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Gennadi V Glinsky - One of the best experts on this subject based on the ideXlab platform.
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Impacts of genomic networks governed by human-specific regulatory sequences and genetic loci harboring fixed human-specific neuro-regulatory single nucleotide mutations on phenotypic traits of modern humans
Chromosome Research, 2020Co-Authors: Gennadi V GlinskyAbstract:Recent advances in identification and characterization of human-specific regulatory DNA sequences set the stage for the assessment of their global impact on physiology and pathology of modern humans. Gene set enrichment analyses (GSEA) of 8405 genes linked with 35,074 human-specific neuro-regulatory single-nucleotide changes (hsSNCs) revealed numerous significant associations with morphological structures, physiological processes, and pathological conditions of modern humans. Significantly enriched traits include more than 1000 anatomically distinct regions of the adult human brain, many different types of cells and tissues, more than 200 common human disorders, and more than 1000 records of rare diseases. Thousands of genes connected with neuro-regulatory hsSNCs have been identified, which represent essential genetic elements of the Autosomal Inheritance and offspring survival phenotypes. A total of 1494 hsSNC-linked genes are associated with either Autosomal dominant or recessive Inheritance, and 2273 hsSNC-linked genes have been associated with premature death, embryonic lethality, as well as pre-, peri-, neo-, and post-natal lethality phenotypes of both complete and incomplete penetrance. Differential GSEA implemented on hsSNC-linked loci and associated genes identify a set of 7990 hsSNC-target genes linked to evolutionary distinct classes of human-specific regulatory sequences (HSRS). Notably, the expression of a majority of these genes (5389 genes; 67%) is regulated by stem cell–associated retroviral sequences (SCARS) and SCARS-regulated genes captured a dominant fraction (91%) of significant phenotypic associations linked with hsSNCs. Interrogations of the MGI database revealed readily available mouse models tailored for precise experimental definitions of functional effects of hsSNCs and SCARS on genes causally affecting thousands of mammalian phenotypes and implicated in hundreds of common and rare human disorders. These observations suggest that a preponderance of human-specific traits evolved under a combinatorial regulatory control of distinct classes of HSRS and neuro-regulatory loci harboring hsSNCs that are fixed in humans, distinct from other primates, and located in differentially accessible chromatin regions during brain development.
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impacts of genomic networks governed by human specific regulatory sequences and genetic loci harboring fixed human specific neuro regulatory single nucleotide mutations on phenotypic traits of modern humans
bioRxiv, 2020Co-Authors: Gennadi V GlinskyAbstract:Abstract Recent advances in identification and characterization of human-specific regulatory DNA sequences set the stage for the assessment of their global impact on physiology and pathology of Modern Humans. Gene set enrichment analyses (GSEA) of 8,405 genes linked with 35,074 human-specific neuro-regulatory single-nucleotide changes (hsSNCs) revealed a staggering breadth of significant associations with morphological structures, physiological processes, and pathological conditions of Modern Humans. Significantly enriched traits include more than 1,000 anatomically-distinct regions of the adult human brain, many different types of cells and tissues, more than 200 common human disorders and more than 1,000 records of rare diseases. Thousands of genes connected with neuro-regulatory hsSNCs have been identified, which represent essential genetic elements of the Autosomal Inheritance and offspring survival phenotypes. A total of 1,494 hsSNC- linked genes are associated with either Autosomal dominant or recessive Inheritance and 2,273 hsSNC-linked genes have been associated with premature death, embryonic lethality, as well as pre-, peri-, neo-, and post-natal lethality phenotypes of both complete and incomplete penetrance. Differential GSEA implemented on hsSNC-linked loci and associated genes identify 7,990 genes linked to evolutionary distinct classes of human-specific regulatory sequences (HSRS), expression of a majority of which (5,389 genes; 67%) is regulated by stem cell-associated retroviral sequences (SCARS). Interrogations of the MGI database revealed readily available mouse models tailored for precise experimental definitions of functional effects of hsSNCs and SCARS on genes causally affecting thousands of mammalian phenotypes and implicated in hundreds of common and rare human disorders. These observations suggest that a preponderance of human-specific traits evolved under a combinatorial regulatory control of HSRS and neuro-regulatory loci harboring hsSNCs that are fixed in humans, distinct from other primates, and located in differentially-accessible chromatin regions during brain development.
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human specific regulatory features of brain development manifest staggering breadth of associations with physiological processes and pathological conditions of h sapiens
bioRxiv, 2019Co-Authors: Gennadi V GlinskyAbstract:Abstract In recent years, elucidation of genetic and molecular mechanisms defining the phenotypic uniqueness of Modern Humans attained a significant progress in illuminating the essential role of human-specific regulatory sequences (HSRS). The macromolecules comprising the essential building blocks of life at the cellular and organismal levels remain highly conserved during the evolution of humans and other Great Apes. Identification of nearly hundred thousand candidate HSRS validate the idea that unique to human phenotypes may result from human-specific changes to genomic regulatory sequences defined as “regulatory mutations” (King and Wilson, 1975). The exquisite degree of accuracy of the state-of-art molecular definition of HSRS is illustrated by identification of 35,074 single nucleotide changes (SNCs) that are fixed in humans, distinct from other primates, and located in differentially-accessible (DA) chromatin regions during the human brain development (Kanton et al., 2019). Annotation of SNCs derived and fixed in modern humans that overlap DA chromatin regions during brain development revealed that 99.8% of candidate regulatory SNCs are shared with the archaic humans. This remarkable conservation on the human lineage of candidate regulatory SNCs associated with early stages of human brain development suggest that coding genes expression of which is regulated by human-specific SNCs may have a broad effect on human-specific traits beyond embryonic development. Gene set enrichment analyses of 8,405 genes linked with 35,074 human-specific SNCs revealed the staggering breadth of significant associations with morphological structures, physiological processes, and pathological conditions of Modern Humans, including more than 1,000 anatomically-distinct regions of the adult human brain, many types of human cells and tissues, more than 200 common human disorders and more than 1,000 rare diseases. Thousands of genes connected with human-specific regulatory SNCs represent essential genetic elements of the Autosomal Inheritance and survival of species phenotypes: a total of 1,494 genes linked with either Autosomal dominant or recessive Inheritance as well as 2,273 genes associated with premature death, embryonic survival, and perinatal, neonatal, and postnatal lethality of both complete and incomplete penetrance have been identified in this contribution. Therefore, thousands of heritable traits and critical genes impacting the offspring survival appear placed under the human-specific regulatory control in genomes of Modern Humans. These observations highlight the remarkable translational opportunities with clinical utility potentials afforded by the discovery of genetic regulatory loci harboring human-specific SNCs in the ground-breaking fundamental study of great ape’s cerebral organoids.
Brian A Federici - One of the best experts on this subject based on the ideXlab platform.
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Inheritance stability and dominance of cry resistance in culex quinquefasciatus diptera culicidae selected with the three cry toxins of bacillus thuringiensis subsp israelensis
Journal of Medical Entomology, 2012Co-Authors: Margaret C Wirth, William E Walton, Brian A FedericiAbstract:ABSTRACT Mendelian crosses were used to study the mode of Inheritance of Cry toxin resistance in a Culex quinquefasciatus Say (Diptera: Culicidae) colony (CqAB11A) that evolved insecticide resistance under laboratory selection with a deletion mutant of Bacillus thuringiensis subsp. israelensis de Barjac lacking the Cyt1Aa toxin component but containing its three major Cry toxins, Cry4Aa, Cry4Ba, and Cry11Aa. High levels of resistance were observed to Cry toxins. F1 offspring of reciprocal crosses to a sensitive colony showed intermediate levels of resistance with no maternal effect, indicating Autosomal Inheritance. Dose—response data for backcross offspring deviated significantly from the monofactorial model when tested with Cry4Aa + Cry4Ba + Cry11Aa, Cry4Aa + Cry4Ba, or Cry11Aa. However, tests with Cry11Ba from B. thuringiensis subsp. jegathesan (Seleena, Lee, Lecadet) fit the monofactorial model. Dominance of F1 offspring was calculated at different concentrations of Cry-toxin suspensions and, as repor...
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Inheritance patterns dominance stability and allelism of insecticide resistance and cross resistance in two colonies of culex quinquefasciatus diptera culicidae selected with cry toxins from bacillus thuringiensis subsp israelensis
Journal of Medical Entomology, 2010Co-Authors: Margaret C Wirth, William E Walton, Brian A FedericiAbstract:ABSTRACT Mendelian crosses were used to analyze the patterns of Inheritance of Cry-toxin resistance in two colonies of Culex quinquefasciatus Say larvae resistant to bacterial toxins produced by Bacillus thuringiensis subsp. israelensis de Barjac. Resistance levels exceeded 1000-fold at 95% lethal concentration of the Cry11Aa-resistant colony (Cq11A). F1 offspring of reciprocal crosses to a susceptible colony revealed Autosomal Inheritance and offspring were intermediate in resistance to the susceptible and resistant parental lines. Dose-response tests on backcross offspring were consistent with polyfactorial Inheritance of resistance toward Cry11Aa and Cry4Aa + Cry4Ba, whereas cross-resistance toward Cry11Ba best fit a monofactorial model. Resistance was 600-fold at 95% lethal concentration in the colony selected with Cry4A + Cry4B (Cq4AB). Inheritance of resistance in F1 offspring was Autosomal and intermediate to the susceptible and resistant parents. Inheritance of Cry4Aa + Cry4Ba and Cry11Ba resistan...
Anna Simon - One of the best experts on this subject based on the ideXlab platform.
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dysregulation of innate immunity hereditary periodic fever syndromes
British Journal of Haematology, 2009Co-Authors: Evelien J. Bodar, Anna SimonAbstract:The hereditary periodic fever syndromes encompass a rare group of diseases that have lifelong recurrent episodes of inflammatory symptoms and an acute phase response in common. Clinical presentation can mimic that of lymphoproliferative disorders and patients often go undiagnosed for many years. These syndromes follow an Autosomal Inheritance pattern, and the major syndromes are linked to specific genes, most of which are involved in regulation of the innate immune response through pathways of apoptosis, nuclear factor kappaBeta activation and cytokine production. In others, the link between the protein involved and inflammation is less clear. The recurrent inflammation can lead to complications, such as renal impairment due to amyloidosis and vasculitis, visual impairment, hearing loss, and joint destruction, depending on the specific syndrome. In recent years, treatment options for these diseases have improved significantly. Early establishment of an accurate diagnosis and start of appropriate therapy improves prognosis in these patients.
Margaret C Wirth - One of the best experts on this subject based on the ideXlab platform.
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Inheritance stability and dominance of cry resistance in culex quinquefasciatus diptera culicidae selected with the three cry toxins of bacillus thuringiensis subsp israelensis
Journal of Medical Entomology, 2012Co-Authors: Margaret C Wirth, William E Walton, Brian A FedericiAbstract:ABSTRACT Mendelian crosses were used to study the mode of Inheritance of Cry toxin resistance in a Culex quinquefasciatus Say (Diptera: Culicidae) colony (CqAB11A) that evolved insecticide resistance under laboratory selection with a deletion mutant of Bacillus thuringiensis subsp. israelensis de Barjac lacking the Cyt1Aa toxin component but containing its three major Cry toxins, Cry4Aa, Cry4Ba, and Cry11Aa. High levels of resistance were observed to Cry toxins. F1 offspring of reciprocal crosses to a sensitive colony showed intermediate levels of resistance with no maternal effect, indicating Autosomal Inheritance. Dose—response data for backcross offspring deviated significantly from the monofactorial model when tested with Cry4Aa + Cry4Ba + Cry11Aa, Cry4Aa + Cry4Ba, or Cry11Aa. However, tests with Cry11Ba from B. thuringiensis subsp. jegathesan (Seleena, Lee, Lecadet) fit the monofactorial model. Dominance of F1 offspring was calculated at different concentrations of Cry-toxin suspensions and, as repor...
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Inheritance patterns dominance stability and allelism of insecticide resistance and cross resistance in two colonies of culex quinquefasciatus diptera culicidae selected with cry toxins from bacillus thuringiensis subsp israelensis
Journal of Medical Entomology, 2010Co-Authors: Margaret C Wirth, William E Walton, Brian A FedericiAbstract:ABSTRACT Mendelian crosses were used to analyze the patterns of Inheritance of Cry-toxin resistance in two colonies of Culex quinquefasciatus Say larvae resistant to bacterial toxins produced by Bacillus thuringiensis subsp. israelensis de Barjac. Resistance levels exceeded 1000-fold at 95% lethal concentration of the Cry11Aa-resistant colony (Cq11A). F1 offspring of reciprocal crosses to a susceptible colony revealed Autosomal Inheritance and offspring were intermediate in resistance to the susceptible and resistant parental lines. Dose-response tests on backcross offspring were consistent with polyfactorial Inheritance of resistance toward Cry11Aa and Cry4Aa + Cry4Ba, whereas cross-resistance toward Cry11Ba best fit a monofactorial model. Resistance was 600-fold at 95% lethal concentration in the colony selected with Cry4A + Cry4B (Cq4AB). Inheritance of resistance in F1 offspring was Autosomal and intermediate to the susceptible and resistant parents. Inheritance of Cry4Aa + Cry4Ba and Cry11Ba resistan...
Johannes A Jehle - One of the best experts on this subject based on the ideXlab platform.
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a third type of resistance to cydia pomonella granulovirus in codling moths shows a mixed z linked and Autosomal Inheritance pattern
Applied and Environmental Microbiology, 2017Co-Authors: Annette Juliane Sauer, Eva Fritsch, S Schulzebopp, Karin Undorfspahn, Johannes A JehleAbstract:Different isolates of Cydia pomonella granulovirus (CpGV) are used worldwide to control codling moth larvae (Cydia pomonella) in pome fruit production. Two types of dominantly inherited field resistance of C. pomonella to CpGV have been recently identified: Z-chromosomal type I resistance and Autosomal type II resistance. In the present study, a CpGV-resistant C. pomonella field population (termed SA-GO) from northeastern Germany was investigated. SA-GO individuals showed cross-resistance to CpGV isolates of genome group A (CpGV-M) and genome group E (CpGV-S), whereas genome group B (CpGV-E2) was still infective. Crossing experiments between individuals of SA-GO and the susceptible C. pomonella strain CpS indicated the presence of a dominant Autosomal Inheritance factor. By single-pair inbreeding of SA-GO individuals for two generations, the genetically more homogenous strain CpRGO was generated. Resistance testing of CpRGO neonates with different CpGV isolates revealed that isolate CpGV-E2 and isolates CpGV-I07 and -I12 were resistance breaking. When progeny of hybrid crosses and backcrosses between individuals of resistant strain CpRGO and susceptible strain CpS were infected with CpGV-M and CpGV-S, resistance to CpGV-S appeared to be Autosomal and dominant for larval survivorship but recessive when success of pupation of the hybrids was considered. Inheritance of resistance to CpGV-M, however, is proposed to be both Autosomal and Z linked, since Z linkage of resistance was needed for pupation. Hence, we propose a further type III resistance to CpGV in C. pomonella, which differs from type I and type II resistance in its mode of Inheritance and response to CpGV isolates from different genome groups.IMPORTANCE The baculovirus Cydia pomonella granulovirus (CpGV) is registered and applied as a biocontrol agent in nearly all pome fruit-growing countries worldwide to control codling moth caterpillars in an environmentally friendly manner. It is therefore the most widely used commercial baculovirus biocontrol agent. Since 2005, field resistance of codling moth to CpGV products has been observed in more than 40 field plantations in Europe, threatening organic and integrated apple production. Knowledge of the Inheritance and mechanism(s) of resistance is indispensable for the understanding of host response to baculovirus infection on the population level and the coevolutionary arms race between virus and host, as well as for the development of appropriate resistance management strategies. Here, we report a codling moth field population with a new type of resistance, which appears to follow a highly complex Inheritance in regard to different CpGV isolates.
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novel resistance to cydia pomonella granulovirus cpgv in codling moth shows Autosomal and dominant Inheritance and confers cross resistance to different cpgv genome groups
PLOS ONE, 2017Co-Authors: Annette Juliane Sauer, Eva Fritsch, Karin Undorfspahn, Petr Nguyen, Frantisek Marec, David G Heckel, Johannes A JehleAbstract:Commercial Cydia pomonella granulovirus (CpGV) products have been successfully applied to control codling moth (CM) in organic and integrated fruit production for more than 30 years. Since 2005, resistance against the widely used isolate CpGV-M has been reported from different countries in Europe. The Inheritance of this so-called type I resistance is dominant and linked to the Z chromosome. Recently, a second form (type II) of CpGV resistance in CM was reported from a field population (NRW-WE) in Germany. Type II resistance confers reduced susceptibility not only to CpGV-M but to most known CpGV isolates and it does not follow the previously described Z-linked Inheritance of type I resistance. To further analyze type II resistance, two CM strains, termed CpR5M and CpR5S, were generated from parental NRW-WE by repeated mass crosses and selection using the two isolates CpGV-M and CpGV-S, respectively. Both CpR5M and CpR5S were considered to be genetically homogeneous for the presence of the resistance allele(s). By crossing and backcrossing experiments with a susceptible CM strain, followed by resistance testing of the offspring, an Autosomal dominant Inheritance of resistance was elucidated. In addition, cross-resistance to CpGV-M and CpGV-S was detected in both strains, CpR5M and CpR5S. To test the hypothesis that the Autosomal Inheritance of type II resistance was caused by a large interchromosomal rearrangement involving the Z chromosome, making type I resistance appear to be Autosomal in these strains; fluorescence in situ hybridization with bacterial artificial chromosome probes (BAC-FISH) was used to physically map the Z chromosomes of different CM strains. Conserved synteny of the Z-linked genes in CpR5M and other CM strains rejects this hypothesis and argues for a novel genetic and functional mode of resistance in CM populations with type II resistance.