The Experts below are selected from a list of 195 Experts worldwide ranked by ideXlab platform
William B Zipf - One of the best experts on this subject based on the ideXlab platform.
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modular variations of the human major histocompatibility complex class iii genes for serine threonine kinase rp Complement Component C4 steroid 21 hydroxylase cyp21 and tenascin tnx the rccx module a mechanism for gene deletions and disease associati
Journal of Biological Chemistry, 1999Co-Authors: Zhenyu Yang, Anna R Mendoza, Thomas R Welch, William B ZipfAbstract:Abstract The frequent variations of human Complement Component C4 gene size and gene numbers, plus the extensive polymorphism of the proteins, render C4 an excellent marker for major histocompatibility complex disease associations. As shown by definitive RFLPs, the tandemly arranged genes RP, C4,CYP21, and TNX are duplicated together as a discrete genetic unit termed the RCCX module. Duplications of the RCCX modules occurred by the addition of genomic fragments containing a long (L) or a short (S) C4 gene, a CYP21A or aCYP21B gene, and the gene fragments TNXA andRP2. Four major RCCX structures with bimodular L-L, bimodular L-S, monomodular L, and monomodular S are present in the Caucasian population. These modules are readily detectable byTaqI RFLPs. The RCCX modular variations appear to be a root cause for the acquisition of deleterious mutations from pseudogenes or gene segments in the RCCX to their corresponding functional genes. In a patient with congenital adrenal hyperplasia, we discovered aTNXB-TNXA recombinant with the deletion ofRP2-C4B-CYP21B. Elucidation of the DNA sequence for the recombination breakpoint region and sequence analyses yielded definitive proof for an unequal crossover betweenTNXA from a bimodular chromosome and TNXB from a monomodular chromosome.
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Modular Variations of the Human Major Histocompatibility Complex Class III Genes for Serine/Threonine Kinase RP, Complement Component C4, Steroid 21-Hydroxylase CYP21, and Tenascin TNX (the RCCX Module) A MECHANISM FOR GENE DELETIONS AND DISEASE ASSO
The Journal of biological chemistry, 1999Co-Authors: Zhenyu Yang, Anna R Mendoza, Thomas R Welch, William B ZipfAbstract:The frequent variations of human Complement Component C4 gene size and gene numbers, plus the extensive polymorphism of the proteins, render C4 an excellent marker for major histocompatibility complex disease associations. As shown by definitive RFLPs, the tandemly arranged genes RP, C4, CYP21, and TNX are duplicated together as a discrete genetic unit termed the RCCX module. Duplications of the RCCX modules occurred by the addition of genomic fragments containing a long (L) or a short (S) C4 gene, a CYP21A or a CYP21B gene, and the gene fragments TNXA and RP2. Four major RCCX structures with bimodular L-L, bimodular L-S, monomodular L, and monomodular S are present in the Caucasian population. These modules are readily detectable by TaqI RFLPs. The RCCX modular variations appear to be a root cause for the acquisition of deleterious mutations from pseudogenes or gene segments in the RCCX to their corresponding functional genes. In a patient with congenital adrenal hyperplasia, we discovered a TNXB-TNXA recombinant with the deletion of RP2-C4B-CYP21B. Elucidation of the DNA sequence for the recombination breakpoint region and sequence analyses yielded definitive proof for an unequal crossover between TNXA from a bimodular chromosome and TNXB from a monomodular chromosome.
Torleiv O. Rognum - One of the best experts on this subject based on the ideXlab platform.
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The Complement Component C4 in sudden infant death.
European journal of pediatrics, 1999Co-Authors: Siri H. Opdal, Åshild Vege, A. K. Stave, Torleiv O. RognumAbstract:The aim of the present study was to compare partial deletions of the Complement C4 gene in victims of totally unexplained sudden infant death (SID) (n = 89) and borderline SID (n = 15) with and without slight infections prior to death, in cases of infectious death (n = 19), and in living infants with and without infections (n = 84). The SID and borderline SID groups were pooled. In this total SID group slight infections prior to death was associated with deletion of either the C4A or the C4B gene (P = 0.033), and the SID victims with such infections had a higher deletion frequency than the controls (P = 0.039). There were no differences between the living infants with and without upper airway infections. The present study confirms that partial deletions of the C4 gene in combination with slight upper airway infections may be a risk factor in sudden infant death.
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the Complement Component C4 in sudden infant death
European Journal of Pediatrics, 1999Co-Authors: Siri H. Opdal, Åshild Vege, A. K. Stave, Torleiv O. RognumAbstract:The aim of the present study was to compare partial deletions of the Complement C4 gene in victims of totally unexplained sudden infant death (SID) (n = 89) and borderline SID (n = 15) with and without slight infections prior to death, in cases of infectious death (n = 19), and in living infants with and without infections (n = 84). The SID and borderline SID groups were pooled. In this total SID group slight infections prior to death was associated with deletion of either the C4A or the C4B gene (P = 0.033), and the SID victims with such infections had a higher deletion frequency than the controls (P = 0.039). There were no differences between the living infants with and without upper airway infections.
Anna R Mendoza - One of the best experts on this subject based on the ideXlab platform.
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modular variations of the human major histocompatibility complex class iii genes for serine threonine kinase rp Complement Component C4 steroid 21 hydroxylase cyp21 and tenascin tnx the rccx module a mechanism for gene deletions and disease associati
Journal of Biological Chemistry, 1999Co-Authors: Zhenyu Yang, Anna R Mendoza, Thomas R Welch, William B ZipfAbstract:Abstract The frequent variations of human Complement Component C4 gene size and gene numbers, plus the extensive polymorphism of the proteins, render C4 an excellent marker for major histocompatibility complex disease associations. As shown by definitive RFLPs, the tandemly arranged genes RP, C4,CYP21, and TNX are duplicated together as a discrete genetic unit termed the RCCX module. Duplications of the RCCX modules occurred by the addition of genomic fragments containing a long (L) or a short (S) C4 gene, a CYP21A or aCYP21B gene, and the gene fragments TNXA andRP2. Four major RCCX structures with bimodular L-L, bimodular L-S, monomodular L, and monomodular S are present in the Caucasian population. These modules are readily detectable byTaqI RFLPs. The RCCX modular variations appear to be a root cause for the acquisition of deleterious mutations from pseudogenes or gene segments in the RCCX to their corresponding functional genes. In a patient with congenital adrenal hyperplasia, we discovered aTNXB-TNXA recombinant with the deletion ofRP2-C4B-CYP21B. Elucidation of the DNA sequence for the recombination breakpoint region and sequence analyses yielded definitive proof for an unequal crossover betweenTNXA from a bimodular chromosome and TNXB from a monomodular chromosome.
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Modular Variations of the Human Major Histocompatibility Complex Class III Genes for Serine/Threonine Kinase RP, Complement Component C4, Steroid 21-Hydroxylase CYP21, and Tenascin TNX (the RCCX Module) A MECHANISM FOR GENE DELETIONS AND DISEASE ASSO
The Journal of biological chemistry, 1999Co-Authors: Zhenyu Yang, Anna R Mendoza, Thomas R Welch, William B ZipfAbstract:The frequent variations of human Complement Component C4 gene size and gene numbers, plus the extensive polymorphism of the proteins, render C4 an excellent marker for major histocompatibility complex disease associations. As shown by definitive RFLPs, the tandemly arranged genes RP, C4, CYP21, and TNX are duplicated together as a discrete genetic unit termed the RCCX module. Duplications of the RCCX modules occurred by the addition of genomic fragments containing a long (L) or a short (S) C4 gene, a CYP21A or a CYP21B gene, and the gene fragments TNXA and RP2. Four major RCCX structures with bimodular L-L, bimodular L-S, monomodular L, and monomodular S are present in the Caucasian population. These modules are readily detectable by TaqI RFLPs. The RCCX modular variations appear to be a root cause for the acquisition of deleterious mutations from pseudogenes or gene segments in the RCCX to their corresponding functional genes. In a patient with congenital adrenal hyperplasia, we discovered a TNXB-TNXA recombinant with the deletion of RP2-C4B-CYP21B. Elucidation of the DNA sequence for the recombination breakpoint region and sequence analyses yielded definitive proof for an unequal crossover between TNXA from a bimodular chromosome and TNXB from a monomodular chromosome.
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Complement Component C4 gene intron 9 as a phylogenetic marker for primates: long terminal repeats of the endogenous retrovirus ERV-K(C4) are a molecular clock of evolution.
Immunogenetics, 1995Co-Authors: Andrew W. Dangel, Bradley J. Baker, Anna R MendozaAbstract:The Complement Component C4 genes of Old World primates exhibit a long/short dichotomous size variation, except that chimpanzee and gorilla only contain short C4 genes. In human it has been shown that the long C4 gene is attributed to the integration of an endogenous retrovirus, HERV-K(C4), into intron 9. This 6.36 kilobase retroviral element is absent in short C4 genes. Here it is shown that the homologous endogenous retrovirus, ERV-K(C4), is present precisely at the same position in the long C4 gene of orangutan and African green monkey. Determination of the short C4 gene intron 9 sequences from human, three apes, two Old World monkeys, and a New World monkey allowed the establishment of consistent phylogenetic trees for primates, which favors a chimpanzee-gorilla clade. The 5′ long terminal repeats (LTR) and 3′ LTR of ERV-K(C4) in long C4 genes of human, orangutan, and African green monkey have similar sequence divergence values of 9.1%–10.5%. These values are more than five-fold higher than the sequence divergence of the homologous intron 9 sequences between the long and short C4 genes in higher primates. The latter is probably a result of homogenization or concerted evolution. We suggest that the 5′ LTR and 3′ LTR of an endogenous retrovirus can serve as a reliable reference point or a molecular clock for studies of gene duplication and gene evolution. This is because the 5′/3′ LTR sequences were identical at the time of retroviral integration and evolved independently of each other afterwards. Our data provides strong evidence for the short C4 gene being the ancestral form in primates, trans-species evolution, and the “slow-down” phenomenon of the sequence divergence in great apes.
Zhenyu Yang - One of the best experts on this subject based on the ideXlab platform.
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modular variations of the human major histocompatibility complex class iii genes for serine threonine kinase rp Complement Component C4 steroid 21 hydroxylase cyp21 and tenascin tnx the rccx module a mechanism for gene deletions and disease associati
Journal of Biological Chemistry, 1999Co-Authors: Zhenyu Yang, Anna R Mendoza, Thomas R Welch, William B ZipfAbstract:Abstract The frequent variations of human Complement Component C4 gene size and gene numbers, plus the extensive polymorphism of the proteins, render C4 an excellent marker for major histocompatibility complex disease associations. As shown by definitive RFLPs, the tandemly arranged genes RP, C4,CYP21, and TNX are duplicated together as a discrete genetic unit termed the RCCX module. Duplications of the RCCX modules occurred by the addition of genomic fragments containing a long (L) or a short (S) C4 gene, a CYP21A or aCYP21B gene, and the gene fragments TNXA andRP2. Four major RCCX structures with bimodular L-L, bimodular L-S, monomodular L, and monomodular S are present in the Caucasian population. These modules are readily detectable byTaqI RFLPs. The RCCX modular variations appear to be a root cause for the acquisition of deleterious mutations from pseudogenes or gene segments in the RCCX to their corresponding functional genes. In a patient with congenital adrenal hyperplasia, we discovered aTNXB-TNXA recombinant with the deletion ofRP2-C4B-CYP21B. Elucidation of the DNA sequence for the recombination breakpoint region and sequence analyses yielded definitive proof for an unequal crossover betweenTNXA from a bimodular chromosome and TNXB from a monomodular chromosome.
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Modular Variations of the Human Major Histocompatibility Complex Class III Genes for Serine/Threonine Kinase RP, Complement Component C4, Steroid 21-Hydroxylase CYP21, and Tenascin TNX (the RCCX Module) A MECHANISM FOR GENE DELETIONS AND DISEASE ASSO
The Journal of biological chemistry, 1999Co-Authors: Zhenyu Yang, Anna R Mendoza, Thomas R Welch, William B ZipfAbstract:The frequent variations of human Complement Component C4 gene size and gene numbers, plus the extensive polymorphism of the proteins, render C4 an excellent marker for major histocompatibility complex disease associations. As shown by definitive RFLPs, the tandemly arranged genes RP, C4, CYP21, and TNX are duplicated together as a discrete genetic unit termed the RCCX module. Duplications of the RCCX modules occurred by the addition of genomic fragments containing a long (L) or a short (S) C4 gene, a CYP21A or a CYP21B gene, and the gene fragments TNXA and RP2. Four major RCCX structures with bimodular L-L, bimodular L-S, monomodular L, and monomodular S are present in the Caucasian population. These modules are readily detectable by TaqI RFLPs. The RCCX modular variations appear to be a root cause for the acquisition of deleterious mutations from pseudogenes or gene segments in the RCCX to their corresponding functional genes. In a patient with congenital adrenal hyperplasia, we discovered a TNXB-TNXA recombinant with the deletion of RP2-C4B-CYP21B. Elucidation of the DNA sequence for the recombination breakpoint region and sequence analyses yielded definitive proof for an unequal crossover between TNXA from a bimodular chromosome and TNXB from a monomodular chromosome.
Edouard Louis - One of the best experts on this subject based on the ideXlab platform.
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Genome-Wide Copy Number Variation Scan Identifies Complement Component C4 as Novel Susceptibility Gene for Crohn's Disease.
Inflammatory bowel diseases, 2016Co-Authors: Isabelle Cleynen, Leila Amininejad, Michel Georges, Paul Rutgeerts, Debby Laukens, Ingrid Arijs, Edouard Louis, Joris Vermeesch, Caroline Robberecht, Yves Moreau, Emilie Théâtre, Kristel Van Steen, Peter Konings, Martine De Vos, Denis Franchimont, Kathleen Machiels, Severine VermeireAbstract:BACKGROUND The genetic Component of Crohn's disease (CD) is well known, with 140 susceptibility loci identified so far. In addition to single nucleotide polymorphisms typically studied in genome-wide scans, copy number variation is responsible for a large proportion of human genetic variation. METHODS We performed a genome-wide search for copy number variants associated with CD using array comparative genomic hybridization. One of the found regions was validated independently through real-time PCR. Serum levels of the found gene were measured in patients and control subjects. RESULTS We found copy number differences for the C4S and C4L gene variants of Complement Component C4 in the central major histocompatibility complex region on chromosome 6p21. Specifically, we saw that CD patients tend to have lower C4L and higher C4S copies than control subjects (P = 5.00 × 10 and P = 9.11 × 10), which was independent of known associated classical HLA I and II alleles (P = 7.68 × 10 and P = 6.29 × 10). Although C4 serum levels were not different between patients and control subjects, the relationship between C4 copy number and serum level was different for patients and control subjects with higher copy numbers leading to higher serum concentrations in control subjects, compared with CD patients (P < 0.001). CONCLUSIONS C4 is part of the classical activation pathway of the Complement system, which is important for (auto)immunity. Low C4L or high C4S copy number, and corresponding effects on C4 serum level, could lead to an exaggerated response against infections, possibly leading to (auto)immune disease.
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Genome-Wide Copy Number Variation Scan Identifies Complement Component C4 as Novel Susceptibility Gene for Crohn's Disease
Inflammatory bowel diseases, 2016Co-Authors: Isabelle Cleynen, Leila Amininejad, Kathleen Machiels, Peter Konings, Caroline Robberecht, Ingrid Arijs, Debby Laukens, Paul Rutgeerts, Emilie Théâtre, Edouard LouisAbstract:The genetic Component of Crohn's disease (CD) is well known, with 140 susceptibility loci identified so far. In addition to single nucleotide polymorphisms typically studied in genome-wide scans, copy number variation is responsible for a large proportion of human genetic variation. We performed a genome-wide search for copy number variants associated with CD using array comparative genomic hybridization. One of the found regions was validated independently through real-time PCR. Serum levels of the found gene were measured in patients and control subjects. We found copy number differences for the C4S and C4L gene variants of Complement Component C4 in the central major histocompatibility complex region on chromosome 6p21. Specifically, we saw that CD patients tend to have lower C4L and higher C4S copies than control subjects (P = 5.00 × 10 and P = 9.11 × 10), which was independent of known associated classical HLA I and II alleles (P = 7.68 × 10 and P = 6.29 × 10). Although C4 serum levels were not different between patients and control subjects, the relationship between C4 copy number and serum level was different for patients and control subjects with higher copy numbers leading to higher serum concentrations in control subjects, compared with CD patients (P < 0.001). C4 is part of the classical activation pathway of the Complement system, which is important for (auto)immunity. Low C4L or high C4S copy number, and corresponding effects on C4 serum level, could lead to an exaggerated response against infections, possibly leading to (auto)immune disease.