Papers by Maria-Luiza Petzl-Erler
Human Immunology, 2016
We hereby report the KIR gene frequencies and the frequencies of HLA ligands of KIR for Brazilian... more We hereby report the KIR gene frequencies and the frequencies of HLA ligands of KIR for Brazilians of Japanese ancestry. A total of 51 individuals were genotyped for presence/absence of KIR (killer cell immunoglobulin-like receptors) genes and presence of HLA (human leukocyte antigens) ligands. KIR was genotyped using two pairs of sequence-specific primers (PCR-SSP) and HLA ligands were typed by LABType® SSO reagent kits (One Lambda, USA). These data are fully available in Allele Frequencies Net Database, under the population name "Brazil Curitiba Japanese KIR".
Arzneimittel-Forschung
The proliferative response of lymphocyte cultures upon the addition of a mixture of antigens from... more The proliferative response of lymphocyte cultures upon the addition of a mixture of antigens from the lysates of different bacteria (Paspat) to the culture medium was investigated using lymphocytes of groups of probands that investigated using lymphocytes of groups of probands that had been treated with the i.c. test preparation (T.P.1, group I), the lyophilized test preparation given orally (T.P.2, group II), a commercially available lyophilized bacterial lysate of similar composition given orally (T.P.3, group III), or with placebo (group IV). Lymphocyte cultures were set up on day 0 (before treatment), day 40 and day 70 (after treatment). The results show, that T.P.1 and T.P.2 produce a dose dependent proliferative response in lymphocyte cultures with a peak reactivity between 70 and 210 micrograms/ml. The degree of stimulation obtained with the bacterial lysate in different concentrations is increased in groups I and II over the stimulation obtained before treatment. Groups I and II which were treated with T.P.1 (i.c.) and T.P.2 (orally) are significantly different in their response to the bacterial lysate from the groups treated with T.P.3 or placebo on days 40 and 70. Evidence is presented that the stimulation obtained is predominantly a proliferation of T-cells.
International Journal of Immunogenetics
Genetics
Microsatellites have been widely used to reconstruct human evolution. However, the efficient use ... more Microsatellites have been widely used to reconstruct human evolution. However, the efficient use of these markers relies on information regarding the process producing the observed variation. Here, we present a novel approach to the locus-by-locus characterization of this process. By analyzing somatic mutations in cancer patients, we estimated the distributions of mutation size for each of 20 loci. The same loci were then typed in three ethnically diverse population samples. The generalized stepwise mutation model was used to test the predicted relationship between population and mutation parameters under two demographic scenarios: constant population size and rapid expansion. The agreement between the observed and expected relationship between population and mutation parameters, even when the latter are estimated in cancer patients, confirms that somatic mutations may be useful for investigating the process underlying population variation. Estimated distributions of mutation size differ substantially amongst loci, and mutations of more than one repeat unit are common. A new statistic, the normalized population variance, is introduced for multilocus estimation of demographic parameters, and for testing demographic scenarios. The observed population variation is not consistent with a constant population size. Time estimates of the putative population expansion are in agreement with those obtained by other methods.
Medical Principles and Practice, 2015
The aim of this study was to investigate the frequency of the LCT*-13910C&amp... more The aim of this study was to investigate the frequency of the LCT*-13910C>T polymorphism associated with a high expression of lactase in the small intestine during adulthood, and to infer the lactase persistence and adult-type hypolactasia phenotypes among Euro-Brazilians and Mennonites from South Brazil. Materials and Meth ods: A sequence-specific PCR method to genotype the LCT*-13910C>T polymorphism in 292 Euro-Brazilians and 151 Mennonites (a group with European ancestry and a long history of endogamy) was developed. Using an exact test of population differentiation, the genotype and allele frequency between these and other Brazilian populations were compared. The frequency of -13910*T was significantly higher among the Mennonites when compared to the Euro-Brazilian cohort (0.63 vs. 0.33, p < 0.000001). Accordingly, Mennonites had a higher prevalence of the lactase persistence genotype (88.1 vs. 55.5%, p < 0.000001). The distribution of -13910*T differed between Mennonites and all other Brazilian groups (p < 0.0001). The Euro-Brazilians from Curitiba displayed differences when compared to all other Brazilian groups (p < 0.0001), even to Euro-Brazilians from a different geographic region (p = 0.0003), but were similar to those from Porto Alegre (p = 0.2). Differences in the -13910*T-associated lactase persistence distribution among Euro-Brazilian groups reflect the ancestry and admixture of each…
Cancer Epidemiology Biomarkers & Prevention
Infection with high-risk human papillomavirus (HPV) is the major risk factor for the development ... more Infection with high-risk human papillomavirus (HPV) is the major risk factor for the development of malignant lesions in the uterine cervix. Environmental, behavioral, and ill-defined genetic factors also have been implicated in the pathogenesis of this disease. Associations between human leukocyte antigens (HLAs) and cervical cancer, precursor lesions, and HPV infections have been reported in several populations. To verify whether HLA-DRB1, -DQA1, and -DQB1 diversity is related to cervical cancer in the Brazilian population, 161 cases and 257 controls were HLA typed. Variants of DQA1 and DQB1 promoter regions were also typed in 92 cases and 228 controls. Polymorphism in HLA genes and promoters was distinguished by PCR-based methods, and the magnitude of associations was determined by logistic regression analysis. DRB1*15 [confounder-adjusted odds ratio (OR), 2.24; 95% confidence interval (CI), 1.29-3.90], DRB1*1503 (OR, 2.52; 95% CI, 1.16-5.48), and haplotype DRB1*15-DQB1*0602 (OR, 2.04; 95% CI, 1.15-3.61) were positively associated with cervical cancer. When we considered only DR15 haplotypes that did not carry the DQB1*0602 allele, the risk attributed to DRB1*15 more than doubled. A negative association was found between DQB1*05 and cervical cancer (OR, 0.57; 95% CI, 0.35-0.92), and similar trends were observed for DQA1*0101/04, DRB1*0101, and DRB1*1302. HPV positivity among controls was associated with DRB1*1503 (OR, 4.60; 95% CI, 1.33-15.9), DRB1*0405 (OR, 6.21; 95% CI, 1.66-23.2), and DQB1*0602 (OR, 2.48; 95% CI, 1.06-5.80). We suggest that HLA class II polymorphisms are involved in genetic susceptibility to cervical cancer and HPV infection in a Brazilian population from an area with a high incidence of this neoplasia.
PLOS ONE, 2015
The diversity of the five single nucleotide polymorphisms located in genes of the TP53 pathway (T... more The diversity of the five single nucleotide polymorphisms located in genes of the TP53 pathway (TP53, rs1042522; MDM2, rs2279744; MDM4, rs1563828; USP7, rs1529916; and LIF, rs929271) were studied in a total of 282 individuals belonging to Quechua, Aymara, Chivay, Cabanaconde, Yanke, Taquile, Amantani, Anapia, Uros, Guarani Ñandeva, and Guarani Kaiowá populations, characterized as Native American or as having a high level (> 90%) of Native American ancestry. In addition, published data pertaining to 100 persons from five other Native American populations (Surui, Karitiana, Maya, Pima, and Piapoco) were analyzed. The populations were classified as living in high altitude ( 2,500 m) or in lowlands (< 2,500 m). Our analyses revealed that alleles USP7-G, LIF-T, and MDM2-T showed significant evidence that they were selected for in relation to harsh environmental variables related to high altitudes. Our results show for the first time that alleles of classical TP53 network genes have been evolutionary co-opted for the successful human colonization of the Andes.
Nature, 2015
Genetic studies have consistently indicated a single common origin of Native American groups from... more Genetic studies have consistently indicated a single common origin of Native American groups from Central and South America. However, some morphological studies have suggested a more complex picture, whereby the northeast Asian affinities of present-day Native Americans contrast with a distinctive morphology seen in some of the earliest American skeletons, which share traits with present-day Australasians (indigenous groups in Australia, Melanesia, and island Southeast Asia). Here we analyse genome-wide data to show that some Amazonian Native Americans descend partly from a Native American founding population that carried ancestry more closely related to indigenous Australians, New Guineans and Andaman Islanders than to any present-day Eurasians or Native Americans. This signature is not present to the same extent, or at all, in present-day Northern and Central Americans or in a ∼12,600-year-old Clovis-associated genome, suggesting a more diverse set of founding populations of the Americas than previously accepted.
Human Genetics, 2015
defense (Shifrin et al. 2014) and early placentation (Trowsdale and Moffett 2008).
Major histocompatibility complex (MHC ) genes have been investigated because of their crucial rol... more Major histocompatibility complex (MHC ) genes have been investigated because of their crucial role in the defense against pathogens and their high degree of polymorphism. We performed a case-control study to assess a genetic association of MHC genes with susceptibility to tuberculosis (TB). The allelic lineages HLA-A*02 and B*18 were significantly less frequent in TB patients (n = 112, 44.6% women) than in controls (n = 224, 51.5% women): 18.8% vs 26.5%; odds ratio (OR) = 0.64; P = 0.037 and 2.7% vs 6.9%; OR = 0.37; P = 0.041. The negative association with haplotype HLA-B*18-MICA*018 (2.3% patients vs 6.4% controls; OR = 0.34; P = 0.035) was significant as a consequence of strong linkage disequilibrium (D = 0.827 for patients and 0.923 for controls). These findings suggest a trend toward protection of the HLA-A*02 and HLA-B*18 alleles.
Biochemical genetics, 2003
An electrophoretic band with butyrylcholinesterase activity was detected in 71 CHE2 C5+ and 378 C... more An electrophoretic band with butyrylcholinesterase activity was detected in 71 CHE2 C5+ and 378 CHE2 C5- individuals and was named C4/5 in view of its similar mobility to either C4 or C5, depending on the pH of the agar gel used. The present data suggest that C4/5 is a heterologous complex of butyrylcholinesterase. Although the C4/5 band may have the same mobility as C5, depending on the conditions of electrophoresis, our hypothesis is that these two bands result from the association of BChE with different molecules.
Human biology, 1998
Nucleotide sequence polymorphism of the HLA-DQA1 and HLA-DQB1 class II genes was analyzed in the ... more Nucleotide sequence polymorphism of the HLA-DQA1 and HLA-DQB1 class II genes was analyzed in the Kaingang and Guarani Amerindians from southern Brazil using PCR sequence-specific oligonucleotide typing methods. Four different DQA1-DQB1 haplotypes were found: DQA1*0401-DQB1*0402 (associated with DRB1*0802, DRB1*08041, and DRB1*0807), DQA1*0501-DQB1*0301 (associated with DRB1*1602, DRB1*1413, and DRB1*1402), DQA1*03-DQB1*0302 (associated with DRB1*0404 and DRB1*0411), and DQA1*03-DQB1*03032 (associated with DRB1*09012). These HLA-DQA1 and HLA-DQB1 alleles and haplotypes are common in many other populations of all major ethnic groups. Alleles and haplotypes introduced into the populations by post-Columbian admixture were seen at low frequency both in the Kaingang (3.2%) and in the Guarani (3.8%). No novel HLA-DQA1 and HLA-DQB1 alleles have thus far been identified in Amerindians. This differs from previous results for HLA-DRB1, another class II locus presenting novel alleles (i.e., all...
Human biology, 1995
The genetic variability of butyrylcholinesterase, determined by the BCHE and CHE2 loci, was exami... more The genetic variability of butyrylcholinesterase, determined by the BCHE and CHE2 loci, was examined in nine Brazilian Indian groups. In addition, a search for the presence of the BCHE*F allele was also performed in eight other Brazilian Indian samples and in five admixed (black-Indian-white) rural Amazonian communities previously studied for the CHE2 locus and the BCHE*A allele. In the Indian populations the frequency of the BCHE*F allele varied from 0 to 7.1% +/- 3.4 and the frequency of the CHE2 C5+ phenotype ranged from 1.4% +/- 1.4 to 45.9% +/- 3.8. This study seems to be the first to report the presence of the BCHE*F allele in native Americans. The BCHE*A allele appeared in one Indian group (1.4% +/- 1.0), and we suggest that its existence in this tribe and in other native Americans can be explained by gene flow from white populations. Gene flow may also be the reason for the occurrence of the BCHE*F allele in Brazilian Indians, whereas the CHE2*C5+ allele may have been presen...
Frontiers in Immunology, 2013
ABSTRACT MicroRNAs are a class of small non-coding RNAs ranging from 18 to 25 nucleotides that re... more ABSTRACT MicroRNAs are a class of small non-coding RNAs ranging from 18 to 25 nucleotides that regulate gene expression by complementary binding to mRNA sites. MicroRNAs have been increasingly implicated in normal immune function. Pemphigus foliaceus (PF) is a blistering autoimmune skin disease characterized by a Th2-dependet production of pathogenic IgG autoantibodies. We quantified by qRT-PCR six candidate microRNAs (miR-145, miR-146a, miR-148a, miR-155, miR-338-5p, and miR-1321) in three lymphocyte subpopulations (CD4+CD294+ Th2-like, CD4+C25+ T, and IgG expressing B cells [IgG+ B cells]) from six healthy controls, six patients with inactive disease (iPF) and seven patients with active lesions (aPF). In Th2-like cells, miR-146a was 4-fold upregulated in patients with inactive disease compared to patients with active lesions (P=0.014), suggesting that the expression of this microRNA might be negatively related to disease activity. In IgG+ B cells, miR-155 was 2-fold upregulated in patients with inactive disease compared to healthy controls (P=0.009) and exhibited a tendency for upregulation in these patients when compared to those with active lesions (P=0.082), allowing us to hypothesize that this microRNA might have a relevant role in PF remission. Moreover, miR-1321 revealed a tendency of upregulation in Th2-like cells of PF patients (iPF+aPF) compared to healthy controls (P=0.079). Expression of miR-1321 in these cells negatively correlated to that of its predicted target BLYS (BAFF), a B cell stimulator known to be important for PF pathogenesis (iPF, rS=-1.00, P&lt;0.05; aPF, rS=-0.49, ns). In conclusion, miR-146a, miR-155 and miR-1321 arise as potentially new mediators of therapeutic intervention for PF.
Human Immunology, 2015
Killer-cell immunoglobulin-like receptors (KIR) are highly polymorphic and have been associated t... more Killer-cell immunoglobulin-like receptors (KIR) are highly polymorphic and have been associated to several diseases. Their ligands are specific human leukocyte antigens (HLA) molecules, expressed on the majority of cells. Only few genetically isolated populations have been characterized for the frequency of KIR-HLA combinations. The aim of this work was summarize and reanalyze the data described in recent publications regarding KIR and HLA in Amerindians. In total, 1258 individuals from 23 Amerindian populations were analyzed. All population samples were previously genotyped for KIR presence/absence polymorphism; KIR allelic content was poorly described. Only 9 of the 23 populations were genotyped for HLA class I. Based on the KIR gene-content profiles, we estimated the most common Amerindian KIR gene-content haplotypes, information never reported before for many of these populations. When the HLA genes started to be analyzed in many of these groups, KIR genes were still not well characterized. Therefore, they have never been analyzed in a joint context. We thoroughly examined the HLA haplotypes of these populations; for the first time, we are showing the frequencies of the known HLA ligands of most of these populations, which had been separately studied for both KIR and HLA. Amerindians exhibits a low diversity of KIR gene-content haplotypes when compared to most worldwide population. We compared the KIR-HLA diversity within and between Amerindian groups trying to understand the natural causes of variation. This study corroborates the hypothesis that demographic factors such as founder effect played a major role in shaping KIR diversity in Amerindians and may contribute to understand the importance of KIR-HLA for human health and disease.
Tissue Antigens, 1993
The HLA-A. B, C, DR and DQ antigens of 240 Kaingang and 98 Guarani individuals have been characte... more The HLA-A. B, C, DR and DQ antigens of 240 Kaingang and 98 Guarani individuals have been characterized. The most frequent antigens found among the Kaingang are A3 I , 2, 24; B35, 5 I , 39.48; Cw4, 7. 3. 1; DR8, 4, 2; DQ blank, 3. In the Guarani, they are A2, 28, 31; B40. 62, "53G"; Cw3, 4; DR2, 4, 8, 6; DQ3, blank. B"53G" is an unusual antigen of the B5 cross-reactive group. DQ blank possibly corresponds to DQ4. not tested in this study, The reaction patterns of B35, B40 and DR4 indicate intra-tribal (of B35 and B40), and inter-tribal (DR4, B40 and 835) heterogeneity of these antigens. 408 Kaingang and 141 Guarani haplotypes were defined by segregation analysis. Of the commonest 10 Guarani and 9 Kaingang haplotypes, only one is shared by both tribes. Significant, positive linkage disequilibrium values for HLA-A,B; HLA-A.C; HLA-B,DR and most HLA-B,C antigen pairs were also different for the two populations. Genetic distance estimates between these two and another seven South-American Indian populations. and relative to the major human races (negroids, Caucasoids, and mongoloids) reveal a comparatively high degree of divergence between the Kaingang and the Guarani, which is uncommon for Amerindian populations living close one 1 to another.
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Papers by Maria-Luiza Petzl-Erler