High Genetic Polymorphism Research Articles

Genetic diversity and phylogeography of the global Theileria orientalis isolates inferred from MPSP gene sequences.

Theileria orientalis is a non-transforming Theileria species infecting cattle and water buffaloes. Several outbreaks of oriental theileriosis accompanied by considerable economic loss were documented in Asia, Australia, and New Zealand. The major piroplasm surface protein (MPSP) gene has frequently been used to molecularly characterize T. orientalis isolates worldwide. Various MPSP genotypes were detected with significant virulence variations. The present study provides the first in silico analysis for all globally published T. orientalis MPSP isolates to evaluate their phylogeny, diversity, and population structure. All studies that tested T. orientalis isolates using PCR-MPSP protocols were systematically collected from various databases. Theileria orientalis MPSP-sequenced isolates on the GenBank were collected and the sequences were tested for their phylogenetic relatedness, genetic diversity, recombination, natural selection, and population structure using various software. The collected T. orientalis-MPSP isolates (n = 795) were clustered into 12 genotypes, including types 1 (Chitose), 2 (Ikeda), 3 (Buffeli), 4, 5, 7, 8, and N1-N5. The previously identified type 6 belonged to a separate species (Theileria sinensis). The previously identified type 9 was transferred to type 4. Two unidentified isolates from water buffaloes in India were clustered into a new suggested genotype "type N5". Of the 12 genotypes, Ikeda (type 2) is the most virulent in cattle. However, a few clinical cases have also been linked to types 1 (Chitose) and 7. In water buffaloes, T. orientalis outbreaks have been linked to genotypes N2 and N5. Geographic mapping of various genotypes revealed the dispersal of types 1 and 3 worldwide. Overall, the 795 isolates comprised 532 haplotypes and displayed very high nucleotide (π = 0.14) and haplotype (Hd = 0.995) diversities. As a result, a very low sequence conservation value (C = 0.207) was determined. The twelve genotypes displayed comparable haplotype diversities accompanied by statistically significant negative Tajima's D and Fu's Fs values suggesting population expansion. A high value for the minimum number of recombination events (Rm = 65) was estimated for the 795 isolates, and this value varied from 0 to 23 at the genotype level. Most types also displayed significant positive selection (dn/ds ratio > 1). This suggests that both recombination and positive selection occur in T. orientalis MPSP gene, which could explain the very high genetic diversity among various T. orientalis types. Different patterns were detected for the gene flow among T. orientalis populations from various hosts and geographies; however, there is evidence for the genetic relatedness between populations from neighbouring countries. The high genetic polymorphism and different associated pathogenicity in T. orientalis-MPSP genotypes highlight the need for further investigations employing whole genome sequencing technology to provide accurate comparative gene-level analyses and help further understand their pathogenicity.

Current views on etiology, diagnosis, epidemiology and gene therapy of maturity onset diabetes in the young.

MODY, or maturity-onset diabetes of the young, is a group of monogenic diseases characterized by autosomal dominant inheritance of a non-insulin-dependent form of diabetes that classically manifests in adolescence or in young adults under 25 years of age. MODY is a rare cause of diabetes, accounting for 1% of all cases, and is often misdiagnosed as type 1 or type 2 diabetes. It is of great importance to accurately diagnose MODY, as this allows for the most appropriate treatment of patients and facilitates early diagnosis for them and their families. This disease has a high degree of phenotypic and genetic polymorphism. The most prevalent forms of the disease are attributed to mutations in three genes: GCK (MODY 2) and (HNF)1A/4A (MODY 3 and MODY 1). The remaining MODY subtypes, which are less prevalent, have been identified by next generation sequencing (NGS) in the last decade. Mutations in the GCK gene result in asymptomatic, stable fasting hyperglycemia, which does not require specific treatment. Mutations in the HNF1A and HNF4A genes result in pancreatic β-cell dysfunction, which in turn causes hyperglycemia. This often leads to diabetic angiopathy. The most commonly prescribed drugs for the treatment of hyperglycemia are sulfonylurea derivatives. Nevertheless, with advancing age, some patients may require insulin therapy due to the development of resistance to sulfonylurea drugs. The strategy of gene therapy for monogenic forms of MODY is still an experimental approach, and it is unlikely to be widely used in the clinic due to the peculiarities of MODY structure and the high genetic polymorphism and clinical variability even within the same form of the disease. Furthermore, there is a lack of clear gene-phenotypic correlations, and there is quite satisfactory curability in the majority of patients. This review presents the main clinical and genetic characteristics and mutation spectrum of common and rarer forms of MODY, with a detailed analysis of the field of application of AVV vectors in the correction of hyperglycemia and insulin resistance.

Navigating Host Immunity and Concurrent Ozone Stress: Strain-Resolved Metagenomics Reveals Maintenance of Intraspecific Diversity and Genetic Variation in Xanthomonas on Pepper.

The evolving threat of new pathogen variants in the face of global environmental changes poses a risk to a sustainable crop production. Predicting and responding to how climate change affects plant-pathosystems is challenging, as environment affects host-pathogen interactions from molecular to the community level, and with eco-evolutionary feedbacks at play. To address this knowledge gap, we studied short-term within-host eco-evolutionary changes in the pathogen, Xanthomonas perforans, on resistant and susceptible pepper in the open-top chambers (OTCs) under elevated Ozone (O3) conditions in a single growing season. We observed increased disease severity with greater variance on the resistant cultivar under elevated O3, yet no apparent change on the susceptible cultivar. Despite the dominance of a single pathogen genotype on the susceptible cultivar, the resistant cultivar supported a heterogeneous pathogen population. Altered O3 levels led to a strain turnover, with a relatively greater gene flux on the resistant cultivar. Both standing genetic variation and de novo parallel mutations contributed toward evolutionary modifications during adaptation onto the resistant cultivar. The presence of elevated O3, however, led to a relatively higher genetic polymorphism, with random and transient mutations. Population heterogeneity along with genetic variation, and the promotion of interdependency are mechanisms by which pathogen responds to stressors. While parallel mutations may provide clues to predicting long-term pathogen evolution and adaptive potential. And,a high proportion of transient mutations suggest less predictable pathogen evolution under climatic alterations. This knowledge is relevant as we study the risk of pathogen emergence and the mechanisms and constraints underlying long-term pathogen adaptation under climatic shifts.

Determining the Association Between MSP1/2 Variant and Multiplicity of Infection on Incidence of Severe Malaria in Sudanese Children in Gezira State, Sudan

The Almanagil province located in Gezira scheme, Gezira state, Sudan, represents a suitable environment for the breeding of malaria-carrying mosquitoes. An estimated 5.9% of Sudanese people suffer from malaria, with 87.6% of cases caused by Plasmodium falciparum and 12.4% by Plasmodium vivax. Clinical manifestation of malaria cases range from mild uncomplicated to severe and fatal complications and the genetic variants and multiplicity of falciparum infection can worsen the manifestations of malaria. The objective of this work is to determine the degree of genetic variation in P. falciparum infection in a high-transmission region of central Sudan by analyzing merozoite surface protein-1 (msp1) and merozoite surface protein-2 (msp2) variations. During the rainy season of 2022, Eighty-nine children with confirmed severe falciparum malaria whom admitted to Almanagil Pediatric Hospital were included in this study. Dry blood spots were used to extract the DNA and amplification of three msp1 and two of msp2 allelic subfamilies, namely K1, RO33 and MAD20 and FC27 and IC/3D7, respectively. The data was analyzed by using SPSS computer program (v 23.0). The three genetic subfamilies of msp1 (K1, RO33 and MAD20) and the two alleles of msp2 (FC27 and IC/3D7) were identified. Msp1 variants represent K1 (64/89, 71.9%), RO33 (56/89, 62.9%) and MAD20 (72/89, 80.9%), while msp2 diversity represents ICI/3D7 (52/89, 58.4%), FC27 (62/89, 69.6%) and ICI/3D7/FC27(33/89, 37.1%). The MAD20 and FC27 showed high genetic diversity among both genes respectively. RO33 allele shows a strong association with severity of falciparum malaria (OR 2.572, P 0.045 ), while the K1 was the lowest risk factor for malaria severity. The allele subfamily K1 and MAD20 of msp1 were associated with hypoglycemia (OR 4.21 and 2.91) respectively. Our study revealed high genetic polymorphisms of msp1 and msp2. Among Central Sudanese children with high MOI of P. falciparum isolates, there was a significant frequency of msp1, a strong association between the K1 allele and hypoglycemia, and a substantial association between the RO33 and MAD20 alleles with the severity of the infection. These findings could help develop malaria control strategies.

Forensic characteristics of 38 Y-STR loci in the Hui population from Shaanxi Province, Northwest China

In this study, we genotyped 939 unrelated healthy individuals to investigate the genetic polymorphisms of 38 Y chromosome short tandem repeats(Y-STRs) loci included in the Yfiler™ Platinum kit in the Hui population of Shaanxi Province. Comprehensive population comparisons were performed using analysis of molecular variance(AMOVA), multidimensional scaling(MDS), and molecular evolutionary genetics analysis(MEGA) to explore population relationships. The allele frequencies of the single-copy loci ranged from 0.001 to 0.940 (DYS645), while those of the multi-copy loci ranged from 0.001 to 0.138 (DYS527). The highest genetic diversity (GD) value was observed for DYS385 (0.9723), and the lowest for DYS645 (0.1138). A total of 849 distinct haplotypes were identified among the 939 Hui individuals, with 808 (95.2 %) being unique. Haplotype diversity (HD), haplotype match probability, and discriminatory power (DC) in the Shaanxi Hui population were 0.9996, 0.0015, and 0.9041, respectively. Interpopulation comparisons based on Rst genetic distance values, phylogenetic trees, and MDS indicated that the Shaanxi Hui population has a close genetic relationship with the Ningxia Hui, Qinghai Hui, Xinjiang Hui, and Yunnan Hui populations. The population genetic stratification largely coincides with geographic distribution and language families. Our study revealed that the 38 Y-STR loci exhibit high genetic polymorphisms in the Hui population from Shaanxi Province.

Optimizing Strategy for Whole-Genome Genotype Imputation in Scallops

Advancements in sequencing technologies have facilitated low-coverage whole-genome sequencing (lcWGS) for detecting millions of single nucleotide polymorphisms (SNPs) in large populations at low cost. The effectiveness of this approach relies on genotype imputation following lcWGS. While several imputation methods have been applied in human and other terrestrial animals, their performance in aquaculture organisms, particularly mollusks, remains unassessed. Mollusks contribute 70% of mariculture production in China and are characterized by high genetic polymorphism. In this study, we aimed to optimize reference panel construction and evaluate imputation strategies for SNP detection in two scallops, Chlamys farreri and Patinopecten yessoensis, both important bivalve species. High-coverage whole-genome sequencing (hcWGS) data were used to construct haplotype reference panels, and three imputation methods were applied: Beagle5.4, GLIMPSE2, and QUILT. QUILT outperformed other methods, achieving imputation quality scores (IQS) exceeding 0.930 in C. farreri and 0.946 in P. yessoensis, and yielded the highest number of imputed loci in both species. Furthermore, panel construction was optimized by adjusting for genotype quality (GQ) and minor allele frequency (MAF); we determined that a GQ threshold > 20 and an MAF threshold > 0.01 were optimal. We observed that imputation quality improved with increased sequencing depth, plateauing at 0.5×, and varied with sample size depending on the imputation method. A negative correlation was observed between imputation quality and the ratio of non-synonymous to synonymous substitution rates (Ka/Ks) across chromosomal segments, highlighting the influence of selection pressure on imputation efficacy. Collectively, our findings provide an optimized framework for SNP genotyping using lcWGS in scallops, with implications for aquaculture breeding and genetic research.

Inter and intra population genetic variability in ducks under conservation programs

This study focuses on estimation of the inter and intra population genetic variability of 6 duck populations. Microsatellite loci were used to assess the genetic variation and population structure of 6 duck populations under a conservation program in Poland. DNA polymorphism was assessed using 24 microsatellite markers and 50 individuals from each population. Polymorphism information content (PIC), heterozygosity with 2 estimators of genetic differentiation (FST and GST), and Nei's standard genetic distance were calculated. The results showed that these 6 endangered duck populations showed high genetic polymorphism. Observed heterozygosity within populations ranged from 0.14 to 0.83, with the average value of 0.58. PIC within populations ranged from 0.038 (P-8 and P-9 lines) to 0.89 (LsA line). Average number of alleles in the studied populations ranged from 4.5 (KhO-1 line) to 7.3 (LsA line). Based on the results, the pairs of lines LsA: P-33 and P-8: P-9 were found to be the most related; and the most genetically distant group was KhO-1 line, which originated as a cross between Khaki Campbell with Orpington duck.

Origin and Persistence of Lycopodium clavatum and Lycopodium annotinum (Lycopodiaceae) in Scots Pine Forests.

Understanding the growth dynamics of spore-bearing clonal plant sporophytes and the influence of abiotic and biotic factors is crucial for predicting the persistence of club moss populations and implementing effective habitat management techniques. Despite this, the longevity and development of club-moss populations are rarely studied. This study adopted an integrated approach to assess the probability of repetitive young sporophyte recruitment via sexual propagation in Lycopodium annotinum L. and Lycopodium clavatum L. The size-age problem of clonal spore-bearing forest plants and their niche segregation were addressed. The canopy characteristics, insolation, small-scale disturbance, and genetic polymorphism were studied in temperate semi-natural Scots pine forests in Lithuania. Based on the size of the clones discovered, we hypothesize that initial sporophyte emergence occurred in 20-year-old pine stands, with subsequent sporophyte emergence continuing over time. The emergence was related to small-scale disturbances. High genetic polymorphism indicates that all sporophyte stands studied likely emerged via sexual reproduction. According to Ellenberg values, L. annotinum is related to shady habitats, but our findings show both species coexisting abundantly in the more open habitat, supposedly more suitable for L. clavatum.No significant differences in vegetation relevés and light availability was detected using hemispheric images.

Assessment of Genetic Diversity in Tomato (Solanum lycopersicum) Varieties by Using RAPD Markers

Aim: Assessment of genetic diversity in Tomato (Solanum lycopersicum) varieties by using RAPD markers. Place and Duration of Study: Department of Plant Biotechnology of K. K. Wagh College of Agricultural Biotechnology, Nashik, Maharashtra. Methodology: Tomato is one of the most important vegetable crops in the world and normally human being daily consumed in diet. The five Varities were collected from Mahalaxmi Hi-Tech Nursery Nashik. The present study was conducted at K K Wagh college of Agricultural Biotechnology Nashik. DNA was isolated by using modified CTAB method Five Varities were analyzed through RAPD markers to determine the molecular characterization at individual level. Results: Six arbitrary oligonucleotide primers used in the RAPD-PCR produced a total 38 different marker bands with an average 8 band per primer. Based on the banding pattern 100% polymorphism observed among the tomato varieties. Size range of amplified DNA bands varied from 0.1-10 kb. A total of 14 unique bands were amplified from the genome of the 5 tomato varieties. The dendrogram clustered the tomato varieties into two major clusters. The clusters were subdivided into small groups including the highly related Keshar and 0225, Anisha and Sai-22 varieties. The other Cluster included an isolated variety of Aryaman as a distinctive one. The RAPD data revealed a high genetic polymorphism that can be used to select diverse parents in breeding programs and maintain genetic variation.

Genetic Diversity in Katchaikatty Sheep based on Microsatellites Polymorphism

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

Genetic polymorphism analysis and forensic application evaluation of 57 insertion/deletion polymorphisms from Yi ethnic group in Yunnan

Background As a new kind of diallelic genetic marker, insertion/deletion (InDel) polymorphisms have recently been used in forensic science. However, there are relatively few studies on the forensic evaluation of InDel genetic polymorphisms from different populations. Aim The aim of the present work is to assess the genetic polymorphism and forensic applicability of 57 InDels from the Yi ethnic group and explore the genetic background of this group. Subjects and methods A total sample of 122 unrelated individuals of Yi group from the Yunnan province were genotyped by the AGCU indel 60 Kit. Multiplex population genetic analyses on the same 57 InDels were carried out among the Yunnan Yi group and 29 reference populations. Results The average allele frequency of these loci in the Yi ethnic group was 0.485. Heterozygosity, polymorphism information content, and the power of discrimination were 0.477, 0.362, and 0.612, respectively. The combined power of discrimination and the combined power of exclusion reached to 0.99999999999999999669 and 0.999962965, respectively. The results showed that 57 InDels polymorphisms have high genetic polymorphisms in the Yi ethnic group. Conclusions The 57 InDels could be used for forensic individual identification, paternity testing, and intercontinental population discrimination, with the potential for use in biogeographic ancestry inference.

Forensic efficiency and population genetic construction of Guizhou Gelao minority from Southwest China revealed by a panel of 23 autosomal STR loci.

The first batch of genetic data for 23 autosomal STRs in 490 Geolao individuals from Guizhou was provided.The 23 STR panel can afford high genetic polymorphisms and discrimination power and can be efficiently applied to forensic practice in Guizhou Gelao population.A complex phylogenetic model influenced by ethnic, geographic, and linguistic factors was uncovered.

Genetic polymorphism and clustering of the Plasmodium cynomolgi Duffy binding protein 1 region II of recent macaque isolates from Peninsular Malaysia.

Plasmodium cynomolgi is a simian malaria parasite that has been increasingly infecting humans. It is naturally present in the long-tailed and pig-tailed macaques in Southeast Asia. The P. cynomolgi Duffy binding protein 1 region II [PcDBP1(II)] plays an essential role in the invasion of the parasite into host erythrocytes. This study investigated the genetic polymorphism, natural selection and haplotype clustering of PcDBP1(II) from wild macaque isolates in Peninsular Malaysia. The genomic DNA of 50 P. cynomolgi isolates was extracted from the macaque blood samples. Their PcDBP1(II) gene was amplified using a semi-nested PCR, cloned into a plasmid vector and subsequently sequenced. The polymorphism, natural selection and haplotypes of PcDBP1(II) were analysed using MEGA X and DnaSP ver.6.12.03 programmes. The analyses revealed high genetic polymorphism of PcDBP1(II) (π = 0.026 ± 0.004; Hd = 0.996 ± 0.001), and it was under purifying (negative) selection. A total of 106 haplotypes of PcDBP1(II) were identified. Phylogenetic and haplotype analyses revealed two groups of PcDBP1(II). Amino acid length polymorphism was observed between the groups, which may lead to possible phenotypic difference between them.

Genetic Characterization and Allele Frequencies of Three Populations of Systomus sarana (Hamilton, 1822) of Madhya Pradesh Reveled by Random Amplified Polymorphic DNA

The random amplified polymorphic DNA (RAPD-PCR) technique was examined as a potential tool for identification of genetic stock, gene diversity/gene frequencies studies. During this investigation, total 17 specimens from three study sites i.e., Upper Lake (Bhopal), Kshipra dam (Ujjain) and Wainganga river (Balaghat) were studied and delineated genetic studies and allele frequencies studies among the three populations. Total numbers of multiple loci/DNA fingerprints were 27 in all three populations of which number of polymorphic loci were in 8 in Upper Lake, 11 Kshipra Dam, 8 Wainganga River. Genetic differentiation (GST) among the populations was found to be as 0.5926, estimated gene flow between population as Nm=0.3437, intra-population heterozygosity as HS=0.1518 and total heterozygosity as HT=0.3726 clearly reflecting high genetic polymorphism. Nei’s unbiased genetic identity and genetic distance was obtained as highest distance between Upper Lake and Kishpra dam as 0.7223 however, less genetic distance was obtained between Wainganga River and Khipra dam populations. However, population wise, the genetic analyses in Upper Lake Bhopal indicated lower genetic polymorphism (P) as 29.63% as compared to rest of population’s i.e., Kshipra Dam 40.74% and Wainganga River 62.96%. Nei’s gene diversity (h) was observed as 0.1306 in Upper Lake Bhopal, 0.1288 in Kshipra Dam and 0.1956 Wainganga River reflecting much higher gene diversity in Wainganga River. This may be due to declined of genetic variation in the stocks which could cause by manipulation of habitat as the natural habitat or pressure of anthropogenic activities around the reservoir which may cause the threats of fish habitats.

Genetic polymorphism and variability in the Guangdong Hakka, Teochew, and Cantonese groups: A comprehensive analysis of 19 X-STRs.

X chromosomeshort tandem repeat (X-STR) loci are playing an increasingly important role inforensic work, identifying female traces in male contamination and explainingcomplex kinship analyses. In this study, we analyzed thegenetic polymorphism of 19 X-STR loci in the Guangdong Hakka, Teochew and Cantonese groups, respectively, aswell as in the Guangdong Hakka, Teochew andCantonese pooled Han. The genetic diversity and forensic characteristics of the19 X-STRs and 7 linkage groups were investigated, respectively. The experiments showed that the genetic diversity (GD) and polymorphism information content (PIC) in the pooledGuangdong Han ranged from 0.5320 to 0.9234 and 0.4369 to 0.9171, respectively, and the cumulative power of discrimination for males (PDM), power of discrimination for females (PDF) and mean paternity exclusion chance (MEC) were higher than 0.9999999, indicating that the 19 X-STRs had high geneticpolymorphism and discriminatory power. Genetic differences among Chinese Hansubgroups and among different Chinese populations were investigated byphylogenetic reconstruction and principal component analysis (PCA), respectively. Genetic analyses based on neighbor-joining (NJ) tree and principal component analysis plot showed that Cantonese, Teochew and Hakka were closely genetically related, and different populations with closer linguistic components had more genetic affinity. This study adds to the forensic X-STR database and demonstrates the forensic efficiency of 19 X-STRs for the Hakka, Teochewand Cantonese populations in Guangdong, and the pooled Han of Hakka, Teochewand Cantonese people in Guangdong.

Characterization of 15 CYP2J2 variants identified in the Chinese Han population on the metabolism of ebastine and terfenadine in vitro.

Genetic polymorphism of the cytochrome P450 (CYP) gene can significantly influence the metabolism of endogenous and xenobiotic compounds. However, few studies have focused on the polymorphism of CYP2J2 and its impact on drug catalytic activity, especially in the Chinese Han population. In this study, we sequenced the promoter and exon regions of CYP2J2 in 1,163 unrelated healthy Chinese Han individuals using the multiplex PCR amplicon sequencing method. Then, the catalytic activities of the detected CYP2J2 variants were evaluated after recombinant expression in S. cerevisiae microsomes. As a result, CYP2J2*7, CYP2J2*8, 13 variations in the promoter region and 15 CYP2J2 nonsynonymous variants were detected, of which V15A, G24R, V68A, L166F and A391T were novel missense variations. Immunoblotting results showed that 11 of 15 CYP2J2 variants exhibited lower protein expression than wild-type CYP2J2.1. In vitro functional analysis results revealed that the amino acid changes of 14 variants could significantly influence the drug metabolic activity of CYP2J2 toward ebastine or terfenadine. Specifically, 4 variants with relatively higher allele frequencies, CYP2J2.8, 173_173del, K267fs and R446W, exhibited extremely low protein expression and defective catalytic activities for both substrates. Our results indicated that a high genetic polymorphism of CYP2J2 could be detected in the Chinese Han population, and most genetic variations in CYP2J2 could influence the expression and catalytic activity of CYP2J2. Our data significantly enrich the knowledge of genetic polymorphisms in CYP2J2 and provide new theoretical information for corresponding individualized medication in Chinese and other Asian populations.

Influence of the High Mobility Group A1 genetic polymorphism on indices of metabolic syndrome and insulin resistance in the Iraqi population: Case-control study

ABSTRACT: The high mobility group A1 gene (HMGA1) rs139876191 variant has been related to metabolic syndrome and type 2 diabetes, but data are lacking in Middle Eastern populations. The study aimed to assess whether the HMGA1 rs139876191 variant is associated with metabolic syndrome risk and whether this variant predicts the risk of insulin resistance. This case-control study was carried out at single center in Kirkuk city/ Iraq from February to August 2022. Polymorphisms in HMGA1 and genotyping were identified by Sanger sequencing of genomic DNA obtained from 91 Iraqi participants (61 patients with metabolic syndrome and 30 control). Lipid profile, serum (glucose and insulin), glycated hemoglobin, blood pressure, body mass index, and waist circumference were also measured. The high prevalence of the del/del genotype of rs139876191 was found. Minor allele frequency of rs139876191 was (0.16) in both metabolic syndrome and the control group. A non-significant difference in genotyping was identified between total metabolic syndrome and the control group. The del/ins variant was associated with significantly higher waist circumference, triglyceride(TG), low-density lipoprotein(LDL), very low-density lipoprotein(VLDL), and glycated hemoglobin(HbA1c) (P=0.03, 0.041, 0.007, 0.034, and 0.001 respectively), and with significantly lower high-density lipoprotein(HDL) (p=0.000). Linear regression analysis showed no significant effect of the variant (del/ins) on developing insulin resistance. Thus, rs139876191 polymorphism with del/ins genotype in the HMGA1 gene was not associated with metabolic syndrome risk but it was associated with indices of metabolic syndrome including waist circumference, TG, HDL, LDL, VLDL, and HbA1c. Besides, this variant did not predict the risk of insulin resistance.

Identification and drug metabolic characterization of four new CYP2C9 variants CYP2C9*72-*75 in the Chinese Han population.

Cytochrome 2C9 (CYP2C9), one of the most important drug metabolic enzymes in the human hepatic P450 superfamily, is required for the metabolism of 15% of clinical drugs. Similar to other CYP2C family members, CYP2C9 gene has a high genetic polymorphism which can cause significant racial and inter-individual differences in drug metabolic activity. To better understand the genetic distribution pattern of CYP2C9 in the Chinese Han population, 931 individuals were recruited and used for the genotyping in this study. As a result, seven synonymous and 14 non-synonymous variations were identified, of which 4 missense variants were designated as new alleles CYP2C9*72, *73, *74 and *75, resulting in the amino acid substitutions of A149V, R150C, Q214H and N418T, respectively. When expressed in insect cell microsomes, all four variants exhibited comparable protein expression levels to that of the wild-type CYP2C9 enzyme. However, drug metabolic activity analysis revealed that these variants exhibited significantly decreased catalytic activities toward three CYP2C9 specific probe drugs, as compared with that of the wild-type enzyme. These data indicate that the amino acid substitution in newly designated variants can cause reduced function of the enzyme and its clinical significance still needs further investigation in the future.

Allelic and haplotypic polymorphisms and paternal genetic analysis of Chinese Shaanxi Han population utilizing a multiplex Y-STR set

Background The analysis of Y chromosomal genetic markers is of great significance in human genetic fields related to male individuals. The Han nationality is the most populous ethnic group. It is critical to investigate the Y-chromosome short tandem repeat (Y-STR) genetic informativeness of Han nationalities in different Chinese regions in order to gain a comprehensive understanding of their paternal genetic relationships and origin. Aim To assess the allelic and haplotypic polymorphisms of the novel AGCU Y SUPP STR amplification system containing seven Y-STRs in the maximal dataset of the Y-STR Haplotype Reference Database (YHRD) and 17 newly included Y-STRs, and explore the genetic relationships among the Shaanxi Han population and 12 reference populations from China. Subjects and methods A total sample of 220 Han male subjects were obtained from the Shaanxi Province, China, and genotyped by the novel AGCU Y SUPP STR amplification system. Multiplex population genetic analyses derived from the same 16 Y-STR loci were carried out among the Shaanxi Han population and 12 reference populations from China. Results The gene diversities (GD) ranged from the maximum value of 0.9609 (DYS385a,b) to the minimum value of 0.5441 (DYS531). Besides, 217 distinct haplotypes were detected wholly in 220 individuals, of which 214 (98.62%) were exclusive. The entire haplotype diversity (HD) and discrimination capacity (DC) were 0.9999 and 0.9864, respectively, while the haplotype match probability (HMP) was 0.0045. Among the reference populations, the obtained results of population genetic analyses revealed that the Shaanxi Han population had the largest genetic distance with the Guangxi Yao group, but the smallest genetic distance with the Hunan Tujia group. Conclusions These Y-STR loci in the AGCU Y SUPP STR amplification system were of high genetic polymorphisms and the amplification system could be used as a prospective complementary tool for forensic application and paternal genetics in the Shaanxi Han population.

Benchmarking freely available HLA typing algorithms across varying genes, coverages and typing resolutions.

Identifying the specific human leukocyte antigen (HLA) allele combination of an individual is crucial in organ donation, risk assessment of autoimmune and infectious diseases and cancer immunotherapy. However, due to the high genetic polymorphism in this region, HLA typing requires specialized methods. We investigated the performance of five next-generation sequencing (NGS) based HLA typing tools with a non-restricted license namely HLA*LA, Optitype, HISAT-genotype, Kourami and STC-Seq. This evaluation was done for the five HLA loci, HLA-A, -B, -C, -DRB1 and -DQB1 using whole-exome sequencing (WES) samples from 829 individuals. The robustness of the tools to lower depth of coverage (DOC) was evaluated by subsampling and HLA typing 230 WES samples at DOC ranging from 1X to 100X. The HLA typing accuracy was measured across four typing resolutions. Among these, we present two clinically-relevant typing resolutions (P group and pseudo-sequence), which specifically focus on the peptide binding region. On average, across the five HLA loci examined, HLA*LA was found to have the highest typing accuracy. For the individual loci, HLA-A, -B and -C, Optitype's typing accuracy was the highest and HLA*LA had the highest typing accuracy for HLA-DRB1 and -DQB1. The tools' robustness to lower DOC data varied widely and further depended on the specific HLA locus. For all Class I loci, Optitype had a typing accuracy above 95% (according to the modification of the amino acids in the functionally relevant portion of the HLA molecule) at 50X, but increasing the DOC beyond even 100X could still improve the typing accuracy of HISAT-genotype, Kourami, and STC-seq across all five HLA loci as well as HLA*LA's typing accuracy for HLA-DQB1. HLA typing is also used in studies of ancient DNA (aDNA), which is often based on sequencing data with lower quality and DOC. Interestingly, we found that Optitype's typing accuracy is not notably impaired by short read length or by DNA damage, which is typical of aDNA, as long as the DOC is sufficiently high.