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Journal of Applied Oral Science :... 2023Periodontitis Stage III-IV, Grade C (PerioC) is a severe form of Periodontitis. The individual genetic background has been shown to be an important etiopathogenic factor...
BACKGROUND
Periodontitis Stage III-IV, Grade C (PerioC) is a severe form of Periodontitis. The individual genetic background has been shown to be an important etiopathogenic factor for the development of this disease in young, systemically healthy, and non-smokers patients. Recently, after exome sequencing of families with a history of the disease, PerioC was associated with three single nucleotide variations (SNVs) - rs142548867 (EEFSEC), rs574301770 (ZNF136), and rs72821893 (KRT25) - which were classified as deleterious or possibly harmful by prediction algorithms.
OBJECTIVE
Seeking to validate these findings in a cohort evaluation, this study aims to characterize the allele and genotypic frequency of the SNVs rs142548867, rs574301770, and rs72821893 in the Brazilian population with PerioC and who were periodontally healthy (PH).
METHODOLOGY
Thus, epithelial oral cells from 200 PerioC and 196 PH patients were harvested at three distinct centers at the Brazilian Southern region, their DNA were extracted, and the SNVs rs142548867, rs574301770, rs72821893 were genotyped using 5'-nuclease allelic discrimination assay. Differences in allele and genotype frequencies were analyzed using Fisher's Exact Test. Only the SNV rs142548867 (C > T) was associated with PerioC.
RESULTS
The CT genotype was detected more frequently in patients with PerioC when compared with PH subjects (6% and 0.5% respectively), being significantly associated with PerioC (odds ratio 11.76, p=0.02).
CONCLUSION
rs142548867 represents a potential risk for the occurrence of this disease in the Brazilian population.
Topics: Humans; Brazil; Polymorphism, Single Nucleotide; Periodontitis; Genotype; Alleles; Gene Frequency; Case-Control Studies; Genetic Predisposition to Disease; Peptide Elongation Factors
PubMed: 37466550
DOI: 10.1590/1678-7757-2023-0058 -
HLA Oct 2023The novel HLA-B *56:04:05 allele differs from its most closely related allele B*56:04:01:01 in exon 4.
The novel HLA-B *56:04:05 allele differs from its most closely related allele B*56:04:01:01 in exon 4.
Topics: Humans; Alleles; East Asian People; Asian People; HLA-B Antigens; High-Throughput Nucleotide Sequencing
PubMed: 37339910
DOI: 10.1111/tan.15136 -
Current Research in Translational... Mar 2024The current study aimed to detect the frequency of normal and mutated APOL1 alleles in sickle cell disease (SCD) patients and test their relation with Microalbuminuria,...
PURPOSE OF THE STUDY
The current study aimed to detect the frequency of normal and mutated APOL1 alleles in sickle cell disease (SCD) patients and test their relation with Microalbuminuria, Creatinine, Urea, Glomerular Filtration Rate (GFR), and Body Mass Index (BMI).
PATIENTS AND METHODS
The study included 156 SCD subjects. Serum Creatinine (mg/dl) and Urea (mg/dl) as well as Microalbuminuria (mg/l) level were measured by using Biosystems kit (Biosystems, Barcelona, Spain) and Mindary BA88A semi-automated biochemistry analyzer. Glomerular filtration rate and body mass index were calculated by equations. Blood DNA extraction was achieved by using the modified G-DEX™IIb Genomic DNA Extraction Kit protocol. The PCR was done for the detection of the APOL1 G2 rs60910145 alleles by using allele-specific PCR and primers.
RESULTS
The CC allele was more frequent in study cases (66.7%) than TT allele. The frequency of a mutated allele (CC) was insignificantly higher in males (67.8%) than in females (65.2%) and in rural (70.9%) than urban areas. It is also higher in Shankhab compared to other tribes and subjects 26-37 years compared to other, P˃0.05. Interstingly, the subjects who carry the CC allele showed a significantly higher level of Microalbuminuria, Creatinine, BMI, and Urea compared to those carry TT allele. Moreover, GFR is also higher in subjects who carry CC than TT allele but it is not significant.
CONCULSION
Altogether, the study findings highlighted the link of normal and mutated APOL1 G2 rs60910145 alleles with SCD and displayed the significant value of mutated APOL1 allele in the prediction of early nephropathy in SCD patients.
Topics: Male; Female; Humans; Alleles; Body Mass Index; Apolipoprotein L1; Creatinine; Anemia, Sickle Cell; Biomarkers; Kidney; Urea; DNA
PubMed: 38246019
DOI: 10.1016/j.retram.2023.103414 -
International Journal of Molecular... Jan 2024The CRISPR-Cas12a platform has attracted interest in the genome editing community because the prototypical Acidaminococcus Cas12a generates a staggered DNA double-strand...
The CRISPR-Cas12a platform has attracted interest in the genome editing community because the prototypical Acidaminococcus Cas12a generates a staggered DNA double-strand break upon binding to an AT-rich protospacer-adjacent motif (PAM, 5'-TTTV). The broad application of the platform in primary human cells was enabled by the development of an engineered version of the natural Cas12a protein, called Cas12a Ultra. In this study, we confirmed that CRISPR-Cas12a Ultra ribonucleoprotein complexes enabled allelic gene disruption frequencies of over 90% at multiple target sites in human T cells, hematopoietic stem and progenitor cells (HSPCs), and induced pluripotent stem cells (iPSCs). In addition, we demonstrated, for the first time, the efficient knock-in potential of the platform in human iPSCs and achieved targeted integration of a marker gene into the safe harbor site and a super-exon into in up to 90% of alleles without selection. Clonal analysis revealed bi-allelic integration in >50% of the screened iPSC clones without compromising their pluripotency and genomic integrity. Thus, in combination with the adeno-associated virus vector system, CRISPR-Cas12a Ultra provides a highly efficient genome editing platform for performing targeted knock-ins in human iPSCs.
Topics: Humans; CRISPR-Cas Systems; Pluripotent Stem Cells; Induced Pluripotent Stem Cells; Hematopoietic Stem Cells; Alleles
PubMed: 38256061
DOI: 10.3390/ijms25020985 -
HLA Aug 2023Compared with HLA-A*33:03:01:01, the HLA-A*33:03:55 allele shows one nucleotide substitution at position 6. (Comparative Study)
Comparative Study
Compared with HLA-A*33:03:01:01, the HLA-A*33:03:55 allele shows one nucleotide substitution at position 6.
Topics: Humans; Alleles; Asian People; East Asian People; High-Throughput Nucleotide Sequencing; HLA-A Antigens
PubMed: 37016751
DOI: 10.1111/tan.15060 -
BMC Biology Aug 2023Autopolyploidy is a valuable model for studying whole-genome duplication (WGD) without hybridization, yet little is known about the genomic structural and functional...
BACKGROUND
Autopolyploidy is a valuable model for studying whole-genome duplication (WGD) without hybridization, yet little is known about the genomic structural and functional changes that occur in autopolyploids after WGD. Cyclocarya paliurus (Juglandaceae) is a natural diploid-autotetraploid species. We generated an allele-aware autotetraploid genome, a chimeric chromosome-level diploid genome, and whole-genome resequencing data for 106 autotetraploid individuals at an average depth of 60 × per individual, along with 12 diploid individuals at an average depth of 90 × per individual.
RESULTS
Autotetraploid C. paliurus had 64 chromosomes clustered into 16 homologous groups, and the majority of homologous chromosomes demonstrated similar chromosome length, gene numbers, and expression. The regions of synteny, structural variation and nonalignment to the diploid genome accounted for 81.3%, 8.8% and 9.9% of the autotetraploid genome, respectively. Our analyses identified 20,626 genes (69.18%) with four alleles and 9191 genes (30.82%) with one, two, or three alleles, suggesting post-polyploid allelic loss. Genes with allelic loss were found to occur more often in proximity to or within structural variations and exhibited a marked overlap with transposable elements. Additionally, such genes showed a reduced tendency to interact with other genes. We also found 102 genes with more than four copies in the autotetraploid genome, and their expression levels were significantly higher than their diploid counterparts. These genes were enriched in enzymes involved in stress response and plant defense, potentially contributing to the evolutionary success of autotetraploids. Our population genomic analyses suggested a single origin of autotetraploids and recent divergence (~ 0.57 Mya) from diploids, with minimal interploidy admixture.
CONCLUSIONS
Our results indicate the potential for genomic and functional reorganization, which may contribute to evolutionary success in autotetraploid C. paliurus.
Topics: Humans; Alleles; Tetraploidy; Gene Duplication; Polyploidy; Genomics
PubMed: 37553642
DOI: 10.1186/s12915-023-01668-1 -
Vox Sanguinis Jan 2024The presence of blood subtypes may lead to difficulties in blood group identification; however, third-generation sequencing (TGS) can help in accurately identifying...
BACKGROUND AND OBJECTIVES
The presence of blood subtypes may lead to difficulties in blood group identification; however, third-generation sequencing (TGS) can help in accurately identifying difficult blood groups, and study the serological characteristics and molecular mechanism of Ael subtypes.
MATERIALS AND METHODS
ABO blood group was identified by the standard serological technique, weak blood group antigen was identified by adsorption-elution experiments, ABH substance in the saliva was determined and glycosyltransferase activity of A and B was detected. The ABO gene full-length sequence and promoter region were amplified by specific primers using single-molecule real-time sequencing, with the amplified products being sequenced directly and analysed in real time.
RESULTS
The patient was serologically identified as Ael subtype, and TGS analysis revealed new intron mutations in Ael patients (c.467C>T; c.29-10T>A).
CONCLUSION
The discovery of the new allele and the identification of ABO subtypes can be combined with serological characterization and molecular biological methods.
Topics: Humans; Alleles; Phenotype; Mutation; ABO Blood-Group System; Genotype
PubMed: 37937512
DOI: 10.1111/vox.13557 -
HLA Jan 2024The data enabling the estimation of the possibility of finding a matched unrelated donor (MUD) within a relatively short time is important for the success of...
The data enabling the estimation of the possibility of finding a matched unrelated donor (MUD) within a relatively short time is important for the success of hematopoietic stem cell transplantation (HSCT). In the present study, 738 unrelated Croatian patients in the program of unrelated HSCT were retrospectively analyzed for gender matching, donor origin (national or international), the distribution of HLA alleles and haplotypes, as well as for the probability of finding a 9-10/10 MUD. Almost 70% of the patients in our study group had a 10/10 MUD, while among the patients with a 9/10 MUD, a 1st field resolution level mismatched donor was selected for 55.0% of patients. The majority of pairs were HLA-A mismatched (33.8%). A comparison of HLA allele frequencies between two subgroups of patients revealed significant differences for 13 alleles. However, after p value correction, the difference in frequency remained significant only for four alleles; three HLA alleles (B*08:01, C*07:01, and DRB1*03:01) demonstrated a significantly higher frequency among patients with a 10/10 MUD (Pcorr < 0.0001, Pcorr = 0.0096, and Pcorr < 0.0001, respectively), while the B*35:08 allele was significantly more present among patients with a 9/10 MUD (Pcorr = 0.0328). The comparison of the distribution of HLA haplotypes between patients with a 10/10 MUD and patients with a 9/10 MUD showed significant differences for a number of two-locus and three-locus haplotypes, as well as for one five-locus haplotype (HLA-A*01:01~B*08:01~C*07:01~DRB1*03:01~DQB1*02:01), which was significantly more present in the group of patients with a 10/10 MUD. At least one HLA haplotype from the group of non-frequent HLA haplotypes (positions >1000) was carried by patients with a 9/10 MUD. The data obtained by the present study will contribute to a better estimation of the probability of finding a suitable 9-10/10 MUD for Croatian patients in need of HSCT.
Topics: Humans; Alleles; Retrospective Studies; Tissue Donors; Registries; HLA-A Antigens
PubMed: 38265197
DOI: 10.1111/tan.15348 -
Scientific Reports Sep 2023The BTB/POZ family of proteins is widespread in plants and animals, playing important roles in development, growth, metabolism, and environmental responses. Although...
The BTB/POZ family of proteins is widespread in plants and animals, playing important roles in development, growth, metabolism, and environmental responses. Although members of the expanded BTB/POZ gene family (OsBTB) have been identified in cultivated rice (Oryza sativa), their conservation, novelty, and potential applications for allele mining in O. rufipogon, the direct progenitor of O. sativa ssp. japonica and potential wide-introgression donor, are yet to be explored. This study describes an analysis of 110 BTB/POZ encoding gene loci (OrBTB) across the genome of O. rufipogon as outcomes of tandem duplication events. Phylogenetic grouping of duplicated OrBTB genes was supported by the analysis of gene sequences and protein domain architecture, shedding some light on their evolution and functional divergence. The O. rufipogon genome encodes nine novel BTB/POZ genes with orthologs in its distant cousins in the family Poaceae (Sorghum bicolor, Brachypodium distachyon), but such orthologs appeared to have been lost in its domesticated descendant, O. sativa ssp. japonica. Comparative sequence analysis and structure comparisons of novel OrBTB genes revealed that diverged upstream regulatory sequences and regulon restructuring are the key features of the evolution of this large gene family. Novel genes from the wild progenitor serve as a reservoir of potential new alleles that can bring novel functions to cultivars when introgressed by wide hybridization. This study establishes a foundation for hypothesis-driven functional genomic studies and their applications for widening the genetic base of rice cultivars through the introgression of novel genes or alleles from the exotic gene pool.
Topics: Animals; Alleles; Oryza; Phylogeny; Genes, Duplicate; Brachypodium
PubMed: 37726366
DOI: 10.1038/s41598-023-41269-0 -
Genetics, Selection, Evolution : GSE Jul 2023Genomic selection has increased genetic gain in dairy cattle, but in some cases it has resulted in higher inbreeding rates. Therefore, there is need for research on...
BACKGROUND
Genomic selection has increased genetic gain in dairy cattle, but in some cases it has resulted in higher inbreeding rates. Therefore, there is need for research on efficient management of inbreeding in genomically-selected dairy cattle populations, especially for local breeds with a small population size. Optimum contribution selection (OCS) minimizes the increase in average kinship while it maximizes genetic gain. However, there is no consensus on how to construct the kinship matrix used for OCS and whether it should be based on pedigree or genomic information. VanRaden's method 1 (VR1) is a genomic relationship matrix in which centered genotype scores are scaled with the sum of 2p(1-p) where p is the reference allele frequency at each locus, and VanRaden's method 2 (VR2) scales each locus with 2p(1-p), thereby giving greater weight to loci with a low minor allele frequency. We compared the effects of nine kinship matrices on genetic gain, kinship, inbreeding, genetic diversity, and minor allele frequency when applying OCS in a simulated small dairy cattle population. We used VR1 and VR2, each using base animals, all genotyped animals, and the current generation of animals to compute reference allele frequencies. We also set the reference allele frequencies to 0.5 for VR1 and the pedigree-based relationship matrix. We constrained OCS to select a fixed number of sires per generation for all scenarios. Efficiency of the different matrices were compared by calculating the rate of genetic gain for a given rate of increase in average kinship.
RESULTS
We found that: (i) genomic relationships were more efficient than pedigree-based relationships at managing inbreeding, (ii) reference allele frequencies computed from base animals were more efficient compared to reference allele frequencies computed from recent animals, and (iii) VR1 was slightly more efficient than VR2, but the difference was not statistically significant.
CONCLUSIONS
Using genomic relationships for OCS realizes more genetic gain for a given amount of kinship and inbreeding than using pedigree relationships when the number of sires is fixed. For a small genomic dairy cattle breeding program, we recommend that the implementation of OCS uses VR1 with reference allele frequencies estimated either from base animals or old genotyped animals.
Topics: Animals; Cattle; Inbreeding; Genotype; Gene Frequency; Genomics; Pedigree; Alleles; Selection, Genetic
PubMed: 37460999
DOI: 10.1186/s12711-023-00826-x