРИЛИЗИНА (MME) С УРОВНЕМ НАТРИЙУРЕТИЧЕСКИХ ПЕПТИДОВ И ЕГО КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ У ПАЦИЕНТОВ С СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ И ФИБРИЛЛЯЦИЕЙ ПРЕДСЕРДИЙ

Background. The variability in the activity of natriuretic peptides (NUPs) is determined genetically, as evidenced by the association of polymorphic variants encoding brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) with an increased risk of cardiovascular (CV) disease. The aim of the study. To determine the frequency of alleles and genotypes of the SNP rs989692 of the neprilysin gene (MME). To determine the association of SNP rs989692 in MME with the concentration of NUP and soluble neprilysin and to evaluate its prognostic value in relation to the development of adverse cardiovascular events in patients with heart failure (HF) associated with a left ventricular ejection fraction (LVEF) &lt;50% and persistent or long-term persistent atrial fibrillation (AF). Material and methods. The main group included 152 patients with HF, the control group included 35 individuals without CV disease. The levels of ANP, BNP, NT-proBNP and soluble neprilysin were determined for all patients. The genetic study of the SNP rs989692 in the MME gene was carried out by polymerase chain reaction. The endpoint: hospitalization due to HF progression. The composite endpoint: hospitalization due to HF progression, new onset or progressive exertional angina pectoris, myocardial infarction. Results. The frequency distribution of genotypes and alleles of the SNP rs989692 in MME did not differ significantly between the control and experimental groups. The levels of ANP, BNP and neprilysin in patients with HF in combination with AF did not differ depending on the SNP rs989692 in MME genotype. Patients with HF associated with LVEF &lt;50%, AF and TT genotype rs989692 in MME had higher levels of NT-proBNP (those with CC genotype – 964 [655.1; 1724] pg/ml, those with TC genotype – 1074.1 [857; 1944] pg/ml, those with the TT genotype – 2992 [886; 4885] pg/ml, p&lt;0.05). The presence of the homozygous TT genotype in patients with HF combined with LVEF &lt;50% and AF was associated with an increased risk of developing adverse CV events, OR=1.9 [95% CI from 1.2 to 3.09]. Conclusion. Patients with HF associated with LVEF &lt;50% in combination with permanent or long-term persistent AF with homozygous TT genotype rs989692 of the MME gene have higher levels of NT-proBNP and a higher risk of developing adverse cardiovascular events.