The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.

There is general agreement that the Native American founder populations migrated from Asia into America through Beringia sometime during the Pleistocene, but the hypotheses concerning the ages and the number of these migrations and the size of the ancestral populations are surrounded by controversy. DNA sequence variations of several regions of the genome of Native Americans, especially in the mitochondrial DNA (mtDNA) control region, have been studied as a tool to help answer these questions. However, the small number of nucleotides studied and the nonclocklike rate of mtDNA control-region evolution impose several limitations to these results. Here we provide the sequence analysis of a continuous region of 8.8 kb of the mtDNA outside the D-loop for 40 individuals, 30 of whom are Native Americans whose mtDNA belongs to the four founder haplogroups. Haplogroups A, B, and C form monophyletic clades, but the five haplogroup D sequences have unstable positions and usually do not group together. The high degree of similarity in the nucleotide diversity and time of differentiation (i.e., approximately 21,000 years before present) of these four haplogroups support a common origin for these sequences and suggest that the populations who harbor them may also have a common history. Additional evidence supports the idea that this age of differentiation coincides with the process of colonization of the New World and supports the hypothesis of a single and early entry of the ancestral Asian population into the Americas.

Toxoplasma gondii is a cosmopolitan protozoan parasite of warm-blooded animals that causes high rates of infection in mammals and birds. Sparrows (Passer domesticus) are synantropic birds which are distributed worldwide. They serve as intermediate hosts for the parasite but are quite resistant to toxoplasmosis. The aims of this study were to determine the frequency of T. gondii infection in sparrows using serologic and molecular tests, and to investigate related parasites, such as Neospora caninum and Hammondia sp., using a nested PCR for Toxoplasmatinae DNA followed by sequence analysis of the PCR amplicons. A total of 293 sparrows were trapped at the states of Bahia and Pernambuco, Brazil. Tissues of 40 animals were available for molecular tests. Antibodies to T. gondii were found in 1.02% (3/293) of animals using a hemagglutination test, with titers ranging from 1:32 to 1:128. Toxoplasmatinae DNA was detected in 10/40 (25%) sparrows; after nucleotide sequencing, T. gondii was confirmed in 7/40 (17.5%) birds and N. caninum in 3/40 (7.5%) animals. Sparrows from Brazil were confirmed as intermediate hosts of T. gondii, that reinforces the potential importance of these birds on the transmission of the parasite to cats and other animals that may predate sparrows. In addition, N. caninum was detected for the first time in sparrows. To the authors' knowledge, this is the first wild synantropic bird species identified as intermediate host of N. caninum. These findings seem to have a great epidemiologic impact because of the cosmopolitan distribution of sparrows and due to their increasing population in urban and rural areas.

No abstract

2012IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population LIVER INTERNATIONAL, HOBOKEN, v. 32, n. 3, pp. 476-486, MAR, 2012 http://www.producao.usp Abstract Background: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. Aims: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. Methods: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. Results: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 9 10

Considering the importance of BRCA1, BRCA2, CHEK2 and TP53 in the development of hereditary early-onset breast and ovarian cancer and that the genetic susceptibility profile of the Northeast population from Brazil has never been analyzed, this study aimed to verify the frequency of mutations of clinical significance in these genes in high-risk hereditary breast and ovarian cancer (HBOC) syndrome patients from that region. DNA samples from 106 high-risk unrelated patients mostly from Bahia, the biggest state in the Northeast region, were analyzed. These patients underwent full BRCA1 gene sequencing, screening for common founder mutations in the BRCA2, CHEK2 and TP53 genes and genetic ancestry analysis with nine ancestry informative markers. The positive results were confirmed by two sequencing reactions. Three mutations of clinical significance were found: BRCA1 p.R71G (4.71%), 3450del4 (3.77%) and TP53 p.R337H (0.94%). The genetic ancestry analysis showed a high European ancestry contribution (62.2%) as well as considerable African (31.2%) and Amerindian (6.6%) ancestry contributions (r2=0.991); this degree of heterogeneity was also significant in the population structure analysis (r=0.604). This population is highly admixed with a different spectrum of genetic susceptibility, with the Galician founder mutation BRCA1 p.R71G accounting for 50% of all identified mutations in high-risk HBOC patients. TP53 p.R337H was also significantly frequent; thus, the combined screening of BRCA1/2 and TP53 should be offered to high-risk HBOC patients from Northeast Brazil.

No abstract

Neospora caninum, Hammondia sp., and Toxoplasma gondii are parasites with morphological and genetic similarities. N. caninum and T. gondii are important abortive agents of cattle and sheep, respectively, and may infect numerous animal species. Hammondia sp. is not known to induce disease in animals, but may cause confusion in the identification of closely related coccidia. The aim of this study was to investigate infection rates caused by N. caninum, Hammondia sp., and T. gondii in beef cattle using a nested PCR for Toxoplasmatinae rDNA, followed by sequencing of the PCR products. Antibodies to N. caninum and T. gondii were also investigated in the tested animals. Brains and hearts were obtained from 100 beef cattle in a slaughterhouse in Bahia. Seven samples from brain tested positive for Toxoplasmatinae DNA. No positive reactions were found in heart tissues. After sequencing of the PCR products from all positive tissues, five sequences matched with N. caninum and two matched with T. gondii. Antibodies to N. caninum and T. gondii were found in 20% and 26% of the animals, respectively. The confirmation of N. caninum and the absence of Hammondia heydorni in the tested animals is suggestive that cattle are not efficient intermediate hosts of H. heydorni; however further studies need to be performed using a greater variety of tissues and a higher sample size. The detection of T. gondii DNA in bovine tissues reinforces the potential risk of transmission of this parasite to humans and other animals through the consumption of bovine meat.