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Masato Nose - One of the best experts on this subject based on the ideXlab platform.
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A polygene network model for the complex pathological phenotypes of Collagen Disease.
Pathology international, 2011Co-Authors: Masato NoseAbstract:Almost 70 years after the description of 'Collagen Disease' by P. Klemperer et al., it is still controversial whether the diversity and similarity of pathological manifestations among the Collagen Diseases depends on ambiguity in diagnosis or is an intrinsic quality of the Collagen Diseases themselves. A genome wide analysis of the MRL mouse models of Collagen Disease may shed some light on the complex pathological manifestations. Study of the susceptibility loci to each type ofCollagen Disease (such as glomerulonephritis, vasculitis, arthritis, sialoadenitis and dacryoadenitis) in the mice, revealed that these lesions developed because of a cumulative effect of multiple gene loci, none of which can induce the related phenotype alone. This may indicate that Collagen Disease develops in 'a polygenic system', as proposed by K. Mather in 1949. Each lesion in the mice developed because of an additive effect of the polygenes, which is also, in part, hierarchical. Some of the polygenes seemed to be common to those in other Collagen Diseases as well. Some of the positional candidate genes involved an allelic polymorphism in the coding or promoter regions, thus possibly causing a qualitative or quantitative difference in their function, respectively. As a result, a particular combination of the polygenes with such an allelic polymorphism may thus play a critical role in leading the cascade reaction to developing Collagen Disease, and also the regular variation in the pathological manifestations. We herein describe this as a polygene network of Collagen Disease.
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Polygene network in Collagen Disease.
Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology, 2010Co-Authors: Masato NoseAbstract:The pathological findings in Collagen Disease, which was originally proposed by Klemperer et al. in 1942, show complex lesions with glomerulonephritis, vasculitis, polyarthritis and/or sialoadenitis etc. It is still controversial whether such diversity and similarity of the lesions among Collagen Diseases depend on an ambiguity in diagnosis or an intrinsic quality of the Diseases. In the study of susceptibility loci to Collagen Disease in MRL mouse models, we learned that several lesions such as glomerulonephritis, vasculitis, arthritis and sialoadenitis developed in a cumulative effect of multiple gene loci, each of which by itself did not have a significant effect to induce the related phenotype, thus indicating a polygenic system. The mice developed each lesion in an additive manner with a hierarchical effect. Some of the susceptibility loci seemed to be common to those in other Collagen Diseases as well. Some of the positional candidate genes showed an allelic polymorphism in the coding region, possibly causing a qualitative difference in their function. As a result, a particular combination of polygenes with such an allelic polymorphism may thus play a critical role in leading the cascade reaction to develop lesions, and also a regular variation of Collagen Disease. This is designated as the polygene network in Collagen Disease.
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genome analysis of Collagen Disease in mrl lpr mice polygenic inheritance resulting in the complex pathological manifestations
International Journal of Cardiology, 2000Co-Authors: Masato Nose, Miyuki Nishihara, Miho Terada, Junji Kamogawa, Weimin Qu, Shiro Mori, Tatsuhiko Miyazaki, Syuichi NakatsuruAbstract:Abstract MRL/MpJ- lpr / lpr (MRL/lpr) mice develop Collagen Disease involving vasculitis, glomerulonephritis, arthritis and sialoadenitis, each of which has been studied as a model for polyarteritis, lupus nephritis, rheumatoid arthritis and Sjogren's syndrome, respectively. In the previous studies, we observed genetic segregation of these complex pathological manifestations throughout the genome recombination with a C57Bl/6- lpr / lpr or a C3H/HeJ- lpr / lpr (C3H/lpr) strain of mice which rarely develops such lesions, indicating that development of Collagen Disease is dependent on an MRL host genetic background. To clarify the mode of inheritance and the gene loci affecting four types of the lesions in MRL/lpr mice; vasculitis, glomerulonephritis, arthritis and sialoadenitis, a genetic dissection of the lesions was carried out by using MRL/lpr, C3H/lpr, (MRL/lpr×C3H/lpr) F1 intercross, and MRL/lpr×(MRL/lpr×C3H/lpr) F1 backcross mice. Definition of each lesion was performed by histopathology under light microscopy, and genomic DNA of the backcross mice were subjected to association studies by chi-square analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. We observed that gene loci recessively associated with each lesion were mapped on different chromosomal positions. We conclude that each of four types of the lesions in MRL/lpr mice is under the control of different set of genes, suggesting the complex pathological manifestations of Collagen Disease result from polygenic inheritance.
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Genome analysis of Collagen Disease in MRL/lpr mice: polygenic inheritance resulting in the complex pathological manifestations.
International journal of cardiology, 2000Co-Authors: Masato Nose, Miyuki Nishihara, Miho Terada, Junji Kamogawa, Weimin Qu, Shiro Mori, Tatsuhiko Miyazaki, Syuichi NakatsuruAbstract:MRL/MpJ-lpr/lpr (MRL/lpr) mice develop Collagen Disease involving vasculitis, glomerulonephritis, arthritis and sialoadenitis, each of which has been studied as a model for polyarteritis, lupus nephritis, rheumatoid arthritis and Sjögren's syndrome, respectively. In the previous studies, we observed genetic segregation of these complex pathological manifestations throughout the genome recombination with a C57Bl/6-lpr/lpr or a C3H/HeJ-lpr/lpr (C3H/lpr) strain of mice which rarely develops such lesions, indicating that development of Collagen Disease is dependent on an MRL host genetic background. To clarify the mode of inheritance and the gene loci affecting four types of the lesions in MRL/lpr mice; vasculitis, glomerulonephritis, arthritis and sialoadenitis, a genetic dissection of the lesions was carried out by using MRL/lpr, C3H/lpr, (MRL/lprxC3H/lpr) F1 intercross, and MRL/lprx(MRL/lprxC3H/lpr) F1 backcross mice. Definition of each lesion was performed by histopathology under light microscopy, and genomic DNA of the backcross mice were subjected to association studies by chi-square analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. We observed that gene loci recessively associated with each lesion were mapped on different chromosomal positions. We conclude that each of four types of the lesions in MRL/lpr mice is under the control of different set of genes, suggesting the complex pathological manifestations of Collagen Disease result from polygenic inheritance.
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Genetic basis of the complex pathological manifestations of Collagen Disease: lessons from MRL/lpr and related mouse models.
International reviews of immunology, 2000Co-Authors: Masato Nose, Miyuki Nishihara, Hiroshi FujiiAbstract:The pathological findings in Collagen Disease including systemic lupus erythematosus show complex lesions such as glomerulonephritis, systemic vasculitis, polyarthritis, sialoadenitis, etc. Moreover, some cases of Collagen Disease are categorized into overlapping syndromes. It is still controversial whether such diversity and similarity of pathological manifestations among the Collagen Disease depends on ambiguity in diagnosis or is an intrinsic quality of the Collagen Diseases themselves. In this paper, we reviewed this subject focusing on a series of our genetic studies of murine models of Collagen Disease, MRL strains of mice with a deficit in Fas-mediated apoptosis, which spontaneously develop glomerulonephritis, systemic vasculitis, polyarthritis and sialoadenitis. We observed that each lesion was controlled by a different set of genes and they appeared to act in an additve manner on the development of each lesion. We conclude that various Disease categories in Collagen Disease will be a result of th...
Janina M Jeff - One of the best experts on this subject based on the ideXlab platform.
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genetic identification of a common Collagen Disease in puerto ricans via identity by descent mapping in a health system
eLife, 2017Co-Authors: Gillian M Belbin, Elena P Sorokin, Jacqueline Odgis, Sumita Kohli, Benjamin S Glicksberg, Christopher R Gignoux, Genevieve L Wojcik, Muhching Yee, Tielman Van Vleck, Janina M JeffAbstract:Diseases often run in families. These Disease are frequently linked to changes in DNA that are passed down through generations. Close family members may share these Disease-causing mutations; so may distant relatives who inherited the same mutation from a common ancestor long ago. Geneticists use a method called linkage mapping to trace a Disease found in multiple members of a family over generations to genetic changes in a shared ancestor. This allows scientists to pinpoint the exact place in the genome the Disease-causing mutation occurred. Using computer algorithms, scientists can apply the same technique to identify mutations that distant relatives inherited from a common ancestor. Belbin et al. used this computational technique to identify a mutation that may cause unusually short stature or bone and joint problems in up to 2% of people of Puerto Rican decent. In the experiments, the genomes of about 32,000 New Yorkers who have volunteered to participate in the BioMe Biobank and their health records were used to search for genetic changes linked to extremely short stature. The search revealed that people who inherited two copies of this mutation from their parents were likely to be extremely short or to have bone and joint problems. People who inherited one copy had an increased likelihood of joint or bone problems. This mutation affects a gene responsible for making a form of protein called Collagen that is important for bone growth. The analysis suggests the mutation first arose in a Native American ancestor living in Puerto Rico around the time that European colonization began. The mutation had previously been linked to a disorder called Steel syndrome that was thought to be rare. Belbin et al. showed this condition is actually fairly common in people whose ancestors recently came from Puerto Rico, but may often go undiagnosed by their physicians. The experiments emphasize the importance of including diverse populations in genetic studies, as studies of people of predominantly European descent would likely have missed the link between this Disease and mutation.
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genetic identification of a common Collagen Disease in puerto ricans via identity by descent mapping in a health system
bioRxiv, 2017Co-Authors: Gillian M Belbin, Elena P Sorokin, Jacqueline Odgis, Sumita Kohli, Benjamin S Glicksberg, Christopher R Gignoux, Genevieve L Wojcik, Tielman Van Vleck, Janina M Jeff, Michael D LindermanAbstract:Achieving confidence in the causality of a Disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with genetic relatedness that also underlies extreme short stature. We link the gene, COL27A1, with a little-known genetic Disease, previously thought to be rare and recessive. We demonstrate that Disease manifests in both heterozygotes and homozygotes, indicating a common Collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian Disease.
Gillian M Belbin - One of the best experts on this subject based on the ideXlab platform.
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genetic identification of a common Collagen Disease in puerto ricans via identity by descent mapping in a health system
eLife, 2017Co-Authors: Gillian M Belbin, Elena P Sorokin, Jacqueline Odgis, Sumita Kohli, Benjamin S Glicksberg, Christopher R Gignoux, Genevieve L Wojcik, Muhching Yee, Tielman Van Vleck, Janina M JeffAbstract:Diseases often run in families. These Disease are frequently linked to changes in DNA that are passed down through generations. Close family members may share these Disease-causing mutations; so may distant relatives who inherited the same mutation from a common ancestor long ago. Geneticists use a method called linkage mapping to trace a Disease found in multiple members of a family over generations to genetic changes in a shared ancestor. This allows scientists to pinpoint the exact place in the genome the Disease-causing mutation occurred. Using computer algorithms, scientists can apply the same technique to identify mutations that distant relatives inherited from a common ancestor. Belbin et al. used this computational technique to identify a mutation that may cause unusually short stature or bone and joint problems in up to 2% of people of Puerto Rican decent. In the experiments, the genomes of about 32,000 New Yorkers who have volunteered to participate in the BioMe Biobank and their health records were used to search for genetic changes linked to extremely short stature. The search revealed that people who inherited two copies of this mutation from their parents were likely to be extremely short or to have bone and joint problems. People who inherited one copy had an increased likelihood of joint or bone problems. This mutation affects a gene responsible for making a form of protein called Collagen that is important for bone growth. The analysis suggests the mutation first arose in a Native American ancestor living in Puerto Rico around the time that European colonization began. The mutation had previously been linked to a disorder called Steel syndrome that was thought to be rare. Belbin et al. showed this condition is actually fairly common in people whose ancestors recently came from Puerto Rico, but may often go undiagnosed by their physicians. The experiments emphasize the importance of including diverse populations in genetic studies, as studies of people of predominantly European descent would likely have missed the link between this Disease and mutation.
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genetic identification of a common Collagen Disease in puerto ricans via identity by descent mapping in a health system
bioRxiv, 2017Co-Authors: Gillian M Belbin, Elena P Sorokin, Jacqueline Odgis, Sumita Kohli, Benjamin S Glicksberg, Christopher R Gignoux, Genevieve L Wojcik, Tielman Van Vleck, Janina M Jeff, Michael D LindermanAbstract:Achieving confidence in the causality of a Disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with genetic relatedness that also underlies extreme short stature. We link the gene, COL27A1, with a little-known genetic Disease, previously thought to be rare and recessive. We demonstrate that Disease manifests in both heterozygotes and homozygotes, indicating a common Collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian Disease.
Syuichi Nakatsuru - One of the best experts on this subject based on the ideXlab platform.
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genome analysis of Collagen Disease in mrl lpr mice polygenic inheritance resulting in the complex pathological manifestations
International Journal of Cardiology, 2000Co-Authors: Masato Nose, Miyuki Nishihara, Miho Terada, Junji Kamogawa, Weimin Qu, Shiro Mori, Tatsuhiko Miyazaki, Syuichi NakatsuruAbstract:Abstract MRL/MpJ- lpr / lpr (MRL/lpr) mice develop Collagen Disease involving vasculitis, glomerulonephritis, arthritis and sialoadenitis, each of which has been studied as a model for polyarteritis, lupus nephritis, rheumatoid arthritis and Sjogren's syndrome, respectively. In the previous studies, we observed genetic segregation of these complex pathological manifestations throughout the genome recombination with a C57Bl/6- lpr / lpr or a C3H/HeJ- lpr / lpr (C3H/lpr) strain of mice which rarely develops such lesions, indicating that development of Collagen Disease is dependent on an MRL host genetic background. To clarify the mode of inheritance and the gene loci affecting four types of the lesions in MRL/lpr mice; vasculitis, glomerulonephritis, arthritis and sialoadenitis, a genetic dissection of the lesions was carried out by using MRL/lpr, C3H/lpr, (MRL/lpr×C3H/lpr) F1 intercross, and MRL/lpr×(MRL/lpr×C3H/lpr) F1 backcross mice. Definition of each lesion was performed by histopathology under light microscopy, and genomic DNA of the backcross mice were subjected to association studies by chi-square analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. We observed that gene loci recessively associated with each lesion were mapped on different chromosomal positions. We conclude that each of four types of the lesions in MRL/lpr mice is under the control of different set of genes, suggesting the complex pathological manifestations of Collagen Disease result from polygenic inheritance.
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Genome analysis of Collagen Disease in MRL/lpr mice: polygenic inheritance resulting in the complex pathological manifestations.
International journal of cardiology, 2000Co-Authors: Masato Nose, Miyuki Nishihara, Miho Terada, Junji Kamogawa, Weimin Qu, Shiro Mori, Tatsuhiko Miyazaki, Syuichi NakatsuruAbstract:MRL/MpJ-lpr/lpr (MRL/lpr) mice develop Collagen Disease involving vasculitis, glomerulonephritis, arthritis and sialoadenitis, each of which has been studied as a model for polyarteritis, lupus nephritis, rheumatoid arthritis and Sjögren's syndrome, respectively. In the previous studies, we observed genetic segregation of these complex pathological manifestations throughout the genome recombination with a C57Bl/6-lpr/lpr or a C3H/HeJ-lpr/lpr (C3H/lpr) strain of mice which rarely develops such lesions, indicating that development of Collagen Disease is dependent on an MRL host genetic background. To clarify the mode of inheritance and the gene loci affecting four types of the lesions in MRL/lpr mice; vasculitis, glomerulonephritis, arthritis and sialoadenitis, a genetic dissection of the lesions was carried out by using MRL/lpr, C3H/lpr, (MRL/lprxC3H/lpr) F1 intercross, and MRL/lprx(MRL/lprxC3H/lpr) F1 backcross mice. Definition of each lesion was performed by histopathology under light microscopy, and genomic DNA of the backcross mice were subjected to association studies by chi-square analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. We observed that gene loci recessively associated with each lesion were mapped on different chromosomal positions. We conclude that each of four types of the lesions in MRL/lpr mice is under the control of different set of genes, suggesting the complex pathological manifestations of Collagen Disease result from polygenic inheritance.
Genevieve L Wojcik - One of the best experts on this subject based on the ideXlab platform.
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genetic identification of a common Collagen Disease in puerto ricans via identity by descent mapping in a health system
eLife, 2017Co-Authors: Gillian M Belbin, Elena P Sorokin, Jacqueline Odgis, Sumita Kohli, Benjamin S Glicksberg, Christopher R Gignoux, Genevieve L Wojcik, Muhching Yee, Tielman Van Vleck, Janina M JeffAbstract:Diseases often run in families. These Disease are frequently linked to changes in DNA that are passed down through generations. Close family members may share these Disease-causing mutations; so may distant relatives who inherited the same mutation from a common ancestor long ago. Geneticists use a method called linkage mapping to trace a Disease found in multiple members of a family over generations to genetic changes in a shared ancestor. This allows scientists to pinpoint the exact place in the genome the Disease-causing mutation occurred. Using computer algorithms, scientists can apply the same technique to identify mutations that distant relatives inherited from a common ancestor. Belbin et al. used this computational technique to identify a mutation that may cause unusually short stature or bone and joint problems in up to 2% of people of Puerto Rican decent. In the experiments, the genomes of about 32,000 New Yorkers who have volunteered to participate in the BioMe Biobank and their health records were used to search for genetic changes linked to extremely short stature. The search revealed that people who inherited two copies of this mutation from their parents were likely to be extremely short or to have bone and joint problems. People who inherited one copy had an increased likelihood of joint or bone problems. This mutation affects a gene responsible for making a form of protein called Collagen that is important for bone growth. The analysis suggests the mutation first arose in a Native American ancestor living in Puerto Rico around the time that European colonization began. The mutation had previously been linked to a disorder called Steel syndrome that was thought to be rare. Belbin et al. showed this condition is actually fairly common in people whose ancestors recently came from Puerto Rico, but may often go undiagnosed by their physicians. The experiments emphasize the importance of including diverse populations in genetic studies, as studies of people of predominantly European descent would likely have missed the link between this Disease and mutation.
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genetic identification of a common Collagen Disease in puerto ricans via identity by descent mapping in a health system
bioRxiv, 2017Co-Authors: Gillian M Belbin, Elena P Sorokin, Jacqueline Odgis, Sumita Kohli, Benjamin S Glicksberg, Christopher R Gignoux, Genevieve L Wojcik, Tielman Van Vleck, Janina M Jeff, Michael D LindermanAbstract:Achieving confidence in the causality of a Disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with genetic relatedness that also underlies extreme short stature. We link the gene, COL27A1, with a little-known genetic Disease, previously thought to be rare and recessive. We demonstrate that Disease manifests in both heterozygotes and homozygotes, indicating a common Collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian Disease.