Search

In his 1972 paper ‘The apportionment of human diversity’, Lewontin showed that, when averaged over loci, genetic diversity is predominantly attributable to differences among individuals within populations. However, selection can alter the apportionment of diversity of specific genes or genomic regions. We examine genetic diversity at the human leucocyte antigen (HLA) loci, located within the major histocompatibility complex (MHC) region. HLA genes code for proteins that are critical to adaptive immunity and are well-documented targets of balancing selection. The single-nucleotide polymorphisms (SNPs) within HLA genes show strong signatures of balancing selection on large timescales and are broadly shared among populations, displaying low FST values. However, when we analyse haplotypes defined by these SNPs (which define ‘HLA alleles’), we find marked differences in frequencies between geographic regions. These differences are not reflected in the FST values because of the extreme polymorphism at HLA loci, illustrating challenges in interpreting FST. Differences in the frequency of HLA alleles among geographic regions are relevant to bone-marrow transplantation, which requires genetic identity at HLA loci between patient and donor. We discuss the case of Brazil's bone marrow registry, where a deficit of enrolled volunteers with African ancestry reduces the chance of finding donors for individuals with an MHC region of African ancestry. [ABSTRACT FROM AUTHOR]

Genotyping of polymorphic short tandem repeats (STRs) loci is widely used in forensic DNA analysis. STR loci eventually present tri-allelic pattern as a genotyping irregularity and, in that situation, the doubt about the tri-allele locus frequency calculation can reduce the analysis strength. In the TPOX human STR locus, tri-allelic genotypes have been reported with a widely varied frequency among human populations. We investigate whether there is a single extra allele (the third allele) in the TPOX tri-allelic pattern, what it is, and where it is, aiming to understand its genomic anatomy and to propose the knowledge of this TPOX extra allele from genetic profile, thus preserving the two standard TPOX alleles in forensic analyses. We looked for TPOX tri-allelic subjects in 75,113 Brazilian families. Considering only the parental generation (mother+father) we had 150,226 unrelated subjects evaluated. From this total, we found 88 unrelated subjects with tri-allelic pattern in the TPOX locus (0.06%; 88/150,226). Seventy three of these 88 subjects (73/88; 83%) had the Clayton's original Type 2 tri-allelic pattern (three peaks of even intensity). The remaining 17% (15/88) show a new Type 2 derived category with heterozygote peak imbalance (one double dose peak plus one regular sized peak). In this paper we present detailed data from 66 trios (mother+father+child) with true biological relationships. In 39 of these families (39/66; 59%) the extra TPOX allele was transmitted either from the mother or from the father to the child. Evidences indicated the allele 10 as the extra TPOX allele, and it is on the X chromosome. The present data, which support the previous Lane hypothesis, improve the knowledge about tri-allelic pattern of TPOX CODIS' locus allowing the use of TPOX profile in forensic analyses even when with tri-allelic pattern. This evaluation is now available for different forensic applications., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Mutations in the GJB2 gene, which encodes the protein connexin 26, are a major cause of autosomal recessive deafness. The most frequent mutation, 35delG, has a carrier frequency as high as 4% in some countries, and this frequency varies in different ethnic groups. Most of the Brazilian population results from interethnic crosses of people from three continents (European, African, and Amerindian), and the proportion of each varies according to the geographical region of the country. To verify if the different ethnic composition of Brazilian regions leads to variable 35delG carrier frequencies, we performed the screening of the 35delG mutation using DNA from dried-blood filter paper samples obtained from 1,856 newborns from 10 cities in different regions. The 35delG mutation was found in 25 individuals (1.35%), indicating an overall carrier frequency of 1:74. This frequency was 1:47 in the north, 1:64 in the southeast, 1:85 in the south and 1:124 in the northeast, but these differences were not significant. The overall frequency of the 35delG allele was estimated as 0.0067, and comparison between expected and observed genotype frequencies indicates that the population is in Hardy-Weinberg equilibrium.

The genetic predisposition to type 1 diabetes (DM1) is associated with genes of the human leukocyte antigen (HLA) system, specially the HLA-DR and -DQ. In Caucasians, the HLA-DR3 and -DR4 antigens are associated with susceptibility and the -DR2, with protection. In Brazil, a country with a large miscegenation of European Caucasians, Native Amerindians and African Blacks, the genetic basis of DM1 has not been adequately studied. The aim of this paper is to present a critical review of articles indexed in the MEDLINE and LILACS-BIREME data basis about the association of HLA with DM1 in Brazilians. Eight papers, all of them from the Southeast region, were found. Immunogenetic susceptibility to DM1 in Brazilians was associated with HLA-DRB1*03, -DRB*04, -DQB1*0201, -DQB1*0302 alleles, and protection against DM1 was associated with HLA-DQB1*0602, -DQB1*0301 alleles and -DR2 and -DR7 antigens. Since the Brazilian population is not racially homogeneous, it is not possible to extrapolate studies from a single region to the remainder of the country. It is necessary to study populations from different regions to identify new associations or to strengthen associations with the ones already identified. This knowledge will contribute to future prophylactic or therapeutic interventions in the group of Brazilians at risk of developing DM1.

In Brazil, high levels of agricultural activity are reflected in the consumption of enormous amounts of pesticides. The production of grain in Brazil has been estimated at 289.8 million tons in the 2022 harvest, an expansion of 14.7% compared with 2021. These advances are likely associated with a progressive increase in the occupational exposure of a population to pesticides. The Paraoxonase 1 gene (PON1) is involved in liver detoxification; the rs662 variant of this gene modifies the activity of the enzyme. The repair of pesticide-induced genetic damage depends on the protein produced by the X-Ray Repair Cross-Complementing Group 1 gene (XRCC). Its function is impaired due to an rs25487 variant. The present study describes the frequencies of the rs662 and rs25487 and their haplotypes in a sample population from Goiás, Brazil. It compares the frequencies with other populations worldwide to verify the variation in the distribution of these SNPs, with 494 unrelated individuals in the state of Goiás. The A allele of the rs25487 variant had a frequency of 26% in the Goiás population, and the modified rs662 G allele had a frequency of 42.8%. Four haplotypes were recorded for the rs25487 (G > A) and rs662 (A > G) markers, with a frequency of 11.9% being recorded for the A–G haplotype (both modified alleles), 30.8% for the G–G haplotype, 14.3% for the A–A haplotype, and 42.8% for the G–A haplotype (both wild-type alleles). We demonstrated the distribution of important SNPs associated with pesticide exposure in an area with a high agricultural activity level, Central Brazil. [ABSTRACT FROM AUTHOR]

The Kaingang and Guarani are culturally and linguistically distinct tribes of southern Brazil. Like all Amerindian groups they show limited HLA polymorphism, which probably reflects the small founder populations that colonized America by overland migration from Asia 11,000-40,000 years ago. We find the nucleotide sequences of HLA-B alleles from the Kaingang and Guarani to be distinct from those characterized in caucasian, oriental and other populations. By comparison, the HLA-A and C alleles are familiar. These results and those reported in the accompanying paper on the Waorani of Ecuador reveal that a marked evolution of HLA-B has occurred since humans first entered South America. New alleles have been formed through recombination between pre-existing alleles, not by point mutation, giving rise to distinctive diversification of HLA-B in different South American Indian tribes.

Background. Several mutations in voltage gated sodium channel (NaV) have been identified in Aedes aegypti populations worldwide. However, only few are related to knockdown resistance to pyrethroids, most of which with variations in the 1016 and 1534 NaV sites. In Brazil, at least two NaV alleles are known: NaVR1, with a substitution in the 1534 (1016 Val+ + 1534 Ilekdr) and NaVR2, with substitutions in both 1016 and sites (1016Ilekdr + 1534Cyskdr). There is also the duplication in the NaV gene, with one copy carrying the substitution Ile1011Met, although its effects on pyrethroid resistance remain to be clarified. Our goals in this study were (1) to determine the role of each kdr NaV allele and the duplication on pyrethroid resistance and (2) to screen the frequency of the kdr alleles in 27 several natural Ae. aegypti populations from the metropolitan region of Rio de Janeiro. Methods. Pyrethroid resistance was evaluated by a knockdown time (KdT) assay, an adaptation of the WHO test tubes with paper impregnated with deltamethrin. We used laboratory-selected Ae. aegypti lineages: R1R1 and R2R2 (homozygous for the kdr NaVR1 and NaVR2 alleles, respectively), Dup (with duplication in the NaV gene), Rockefeller (the susceptibility reference control), and F1 hybrids among them. Genotyping of both 1016 and 1534 NaV sites was performed in 811 Ae. aegypti sampled from 27 localities from Rio de Janeiro (17), Niterói (6) and Nova Iguaçu (4) cities, Rio de Janeiro State, Brazil, with a TaqMan real time PCR approach. Results. The laboratory lineages R1R1, R2R2, and R1R2 were the only ones that needed more than 60 minutes to knock down all the insects exposed to the pyrethroid, being the KdT R2R2 > R1R2 > R1R1, corroborating the recessive nature of the kdr mutations. Frequency of kdr alleles NaVR1 and NaVR2 in field-caught mosquitoes varied from 0 to 52% and 43 to 86%, respectively, evidencing high levels of “resistant genotypes” (R1R1, R1R2, and R2R2), which together summed 60 to 100% in Ae. aegypti populations from Rio de Janeiro. Conclusions. The NaVR1 and NaVR2 kdr alleles confer resistance to the pyrethroid deltamethrin in homozygotes and R1R2 heterozygotes, being the R2R2 most resistant genotype. The allele containing duplication in the NaV gene, with a mutation in the 1011 site, did not confer resistance under the tested conditions. The frequencies of the “resistant genotypes” are elevated in Ae. aegypti natural populations from Rio de Janeiro. [ABSTRACT FROM AUTHOR]

Filocamo et al. recently published a paper describing the presence of a pseudodeficiency allele, constituted by p.Ser141Ser and p.Arg737Gly polymorphisms at the NAGLU gene, which leads to a reduced level of the alpha-N-acetyl-D-glucosaminidase activity. Based on analysis performed in Brazilian patients, using a customized gene panel containing SGSH, NAGLU, HGSNAT and GNS we observed that p.Ser141Ser (rs659497) and p.Arg737Gly (rs86312) variants were present in homozygosis in all of our MPS IIIB patients and in the majority of MPS IIIA, IIIC and IIID patients, and there was no significant decrease of the alpha-N-acetyl-D-glucosaminidase enzyme activity in this group when compared with those without the "pseudodeficiency allele". Thus, we suggest that these two variants are not producing a pseudodeficiency allele. [ABSTRACT FROM AUTHOR]

Purpose: The establishment of candidate genetic determinants associated with tuberculosis (TB) is a challenge, considering the divergent frequencies among populations. The objective of this study was to evaluate the association between MIF − 794 CATT 5−8 polymorphism and susceptibility to TB. Methods: Case–control study. Patients > 18 years, with pulmonary TB were included. The control group consisted of blood donors and household contacts, not relatives, healthy and > 18 years. MIF − 794 CATT 5−8 were genotyped using sequencing of PCR and capillary electrophoresis. Results: 126 patients and 119 controls were included. The genotype 5/5 was more frequent among cases (15.1%) than in controls (5.9%) (p = 0.019). Cases had more frequently the allele 5 (29.4%) as compared with controls (19.3%) (p = 0.010). Prevalence of 7/X + 8/X genotypes was not different between cases and controls (p = 0.821). There was no difference between patients with alleles 7 and 8 and those with alleles 5 and 6 (p = 0.608). Conclusions: The genotype 5/5 and the allele 5 of MIF − 794 CATT 5−8 were more frequent among TB patients than in controls. [ABSTRACT FROM AUTHOR]

Strong phosphine resistance in Tribolium castaneum is due to point mutations in DNA that code for amino acid changes of P45S and/or G131S in the enzyme dihydrolipoamide dehydrogenase (DLD). One allele coding for P45S is the most common in all phosphine-resistant US populations and in one strain from Brazil (TCBR), whereas another allele, G131S, occurs only in Australian beetles. Dose-mortality studies found that the TCBR strain was more resistant to phosphine than US populations. To investigate strong resistance mutations in TCBR, we sequenced cDNA for DLD in TCBR and compared results with a US population from Kansas. The common P45S mutation was detected in both populations, but two additional mutations G131D and V167A were identified only from TCBR. We used a CAPS marker (Cleaved Amplified Polymorphic Sequence) for P45S, herein designated M1, to survey this resistance allele in TCBR. We also developed a marker for the G131D mutation, designated M2. Only two genotypes, R1R1S2S2 (homozygous for resistance at M1, but homozygous susceptible at the M2 site) and R1S1R2S2 (heterozygous for resistance at M1 and M2) existed in TCBR. However, phosphine resistance levels were similar between individuals with the two genotypes. Beetles with strong resistance in TCBR may be homozygous for either the presence of the common P45S allele, or heterozygous for two resistance alleles at a second locus, G131D. The strong resistance phenotype in TCBR may be expressed differently based on previously unknown mutations at the DLD locus, but this will require further research to resolve. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of Bt plants has been the main strategy for controlling the fall armyworm Spodoptera frugiperda (J. E. Smith) in Brazil. However, many resistance cases were already registered. The resistance of S. frugiperda to the Vip3Aa20 protein was recently characterized under laboratory conditions but it is still efficient under field conditions. Here, resistance monitoring studies were conducted using phenotypic (purified protein and Bt maize leaves) and genotypic (F1 and F2 screen) methods to support insect resistance management (IRM) programs and preserve Vip3Aa20 technology on maize. RESULTS: Phenotypic monitoring with purified protein showed two populations significantly different from the susceptible strain on the second crop season in 2016. This number increased for the first and second crop seasons in 2017 in several regions. The genotypic monitoring estimated a mean frequency of the resistance allele of 0.0027 for the F1 screen and 0.0033 for the F2 screen. Three new resistant strains to Vip3Aa20 were selected from F2 screen assays. Complementation tests on these new resistant strains were positive with the previous resistant strain. CONCLUSION: Here we showed that the resistance allele of S. frugiperda to Vip3Aa20 protein is widely distributed in maize‐producing regions in Brazil and its frequency increases throughout crop seasons. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Azithromycin is one of the drugs used in the combined therapy for syndromic treatment of gonorrhoea in many countries, including Brazil. Our research group, which receives isolates from clinical laboratories since 2006, has detected, after 2016, a tendency of rising rates of azithromycin resistance, with isolates showing higher minimal inhibitory concentrations (MICs) than those previously reported in this country. In this study, we report the susceptibility to azithromycin of 93 N. gonorrhoeae isolates obtained between 2014 and 2017. Strains with MIC ≥2 μg/mL were characterized according to azithromycin resistance mechanisms and strain typing. Results indicate that azithromycin resistance has emerged in all these years in unrelated MLST-STs, but after 2016 a clonal complex connected with ST1901 has been more frequently detected, grouping isolates with MIC varying from 2 to 64 μg/mL, with DelA mutations at the mtrR promoter region associated or not with mutations at rrl alleles. High rates of azithromycin resistance may compromise the use of this drug in the combined therapy with ceftriaxone. Inclusion of Rio de Janeiro in the Brazilian gonococcal surveillance program is important to evaluate if this data indicates an epidemiological phenomenon in the country. [ABSTRACT FROM AUTHOR]

The novel HLA‐DQB1*03:491 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

The novel HLA‐C*04:01:145 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

The novel HLA‐B*41:01:08 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

The antimicrobial peptides human β-defensins (hBDs) are encoded by β-defensin genes (DEFBs) and are possibly involved in caries susceptibility. In this study we aimed (1) to investigate the relationship between salivary hBDs and caries and (2) to evaluate the association of genetic polymorphisms in DEFB1 and microRNA202 (miRNA202) with salivary levels of hBDs and caries experience. Two data sets were available for this study, totalizing 678 Brazilian children. Dental examination and saliva collection were performed in all included children. The salivary level for hDB1, hBD2, and hBD4 was assessed by ELISA sandwich technique in 168 children. The DNA was extracted from saliva, and polymorphisms in DEFB1 and miRNA202 were analyzed by real-time PCR. Statistical analysis was performed to investigate the associations between caries experience, hBD salivary level, genotype, and allele distribution, with an alpha of 0.05. The hBD1 level was significantly higher in caries-free children (p < 0.0001). The miRNA202 was associated with a lower level of salivary hBD1 (p < 0.05). Also, the polymorphic distribution of miRNA202 was associated with caries (p = 0.006). The polymorphisms in DEFB1 were not associated with hBD salivary level and caries experience (p > 0.05). In conclusion, our results indicate that genetic polymorphism in miRNA202 is involved in hBD1 salivary level as well as caries experience in children. [ABSTRACT FROM AUTHOR]

Background/objectives: Homocysteine (Hcy) is a key intermediate in methionine metabolism. A high plasma concentration of Hcy is an independent risk factor for cardiovascular diseases among other determinants. In this study, we aimed to investigate the interactions between methylenetetrahydrofolate reductase enzyme gene (MTHFR) polymorphisms and lifestyle variables (smoking, alcohol intake and physical activity) on Hcy concentrations in a young Brazilian population.Subjects/methods: The study population comprised 3803 individuals from the Pelotas Birth Cohort, aged 22-23 years. Allelic discrimination assays and chemiluminescence immunoassays were performed for genotyping and serum Hcy measurements, respectively. Linear regression models were used to explore the effect of gene-lifestyle interactions on Hcy concentrations.Results: Men carrying the MTHFR 677TT genotype, who were also smokers and drinkers (⩾15 g of alcohol per day), had the highest concentration of Hcy (P-value for the interaction <0.001 for smoking and 0.002 for alcohol intake). In contrast, high folate concentrations attenuated the effects of the MTHFR C677T genotype on serum Hcy concentrations (P-value for interaction <0.001). Also, among males, blood folate concentration was the only lifestyle variable able to modify the influence of MTHFR A1298C genotypes on Hcy concentrations (P-value for the interaction <0.001). There was no strong evidence of an interaction between the MTHFR genotypes and the lifestyle variables in women.Conclusions: In summary, our study demonstrates a sex difference in Hcy concentrations among Brazilian young adults regarding MTHFR C677T-lifestyle interactions that are worsened under conditions of low blood folate. Identification of potentially modifiable factors related to an increase in homocysteine in young adults, especially in those who are genetically susceptible, is important to prevent negative health consequences in the future. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit/hyperactivity disorder (ADHD) symptoms are dimensionally distributed in the population. This study aimed to assess the role of the catechol-O-methyltransferase (COMT) and of the dopamine transporter (DAT1) genes on ADHD symptoms in the general population. Methods: We investigated 4101 individuals from the 1993 Pelotas Birth Cohort Study using the parent version of the Strengths and Difficulties Questionnaire (SDQ) at ages 11 and 15 years. The SDQ hyperactivity/inattention scores were the main outcomes. Results: Linear regression analyses demonstrated that the increasing number of COMT158Val and DAT1 10R alleles significantly predicted increasing SDQ hyperactivity/inattention scores in boys at both 11 and 15 years of age (β coefficient = 0.049, f = 2.189, p = 0.029, R² = 0.012, and β coefficient = 0.064, f = 2.832, p = 0.005, R² = 0.008, respectively). The presence of both COMT158Val and DAT1 10R alleles was also associated with full categorical ADHD diagnosis at 18 years of age in boys (χ² = 4.561, p = 0.033, odds ratio 2.473, 95% confidence interval 1.048-5.838) from this cohort. We did not observe these associations in girls. Limitations: Our analyses of SDQ hyperactivity/inattention scores were not corrected for SDQ scores of conduct problems because these variables were highly correlated. Conclusion: This study demonstrates a role for COMT and DAT1 genes on hyperactivity/inattention symptoms and provides further support for ADHD as the extreme of traits that vary in the population. It also confirms previous evidence for sexual dimorphism on COMT and DAT1 gene expression. [ABSTRACT FROM AUTHOR]

The novel HLA‐A*02:01:202 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

The novel HLA‐A*29:158 allele, first described in potential bone marrow donors from Brazil. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to evaluate the association between Fc gamma receptor IIIb polymorphism and susceptibility to systemic lupus erythematosus and clinical traits of the disease. Methods Genomic DNA was obtained from 303 consecutive systemic lupus erythematosus patients and 300 healthy blood donors from the southeastern region of Brazil. The polymorphic region of the FCGR3B gene was sequenced and the alleles FCGR3B*01, FCGR3B*02 and FCGR3B*03 were analyzed. Results The FCGR3B*01 allele was more frequent in systemic lupus erythematosus patients (43.1%) while the FCGR3B*02 allele prevailed among controls (63.7%) (P = 0.001). The FCGR3B*03 allele was found equally in both groups. The FCGR3B*01/*01 (20.7%) and FCGR3B*01/*02 (41.1%) genotypes were more frequent among systemic lupus erythematosus patients (P = 0.028 and P = 0.012, respectively) while the FCGR3B*02/*02 genotype was more frequent in controls (45.5%) (P < 0.001). One variant of the FCGR3B*01 allele previously described in Germany was found in only one control. A new variant of the FCGR3B*01 allele with two substitutions (A227G/G277A) was found in one control. Three variants of the FCGR3B*02 allele previously described in African-Americans, Brazilians, Chinese and Japanese were found in ten 10 patients and two controls. In addition, several single nucleotide polymorphisms at non-polymorphic positions were identified in both patients and controls. Conclusion Susceptibility to systemic lupus erythematosus was associated with the FCGR3B*01 allele, as well as with the FCGR3B*01/*01 and FCGR3B*01/*02 genotypes. No association was found between FCGR3B genotypes and clinical manifestations, disease severity or the presence of autoantibodies. [ABSTRACT FROM AUTHOR]

Background Matrix metalloproteinases and their inhibitors might be involved in enamel formation. Aim This study aimed to evaluate the association between polymorphisms in MMP2, MMP3, MMP9, MMP20, TIMP1, and TIMP2 with white spot lesions ( WSL) and early childhood caries ( ECC). Design A cross-sectional study was performed on 786 children aged from 2 to 6 years in Brazil. After clinical evaluation, they were classified into groups with disease (the presence of WSL and/or ECC) and without disease (the absence of WSL or ECC). Genotyping of the selected polymorphisms was carried out with TaqMan real-time PCR, using genomic DNA extracted from buccal cells. Allele and genotype frequencies were compared between groups. Chi-square test, odds ratio ( OR), and logistic regression were used ( P ≤ 0.05). Results The dmft score was 1.3 ( SD: 2.4), and 41.34% of the children have at least one caries lesion. In MMP9, the GG genotype was more frequent in the group without disease ( P = 0.006). In a recessive model, WSL was associated with the marker rs1711437 in MMP20 ( P = 0.019; OR = 1.20, 95% CI 1.02-1.42). The marker rs1784418 in MMP20 showed an association between the allele G distribution for the WSL group ( P = 0.020; OR = 0.73, 95% CI 0.55-0.96). Conclusion MMP9 and MMP20 are involved in WSL and ECC development. [ABSTRACT FROM AUTHOR]

The novel HLA‐DQA1*03:03:05 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

The novel HLA‐A*68:272 allele, first described in a potential bone marrow donor from Brazil. [ABSTRACT FROM AUTHOR]

Introduction This study aimed to verify the association between the JAK2 46/1 haplotype (V617F positive) and some hematological parameters in BCR- ABL-negative chronic myeloproliferative neoplasms ( cMPNs) in our population. Methods The blood samples obtained from the patients with cMPN were genotyped for the JAK2 V617F mutation and JAK2 rs10974944 SNP screening using a PCR- RFLP assay. Results The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of rs10974944 was more frequent in all MPNs, especially those that were JAK2 V617F positive, than in the control population. We also compared the 46/1 haplotype status in each MPN disease entity, polycythemia vera ( PV), essential thrombocythemia ( ET), primary myelofibrosis ( PMF), and MPNu with controls. The G allele frequency relative to controls was significantly enriched in patients with PV and ET, but not in those with PMF and MPNu. PV and ET patients especially, all of whom had the JAK2 V617F mutation, showed significant excess of the G allele. The frequency of JAK2 V617F mutation was associated with elevated hematological parameters, but when we analyze the occurrence of the mutation and the presence of the G allele, just the high hemoglobin was significantly. Conclusion In agreement with previous reports, JAK2 46/1 haplotype for JAK2 V617F was associated with cMPN positive in Brazilian patients. [ABSTRACT FROM AUTHOR]

Objectives We investigated the relationship between non-syndromic cleft lip/palate ( NSCLP) and polymorphisms in methylenetetrahydrofolate reductase ( MTHFR), methionine synthase ( MTR), methionine synthase reductase ( MTRR), and RFC1, as well as the corresponding interactions with environmental factors. Subjects and Methods One hundred and forty NSCLP patients and their mothers, as well as 175 control individuals and their mothers, were recruited. Information regarding smoking and alcohol consumption was recorded. Blood samples were obtained in order to measure serum folate and cobalamin, as well as, plasma total homocysteine concentrations and to extract DNA. Polymorphisms in MTHFR(677C>T and 1298A>C), MTR(2756A>G), MTR(66A>G), and RFC1(80A>G) were analyzed by PCR-restriction fragment length polymorphism. Results Among the patients, 59.5% had cleft lip and palate, 22.0% had cleft palate, and 18.5% had cleft lip only. Maternal alcohol consumption and reduced folic acid concentrations in both children and mothers ( P < 0.001 and P = 0.003, respectively) were risk factors for NSCLP. Patients and their mothers carrying the MTHFR 667T allele showed lower serum folate than CC ( P = 0.011 and P = 0.030, respectively). Mothers who carried the MTHFR 1298C allele exhibited increased risk of having a child with NSCLP, after adjusting for alcohol consumption ( OR: 1.75, 95% CI: 1.03-2.99, P = 0.038). Conclusions Reduced folic acid levels, alcohol consumption, and the MTHFR 677T and 1298C alleles may have contributed to NSCLP development in this sample population from Rio Grande do Norte. [ABSTRACT FROM AUTHOR]

Characterization of three novel HLA‐DQA1 alleles: HLA‐DQA1*01:02:01:15, ‐DQA1*03:03:01:15, and ‐DQA1*05:05:01:26. [ABSTRACT FROM AUTHOR]

Aim: To identify the main variations sites at the coding region of the HFE gene in the Brazilian population, construct haplotypes and suggest a nomenclature. Methods: We sequenced the HFE coding region (exon 2, 3, 4, 5) and intron boundaries in a population sample of 100 healthy individuals and 184 patients (hereditary hemochromatosis, hepatitis C and hepatocellular cancer) from Ribeirão Preto, Southeastern Brazil. Exons were chosen since they code the major domains of HFE protein. The variations observed were used for the inference of 13 HFE alleles using the ARLEQUIN, and PHASE softwares. Haplotypes were named following the IMGT nomenclature rules. Results: Seven variation were observed at the HFE gene: H63D C>G in exon 2 (rs1799945) a , IVS2 (+4) T>C in intron 2 (rs2071303) b , the intron 3 C>G (rs807209) c , C282Y G>A in exon 4 (rs1800562) d , intron 4 G>A (rs2794717) e , IVS4 (-44) T>C (rs1800708) f , in intron 5 a new deletion G>del g . The reconstructed haplotype are shown in Table 1. Conclusions: This study presents a comprehensive evaluation of the variability of the HFE gene in the Brazilian population. It provides a contribution for population genetics and case-control association studies. Finally, this paper proposes a standardized nomenclature. [Copyright &y& Elsevier]

Abstract: The CYP2D6 enzyme is one of the most important members of the cytochrome P450 superfamily. This enzyme metabolizes approximately 25% of currently prescribed medications. The CYP2D6 gene presents a high allele heterogeneity that determines great inter-individual variation. The aim of this study was to evaluate the variability of CYP2D6 alleles, genotypes and predicted phenotypes in Brazilians. Eleven single nucleotide polymorphisms and CYP2D6 duplications/multiplications were genotyped by TaqMan assays in 1020 individuals from North, Northeast, South, and Southeast Brazil. Eighteen CYP2D6 alleles were identified in the Brazilian population. The CYP2D6*1 and CYP2D6*2 alleles were the most frequent and widely distributed in different geographical regions of Brazil. The highest number of CYPD6 alleles observed was six and the frequency of individuals with more than two copies ranged from 6.3% (in Southern Brazil) to 10.2% (Northern Brazil). The analysis of molecular variance showed that CYP2D6 is homogeneously distributed across different Brazilian regions and most of the differences can be attributed to inter-individual differences. The most frequent predicted metabolic status was EM (83.5%). Overall 2.5% and 3.7% of Brazilians were PMs and UMs respectively. Genomic ancestry proportions differ only in the prevalence of intermediate metabolizers. The IM predicted phenotype is associated with a higher proportion of African ancestry and a lower proportion of European ancestry in Brazilians. PM and UM classes did not vary among regions and/or ancestry proportions therefore unique CYP2D6 testing guidelines for Brazilians are possible and could potentially avoid ineffective or adverse events outcomes due to drug prescriptions. [ABSTRACT FROM AUTHOR]

This study describes the frequency of spinocerebellar ataxias and of CAG repeats range in different geographical regions of Brazil, and explores the hypothetical role of normal CAG repeats at ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 genes on age at onset and on neurological findings. Patients with symptoms and family history compatible with a SCA were recruited in 11 cities of the country; clinical data and DNA samples were collected. Capillary electrophoresis was performed to detect CAG lengths at SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA12, SCA17, and DRPLA associated genes, and a repeat primed PCR was used to detect ATTCT expansions at SCA10 gene. Five hundred forty-four patients (359 families) were included. There were 214 SCA3/MJD families (59.6 %), 28 SCA2 (7.8 %), 20 SCA7 (5.6 %), 15 SCA1 (4.2 %), 12 SCA10 (3.3 %), 5 SCA6 (1.4 %), and 65 families without a molecular diagnosis (18.1 %). Divergent rates of SCA3/MJD, SCA2, and SCA7 were seen in regions with different ethnic backgrounds. 64.7 % of our SCA10 patients presented seizures. Among SCA2 patients, longer ATXN3 CAG alleles were associated with earlier ages at onset ( p < 0.036, linear regression). A portrait of SCAs in Brazil was obtained, where variation in frequencies seemed to parallel ethnic differences. New potential interactions between some SCA-related genes were presented. [ABSTRACT FROM AUTHOR]

Previous work suggests that Brazilian Plasmodium falciparum has limited genetic diversity and a history of bottlenecks, multiple reintroductions due to human migration, and clonal expansions. We hypothesized that Brazilian P. falciparum would exhibit clonal structure. We examined isolates collected across two decades from Amapá, Rondônia, and Pará state (n = 190). By examining more microsatellites markers on more chromosomes than previous studies, we hoped to define the extent of low diversity, linkage disequilibrium, bottlenecks, population structure, and parasite migration within Brazil. We used retrospective genotyping of samples from the 1980s and 1990s to explore the population genetics of SP resistant dhfr and dhps alleles. We tested an existing hypothesis that the triple mutant dhfr mutations 50R/51I/108N and 51I/108N/164L developed in southern Amazon from a single origin of common or similar parasites. We found that Brazilian P. falciparum had limited genetic diversity and isolation by distance was rejected, which suggests it underwent bottlenecks followed by migration between sites. Unlike Peru, there appeared to be gene flow across the Brazilian Amazon basin. We were unable to divide parasite populations by clonal lineages and pairwise FST were common. Most parasite diversity was found within sites in the Brazilian Amazon, according to AMOVA. Our results challenge the hypothesis that triple mutant alleles arose from a single lineage in the Southern Amazon. SP resistance, at both the double and triple mutant stages, developed twice and potentially in different regions of the Brazilian Amazon. We would have required samples from before the 1980s to describe how SP resistance spread across the basin or describe the complex internal migration of Brazilian parasites after the colonization efforts of past decades. The Brazilian Amazon basin may have sufficient internal migration for drug resistance reported in any particular region to rapidly spread to other parts of basin under similar drug pressure. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examinethe association between polymorphism in thecatechol-O-methyltransferase(COMT) gene and Alzheimer's disease (AD) in a Brazilianpopulation. The case-control method was used to study the association between AD and geneticvariants of COMT. Six tag single-nucleotide polymorphisms(SNPs) in the COMT gene were genotyped by RT-PCR. Ourfindings showed that the 6 tag SNPs analyzed in this study were not associated with AD at the alleleand genotype levels in comparison with the control group. No statistical difference was foundbetween groups with and without behavioral and psychological symptoms of dementia (BPSD). Ourresults do not support the hypothesis that the polymorphisms of theCOMT gene may be associated with susceptibility to AD withand without BPSD. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents a case study which identifies silent alleles present in KEL gene of Kell system that reacts with transfused red blood cells in a 49-year-old woman. Topics include the presence of anti-Ku antibodies in the patient's serum, the low prevalence of antigens in the patient's red blood cells, and the use of antigen typing to identify antibody.