Juvenile polyposis of infancy in a child with deletion of BMPR1A and PTEN genes: Surgical approach

Juvenile polyposis of infancy is the most severe and life-threatening form of juvenile polyposis. This disease typically presents in the first two years of life with gastrointestinal bleeding, diarrhea, inanition, and exudative enteropathy. In very few reports concerning this entity, a large deletion in the long arm of chromosome 10 (10q23), encompassing the PTEN and BMPR1A genes, was found. The authors report a case of delayed diagnosis of juvenile polyposis of infancy at 6years of age. A 3.34Mb long de novo deletion was identified at 10q23.1q23.31, encompassing the PTEN and BMPR1A genes. The disease course was severe with diarrhea, abdominal pain, inanition, refractory anemia, rectal bleeding, hypoalbuminemia, and exudative enteropathy. A sub-total colectomy, combined with intraoperative endoscopic removal of ileal and rectal stump polyps, was required for palliative disease control

Tobacco dependence treatment for special populations: challenges and opportunities

Although smoking rates have declined in most of the countries in the world, there are population groups within these countries whose smoking rates remain significantly higher than the general population. These ‘‘forgotten groups’’ who have not been receiving the needed attention in tobacco control policies and tobacco cessation efforts include people with serious mental illness, substance use disorders, tuberculosis, people living with human immunodeficiency virus (HIV), lesbian-gaybisexual-transgender-queer people, and pregnant women. A number of steps are needed at the national level in countries where these disparities exist, including modifications to national smoking cessation treatment guidelines that address the special needs of these populations, as well as targeted smoking cessation research, since these populations are often not included in clinical trials. Because of the higher smoking prevalence in these populations, as well as their lower smoking cessation treatment success rates than the general population, more resources are needed if we are to reduce health disparities in these vulnerable populations. Additionally, we believe that more effort should be focused on integrating smoking cessation treatment in the specialized care settings frequented by these subpopulations

Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia.

Schizophrenia is a severe psychiatric disorder with strong heritability and marked heterogeneity in symptoms, course, and treatment response. There is strong interest in identifying genetic risk factors that can help to elucidate the pathophysiology and that might result in the development of improved treatments. Linkage and genome-wide association studies (GWASs) suggest that the genetic basis of schizophrenia is heterogeneous. However, it remains unclear whether the underlying genetic variants are mostly moderately rare and can be identified by the genotyping of variants observed in sequenced cases in large follow-up cohorts or whether they will typically be much rarer and therefore more effectively identified by gene-based methods that seek to combine candidate variants. Here, we consider 166 persons who have schizophrenia or schizoaffective disorder and who have had either their genomes or their exomes sequenced to high coverage. From these data, we selected 5,155 variants that were further evaluated in an independent cohort of 2,617 cases and 1,800 controls. No single variant showed a study-wide significant association in the initial or follow-up cohorts. However, we identified a number of case-specific variants, some of which might be real risk factors for schizophrenia, and these can be readily interrogated in other data sets. Our results indicate that schizophrenia risk is unlikely to be predominantly influenced by variants just outside the range detectable by GWASs. Rather, multiple rarer genetic variants must contribute substantially to the predisposition to schizophrenia, suggesting that both very large sample sizes and gene-based association tests will be required for securely identifying genetic risk factors. © 2012 The American Society of Human Genetics

Changes in osmotic and ionic indicators in Ananas comosus (L.) cv. MD Gold pre-treated with phytohormones and submitted to saline medium

The aim of this study was to evaluate the effect of NaCl on the hydroponic culture of cv. MD gold pineapple pretreated with the phytohormones naphthaleneacetic acid (NAA) and 6-benzylaminopurine (BAP) using indicators of water stress and osmotic adjustment. Pineapple seedlings from saline treatments in the absence (-NB) and presence (+NB) of the phytohormones during the in vitro culture were grown in Hoagland & Arnon (1950) nutrient solution in the absence and presence of different NaCl concentrations (50; 100 and 150 mm) for 10 days in a greenhouse. Plants obtained from in vitro culture pretreated with phytoregulators (+NB) showed distinct physiological responses compared to non-treated plants (-NB) in relation to dry mass (DM) in roots, electrolyte leakage (EL) and Na+ and K+ concentrations in leaves and roots, and also regarding soluble sugars (TSS), free amino acids (TFAA) and proline (PRO) concentrations in leaves. Additionally, salt treatments induced similar responses in -NB and +NB plants, however differing in relation to intensity and the studied organs. The presence of NaCl in the solution reduced leaf DM in the -NB treatment, the leaf relative water content in -NB and +NB, and root RWC only in the -NB treatment. high levels of NaCl increased leaf EL in the +NB treatment. Potassium levels decreased with the increase of NaCl concentrations in nutrient solution for leaves and roots submitted to -NB treatment and for roots submitted to +NB treatment. Leaf potassium levels increased in +NB treatment regardless of salt treatment. No ionic toxic effects were identified except for roots subjected to 150 mM NaCl solution both for -NB and +NB conditions. TSS concentrations decreased with increasing NaCl concentration in leaves for both -NB and +NB treatments. Furthermore, TFAA and PRO showed increased levels in leaves subjected to saline stress, being more expressive in -NB treatment. In conclusion, pretreatment with growth regulators in pineapple plants minimized the effects of NaCl, despite higher concentrations of this salt affecting most of the evaluated parameters. Additionally, we conclude that the osmotic effect of salt stress was determinative for the physiological changes and that roots have different outcomes regarding the increment of growth regulators and NaCl concentrations.</p

A database for curating the associations between killer cell immunoglobulin-like receptors and diseases in worldwide populations

The killer cell immunoglobulin-like receptors (KIR) play a fundamental role in the innate immune system, through their interactions with human leucocyte antigen (HLA) molecules, leading to the modulation of activity in natural killer (NK) cells, mainly related to killing pathogen-infected cells. KIR genes are hugely polymorphic both in the number of genes an individual carries and in the number of alleles identified. We have previously developed the Allele Frequency Net Database (AFND, http://www.allelefrequencies.net), which captures worldwide frequencies of alleles, genes and haplotypes for several immune genes, including KIR genes, in healthy populations, covering >4 million individuals. Here, we report the creation of a new database within AFND, named KIR and Diseases Database (KDDB), capturing a large quantity of data derived from publications in which KIR genes, alleles, genotypes and/or haplotypes have been associated with infectious diseases (e.g. hepatitis C, HIV, malaria), autoimmune disorders (e.g. type I diabetes, rheumatoid arthritis), cancer and pregnancy-related complications. KDDB has been created through an extensive manual curation effort, extracting data on more than a thousand KIR-disease records, comprising >50 000 individuals. KDDB thus provides a new community resource for understanding not only how KIR genes are associated with disease, but also, by working in tandem with the large data sets already present in AFND, where particular genes, genotypes or haplotypes are present in worldwide populations or different ethnic groups. We anticipate that KDDB will be an important resource for researchers working in immunogenetics. Database URL: http://www.allelefrequencies.net/diseases

Screening the human exome: a comparison of whole genome and whole transcriptome sequencing

BACKGROUND: There is considerable interest in the development of methods to efficiently identify all coding variants present in large sample sets of humans. There are three approaches possible: whole-genome sequencing, whole-exome sequencing using exon capture methods, and RNA-Seq. While whole-genome sequencing is the most complete, it remains sufficiently expensive that cost effective alternatives are important. RESULTS: Here we provide a systematic exploration of how well RNA-Seq can identify human coding variants by comparing variants identified through high coverage whole-genome sequencing to those identified by high coverage RNA-Seq in the same individual. This comparison allowed us to directly evaluate the sensitivity and specificity of RNA-Seq in identifying coding variants, and to evaluate how key parameters such as the degree of coverage and the expression levels of genes interact to influence performance. We find that although only 40% of exonic variants identified by whole genome sequencing were captured using RNA-Seq; this number rose to 81% when concentrating on genes known to be well-expressed in the source tissue. We also find that a high false positive rate can be problematic when working with RNA-Seq data, especially at higher levels of coverage. CONCLUSIONS: We conclude that as long as a tissue relevant to the trait under study is available and suitable quality control screens are implemented, RNA-Seq is a fast and inexpensive alternative approach for finding coding variants in genes with sufficiently high expression levels