Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor

Simple SummaryIt is well-recognised the strong contribution of genetic factors to prostate cancer (PrCa) susceptibility, thus genetic screening is critical for presymptomatic diagnosis and identification of individuals at high-risk. In this context, recurrent founder variants in cancer predisposing genes, by providing specific targets for early identification of carriers at risk of developing the disease, may be leveraged to implement cost-efficient targeted genetic screening strategies. The goal of this study was to investigate whether CHEK2 c.349A>G, the only recurrent "likely pathogenic" variant in CHEK2 gene reported in the Portuguese population, plays an important role in PrCa development, and the possibility of a founder effect behind its origin. Our results clearly demonstrate that c.349A>G in the CHEK2 tumour-suppressor gene is a founder variant significantly associated with an increased risk of PrCa, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families

Displasia craniometafisária: relato de caso Craniometaphyseal dysplasia: case report

Apresentamos um caso de uma criança com dois anos e oito meses de idade,acometida pela forma recessiva da displasia craniometafisária. São enfatizados os achados clínico-radiológicos, bem como seus principais diagnósticos diferenciais, baseados em dados de breve revisão literária.<br>We report a case of a 2 years and 8 months-old child with the recessive form of craniometaphyseal dysplasia. Clinical and radiological features as well as the main differential diagnosis are discussed and compared with data from a brief literature review