Search

The extremely high levels of genetic polymorphism within the human major histocompatibility complex (MHC) limit the usefulness of reference-based alignment methods for sequence assembly. We incorporate a short-read, de novo assembly algorithm into a workflow for novel application to the MHC. MHConstructor is a containerized pipeline designed for high-throughput, haplotype-informed, reproducible assembly of both whole genome sequencing and target capture short-read data in large, population cohorts. To-date, no other self-contained tool exists for the generation of de novo MHC assemblies from short-read data. MHConstructor facilitates wide-spread access to high-quality, alignment-free MHC sequence analysis.

Based on emerging evidence on the role for specific single-nucleotide variants (SNVs) in EIF2AK3 encoding the integrated stress response kinase PERK, in neurodegeneration, we assessed the association of EIF2AK3 SNVs with neurocognitive performance in people with HIV (PWH) using a candidate gene approach. This retrospective study included the CHARTER cohort participants, excluding those with severe neuropsychiatric comorbidities. Genome-wide data previously obtained for 1047 participants and targeted sequencing of 992 participants with available genomic DNA were utilized to interrogate the association of three noncoding and three coding EIF2AK3 SNVs with the continuous global deficit score (GDS) and global neurocognitive impairment (NCI; GDS ≥ 0.5) using univariable and multivariable methods, with demographic, disease-associated, and treatment characteristics as covariates. The cohort characteristics were as follows: median age, 43.1 years; females, 22.8%; European ancestry, 41%; median CD4 + T cell counts, 175/µL (nadir) and 428/µL (current). At first assessment, 70.5% used ART and 68.3% of these had plasma HIV RNA levels ≤ 200 copies/mL. All three noncoding EIF2AK3 SNVs were associated with GDS and NCI (all p  13 were independently associated with GDS and NCI (p

Background: Cytochrome P450 is a superfamily of genes generating hemoproteins that metabolize foreign chemicals as well as endogenous compounds, such as steroids. The human CYP2C genes (CYP2C8, CYP2C9, CYP2C18, CYP2C19) cluster on chromosome 10 and metabolize many clinically useful drugs. CYP2C19 and CYP2C9 have been the most studied while CYP2C8 has been studied less frequently. CYP2C18 has been relatively ignored until recently but its importance has begun to be recognized. Methods and results: We studied the genotypes of 7 pharmacogenetic markers in 3 CYP2C genes: CYP2C19 (rs12248560), CYP2C9 (rs4918758, rs1799853), and CYP2C8 (rs10509681, rs11572103, rs1058930, rs11572080), in one Libyan population and 7 Tunisian populations. Five of the 7 SNPs are in exons and have functional consequences while one intronic SNP is considered to be in close proximity to a regulatory region because of the many studies that report associations with metabolic effects. We carried out principal component analysis (PCA) on the North African populations and 83 other populations from the 1000 Genomes Project and Kidd Laboratory. The geographic clustering observed via PCA was more pronounced when considering multi-SNP haplotype frequencies. Conclusion: This study reveals the intermediate position of North Africans between Europeans and Asians and the varied dissimilarities with other world regions. The genetic variation observed within and between geographic regions have implications for drug metabolism and adverse individual responses to medical treatments. [ABSTRACT FROM AUTHOR]

AbstractBeta-thalassemia is an inherited disorder prevalent in Thailand and Southeast Asia. Several molecular techniques for identifying β-thalassemia mutations have been reported. Next-generation sequencing (NGS) is a type of effective molecular testing with high throughput and accuracy. Hence, this study aims to evaluate a novel barcode-tagged NGS approach based on a short-read assay. A total of 258 samples with 54 different β-thalassemia genotypes related to 32 mutations were gathered and evaluated. A library was constructed with the BTSeqTM kit and sequencing was performed on the Illumina NGS machine. The validation results showed 98.45% concordance with conventional genotypes. Less discordant results (1.55%) were limited to insertional mutations and included one case of each of the following: HBB:c.27dupG, HBB:c.85dupC, HBB:c.216dupT, and HBB:c.440_441dupAC. Five single-nucleotide polymorphisms that derived from the NGS results were also analyzed in terms of allele frequency and revealed significant differences between the wild types and other β-genotypes. Furthermore, this paper is the first to describe rare single-nucleotide polymorphisms including IVS II-109 (C/T), IVS II-258 (G/A), IVS II-613 (T-C), and IVS II-806 (G/C). Interestingly, the C allele of IVS II-806 was found to have 100% linkage with two cases of Hb Tak. The haplotype and phylogenetic analysis was also constructed based on variants and revealed three clusters in the Hb variants, which represented their evolution and genetic background. Finally, NGS with the barcode-tagged method has a high throughput, which is suitable for large population screening. Its cost effectiveness and less complicated process promote its application in further works. [ABSTRACT FROM AUTHOR]

Background: Interferon-induced helicase C domain-containing protein 1 (IFIH1) is one of the main pattern recognition receptors that sense viral RNA and activate host cells to mount an effective antiviral immunity. Methods: A case–control study (90 patients with mild/moderate COVID-19 and 90 matched controls) was performed to explore the association of two variants of the IFIH1 gene with COVID-19 risk using the tetra-primer amplification refractory mutation system-polymerase-chain-reaction method. The first is a missense variant, rs1990760 C/T, and the second is an intergenic variant, rs2111485 A/G. In addition, serum IFIH1 levels were assessed using an ELISA kit. Results: Mutant alleles (T and G, respectively) and corresponding homozygous genotypes (TT and GG, respectively) of both variants were significantly associated with increased risk of COVID-19. IFIH1 levels were significantly higher in patients compared to controls and were favorably affected by the rs1990760 and rs2111485 mutant-type genotypes. Conclusion: IFIH1 protein showed up-regulated levels in the serum of patients with mild/moderate COVID-19. In addition, the IFIH1 gene variants rs1990760 C/T and rs2111485 A/G were associated with susceptibility to COVID-19, and the study suggests that their mutant-type genotypes are not only associated with increased risk of COVID-19 but also contributed to higher serum IFIH1 levels. [ABSTRACT FROM AUTHOR]

Genome-wide association studies typically evaluate the autosomes and sometimes the X Chromosome, but seldom consider the Y or mitochondrial (MT) Chromosomes. We genotyped the Y and MT Chromosomes in heterogeneous stock (HS) rats (Rattus norvegicus), an outbred population created from 8 inbred strains. We identified 8 distinct Y and 4 distinct MT Chromosomes among the 8 founders. However, only 2 types of each nonrecombinant chromosome were observed in our modern HS rat population (generations 81–97). Despite the relatively large sample size, there were virtually no significant associations for behavioral, physiological, metabolome, or microbiome traits after correcting for multiple comparisons. However, both Y and MT Chromosomes were strongly associated with the expression of a few genes located on those chromosomes, which provided a positive control. Our results suggest that within modern HS rats there are no Y and MT Chromosomes differences that strongly influence behavioral or physiological traits. These results do not address other ancestral Y and MT Chromosomes that do not appear in modern HS rats, nor do they address effects that may exist in other rat populations, or in other species. [ABSTRACT FROM AUTHOR]

Rice provides poor yields in acidic soils due to several nutrient deficiencies and metal toxicities. The low availability of phosphorus (P) in acidic soils offers a natural condition for screening genotypes for grain yield and phosphorus utilization efficiency (PUE). The objective of this study was to phenotype a subset of indica rice accessions from 3000 Rice Genome Project (3K-RGP) under acidic soils and find associated genes and alleles. A panel of 234 genotypes, along with checks, were grown under low-input acidic soils for two consecutive seasons, followed by a low-P-based hydroponic screening experiment. The heritability of the agro-morphological traits was high across seasons, and Ward's clustering method identified 46 genotypes that can be used as low-P-tolerant donors in acidic soil conditions. Genotypes ARC10145, RPA5929, and K1559-4, with a higher grain yield than checks, were identified. Over 29 million SNPs were retrieved from the Rice SNP-Seek database, and after quality control, they were utilized for a genome-wide association study (GWAS) with seventeen traits. Ten quantitative trait nucleotides (QTNs) for three yield traits and five QTNs for PUE were identified. A set of 34 candidate genes for yield-related traits was also identified. An association study using this indica panel for an already reported 1.84 Mbp region on chromosome 2 identified genes Os02g09840 and Os02g08420 for yield and PUE, respectively. A haplotype analysis for the candidate genes identified favorable allelic combinations. Donors carrying the superior haplotypic combinations for the identified genes could be exploited in future breeding programs. [ABSTRACT FROM AUTHOR]

Widespread genotyping has enabled the identification of putative recessive mutations that affect fertility through early embryonic fetal loss, or that compromise neonate or calf viability. The use of artificial insemination in the global dairy population can rapidly spread these harmful mutations, and testing for multiple mutations can become relatively expensive if not all tests are available on the same SNP panel. However, it is possible to provide heifer and cow predicted carrier status to farmers at no additional cost if the animals are genotyped with a standard SNP panel. Additionally, for defects where the causal mutation is unknown but a haplotype of markers has been associated with the defect, the carrier status can be predicted based on that haplotype. The aims of this study were 3-fold: (1) to determine the accuracy of imputation of putative causal mutations for recessive deleterious conditions in Australian dairy cattle, (2) to impute carrier status for known recessive deleterious conditions in all genotyped Australian Holstein, Jersey, and Red breed cows, and (3) to determine the changes in carrier frequencies across time for these recessive deleterious mutations. We used the F1 statistic, combining precision and recall, to assess the accuracy of carrier status prediction. We showed that known deleterious mutations can be accurately imputed in Australian Holstein and Jersey cattle that are not directly genotyped for the causal mutation, with F1 ranging between 0.88 and 0.99. For recessive deleterious conditions not included on the standard Australian SNP panel, carrier status could be predicted using a marker haplotype, with F1 ranging from 0.91 to 0.92. Most putative causals and haplotypes were either stable with a low carrier percentage or had a declining carrier percentage. However, several recessive mutations showed a relatively high or increasing percentage, highlighting the importance of detecting carriers to reduce the number of at-risk matings. Furthermore, the high carrier percentage of the recently identified bovine lymphocyte intestinal retention defect mutation emphasizes the importance of detection of novel mutations. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

Aims: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene–gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM). Methods: SNPstats online software (https://www.snpstats.net/start.htm) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus (http://shesisplus.bio-x.cn/SHEsis.html) online software was used for haplotype analysis. Results: A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13–2.01), 1.44 (1.10–1.89) and 1.25 (1.01–1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18–0.79) and 0.37 (0.16–0.80) for codominant and recessive models, respectively. No significant gene–gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68–0.98), P = 0.047. Conclusions: Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk. [ABSTRACT FROM AUTHOR]

Background: Defective hepatitis C virus (HCV) genomes with deletion of the envelope region have been occasionally reported by short-read sequencing analyses. However, the clinical and virological details of such deletion HCV have not been fully elucidated. Methods: We developed a highly accurate single-molecule sequencing system for full-length HCV genes by combining the third-generation nanopore sequencing with rolling circle amplification (RCA) and investigated the characteristics of deletion HCV through the analysis of 21 patients chronically infected with genotype-1b HCV. Result: In 5 of the 21 patients, a defective HCV genome with approximately 2000 bp deletion from the E1 to NS2 region was detected, with the read frequencies of 34–77%, suggesting the trans-complementation of the co-infecting complete HCV. Deletion HCV was found exclusively in decompensated cirrhosis (5/12 patients), and no deletion HCV was observed in nine compensated patients. Comparing the amino acid substitutions between the deletion and complete HCV (DAS, deletion-associated substitutions), the deletion HCV showed higher amino acid mutations in the ISDR (interferon sensitivity-determining region) in NS5A, and also in the TMS (transmembrane segment) 3 to H (helix) 2 region of NS2. Conclusions: Defective HCV genome with deletion of envelope genes is associated with decompensated cirrhosis. The deletion HCV seems susceptible to innate immunity, such as endogenous interferon with NS5A mutations, escaping from acquired immunity with deletion of envelope proteins with potential modulation of replication capabilities with NS2 mutations. The relationship between these mutations and liver damage caused by HCV deletion is worth investigating. [ABSTRACT FROM AUTHOR]

Flowering time of crops is critical for maximizing yield, quality and regional adaptability under target environments. In rice, Heading date 3a (Hd3a) and Rice Flowering Locus T 1 (RFT1) proteins are the key factors of flowering time regulation in the florigen activation complex. However, effects of hd3a and rft1 mutations on the flowering time under long-day conditions are not clear. In this study, we generated single and double mutants of Hd3a and RFT1 in japonica varieties Shen Nong 9816 (SN9816) background, termed hd3a-SNs, rft1-SNs and doub-SNs, by using CRISPR/Cas9 system. The flowering time of hd3a-SN mutants was similar to wild-type (WT); but mutations of RFT1 delayed flowering time by 11 to 14 days comparing to WT under nature long day (NLD) conditions. Double mutants of Hd3a and RFT1 (doub-SNs) exhibited an extremely late flowering phenotype, and they did not flower up to 365 days after regeneration under either NLD or short-day conditions. The leaf emergency rate of RFT1 mutants was similar to WT, suggesting that the late flowering phenotype of rft1-SNs was caused by delayed floral transition, but not by retarded growth. The expression of the key floral organ identity genes was significantly decreased in rft1-SN and doub-SN mutants, resulting in late flowering phenotypes. The expression profiles, evolution and haplotypes of Hd3a and RFT1 was also analyzed. Our studies provide insight into the potential utilization of Hd3a and RFT1 gene resources to improving growth period and regional adaptability in rice breeding. [ABSTRACT FROM AUTHOR]

Introduction: Modern histocompatibility algorithms depend on the comparison and analysis of high-resolution HLA protein sequences and structures, especially when considering epitope-based algorithms, which aim to model the interactions involved in antibody or T cell binding. HLA genotype imputation can be performed in the cases where only low/intermediate-resolution HLA genotype is available or if specific loci are missing, and by providing an individuals' race/ethnicity/ancestry information, imputation results can be more accurate. This study assesses the effect of imputing high-resolution genotypes on molecular mismatch scores under a variety of ancestry assumptions. Methods: We compared molecular matching scores from "ground-truth" highresolution genotypes against scores from genotypes which are imputed from low-resolution genotypes. Analysis was focused on a simulated patient-donor dataset and confirmed using two real-world datasets, and deviations were aggregated based on various ancestry assumptions. Results: We observed that using multiple imputation generally results in lower error in molecular matching scores compared to single imputation, and that using the correct ancestry assumptions can reduce error introduced during imputation. Discussion: We conclude that for epitope analysis, imputation is a valuable and low-risk strategy, as long as care is taken regarding epitope analysis context, ancestry assumptions, and (multiple) imputation strategy. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions The p.Ser71Arg RAB32 variant was recently associated with Parkinson's disease (PD).The aim was to investigate the presence of RAB32 variants in a large multiethnic group of individuals affected and unaffected by PD.We queried our proprietary database that contains exome/genome sequencing data of >180,000 individuals. Additional PD patients were genotyped, and proximal p.Ser71Arg‐associated haplotypes were constructed.p.Ser71Arg was present in 11 PD patients (73% from northern Italy) and in 35 individuals (89% from the Middle East and North Africa [MENA]) aged <50 years without PD‐relevant symptoms. It was found in‐cis to a set of proximal single‐nucleotide polymorphisms. Additional RAB32 variants were comparably frequent in PD and non‐PD individuals.The RAB32 p.Ser71Arg variant defines a cluster of PD patients in northern Italy. Globally, it is most prevalent in MENA. Our data indicate that p.Ser71Arg causes PD and that it occurred only once, through a founder event. Other RAB32 variants are unlikely to cause PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Introduction: Salt stress is one of the significant challenges in sorghum production, greatly impacting the yield of S. bicolor. L-type lectin receptor kinases (LLRKs) are essential for plant stress tolerance, yet a comprehensive genome-level analysis in this species has not been conducted. Materials and methods: Members of the SbLLRLK gene family were identified using bioinformatics methods. Gene structures, motifs, and phylogenetic relationships were analyzed. Subsequently, expression profiles under various stress conditions were examined using transcriptome data. Furthermore, functional validation was performed through homologous gene alignment and transgenic analysis, focusing on the gene SORBI&lowbar;3004G304700. Results: This study identified 49 SbLLRLK genes in Sorghum bicolor, categorized into four groups based on their lectin domain characteristics. Expression analyses revealed diverse patterns under salt, drought, and heat stresses. SORBI&lowbar; 3004G304700 was identified as a negative regulator of salt stress tolerance, with three unique haplotypes identified through haplotype analysis, suggesting a role in salt stress adaptation. Haplotype analysis of SORBI&lowbar;3004G304700 revealed three unique haplotypes, with haplotype1 being the most prevalent, possibly due to selective advantages for salt stress tolerance. Discussion: These findings offer valuable insights into the biological research on the role of the LLRLK gene family in Sorghumbicolor's response to salt stress. The functional characterization of SORBI&lowbar;3004G304700 and the identification of haplotypes associated with salt tolerance provide valuable insights for molecular breeding and genetic enhancement of sorghum. [ABSTRACT FROM AUTHOR]

Background: Fat mass and obesity‐associated gene (FTO) genes rs9939609 is strongly associated with obesity and rs17817449 is an important and potential gene for obesity, have been well established. We aim to evaluate the relationship between FTO gene and overweight/obesity and confirm the influence of obesity on glucose and lipid metabolism parameters. Methods: We investigated 183 normal weight subjects and 193 individuals with overweight/obesity. Firstly, the effect of overweight/obesity on glucose and lipid metabolism parameters was analyzed. Then, the FTO genes rs9939609 and rs17817449 were counted to explore whether polymorphisms were associated with overweight/obesity and metabolic parameters. Results: Significant differences existed in glucose and lipid parameters between the group with overweight/obesity and control group. The rs9939609 and rs17817449 were strongly correlated with overweight/obesity. Haplotype analysis revealed that GA and GT haplotypes had 2.99 and 1.81 fold risk of overweight/obesity. FTO polymorphism also has effects on glucose and lipid metabolism parameters. Conclusions: There is a linkage imbalance between rs9939609 and rs17817449 in a Central China general population cohort, which also reflected the influence of FTO gene on the risk of overweight/obesity and total cholesterol (TC), triglyceride (TG), and high‐density lipoprotein (HDL) disorders. The new findings could provide new clues to predict obesity and metabolic diseases. [ABSTRACT FROM AUTHOR]

Mathematical ability is influenced by genes and environment. This study focused on the effect of DRD2, a candidate gene for working memory, on mathematical ability. The results in child participants revealed associations between the DRD2 gene and mathematical ability. It was found that individual's mathematical ability was influenced by Single Nucleotide Polymorphisms (SNPs) in DRD2, both in the form of haplotypes and in the way of interaction with parental education. These findings suggest that dopaminergic genes are linked to mathematical ability. This study provides evidence for the genetic basis of mathematical ability and offers guidance for personalized intervention in mathematical education. [ABSTRACT FROM AUTHOR]

Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C>T, 1236C>T, 2677G>T/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1–14 days, 15–30 days, 31–60 days, and beyond 60 days post-transplantation. The analysis included allele, genotype, haplotype, and diplotype frequencies of the three SNPs concerning Tc blood levels. Statistical significance was determined, and false discovery rate (PFDR) correction was applied where appropriate. Significant associations were found between the C (ABCB1 C1236T), A alleles (ABCB1 G2677T/A), the CAC haplotype and lower Tc levels. The CAC-TGT and TGT-TGT diplotypes significantly influence how patients metabolize the drug. The TGT haplotype and the AA genotype (ABCB1 G2677T/A) were associated with higher Tc levels, suggesting a long-term genetic influence. Genetic factors, specifically certain SNPs and diplotypes, significantly impact Tc blood levels, with their influence varying over time. [ABSTRACT FROM AUTHOR]

Common single-nucleotide variants (SNVs) of eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) slightly increase the risk of disorders in the periphery and the central nervous system. EIF2AK3 encodes protein kinase RNA-like endoplasmic reticulum kinase (PERK), a key regulator of ER stress. Three exonic EIF2AK3 SNVs form the PERK-B haplotype, which is present in 28% of the global population. Importantly, the precise impact of these SNVs on PERK activity remains elusive. In this study, we demonstrate that PERK-B SNVs do not alter PERK expression or basal activity in vitro and in the novel triple knock-in mice expressing the exonic PERK-B SNVs in vivo. However, the kinase activity of PERK-B protein is higher than that of PERK-A in a cell-free assay and in mouse liver homogenates. Pancreatic tissue in PERK-B/B mice also exhibit increased susceptibility to apoptosis under acute ER stress. Monocyte-derived macrophages from PERK-B/B mice exhibit higher PERK activity than those from PERK-A/A mice, albeit with minimal functional consequences at acute timepoints. The subtle PERK-B-driven effects observed in liver and pancreas during acute stress implicate PERK as a contributor to disease susceptibility. The novel PERK-B mouse model provides valuable insights into ER stress-induced PERK activity, aiding the understanding of the genetic basis of disorders associated with ER stress. [ABSTRACT FROM AUTHOR]

Background: The Csangos are an East-Central European ethnographic group living mainly in east of Transylvania in Romania. Traditionally, ethnography distinguishes three Csango subpopulations, the Moldavian, Gyimes and Burzenland Csangos. In our previous study we found that the Moldavian Csangos have East Asian/Siberian Turkic ancestry components that might be unique in the East-Central European region and might help to better understand the history of Hungarian speaking ethnic groups of the area. Since then, we obtained further Csango samples from Moldavia and from a distinct region of Gyimes, which two Csango subgroups are traditionally different since they live in a degree of isolation not only from other people but also from each other. Here we present the first genomic analysis of Gyimes Csangos, which intended to compare the genetic makeup of these two Csango subgroups using both allele-frequency and haplotype-based methods. The main goal of the study was to investigate the genetic isolation of the Csangos on a genome-wide SNP basis and to assess the isolation of Gyimes Csangos, which in contrast to the Moldavians was not yet studied. Results: Our results show that these two Csango groups show slight differences from each other. We confirmed the genetic isolation of Moldavian Csangos and revealed that Gyimes Csangos have a similar, but detectably weaker isolation. In the case of Gyimes Csangos we detected also a stronger East European or presumably Asian derived ancestry. Conclusion: The Gyimes Csangos show a degree of genetic isolation comparable to that of the Moldavians. The Asian ancestry that differentiates the Moldavian Csango people from the other East-Central European populations may be present in the Gyimes Csangos in an even higher degree, since Gyimes Csango individuals show a more significant share from that ancestry component. [ABSTRACT FROM AUTHOR]

Background: The ethnic diversity of India provides a unique opportunity to study the history of the origin of mutations of genetic disorders. Spinocerebellar ataxia type 27B (SCA27B), a recently identified dominantly inherited cerebellar disorder is caused by GAA-repeat expansions in intron 1 of Fibroblast Growth Factor 14 (FGF14). Predominantly reported in the European population, we aimed to screen this mutation and study the founder haplotype of SCA27B in Indian ataxia patients. Methods: We have undertaken screening of GAA repeats in a large Indian cohort of ~ 1400 uncharacterised ataxia patients and kindreds and long-read sequencing-based GAA repeat length assessment. High throughput genotyping-based haplotype analysis was also performed. We utilized ~ 1000 Indian genomes to study the GAA at-risk expansion alleles. Findings: We report a high frequency of 1.83% (n = 23) of SCA27B in the uncharacterized Indian ataxia cohort. We observed several biallelic GAA expansion mutations (n = 5) with younger disease onset. We observed a risk haplotype (AATCCGTGG) flanking the FGF14-GAA locus over a 74 kb region in linkage disequilibrium. We further studied the frequency of this risk haplotype across diverse geographical population groups. The highest prevalence of the risk haplotype was observed in the European population (29.9%) followed by Indians (21.5%). The observed risk haplotype has existed through ~ 1100 generations (~ 22,000 years), assuming a correlated genealogy. Interpretation: This study provides valuable insights into SCA27B and its Upper Paleolithic origin in the Indian subcontinent. The high occurrence of biallelic expansion is probably relevant to the endogamous nature of the Indian population. [ABSTRACT FROM AUTHOR]

Introduction: Prickles are often deemed undesirable traits in many crops, including roses (Rosa sp.), and there is demand for rose cultivars with no or very few prickles. This study aims to identify new and/or validate reported quantitative trait loci (QTLs) associated with stem and leaf rachis prickle density, characterize the effects of functional haplotypes for major QTLs, and identify the sources of QTL-alleles associated with increased/decreased prickle density in roses. Methods: QTL mapping using pedigree-based analysis (PBA), and haplotype analysis were conducted on two multi-parental diploid rose populations (TX2WOB and TX2WSE). Results and discussion: Twelve QTLs were identified on linkage groups (LGs) 2, 3, 4, and 6. The major QTLs for the stem prickle density were located between 42.25 and 45.66 Mbp on chromosome 3 of the Rosa chinensis genome assembly, with individual QTLs explaining 18 to 49% of phenotypic variance (PVE). The remaining mapped QTLs were minor. As for the rachis prickle density, several QTLs were detected on LG3, 4, and 6 with PVE 8 to 17%. Also, this study identified that ancestors R. wichurana 'Basye's Thornless', 'Old Blush', and the pollen parent of M4-4 were common sources of favorable alleles (q) associated with decreased prickle density, whereas 'Little Chief' and 'Srche Europy' were the source of unfavorable alleles (Q) in the TX2WOB and TX2WSE populations, respectively. The outcomes of this work complement other studies to locate factors that affect prickle density. These results can also be utilized to develop high-throughput DNA tests and apply parental selection to develop prickle-free rose cultivars. [ABSTRACT FROM AUTHOR]

The current study aimed at population genetic characterization of B. vogeli based on the cytochrome b (cyt b) gene sequences (≥ 685 bp) available in the GenBank. Phylogenetic trees placed all the sequences of B. vogeli in a single large monophyletic clade; however, it was further divided into two subclades (Bv1 and Bv2). Out of seven nucleotide variations observed between Bv1 and Bv2 subclades, four were synonymous (G92A, C170T, T488C and A659G), and three were non-synonymous (G324A, C438A and G465A) resulting in amino acid substitutions at three places (V108I, L146I and V155I). Within different B. vogeli populations, the nucleotide and haplotype diversities were low. The median-joining haplotype network revealed only two haplotypes (Hap_1 and Hap_2). A geographical sub-structuring was noticed in the B. vogeli populations, with moderate genetic differentiation (FST = 0.05000; P < 0.05) and a very high gene flow (Nm = 4.75) between Indian and Chinese populations. Neutrality tests and mismatch distributions for the Indian population and the overall dataset of B. vogeli indicated a constant population size. This study provides the first insight into the genetic characterization, population genetics and haplotype network of B. vogeli based on the cyt b gene. [ABSTRACT FROM AUTHOR]

To investigate the genetic relationship between end stage renal disease (ESRD) and human leukocyte antigen (HLA) alleles in the Guangxi Zhuang population. We performed polymerase chain reaction reversed sequence-specific oligonucleotide (PCR-rSSO) in 325 patients with ESRD and genotyped the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci. The direct counting method was used to determine the frequencies of HLA alleles, and Arlequin software (version 3.5.2.2) was used for haplotypic frequency analyses to compare the included ESRD patients with 350 healthy donors from the Guangxi Zhuang population. In our study, 120 HLA alleles, 284 HLA-A-B-DRB1 haplotypes, and 332 HLA-A-C-B-DRB1-DQB1 haplotypes were detected. We found that only A*11:01-B*15:02-DRB1*12:02 had a positive association with ESRD (P = 0.001, Pc = 0.020, OR = 3.106, 95% CI = 1.497–6.446) after Bonferroni correction; thus, individuals with this haplotype may be susceptible to ESRD. A*11:01-B*15:02-DRB1*12:02 is a potentially valuable haplotype for evaluating the risk of ESRD in the Guangxi Zhuang population. [ABSTRACT FROM AUTHOR]

Objective: The genetic background of HLA-B*27 in spondyloarthritis is known, and the search for another gene with similar role is ongoing. We wanted to investigate clinical presentations of HLA-B*44 patients in rheumatology practice. Methods: A cross-sectional retrospective study of 303 HLA-B*44 adult patients from the outpatient rheumatology clinic from 5/2018-5/2024. Clinical phenotype, confirmed or excluded rheumatic diagnosis, therapy used, and data on HLA A, B, and DR alleles inherited with B*44 were analyzed. Results: A female predominance of 2.79:1 was noted. A total of 150 [49.5%] patients were referred due to peripheral joint pain, 77 [25.4%] due to combined spine and peripheral joint pain or spine alone (57 [18.8%]). A total of 19 [6.3%] patients had no symptoms of the musculoskeletal system. Statistically significant peripheral joint affection was proved in females but not in males (p = 0.04). A total of 121 [40%] patients from B*44 group had established rheumatic disease, with the rest being excluded or under observation. The most common working diagnoses were polyarthritis (32 [10.5%]) and mono-oligoarthritis (14 [4.6%]). A second allele in addition to HLA B*44 showed a similar frequency to the general population. Patients with HLA B*44/44 and B*27/44 genotypes were at the most risk for having definitive rheumatic disease (>60%). Conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) were used in 38.6% of patients, non-steroidal anti-inflammatory drugs were used in 31.6% of patients, biologic DMARDs were used in 8.9% of patients, and corticosteroids were used in 7.3% of patients. Conclusions: The most common presentation in HLA-B*44 patients is peripheral joint affection. Most patients with HLA-B*27/44 and B*44/44 genotypes had definitive rheumatic disease. B*44 homozygosity or B*27/44 might be risk factors for arthritis development. [ABSTRACT FROM AUTHOR]

Tiller angle (TA) is one of the most important agronomic traits that directly affects plant architecture, photosynthetic efficiency, and planting density of rice. Although many quantitative trait loci (QTLs) and associated genes for TA have been identified, the detection of TA QTLs still needs attention. This study used 238 micro-core germplasm populations for genome-wide association analysis (GWAS) of the TA. The frequency distribution of TA presented continuity in 2018 and 2019, with five QTLs designated as qTA1, qTA2, qTA6, qTA9, and qTA12. These QTLs explained phenotypic variation ranging from 5.94 to 12.38%. Among them, qTA2 and qTA6 were new QTLs of TA, and only qTA1 was detected repeatedly in 2 years. Then, 253 germplasm from the 3K Rice Genome Project were used for candidate gene and haplotypes analysis; the results showed that LOC_Os01g67770, LOC_Os02g35180, and LOC_Os09g38130 were the candidate genes of qTA1, qTA2, and qTA9, respectively. These results provided insight into the genetic improvement of plant architecture in rice. [ABSTRACT FROM AUTHOR]

Introduction. The Fat Mass and Obesity-Associated (FTO) gene encodes a demethylase, which modulates RNA N6-methyladenosine (m6A) and plays a regulatory role in adipocyte differentiation and the pathogenesis of human obesity. Methods. To understand the potential role of FTO in osteoporosis (OP), we investigated five single nucleotide variations (SNVs) in intron 1 (rs8057044, rs8050136, rs9939609, rs62033406, and rs9930506) of the FTO gene, and a missense SNV i.e., rs3736228 (A1330V), located in exon 18 of the LRP5 gene, in a cohort of postmenopausal women (n = 188) from Central Europe. Genotyping was performed with an allele discrimination assay, while haplotypes were reconstructed in the population by PHASE 2.1. Results. The rs9930506 was strongly associated with OP (p < 0.0035), which was supported by Bonferroni correction (p < 0.0175), and all SNVs located in the FTO gene were more strongly associated with severe OP with fragility fractures. Among seventeen haplotypes detected for the FTO gene, two haplotypes (H1 and H9) were frequent (frequency > 10%) and distributed in three main haplotypes pairs (H1/H1, H1/H9 and H9/H9, respectively). The pathogenic pair H1/H9 was associated with a leaner phenotype, increased fracture risk, and a lower bone mineral density (BMD), and carried the heterozygous GA of rs9930506, while the protective pair H9/H9 was associated with an increased obesity risk and carried AA alleles of rs9939609. Conclusions. Concordant associations with OP, an increased fracture risk, and a lower BMD at all skeletal sites indicate that the FTO gene is a promising candidate for OP, explaining the complex relationship with obesity and offering new perspectives for the study of the epigenetic regulation of bone metabolism. [ABSTRACT FROM AUTHOR]

The European eel (Anguilla anguilla (L.)) is a unique catadromous euryhaline fish and the only anguillid eel species classified as 'critically endangered'. The Baltic Lakeland area contains naturally recruited and introduced eels. There is great uncertainty regarding a baseline for the location and number of naturally dispersed eels in the region. Little is known about the genetic structure of the European eel populations in Baltic countries. The estimation of population genetic structure is important for the efficient management of naturally recruited and introduced eels. Two mitochondrial regions were used to investigate the genetic structure within and between eel samples from 11 waterbodies. In this study, new, unique, and widely distributed haplotypes were revealed. The studied eel population in the Baltic Lakeland shows high genetic diversity, which is possibly a result of intensive restocking programs. Sequences characterized for Anguilla rostrata were revealed in both mitochondrial regions. Understanding the genetic structure of eel populations worldwide is crucial for conservation efforts. Eel restocking in waterbodies where natural migration is restricted contributes to diversity loss for the world gene pool of eels. [ABSTRACT FROM AUTHOR]

Simple Summary: The genetic background of color is a very complex issue in both birds and mammals. Color-related genes may be represented by multiple alleles and show many interactions. Black chicken breeds are special due to their solid uniform pigmentation, which in the case of Ayam Cemani also concerns the bones and skin. One of the crucial genes involved in the melanogenesis pathway is MC1R (melanocortin 1 receptor). It is a one-exon gene that has been already studied in many different species and breeds. In the case of chicken breeds, there are numerous alleles of MC1R and they have a significant impact on the final plumage color of the individual. Here, the Ayam Cemani MC1R complete coding sequence is characterized for the first time. A new MC1R missense substitution has enabled us to distinguish a new haplotype/extended black allele. This is important in terms of completing and supporting current knowledge concerning the genetic background of plumage control, as well as in relation to describing genetic diversity between different breeds. Plumage color is one of the most important traits characterizing chicken breeds. Black-boned chickens constitute a specific group of breeds with a unique phenotype. One of the representatives is the Indonesian Ayam Cemani. The extraordinary black phenotype results from a specific chromosomal rearrangement. We used complete CDS of crucial color-related gene MC1R, which plays a key role in melanin distribution but has not been previously studied in Ayam Cemani. It turned out that Ayam Cemani individuals possess a newly found non-synonymous mutation G355A resulting in amino acid substitution D119N. Together with the presence of G274A (E92K), the new missense variant enabled us to distinguish a new extended black allele at the E locus. All of the investigated birds were heterozygous in terms of the new mutation. Previous studies and our own results indicate a high level of genetic variation within the MC1R gene within and between chicken breeds. Besides the key mutations that make it possible to distinguish particular major alleles, there are also numerous substitutions that give haplotypes more characteristics for individual breeds. [ABSTRACT FROM AUTHOR]

Objective: In the hypothalamic-pituitary-gonadotrophin axis, estrogen plays a key role in the regulation of bone maturation and growth plate closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in a North Indian population. Methods: Four SNPs of ESR1 (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in ISS patients and controls. Linkage disequilibrium (LD) and haplotyping were done by SNPStat and SHEsisPlus software. The extent of LD was determined by calculating D' and R2 values in SNP paired combinations. Results: Fifty-two ISS patients were compared with 68 controls. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility. The frequencies of the rs6557177 CC genotype [p=0.030; odds ratio (OR)=0.13; 95% confidence interval (CI): 0.01-1.10] and rs543650 genotype TT (p=0.043; OR=0.29; 95% CI: 0.09-0.92) were increased in the ISS group compared with controls. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 showed strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. Conclusion: Our study showed that the CC genotype at rs6557177 and TT genotype at rs543650 of ESR1 constituted a risk factor for developing ISS in North Indian children. These findings may lead to a better understanding of the SNPs associated with ISS susceptibility. [ABSTRACT FROM AUTHOR]

Purpose: Sympathetic ophthalmia (SO) is considered as an autoimmune disease with unclear mechanisms. This study investigated the relationship between HLA polymorphisms and SO. Methods: HLA typing was performed using the LABType reverse SSO DNA typing method. The allele and haplotype frequencies were assessed using the PyPop software. Statistical significance of genotype distributions between 116 patients and 84 healthy individuals (control) was determined using Fisher's exact test or Pearson's chi-squared test. Results: The SO group had a higher frequency of HLA-DRB1 * 04:05, HLA-DQB1 * 04:01, DRB1 * 04:05-DQB1 * 04:01 haplotype as compared to the control group (Pc < 0.001 for all). Conclusion: This study revealed that DRB1 * 04:05 and DQB1 * 04:01 alleles, as well as DRB1 * 04:05-DQB1 * 04:01 haplotye could be potential risk factors for SO. [ABSTRACT FROM AUTHOR]

Background: The clinical performance of RHDO‐based NIPD for PKU during early gestation remains under‐evaluated. Furthermore, studies focused on SNP loci obtained by next‐generation sequencing to analyze the genetic evolution of pathogenic variations in PKU is limited. Methods: Maternal peripheral blood, along with proband and paternal samples, was collected between 7 and 12 weeks of gestation. The PAH gene and surrounding high heterozygosity SNPs were targeted for enrichment and sequencing. Fetal genotypes were inferred using RHDO‐based NIPD. High‐resolution PAH haplotypes were used for the analysis of two common pathogenic variants in the Chinese population: c.728G>A and c.1238G>C. Results: Sixty one PKU families participated with an average fetal fraction of 6.08%. The median gestational age was 8+6 weeks. RHDO‐based NIPD successfully identified fetal genotypes in 59 cases (96.72%, 59/62). Two cases failed because of insufficient informative SNPs. In addition, a recombination event was assessed in one fetus of 59 cases. Six, and three haplotypes were identified for c.728G>A(p.Arg243Gln) and c.1238G>C(p.Arg413Pro), respectively. Hap_3 and hap_8 were identified as the ancestral haplotypes for these pathogenic variants, with other haplotypes arising from mutations or recombination based on these ancestral haplotypes. Conclusions: This study validates the feasibility of an RHDO‐based assay for NIPD of PKU in early pregnancy and introduces its application in the demonstration of founder effects in recurrent pathogenic variations, offering new insights into the evolutionary analysis of PAH variations. [ABSTRACT FROM AUTHOR]

Raising cattle is a lucrative business that operates globally but is confronted by many obstacles, such as thermal stress, which results in substantial monetary losses. A vital role of heat shock proteins (HSPs) is to protect cells from cellular damage. HSP90 is a highly prevalent, extremely adaptable gene linked to physiological resilience in thermal stress. This study aimed to find genetic polymorphisms of the HSP90AA1 gene in Karan Fries cattle and explore their relationship to thermal tolerance and production traits. One SNP (g.3292 A > C) was found in the Intron 8 and three SNPs loci (g.4776 A > G, g.5218T > C and g.5224 A > C) were found in the exon 11 of 100 multiparous Karan Fries cattle. The association study demonstrated that the SNP1-g.3292 A > C was significantly (P < 0.01) linked to the variables respiratory rate (RR), heat tolerance coefficient (HTC) and total milk yield (TMY (kg)) attributes. There was no significant correlation identified between any of the other SNP sites (SNP2-g.4776 A > G; SNP3-g.5218T > C; SNP4-g.5224 A > C) with the heat tolerance and production attributes in Karan Fries cattle. Haploview 4.2 and SHEsis software programs were used to analyse pair linkage disequilibrium and construct haplotypes for HSP90AA1. Association studies indicated that the Hap3 (CATA) was beneficial for heat tolerance breeding in Karan Fries cattle. In conclusion, genetic polymorphisms and haplotypes in the HSP90AA1 were associated with thermal endurance attributes. This relationship can be utilized as a beneficial SNP or Hap marker for genetic heat resistance selection in cow breeding platforms. [ABSTRACT FROM AUTHOR]

Stroke is the second leading cause of death and a major contributor to disability worldwide, with the highest prevalence in developing countries. Ischemic stroke (IS) is a complex disease resulting from genetic and environmental interactions. The present work is a pilot study exploring the association of estrogen receptor-α (ESR1) and aryl hydrocarbon receptor (AHR) SNPs with IS in a small Egyptian population of IS patients. Sixty IS patients and 60 matched healthy controls were included in this case–control study. Genotyping of ESR1 PvuII (rs2234693), ESR1 XbaI (rs9340799), and AHR rs2066853 SNPs was performed using real-time PCR. ESR1 PvuII TC and CC genotypes were associated with IS (odds ratio (OR) = 2.821, 95% confidence interval (CI) = 1.204–6.609, p = 0.017, and OR = 9.455, 95% CI = 2.222–40.237, p = 0.002, respectively), and TC genotype in female IS (OR = 4.018, 95% CI = 1.117–14.455, p = 0.033). Additionally, ESR1 XbaI GA and GG genotypes were associated with IS (OR = 2.833, 95% CI = 1.190–6.749, p = 0.019, and OR = 34.000, 95% CI = 6.965–165.980, p < 0.001, respectively), and the AG and GG genotypes in male IS (OR = 3.378, 95% CI = 1.103–10.347, p = 0.033 and OR = 22.8, 95% CI = 2.580–201.488, p = 0.005, respectively) and the GG genotype in female IS (95% CI = 7.259–1115.914, p < 0.001). ESR1 PvuII and XbaI haplotypes C—A, T—G, and C—A increased the risk of IS in both genders, in male IS, and in female IS apart from C—A. The AG genotype of AHR rs2066853 was associated with male IS (OR = 6.900, 95% CI = 2.120–22.457 p = 0.001). ESR1 PvuII, ESR1 XbaI, and AHR rs2066853 SNPs are associated with IS in Egyptians. However, this is a small sample, and the findings should be replicated in a larger population. [ABSTRACT FROM AUTHOR]

Background: Macracanthorhynchus hirudinaceus (Pallas, 1781) is a zoonotic acanthocephalan that parasitizes the small intestine of wild boars. It is a pathogenic that causes economic losses, and poses a public health threat due to increased emergence. Purpose: The aims of this study is describes histopathologically the damage caused by M. hirudinaceus in the small intestine of wild boar Sus scrofa Linnaeus, 1758, and molecularly characterize this parasite (sequences, haplotypes, phylogeny) for the first time in Elazig city, Türkiye. Results: A high prevalence of infection was obtained. Upon separating the worms, it was discovered that there were ulcers resembling craters in the center, of the small intestine mucosa, surrounded by edema. The intestine wall where the parasite attached was damaged, with the villi epithelium and lamina propria in the mucosa being destroyed. The genomic DNA was isolated from all M. hirudinaceus samples, and PCR amplified the 489 bp gene fragments were sequenced and confirmed that all 21 sequences were M. hirudinaceus. The haplotype analysis of the sequences revealed the presence of a central star-shaped haplotype, in addition to four other haplotypes. Conclusion: After conducting sequence analysis, the genetic differences between the M. hirudinaceus sequences obtained in this study and those reported from Europe and Japan suggest that this parasite is endemic to Türkiye's local wild boar population. Also, four haplotypes were identified, distinguishing it from other haplotypes by 1–5 mutation steps. It is essential to consider the worm's sequences and the formation of haplotypes, since these intrinsic characteristics may impact in the epidemiology and pathology of the worm in the future. [ABSTRACT FROM AUTHOR]

Macrophytes harbor numerous potentially invasive species that pose a threat to biodiversity and ecosystem services in freshwater environments. Egeria densa (Hydrocharitaceae) stands out as a prominent invasive species, recognized as a significant global invader across various ecosystems. In this study, we conducted an assessment of the genetic variability of this species in four Brazilian reservoirs, which are part of the species' native range, employing the internal transcribed spacer (ITS) from the nuclear marker and the intergenic chloroplast marker trnL-trnF. The obtained sequences were then compared with those available in GenBank (NCBI). The results of our investigation revealed a low genetic differentiation among the sampled populations. For ITS and trnL-trnF, we identified four and three distinct haplotypes, respectively, with a predominant single haplotype shared by most specimens. Notably, we did not observe a discernible phylogeographic structure. The data we obtained represents the first sequences of E. densa within its native habitat, providing valuable insights on its genetic diversity and helping to understand invasive processes. [ABSTRACT FROM AUTHOR]

Bovine theileriosis is a protozoan disease caused by the intracellular parasite (Theileria spp.) transmitted by ticks and it is considered one of the most significant parasitic diseases, potentially endangering Egyptian cattle herd industry. The present study was conducted for a molecular survey of bovine theileriosis and its associated risk factors (season variations, geographical locations, breeds, age, sex, tick infestation, and acaricide applications) in three Egyptian governorates, Beni-Suef, Al-Faiyum, and Al-Minya for a year extended from December 2021 to November 2022, in addition, genetic diversity of Theileria isolates. A total of 961 cattle were examined for Theileria infection clinically, microscopically, and by Polymerase Chain Reaction (PCR) using 18S rRNA gene for piroplasms DNA detection, Theileria genus-specific primers of the small subunit of rRNA gene, and Theileria annulata specific primers of the Tams-1 gene. The prevalence rate of bovine theileriosis was 9.26%, and 11.86% using Giemsa-stained blood smear and PCR, respectively. All positive samples screened by Theileria genus-specific primers were positive for T. annulata when screened by the specific primers. Based on molecular screening, season, cattle breeds and acaricide applications were considered risk factors for T. annulata infection, while locality, age, sex and tick infestation had insignificant effects with the occurrence of the disease. A potential novel T. annulata haplotype based on the Tam-1 gene was identified with accession numbers OR364144 and OR915851. Therefore, T. annulata was the only Theileria species found and played a significant problem in the cattle population. This study could be the basis for future studies on unexplored regions and different animal species for well-structured prevention and control measures. [ABSTRACT FROM AUTHOR]

Abstract Background Interferon-induced helicase C domain-containing protein 1 (IFIH1) is one of the main pattern recognition receptors that sense viral RNA and activate host cells to mount an effective antiviral immunity. Methods A case–control study (90 patients with mild/moderate COVID-19 and 90 matched controls) was performed to explore the association of two variants of the IFIH1 gene with COVID-19 risk using the tetra-primer amplification refractory mutation system-polymerase-chain-reaction method. The first is a missense variant, rs1990760 C/T, and the second is an intergenic variant, rs2111485 A/G. In addition, serum IFIH1 levels were assessed using an ELISA kit. Results Mutant alleles (T and G, respectively) and corresponding homozygous genotypes (TT and GG, respectively) of both variants were significantly associated with increased risk of COVID-19. IFIH1 levels were significantly higher in patients compared to controls and were favorably affected by the rs1990760 and rs2111485 mutant-type genotypes. Conclusion IFIH1 protein showed up-regulated levels in the serum of patients with mild/moderate COVID-19. In addition, the IFIH1 gene variants rs1990760 C/T and rs2111485 A/G were associated with susceptibility to COVID-19, and the study suggests that their mutant-type genotypes are not only associated with increased risk of COVID-19 but also contributed to higher serum IFIH1 levels.

Abstract The extremely high levels of genetic polymorphism within the human major histocompatibility complex (MHC) limit the usefulness of reference-based alignment methods for sequence assembly. We incorporate a short-read, de novo assembly algorithm into a workflow for novel application to the MHC. MHConstructor is a containerized pipeline designed for high-throughput, haplotype-informed, reproducible assembly of both whole genome sequencing and target capture short-read data in large, population cohorts. To-date, no other self-contained tool exists for the generation of de novo MHC assemblies from short-read data. MHConstructor facilitates wide-spread access to high-quality, alignment-free MHC sequence analysis.

Abstract Mathematical ability is influenced by genes and environment. This study focused on the effect of DRD2, a candidate gene for working memory, on mathematical ability. The results in child participants revealed associations between the DRD2 gene and mathematical ability. It was found that individual’s mathematical ability was influenced by Single Nucleotide Polymorphisms (SNPs) in DRD2, both in the form of haplotypes and in the way of interaction with parental education. These findings suggest that dopaminergic genes are linked to mathematical ability. This study provides evidence for the genetic basis of mathematical ability and offers guidance for personalized intervention in mathematical education.

Abstract Background The Csangos are an East-Central European ethnographic group living mainly in east of Transylvania in Romania. Traditionally, ethnography distinguishes three Csango subpopulations, the Moldavian, Gyimes and Burzenland Csangos. In our previous study we found that the Moldavian Csangos have East Asian/Siberian Turkic ancestry components that might be unique in the East-Central European region and might help to better understand the history of Hungarian speaking ethnic groups of the area. Since then, we obtained further Csango samples from Moldavia and from a distinct region of Gyimes, which two Csango subgroups are traditionally different since they live in a degree of isolation not only from other people but also from each other. Here we present the first genomic analysis of Gyimes Csangos, which intended to compare the genetic makeup of these two Csango subgroups using both allele-frequency and haplotype-based methods. The main goal of the study was to investigate the genetic isolation of the Csangos on a genome-wide SNP basis and to assess the isolation of Gyimes Csangos, which in contrast to the Moldavians was not yet studied. Results Our results show that these two Csango groups show slight differences from each other. We confirmed the genetic isolation of Moldavian Csangos and revealed that Gyimes Csangos have a similar, but detectably weaker isolation. In the case of Gyimes Csangos we detected also a stronger East European or presumably Asian derived ancestry. Conclusion The Gyimes Csangos show a degree of genetic isolation comparable to that of the Moldavians. The Asian ancestry that differentiates the Moldavian Csango people from the other East-Central European populations may be present in the Gyimes Csangos in an even higher degree, since Gyimes Csango individuals show a more significant share from that ancestry component.

Abstract Haplotype information is crucial for biomedical and population genetics research. However, current strategies to produce de novo haplotype-resolved assemblies often require either difficult-to-acquire parental data or an intermediate haplotype-collapsed assembly. Here, we present Graphasing, a workflow which synthesizes the global phase signal of Strand-seq with assembly graph topology to produce chromosome-scale de novo haplotypes for diploid genomes. Graphasing readily integrates with any assembly workflow that both outputs an assembly graph and has a haplotype assembly mode. Graphasing performs comparably to trio phasing in contiguity, phasing accuracy, and assembly quality, outperforms Hi-C in phasing accuracy, and generates human assemblies with over 18 chromosome-spanning haplotypes.

Abstract To investigate the genetic relationship between end stage renal disease (ESRD) and human leukocyte antigen (HLA) alleles in the Guangxi Zhuang population. We performed polymerase chain reaction reversed sequence-specific oligonucleotide (PCR-rSSO) in 325 patients with ESRD and genotyped the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci. The direct counting method was used to determine the frequencies of HLA alleles, and Arlequin software (version 3.5.2.2) was used for haplotypic frequency analyses to compare the included ESRD patients with 350 healthy donors from the Guangxi Zhuang population. In our study, 120 HLA alleles, 284 HLA-A-B-DRB1 haplotypes, and 332 HLA-A-C-B-DRB1-DQB1 haplotypes were detected. We found that only A*11:01-B*15:02-DRB1*12:02 had a positive association with ESRD (P = 0.001, P c = 0.020, OR = 3.106, 95% CI = 1.497–6.446) after Bonferroni correction; thus, individuals with this haplotype may be susceptible to ESRD. A*11:01-B*15:02-DRB1*12:02 is a potentially valuable haplotype for evaluating the risk of ESRD in the Guangxi Zhuang population.

Abstract The current study aimed at population genetic characterization of B. vogeli based on the cytochrome b (cyt b) gene sequences (≥ 685 bp) available in the GenBank. Phylogenetic trees placed all the sequences of B. vogeli in a single large monophyletic clade; however, it was further divided into two subclades (Bv1 and Bv2). Out of seven nucleotide variations observed between Bv1 and Bv2 subclades, four were synonymous (G92A, C170T, T488C and A659G), and three were non-synonymous (G324A, C438A and G465A) resulting in amino acid substitutions at three places (V108I, L146I and V155I). Within different B. vogeli populations, the nucleotide and haplotype diversities were low. The median-joining haplotype network revealed only two haplotypes (Hap_1 and Hap_2). A geographical sub-structuring was noticed in the B. vogeli populations, with moderate genetic differentiation (FST = 0.05000; P

INTRODUCTION: In the hypothalamic-pituitary-gonadotrophin axis, estrogen plays a key role in the regulation of bone maturation and growth plate closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in a North Indian population. METHODS: Four SNPs of ESR1 (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in ISS patients and controls. Linkage disequilibrium (LD) and haplotyping were done by SNPStat and SHEsisPlus software. The extent of LD was determined by calculating D’ and R2 values in SNP paired combinations. RESULTS: Fifty-two ISS patients were compared with 68 controls. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility. The frequencies of the rs6557177 CC genotype [p=0.030; odds ratio (OR)=0.13; 95% confidence interval (CI): 0.01-1.10] and rs543650 genotype TT (p=0.043; OR=0.29; 95% CI: 0.09-0.92) were increased in the ISS group compared with controls. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 showed strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. DISCUSSION AND CONCLUSION: Our study showed that the CC genotype at rs6557177 and TT genotype at rs543650 of ESR1 constituted a risk factor for developing ISS in North Indian children. These findings may lead to a better understanding of the SNPs associated with ISS susceptibility.

Resource-poor areas with moisture deficit lands following aerobic and direct seeded rice (DSR) methods of cultivation face severe problems of iron deficiency. In this study, Bengal and Assam Aus rice panel was phenotyped at the seedling stage using an iron-deprived hydroponic medium for various shoot and root traits. A novel iron deficiency scoring scale was used to classify the tolerance reaction and could range anywhere between 0 and 9, indicating the most tolerant and susceptible, respectively. The GWAS results identified four putative candidate genes; OsFLA for number of leaves and shoot length, OsBIDK1 for root traits; average diameter, volume, biomass, projected area, and surface area, OsHPL3 for chlorophyll index of the third leaf and AKR2B (XBOS252) was for Fe score, (which was earlier reported in relation to Xa21). The nsSNP (nsSNPs) variations in these gene sequences were used to group the panel and identify superior haplotypes and donors. BR16 was identified as a superior donor, with higher chlorophyll index and shoot length than RA23, also higher values for root traits like root average diameter, root volume, root projected area and root surface area followed by Shete Bhado. The impact of identified nsSNPs on protein structure and stability was investigated. The conserved domains detected in the mutated proteins of the superior haplotypes are very informative, highlighting that natural selection favors abiotic stress tolerant variants in resource poor areas. Thus, justifying our choice of Aus landraces for association mapping of Fe deficiency tolerant genes in rice. [ABSTRACT FROM AUTHOR]

The Zhejiang Han population, a subgroup of the Southern Han ethnic group, resides in Zhejiang Province, situated on the southeast coast of China. In this study, we conducted HLA genotyping for 813 voluntary umbilical cord blood donors from the Zhejiang Han population, targeting 11 HLA loci, namely HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1, using the next-generation sequencing method. Our analysis of the alleles and haplotypes revealed a high degree of polymorphism within these loci. A total of 289 unique HLA alleles were identified, with the HLA-B locus exhibiting the most significant diversity, while HLA-DRB4 displayed the lowest variation. Due to the inherent limitations of the sequencing method, some unresolvable alleles in the specific loci, such as HLA-DRB1, HLA-DPA1, and HLA-DPB1, were assigned as G group designation. In our comprehensive analysis across all 11 HLA loci, a total of 1204 haplotypes were estimated. The distribution of these alleles was similar to those of the Chinese Southern Han population while highly different from the Caucasian population. These findings contribute to a deeper understanding of the genetic characteristics of HLA loci within the Chinese Southern Han population. [ABSTRACT FROM AUTHOR]

The structural and environmental heterogeneity within southern Africa has given rise to many morphological forms of Psammophylax rhombeatus distributed throughout the country, with previous studies neglecting the associated molecular significance of these forms. The species' widespread, generalist ecology coupled with the substantial phylogenetic structuring previously acknowledged within the species, makes P. rhombeatus the ideal candidate for phylogeographic analyses. Using 103 samples, representing the full distribution of the species, phylogenetic analyses retrieved four well-supported clades: south-eastern South Africa, south-western South Africa, north-eastern South Africa and western South Africa. Although not variable enough to warrant taxonomic re-evaluation, the clades are phylogenetically distinguishable, with relatively high intraspecific genetic divergence values separating them, irrespective of the small geographic distances separating populations. This is likely a product of the taxon's habitat-generalist lifestyle, enabling them to bypass vicariant barriers that might otherwise cause speciation in less versatile species. The clades are also geographically distinct, with little overlap, indicating previous vicariance, a finding that is supported by the split of P. rhombeatus from P. ocellatus in the mid-Pliocene, followed by the diversification of P. rhombeatus into four clades throughout the Pleistocene. The genetic structuring observed in P. rhombeatus may be a product of population expansion following ancient refugial isolation (potentially Last Glacial Maximum). The morphological groupings highlighted in previous studies are loosely attributable to the molecular clades identified in the phylogenetic reconstruction, highlighting the complex interplay of genetic and morphological characteristics in the process of speciation, and their representation in systematic accounts. [ABSTRACT FROM AUTHOR]

Abstract Drought is a major abiotic stress affecting crop yields. Mapping quantitative trait loci (QTLs) and mining genes for drought tolerance in rice are important for identifying gene functions and targets for molecular breeding. Here, we performed linkage analysis of drought tolerance using a recombinant inbred line population derived from Jileng 1 (drought sensitive) and Milyang 23 (drought tolerant). An ultra-high-density genetic map, previously constructed by our research team using genotype data from whole-genome sequencing, was used in combination with phenotypic data for rice grown under drought stress conditions in the field in 2017–2019. Thirty-nine QTLs related to leaf rolling index and leaf withering degree were identified, and QTLs were found on all chromosomes except chromosomes 6, 10, and 11. qLWD4-1 was detected after 32 days and 46 days of drought stress in 2017 and explained 7.07–8.19% of the phenotypic variation. Two loci, qLRI2-2 and qLWD4-2, were identified after 29, 42, and 57 days of drought stress in 2018. These loci explained 10.59–17.04% and 5.14–5.71% of the phenotypic variation, respectively. There were 281 genes within the QTL interval. Through gene functional annotation and expression analysis, two candidate genes, Os04g0574600 and OsCHR731, were found. Quantitative reverse transcription PCR analysis showed that the expression levels of these genes were significantly higher under drought stress than under normal conditions, indicating positive regulation. Notably, Os04g0574600 was a newly discovered drought tolerance gene. Haplotype analysis showed that the RIL population carried two haplotypes (Hap1 and Hap2) of both genes. Lines carrying Hap2 exhibited significantly or extremely stronger drought tolerance than those carrying Hap1, indicating that Hap2 is an excellent haplotype. Among rice germplasm resources, there were two and three haplotypes of Os04g0574600 and OsCHR731, respectively. A high proportion of local rice resources in Sichuan, Yunnan, Anhui, Guangdong and Fujian provinces had Hap of both genes. In wild rice, 50% of accessions contained Hap1 of Os04g0574600 and 50% carried Hap4; 13.51%, 59.46% and 27.03% of wild rice accessions contained Hap1, Hap2, and Hap3, respectively. Hap2 of Os04g0574600 was found in more indica rice resources than in japonica rice. Therefore, Hap2 has more potential for utilization in future drought tolerance breeding of japonica rice.

Pre-harvest sprouting (PHS) poses a significant global challenge to cereal production, impacting both yield and quality. In this study, we employed genome-wide association studies (GWAS) on diverse rice accessions to identify novel PHS-associated haplotypes. An assessment of 127 cultivated accessions for panicle germination (PHS) and detached grain germination (germination rate of detached grains at the 14th day (D14)) revealed considerable phenotypic variation among rice ecotypes. GWAS analysis identified 91 significant signals at –log10(P-value)>5, including 15 SNPs for PHS and 76 SNPs for D14. A subsequent linkage disequilibrium (LD) block-based GWAS analysis detected 227 significant SNPs for both traits, consisting of 18 nonsynonymous substitutions located on the coding regions of nine genes. Further haplotype analysis identified 32 haplotypes, with 10 specific to cultivated accessions, 19 specific to the wild type, and three shared between them. A phenotypic assessment of major haplotypes revealed significant differences between resistant (Hap1 and Hap2) and susceptible haplotypes (Hap5, Hap27, and Hap28), distinguished by a G/A SNP within a novel gene, Os04g0545200. The identified haplotypes offer promising prospects for haplotype-based breeding aimed at enhancing PHS resistance in rice.

Genetic regulation of the host susceptibility to Mycobacterium tuberculosis (Mtb) and severity of tuberculosis (TB) infection remain incompletely investigated. Identification of particular genes and involved in TB control and immune reactions regulated by these genes is essential for our understanding of pathogenesis of the disease, discovery of drug targets and rational vaccine development. We have shown that mice of the B10.SM (H2ᵛ) strain are extremely TB susceptible; meanwhile, the general genome structure of this mouse strain and the H2ᵛ haplotype itself are poorly characterized. We selected a pool of Mit genetic markers differentiating B10.SM mice from Chr. 17-congenic mice of the B10 strain by the PCR products motility in the electrophoresis setting. TB susceptibility of B10 mice is much lower than that of B10.SM. In the model of infection triggered by two different dosed of Mtb (100 and 600 CFU per mouse) administered via respiratory tract we demonstrated that B10.SM mice have significantly shorter survival time and significantly higher lung mycobacterial multiplication compared to B10 mice. We demonstrated (intracellular staining and ELISA) that IFNγ production in the lungs of infected mice of the two strains corresponds well to their disease phenotypes. Thus, more resistant B10 mice possess significantly more lung IFNγ-positive CD4⁺ T cells and a higher level of IFNγ secretion. We have established (B10х B10.SM) F1 hybrids and demonstrated that the post-infection phenotypes of survival time, lung mycobacterial multiplication and IFNγ production in these mice are intermediate compared to parental mice. Thus, we deal with the genetic trait with incomplete dominance expression. These data were confirmed in F2 hybrids by segregation genetic analysis. To characterize the phenotype of B10.SM mice in more detail, we vaccinated these mice with the BCG vaccine before TB challenge. Vaccination significantly prolonged survival time, diminished mycobacterial multiplication in the lungs and the degree of lung tissue pathology. Thus, a high level of susceptibility to primary infection did not interfere with BCG vaccination efficacy. We intend to continue genetic and immunologic analyses of TB-hyper-susceptible B10.SM mice. Experimental data regarding the cause of extreme disturbances in protection against infection are prerequisite for our better understanding causality of the wide spectrum of TB manifestations in human populations, as well as for rational search for novel vaccines and medications against TB infection.