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Gerontology 2016Sclerostin, mainly produced by osteocytes, is now considered a major regulator of bone formation. Identified from patients with a low bone mass, sclerostin inhibits the... (Review)
Review
Sclerostin, mainly produced by osteocytes, is now considered a major regulator of bone formation. Identified from patients with a low bone mass, sclerostin inhibits the Wnt pathway by binding to LRP5/6 and subsequently increases bone formation. Sclerostin may also play a role in the mediation of systemic and local factors such as calcitriol, PTH, glucocorticoids and tumor necrosis factor-alpha. Circulating sclerostin levels increase with age and with the decline of kidney function. However, they are surprisingly higher in patients with a high bone mineral density, suggesting that sclerostin may be a relevant marker of the pool of mature osteocytes. The anti-anabolic properties lead to the development of anti-sclerostin biotherapies that are under current evaluation. The results of these clinical trials will open new promising opportunities for the treatment of osteoporosis and bone fragility fractures.
Topics: Adaptor Proteins, Signal Transducing; Aging; Bone Morphogenetic Proteins; Bone and Bones; Fractures, Spontaneous; Genetic Markers; Humans; Osteogenesis; Osteoporosis; Wnt Signaling Pathway
PubMed: 27177738
DOI: 10.1159/000446278 -
Genetics Sep 2009The use of all available molecular markers in statistical models for prediction of quantitative traits has led to what could be termed a genomic-assisted selection... (Review)
Review
The use of all available molecular markers in statistical models for prediction of quantitative traits has led to what could be termed a genomic-assisted selection paradigm in animal and plant breeding. This article provides a critical review of some theoretical and statistical concepts in the context of genomic-assisted genetic evaluation of animals and crops. First, relationships between the (Bayesian) variance of marker effects in some regression models and additive genetic variance are examined under standard assumptions. Second, the connection between marker genotypes and resemblance between relatives is explored, and linkages between a marker-based model and the infinitesimal model are reviewed. Third, issues associated with the use of Bayesian models for marker-assisted selection, with a focus on the role of the priors, are examined from a theoretical angle. The sensitivity of a Bayesian specification that has been proposed (called "Bayes A") with respect to priors is illustrated with a simulation. Methods that can solve potential shortcomings of some of these Bayesian regression procedures are discussed briefly.
Topics: Animals; Bayes Theorem; Gene Frequency; Genetic Heterogeneity; Genetic Markers; Genetic Variation; Models, Genetic; Plants
PubMed: 19620397
DOI: 10.1534/genetics.109.103952 -
G3 (Bethesda, Md.) Apr 2024Relatedness coefficients which seek the identity-by-descent of genetic markers are described. The markers are in groups of two, three or four, and if four, can consist...
Relatedness coefficients which seek the identity-by-descent of genetic markers are described. The markers are in groups of two, three or four, and if four, can consist of two pairs. It is essential to use cumulants (not moments) for four-marker-gene probabilities, as the covariance of homozygosity, used in four-marker applications, can only be described with cumulants. A covariance of homozygosity between pairs of markers arises when populations follow a mixture distribution. Also, the probability of four markers all identical-by-descent equals the normalized fourth cumulant. In this article, a "genetic marker" generally represents either a gene locus or an allele at a locus. Applications of three marker coefficients mainly involve conditional regression, and applications of four marker coefficients can involve identity disequilibrium. Estimation of relatedness using genetic marker data is discussed. However, three- and four-marker estimators suffer from statistical and numerical problems, including higher statistical variance, complexity of estimation formula, and singularity at some intermediate allele frequencies.
Topics: Genetic Markers; Gene Frequency; Alleles; Probability; Homozygote; Models, Genetic; Genetics, Population
PubMed: 38411620
DOI: 10.1093/g3journal/jkad236 -
The Plant Journal : For Cell and... Mar 2023Maize (Zea mays ssp. mays) populations exhibit vast ranges of genetic and phenotypic diversity. As sequencing costs have declined, an increasing number of projects have...
Maize (Zea mays ssp. mays) populations exhibit vast ranges of genetic and phenotypic diversity. As sequencing costs have declined, an increasing number of projects have sought to measure genetic differences between and within maize populations using whole-genome resequencing strategies, identifying millions of segregating single-nucleotide polymorphisms (SNPs) and insertions/deletions (InDels). Unlike older genotyping strategies like microarrays and genotyping by sequencing, resequencing should, in principle, frequently identify and score common genetic variants. However, in practice, different projects frequently employ different analytical pipelines, often employ different reference genome assemblies and consistently filter for minor allele frequency within the study population. This constrains the potential to reuse and remix data on genetic diversity generated from different projects to address new biological questions in new ways. Here, we employ resequencing data from 1276 previously published maize samples and 239 newly resequenced maize samples to generate a single unified marker set of approximately 366 million segregating variants and approximately 46 million high-confidence variants scored across crop wild relatives, landraces as well as tropical and temperate lines from different breeding eras. We demonstrate that the new variant set provides increased power to identify known causal flowering-time genes using previously published trait data sets, as well as the potential to track changes in the frequency of functionally distinct alleles across the global distribution of modern maize.
Topics: Humans; Genetic Markers; Zea mays; Plant Breeding; Gene Frequency; Polymorphism, Single Nucleotide
PubMed: 36705476
DOI: 10.1111/tpj.16123 -
Fa Yi Xue Za Zhi Jun 2023To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and...
OBJECTIVES
To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship.
METHODS
(1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting.
RESULTS
(1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99.
CONCLUSIONS
When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.
Topics: Humans; Computer Simulation; Genetic Markers; Genotype; Reproducibility of Results; Siblings
PubMed: 37517014
DOI: 10.12116/j.issn.1004-5619.2023.530107 -
Microbial Cell Factories Feb 2020Yarrowia lipolytica is an oleaginous yeast that can be genetically engineered to produce lipid and non-lipid biochemicals from a variety of feedstocks. Metabolic...
BACKGROUND
Yarrowia lipolytica is an oleaginous yeast that can be genetically engineered to produce lipid and non-lipid biochemicals from a variety of feedstocks. Metabolic engineering of this organism usually requires genetic markers in order to select for modified cells. The potential to combine multiple genetic manipulations depends on the availability of multiple or recyclable selectable markers.
RESULTS
We found that Y. lipolytica has the ability to utilize acetamide as the sole nitrogen source suggesting that the genome contains an acetamidase gene. Two potential Y. lipolytica acetamidase gene candidates were identified by homology to the A. nidulans acetamidase amdS. These genes were deleted in the wild-type Y. lipolytica strain YB-392, and deletion strains were evaluated for acetamide utilization. One deletion strain was unable to grow on acetamide and a putative acetamidase gene YlAMD1 was identified. Transformation of YlAMD1 followed by selection on acetamide media and counterselection on fluoroacetamide media showed that YlAMD1 can be used as a recyclable genetic marker in Saccharomyces cerevisiae and Ylamd1Δ Y. lipolytica.
CONCLUSIONS
These findings add to our understanding of Y. lipolytica nitrogen utilization and expand the set of genetic tools available for engineering this organism, as well as S. cerevisiae.
Topics: Acetamides; Amidohydrolases; Genetic Markers; Metabolic Engineering; Saccharomyces cerevisiae; Transformation, Genetic; Yarrowia
PubMed: 32024536
DOI: 10.1186/s12934-020-1292-9 -
G3 (Bethesda, Md.) Jul 2017is a human pathogen, biofuel producer, and model system that belongs to a basal fungal lineage; however, the genetics of this fungus are limited. In contrast to...
is a human pathogen, biofuel producer, and model system that belongs to a basal fungal lineage; however, the genetics of this fungus are limited. In contrast to ascomycetes and basidiomycetes, basal fungal lineages have been understudied. This may be caused by a lack of attention given to these fungi, as well as limited tools for genetic analysis. Nonetheless, the importance of these fungi as pathogens and model systems has increased. is one of a few genetically tractable organisms in the basal fungi, but it is far from a robust genetic system when compared to model fungi in the subkingdom Dikarya. One problem is the organism is resistant to drugs utilized to select for dominant markers in other fungal transformation systems. Thus, we developed a blaster recyclable marker system by using the gene (encoding an orotidine-5'-phosphate decarboxylase, ortholog of in ). A 237-bp fragment downstream of the gene was tandemly incorporated into the upstream region of the gene, resulting in construction of a marker. To test the functionality of the marker, we disrupted the gene that is involved in carotenoid synthesis in mutant background. The resulting :: mutants exhibit a white colony phenotype due to lack of carotene, whereas wild type displays yellowish colonies. The marker was then successfully excised, generating on 5-FOA medium. The mutants became auxotrophic and required uridine for growth. We then disrupted the calcineurin B regulatory subunit gene in the :: strain, generating mutants with the alleles :: and :: These results demonstrate that the recyclable marker system is fully functional, and therefore the marker can be used for sequential gene deletions in .
Topics: Fungal Proteins; Gene Deletion; Genes, Fungal; Genetic Markers; Humans; Mucor; Mucormycosis
PubMed: 28476909
DOI: 10.1534/g3.117.041095 -
Genes May 2019Gene modification is a promising tool for plant breeding, and gradual application from the laboratory to the field. Selectable marker genes (SMG) are required in the...
Gene modification is a promising tool for plant breeding, and gradual application from the laboratory to the field. Selectable marker genes (SMG) are required in the transformation process to simplify the identification of transgenic plants; however, it is more desirable to obtain transgenic plants without selection markers. Transgene integration mediated by site-specific recombination (SSR) systems into the dedicated genomic sites has been demonstrated in a few different plant species. Here, we present an auto-elimination vector system that uses a heat-inducible to eliminate the selectable marker from transgenic maize, without the need for repeated transformation or sexual crossing. The vector combines an inducible site-specific recombinase () that allows for the precise elimination of the selectable marker gene upon heating. This marker gene is used for the initial positive selection of transgenic tissue. The also functions as a visual marker to demonstrate the effectiveness of the heat-inducible . A second marker gene for anthocyanin pigmentation () is located outside of the region eliminated by and is used for the identification of transgenic offspring in future generations. Using the heat-inducible auto-excision vector, marker-free transgenic maize plants were obtained in a precisely controlled genetic modification process. Genetic and molecular analyses indicated that the inducible auto-excision system was tightly controlled, with highly efficient DNA excision, and provided a highly reliable method to generate marker-free transgenic maize.
Topics: Food, Genetically Modified; Gene Expression Regulation, Plant; Genetic Engineering; Genetic Markers; Genetic Vectors; Hot Temperature; Plants, Genetically Modified; Recombination, Genetic; Transformation, Genetic; Transgenes; Zea mays
PubMed: 31108922
DOI: 10.3390/genes10050374 -
EMBO Molecular Medicine Dec 2021Early embryonic arrest and fragmentation (EEAF) is a common phenotype observed in in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles. The...
Early embryonic arrest and fragmentation (EEAF) is a common phenotype observed in in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles. The phenotype causes female infertility and recurrent failed IVF/ICSI attempts. However, the molecular mechanisms behind EEAF remain largely unknown. In this issue of EMBO Molecular Medicine, Zhang et al (2021) present the novel causative gene MOS in patients with the EEAF phenotype. The relationship between MOS variants and human EEAF is comprehensively established through a series of in vitro and in vivo experiments, thus clarifying the role of MOS during human oocyte maturation and early embryo development. These findings suggest that MOS is a new diagnostic marker of EEAF and is a potential therapeutic target for treatment of EEAF patients.
Topics: Female; Fertilization in Vitro; Genetic Markers; Humans; Infertility, Female; Oocytes; Sperm Injections, Intracytoplasmic
PubMed: 34806827
DOI: 10.15252/emmm.202115323 -
The Plant Cell Jan 2020The ability to predict traits from genome-wide sequence information (i.e., genomic prediction) has improved our understanding of the genetic basis of complex traits and...
The ability to predict traits from genome-wide sequence information (i.e., genomic prediction) has improved our understanding of the genetic basis of complex traits and transformed breeding practices. Transcriptome data may also be useful for genomic prediction. However, it remains unclear how well transcript levels can predict traits, particularly when traits are scored at different development stages. Using maize () genetic markers and transcript levels from seedlings to predict mature plant traits, we found that transcript and genetic marker models have similar performance. When the transcripts and genetic markers with the greatest weights (i.e., the most important) in those models were used in one joint model, performance increased. Furthermore, genetic markers important for predictions were not close to or identified as regulatory variants for important transcripts. These findings demonstrate that transcript levels are useful for predicting traits and that their predictive power is not simply due to genetic variation in the transcribed genomic regions. Finally, genetic marker models identified only 1 of 14 benchmark flowering-time genes, while transcript models identified 5. These data highlight that, in addition to being useful for genomic prediction, transcriptome data can provide a link between traits and variation that cannot be readily captured at the sequence level.
Topics: Genetic Markers; Genetic Variation; Genome, Plant; Genome-Wide Association Study; Genomics; Models, Genetic; Multifactorial Inheritance; Phenotype; Transcriptome; Zea mays
PubMed: 31641024
DOI: 10.1105/tpc.19.00332