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HLA Jan 2023Three novel HLA-DQB1 alleles HLA-DQB1*02:186, -DQB1*06:02:49, and -DQB1*06:391 alleles detected during routine next generation sequencing.
Three novel HLA-DQB1 alleles HLA-DQB1*02:186, -DQB1*06:02:49, and -DQB1*06:391 alleles detected during routine next generation sequencing.
Topics: Humans; Alleles
PubMed: 36114775
DOI: 10.1111/tan.14820 -
Epigenetics 2016While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are...
While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with > 4% of the ∼220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are tissue-specific. These findings contribute to our understanding of the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood.
Topics: Alleles; Brain; DNA Methylation; Epigenesis, Genetic; Female; Genome, Human; Genomic Imprinting; Genotype; Humans; Male; Oligonucleotide Array Sequence Analysis; Organ Specificity; Polymorphism, Single Nucleotide; Sequence Analysis, DNA
PubMed: 26786711
DOI: 10.1080/15592294.2015.1127479 -
Proceedings. Biological Sciences Mar 2024Beneficial reversals of dominance reduce the costs of genetic trade-offs and can enable selection to maintain genetic variation for fitness. Beneficial dominance... (Review)
Review
Beneficial reversals of dominance reduce the costs of genetic trade-offs and can enable selection to maintain genetic variation for fitness. Beneficial dominance reversals are characterized by the beneficial allele for a given context (e.g. habitat, developmental stage, trait or sex) being dominant in that context but recessive where deleterious. This context dependence at least partially mitigates the fitness consequence of heterozygotes carrying one non-beneficial allele for their context and can result in balancing selection that maintains alternative alleles. Dominance reversals are theoretically plausible and are supported by mounting empirical evidence. Here, we highlight the importance of beneficial dominance reversals as a mechanism for the mitigation of genetic conflict and review the theory and empirical evidence for them. We identify some areas in need of further research and development and outline three methods that could facilitate the identification of antagonistic genetic variation (dominance ordination, allele-specific expression and allele-specific ATAC-Seq (assay for transposase-accessible chromatin with sequencing)). There is ample scope for the development of new empirical methods as well as reanalysis of existing data through the lens of dominance reversals. A greater focus on this topic will expand our understanding of the mechanisms that resolve genetic conflict and whether they maintain genetic variation.
Topics: Selection, Genetic; Phenotype; Heterozygote; Alleles; Genetic Variation; Models, Genetic; Genetic Fitness
PubMed: 38471544
DOI: 10.1098/rspb.2023.2816 -
Methods in Molecular Biology (Clifton,... 2019This chapter outlines a method for making unmarked, in-frame deletion mutations in Proteus mirabilis by allelic replacement. This method utilizes an R6K-based suicide...
This chapter outlines a method for making unmarked, in-frame deletion mutations in Proteus mirabilis by allelic replacement. This method utilizes an R6K-based suicide plasmid allowing for integration of the plasmid by homologous recombination via a cloned insert. The plasmid also contains the sacB gene to select for plasmid loss (excision) in the presence of sucrose to create a mutant allele. This method has been applied to the P. mirabilis strains PM7002 and BB2000 and should be generally applicable to other P. mirabilis strains. The same methods described in this chapter can be used to introduce marked or point mutations in a given gene.
Topics: Alleles; Bacterial Proteins; Bacteriological Techniques; Genes, Transgenic, Suicide; Homologous Recombination; Mutagenesis; Plasmids; Proteus mirabilis
PubMed: 31309497
DOI: 10.1007/978-1-4939-9601-8_8 -
Heredity Jan 2019The transition from outcrossing to selfing through the breakdown of distyly to homostyly has occurred repeatedly among families of flowering plants. Homostyles can...
The transition from outcrossing to selfing through the breakdown of distyly to homostyly has occurred repeatedly among families of flowering plants. Homostyles can originate by major gene changes at the S-locus linkage group, or by unlinked polygenic modifiers. Here, we investigate the inheritance of distyly and homostyly in Primula oreodoxa, a subalpine herb endemic to Sichuan, China. Controlled self- and cross-pollinations confirmed that P. oreodoxa unlike most heterostylous species is fully self-compatible. Segregation patterns indicated that the inheritance of distyly is governed by a single Mendelian locus with the short-styled morph carrying at least one dominant S-allele (S-) and long-styled plants homozygous recessive (ss). Crossing data were consistent with a model in which homostyly results from genetic changes at the distylous linkage group, with the homostylous allele (S) dominant to the long-styled allele (s), but recessive to the short-styled allele (S). Progeny tests of open-pollinated seed families revealed high rates of intermorph mating in the L-morph but considerable selfing and possibly intramorph mating in the S-morph and in homostyles. S-morph plants homozygous at the S-locus (SS) occurred in several populations but may experience viability selection. The crossing data from distylous and homostylous plants are consistent with either recombination at the S-locus governing distyly, or mutation at gene(s) controlling sex-organ height; both models predict the same patterns of segregation. Recent studies on the molecular genetics of distyly in Primula demonstrating the hemizygous nature of genes at the S-locus make it more likely that homostyles have resulted from mutation rather than recombination.
Topics: Alleles; Crosses, Genetic; Genetic Linkage; Homozygote; Mutation; Pollen; Pollination; Primula; Reproduction
PubMed: 29728676
DOI: 10.1038/s41437-018-0081-2 -
Molecular Biology and Evolution Jan 2021The detection of introgression from genomic data is transforming our view of species and the origins of adaptive variation. Among the most widely used approaches to...
The detection of introgression from genomic data is transforming our view of species and the origins of adaptive variation. Among the most widely used approaches to detect introgression is the so-called ABBA-BABA test or D-statistic, which identifies excess allele sharing between nonsister taxa. Part of the appeal of D is its simplicity, but this also limits its informativeness, particularly about the timing and direction of introgression. Here we present a simple extension, D frequency spectrum or DFS, in which D is partitioned according to the frequencies of derived alleles. We use simulations over a large parameter space to show how DFS carries information about various factors. In particular, recent introgression reliably leads to a peak in DFS among low-frequency derived alleles, whereas violation of model assumptions can lead to a lack of signal at low frequencies. We also reanalyze published empirical data from six different animal and plant taxa, and interpret the results in the light of our simulations, showing how DFS provides novel insights. We currently see DFS as a descriptive tool that will augment both simple and sophisticated tests for introgression, but in the future it may be usefully incorporated into probabilistic inference frameworks.
Topics: Alleles; Gene Flow; Gene Frequency; Genetic Introgression; Genetic Techniques
PubMed: 32941617
DOI: 10.1093/molbev/msaa239 -
European Review For Medical and... Jun 2022In animal models and humans, mutations in voltage-dependent calcium channel gamma-2 subunit gene (CACNG2) have been associated with neuronal hyperexcitability, including...
OBJECTIVE
In animal models and humans, mutations in voltage-dependent calcium channel gamma-2 subunit gene (CACNG2) have been associated with neuronal hyperexcitability, including neuropathic pain. The objective of this study was to determine the allelic and genotypic frequencies of CACNG2 polymorphisms (rs4820242, rs2284015 and rs2284017) and their association with the risk of chronic peripheral neuropathic pain (CPNP) in the Mexican population.
PATIENTS AND METHODS
Single nucleotide polymorphisms (SNPs) were determined by real-time PCR, and allelic and genotypic frequencies were compared between healthy Mexican subjects and CPNP patients. The risk of association of CACNG2 SNPs with the presence of CPNP and its characteristics was evaluated.
RESULTS
The allele G (OR 2.08, p = 0.01) of rs2284015 was observed as a risk factor for developing CPNP. The allele A of rs4820442 showed a risk of association with a history of surgery (OR 3.92, p = 0.04), radiculopathy (OR 4.29, p = 0.0001), bilateral presentation of pain (OR 3.15, p = 0.003), and neuropraxia (OR 0.36, p = 0.01). The allele C of rs2284015 was associated with an increased risk of burning and allodynia. In the analysis of the association of genotype frequencies and inheritance patterns, as well as in the analysis of interaction with sex, a modification of risk was observed.
CONCLUSIONS
The allele G of rs2284015 and the AGC haplotype of CACNG2 rs4820242, rs2284015 and rs2284017, regardless of sex and etiology could contribute to the risk of CPNP. Certain alleles and genotypes could constitute severity markers in CPNP with sex-biased effects; however, further studies are required to confirm these observations.
Topics: Alleles; Calcium Channels; Genotype; Haplotypes; Humans; Neuralgia; Polymorphism, Single Nucleotide
PubMed: 35776036
DOI: 10.26355/eurrev_202206_29074 -
Turkiye Parazitolojii Dergisi Nov 2022The study aims to determine the presence of L1014F, L1014S, L1014C alleles, which are responsible for knockdown resistance and G119S alleles, which are responsible for...
OBJECTIVE
The study aims to determine the presence of L1014F, L1014S, L1014C alleles, which are responsible for knockdown resistance and G119S alleles, which are responsible for acetylcholinesterase insensitivity in , the secondary vector of malaria in Turkey.
METHODS
In this study, 60 adult females were collected from Aydın, Denizli, and Muğla provinces. Then, allele-specific primers for L1014F, L1014S, and L1014C alleles, and the G119S allele were designed. The presence of these alleles was screened in three populations by allele-specific polymerase chain reaction.
RESULTS
Although L1014S allele frequency was too low in Aydın, Muğla, and Denizli populations, neither L1014F and L1014C nor G119S mutations were found in any population.
CONCLUSION
In this study, L1014S mutation was detected for the first time in the Aegean populations.
Topics: Female; Animals; Alleles; Acetylcholinesterase; Anopheles; Mosquito Vectors; Polymerase Chain Reaction; Mutation
PubMed: 36444406
DOI: 10.4274/tpd.galenos.2022.20592 -
Briefings in Bioinformatics Sep 2023Although current long-read sequencing technologies have a long-read length that facilitates assembly for genome reconstruction, they have high sequence errors. While...
Although current long-read sequencing technologies have a long-read length that facilitates assembly for genome reconstruction, they have high sequence errors. While various assemblers with different perspectives have been developed, no systematic evaluation of assemblers with long reads for diploid genomes with varying heterozygosity has been performed. Here, we evaluated a series of processes, including the estimation of genome characteristics such as genome size and heterozygosity, de novo assembly, polishing, and removal of allelic contigs, using six genomes with various heterozygosity levels. We evaluated five long-read-only assemblers (Canu, Flye, miniasm, NextDenovo and Redbean) and five hybrid assemblers that combine short and long reads (HASLR, MaSuRCA, Platanus-allee, SPAdes and WENGAN) and proposed a concrete guideline for the construction of haplotype representation according to the degree of heterozygosity, followed by polishing and purging haplotigs, using stable and high-performance assemblers: Redbean, Flye and MaSuRCA.
Topics: Sequence Analysis, DNA; Haplotypes; High-Throughput Nucleotide Sequencing; Heterozygote; Alleles
PubMed: 37798248
DOI: 10.1093/bib/bbad337 -
International Journal of Molecular... Apr 2022Although Slavic populations account for over 4.5% of world inhabitants, no centralised, open-source reference database of genetic variation of any Slavic population...
Although Slavic populations account for over 4.5% of world inhabitants, no centralised, open-source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for clinical genetics, biomedical research, as well as archeological and historical studies. The Polish population, which is homogenous and sedentary in its nature but influenced by many migrations of the past, is unique and could serve as a genetic reference for the Slavic nations. In this study, we analysed whole genomes of 1222 Poles to identify and genotype a wide spectrum of genomic variation, such as small and structural variants, runs of homozygosity, mitochondrial haplogroups, and variants. Common variant analyses showed that the Polish cohort is highly homogenous and shares ancestry with other European populations. In rare variant analyses, we identified 32 autosomal-recessive genes with significantly different frequencies of pathogenic alleles in the Polish population as compared to the non-Finish Europeans, including , , , , and . The allele frequencies for small and structural variants, calculated for 1076 unrelated individuals, are released publicly as The Thousand Polish Genomes database, and will contribute to the worldwide genomic resources available to researchers and clinicians.
Topics: Alleles; Gene Frequency; Genetics, Population; Genome, Human; Humans; Mitochondrial Proteins; Poland
PubMed: 35562925
DOI: 10.3390/ijms23094532