RESUMO
Mycobacterium bovis strain 04-303 was isolated from a wild boar living in a free-ranging field in Argentina. This work reports the draft genome sequence of this highly virulent strain and the genomic comparison of its major virulence-related genes with those of M. bovis strain AF2122/97 and Mycobacterium tuberculosis strain H37Rv.
RESUMO
CD80 and CD86 are closely linked genes on chromosome 3 that code for glycoproteins of the immunoglobulin superfamily, expressed on the surface of antigen-presenting cells. These costimulatory molecules play essential roles for stimulation and inhibition of T cells through binding to CD28 and CTLA-4 receptors. In this study, CD80 promoter and CD86 exon 8 polymorphisms were analyzed to investigate the genetic diversity and microevolution of the 2 genes. We genotyped 1,124 individuals, including Brazilians of predominantly European, mixed African and European, and Japanese ancestry, 5 Amerindian populations, and an African sample. All variants were observed in Africans, which suggests their origin in Africa before the human migrations out of that continent. Five new CD80 promoter alleles were identified and confirmed by cloning and sequencing, and promoter 2 is most likely the ancestral allele. Nucleotide -79 is monomorphic in 4 Amerindian populations, where the presence of the -79 G allele is probably the result of gene flow from non-Amerindians.
Assuntos
Antígeno B7-1/genética , Antígeno B7-2/genética , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Alelos , Indígena Americano ou Nativo do Alasca/etnologia , Indígena Americano ou Nativo do Alasca/genética , Povo Asiático/genética , População Negra/etnologia , População Negra/genética , Brasil , Evolução Molecular , Éxons/genética , Frequência do Gene , Variação Genética , Genótipo , Haplótipos , Humanos , Japão/etnologia , Desequilíbrio de Ligação , Filogenia , População Branca/etnologia , População Branca/genéticaRESUMO
Signaling through antigen presenting cells is required to activate T lymphocytes. The antigen-specific signal is given by interaction of the T-cell receptor (TCR) with the major histocompatibility complex (MHC)/peptide complex. Also essential for activation is the interaction of the coreceptor CD28 with ligands of the B7 family (CD80 and CD86) on antigen presenting cells. Coreceptor CTLA-4 is a negative regulator and binds the same B7 isoforms, contributing to immunologic homeostasis and peripheral tolerance. CD28 and CTLA4 are homologous and closely linked genes in 2q33, as are CD80 and CD86 in the 3q21 chromosomal region. Pemphigus foliaceus (PF) is a multifactorial autoimmune blistering disease characterized by keratinocyte detachment and by autoantibodies against desmoglein 1, a desmosomal protein. To investigate the involvement of CD28, CTLA4, CD80, and CD86 genes in PF pathogenesis, 18 polymorphisms in 2q33 and 3q21 chromosomal regions were analyzed in 269 patients and 395 controls subdivided according to predominant ancestry in Euro-Brazilian and Afro-Brazilian individuals. Associations were found with CD86 1057G>A, CTLA4-1722T>C, CTLA4-318C>T, CTLA4(AT)n, CD28(CAA)n, and D2S72(CA)n. There is no evidence of gene-gene interactions. We conclude that polymorphisms in the 2q33 and 3q21 chromosomal regions may influence PF disease susceptibility, most likely affecting CTLA4 and possibly inducible T-cell costimulator, (ICOS) expression, and also CD86 function.
Assuntos
Cromossomos Humanos Par 2/genética , Cromossomos Humanos Par 3/genética , Predisposição Genética para Doença/genética , Pênfigo/genética , Polimorfismo Genético , Alelos , Antígenos CD/genética , Antígeno B7-1/genética , Antígeno B7-2/genética , Brasil , Antígenos CD28/genética , Antígeno CTLA-4 , Frequência do Gene , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Repetições de Microssatélites/genética , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Pemphigus foliaceus is an organ-specific autoimmune disease characterized by autoantibodies against the extracellular region of desmoglein 1, a protein that mediates intercellular adhesion in desmosomes. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a key negative regulator of the T cell immune response, playing an important role in T cell homeostasis and maintenance of peripheral tolerance. Polymorphisms in the CTLA4 gene have been associated with autoimmune diseases and the functional CT60 single nucleotide polymorphism (rs3087243, also named 6230G > A) has been proposed to be a casual variant in several of these diseases. The aim of this study was to ascertain whether this polymorphism is associated with inter-individual variation in susceptibility to pemphigus foliaceus. The population sample in this case-control association study comprised 248 patient and 367 controls. We did not found a significant association of pemphigus foliaceus with the CT60 variants. We conclude that the CTLA4CT60 polymorphism is not an important factor for pemphigus foliaceus pathogenesis in the population analyzed.
RESUMO
Pemphigus foliaceus is an organ-specific autoimmune disease characterized by autoantibodies against the extracellular region of desmoglein 1, a protein that mediates intercellular adhesion in desmosomes. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a key negative regulator of the T cell immune response, playing an important role in T cell homeostasis and maintenance of peripheral tolerance. Polymorphisms in the CTLA4 gene have been associated with autoimmune diseases and the functional CT60 single nucleotide polymorphism (rs3087243, also named 6230G > A) has been proposed to be a casual variant in several of these diseases. The aim of this study was to ascertain whether this polymorphism is associated with inter-individual variation in susceptibility to pemphigus foliaceus. The population sample in this case-control association study comprised 248 patient and 367 controls. We did not found a significant association of pemphigus foliaceus with the CT60 variants. We conclude that the CTLA4 CT60 polymorphism is not an important factor for pemphigus foliaceus pathogenesis in the population analyzed.