Estudo das frequencias de recombinaçao entre o loco da cadeia beta da hemoglobina (Hb beta)e os locos do sistema sangüíneo MNSs e da cadeia delta da hemoglobina (Hb delta)

Orientadora: Profa. Dra. Eleidi A. Chautard Freire MaiaDissertação (mestrado) -Universidade Federal do Paraná, Setor de Ciências Biológicas, Curso de Pós-Graduação em Genética HumanaInclui referências: p. 63-7

Phylogenetic nomenclature and evolution of mannose-binding lectin (MBL2) haplotypes

<p>Abstract</p> <p>Background</p> <p>Polymorphisms of the mannose-binding lectin gene (<it>MBL2</it>) affect the concentration and functional efficiency of the protein. We recently used haplotype-specific sequencing to identify 23 <it>MBL2 </it>haplotypes, associated with enhanced susceptibility to several diseases.</p> <p>Results</p> <p>In this work, we applied the same method in 288 and 470 chromosomes from Gabonese and European adults, respectively, and found three new haplotypes in the last group. We propose a phylogenetic nomenclature to standardize <it>MBL2 </it>studies and found two major phylogenetic branches due to six strongly linked polymorphisms associated with high MBL production. They presented high Fst values and were imbedded in regions with high nucleotide diversity and significant Tajima's D values. Compared to others using small sample sizes and unphased genotypic data, we found differences in haplotyping, frequency estimation, Fu and Li's D* and Fst results.</p> <p>Conclusion</p> <p>Using extensive testing for selective neutrality, we confirmed that stochastic evolutionary factors have had a major role in shaping this polymorphic gene worldwide.</p

Blood groups in Native Americans : a look beyond ABO and Rh

The study presents comparisons between blood group frequencies beyond ABO and Rh blood systems in Native American populations and previously published data from Brazilian blood donors. The frequencies of Diego (c.2561C>T, rs2285644), Kell (c.578C>T, rs8176058), Duffy (c.125A>G, rs12075, c.1−67T>C, rs2814778) and Kidd (c.838A>G, rs1058396) variants in Kaingang (n=72) and Guarani (n=234) populations from Brazil (1990–2000) were obtained and compared with data from these populations sampled during the 1960s and with individuals of different Brazilian regions. Data showed high frequencies of DI*01 and FY*01 alleles: 11.8% and 57.6% in Kaingang and 6.8% and 75.7% in Guarani groups, respectively. The main results indicated: (1) reduction in genetic distance over time of Kaingang and Guarani in relation to other Brazilian populations is suggestive of ongoing admixture; (2) significant differences in some frequencies of blood group markers (especially Diego, Kidd and Duffy) in relation to Native Americans and individuals from different geographical regions of Brazil. Our study shows that the frequency of red blood cell polymorphisms in two Native American groups is very different from that of blood donors, when we evaluated blood groups different from ABO and Rh systems, suggesting that a better ethnic characterization of blood unit receptors is necessary

Complement Receptor 1 (CR1, CD35) Polymorphisms and Soluble CR1: A Proposed Anti-inflammatory Role to Quench the Fire of "Fogo Selvagem" Pemphigus Foliaceus

Pemphigus foliaceus is an autoimmune disease that is sporadic around the world but endemic in Brazil, where it is known as fogo selvagem (FS). Characterized by autoantibodies against the desmosomal cadherin desmoglein 1, FS causes painful erosions, and crusts that may be widespread. The recognition of antigens, including exposed sugar moieties, activates the complement system. Complement receptor 1 (CR1, CD35), which is responsible for the Knops blood group on erythrocytes (York and McCoy antigens), is also expressed by antigen-presenting cells. This regulates the complement system by removing opsonized antigens, blocking the final steps of the complement cascade. Membrane-bound CR1 also fosters antigen presentation to B cells, whereas soluble CR1 has anti-inflammatory properties. CR1 gene polymorphisms have been associated with susceptibility to complex diseases. In order to investigate the association of CR1 polymorphisms with FS susceptibility, we developed a multiplex sequence-specific assay to haplotype eleven polymorphisms in up to 367 FS patients and 242 controls from an endemic area and 289 from a non-endemic area. We also measured soluble CR1 (sCR1) in the serum of 53 FS patients and 27 controls and mRNA levels in the peripheral blood mononuclear cells of 63 genotyped controls. The haplotypes CR1 * 3B2B (with the York antigen-encoded by p.1408Met) and CR1 * 3A2A (with p.1208Arg) were associated with protection against FS (OR = 0.57, P = 0.027, and OR = 0.46, P = 0.014, respectively). In contrast, the CR1 * 1 haplotype (with the McCoy antigen - encoded by p.1590Glu) was associated with FS susceptibility (OR = 4.97, P < 0.001). Heterozygote rs12034383 * A/G individuals presented higher mRNA expression than homozygotes with the G allele (P = 0.04). The lowest sCR1 levels occurred in patients with active disease before treatment (P = 0.036). Patients in remission had higher levels of sCR1 than did healthy controls (P = 0.013). Among those under treatment, patients with localized lesions also presented higher sCR1 levels than those with generalized lesions (P = 0.0073). In conclusion, the Knops blood group seems to modulate susceptibility to the disease. Furthermore, corticosteroid treatment might increase sCR1 serum levels, and higher levels may play an anti-inflammatory role in patients with FS, limiting the distribution of lesions. Based on these results, we suggest CR1 as a potential new therapeutic target for the treatment of FS

Variations in Human Herpesvirus Type 8 Seroprevalence in Native Americans, South America

To determine the epidemiology of human herpesvirus type 8 (HHV-8) among non-Amazonian native populations, we conducted a cross-sectional study in Brazil, Bolivia, and Paraquay. Our data show striking ethnic and geographic variations in the distribution of HHV-8 seroprevalences in Amazonian (77%) and non-Amazonian native populations (range 0%–83%)

Activating KIR and HLA Bw4 Ligands Are Associated to Decreased Susceptibility to Pemphigus Foliaceus, an Autoimmune Blistering Skin Disease

The KIR genes and their HLA class I ligands have thus far not been investigated in pemphigus foliaceus (PF) and related autoimmune diseases, such as pemphigus vulgaris. We genotyped 233 patients and 204 controls for KIR by PCR-SSP. HLA typing was performed by LABType SSO reagent kits. We estimated the odds ratio, 95% confidence interval and performed logistic regression analyses to test the hypothesis that KIR genes and their known ligands influence susceptibility to PF. We found significant negative association between activating genes and PF. The activating KIR genes may have an overlapping effect in the PF susceptibility and the presence of more than three activating genes was protective (OR = 0.49, p = 0.003). A strong protective association was found for higher ratios activating/inhibitory KIR (OR = 0.44, p = 0.001). KIR3DS1 and HLA-Bw4 were negatively associated to PF either isolated or combined, but higher significance was found for the presence of both together (OR = 0.34, p<10−3) suggesting that the activating function is the major factor to interfere in the PF pathogenesis. HLA-Bw4 (80I and 80T) was decreased in patients. There is evidence that HLA-Bw4(80T) may also be important as KIR3DS1 ligand, being the association of this pair (OR = 0.07, p = 0.001) stronger than KIR3DS1-Bw4(80I) (OR = 0.31, p = 0.002). Higher levels of activating KIR signals appeared protective to PF. The activating KIR genes have been commonly reported to increase the risk for autoimmunity, but particularities of endemic PF, like the well documented influence the environmental exposure in the pathogenesis of this disease, may be the reason why activated NK cells probably protect against pemphigus foliaceus

Análise proteômica do estresse hídrico em cafeeiro.

Déficit hídrico é um dos fatores ambientais mais importantes para a diminuição da produtividade do cafeeiro, tanto no Brasil quanto em outros países produtores. O estabelecimento de estratégias para obtenção de cultivares tolerantes ao estresse hídrico depende da compreensão das respostas biológicas ao nível genético, molecular e bioquímico. Para estudar a resposta ao estresse hídrico no gênero Coffea, foi estabelecida uma rede de pesquisa em proteômica (PROTEOPAR ? Programa Proteoma do Paraná) constituída de oito laboratórios. Quatro genótipos de Coffea, com diferentes respostas fisiológicas à seca, foram analisados: C. canephora (Clone 14, tolerante e Clone 109A, sensível) e C. arabica (BA10, tolerante e Geisha, sensível). Proteínas foram extraídas de folhas e raízes de plantas (18 meses de idade) mantidas em casa-de-vegetação, utilizando-se o método de SDS-Fenol modificado. Os regimes hídricos constituíram-se dos seguintes tratamentos: controle irrigado, estresse hídrico severo (-4,0 MPa de potencial de água) e recuperação pós-estresse (36 horas após irrigação). Os extratos protéicos foram distribuídos aos laboratórios do PROTEOPAR para obtenção e análise do padrão de expressão protéica diferencial via eletroforese bidimensional. O método de identificação de proteínas PMF (?Peptide mass fingerprinting?) foi aplicado utilizando-se um espectrômetro de massa (MS) do tipo MALDI-TOF e comparando os espectros de digestão tríptica contra bancos de dados baseados em ESTs de Coffea

CTLA4CT60 gene polymorphism is not associated with differential susceptibility to pemphigus foliaceus

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