Overexpression of chromatin remodeling and tyrosine kinase genes in iAMP21-positive acute lymphoblastic leukemia.

Intrachromosomal amplification of chromosome 21 (iAMP21) is a cytogenetic subtype associated with relapse and poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). The biology behind the high relapse risk is unknown and the aim of this study was to further characterize the genomic and transcriptional landscape of iAMP21. Using DNA arrays and sequencing, we could identify rearrangements and aberrations characteristic for iAMP21.

Correction to: MYC-dependent downregulation of telomerase by FLT3 inhibitors is required for their therapeutic efficacy on acute myeloid leukemia.

The original version of this article contained a mistake. The name of Magnus Björkhom should have been Magnus Björkholm.

High-resolution detection of chromosomal rearrangements in leukemias through mate pair whole genome sequencing.

The detection of recurrent somatic chromosomal rearrangements is standard of care for most leukemia types. Even though karyotype analysis-a low-resolution genome-wide chromosome analysis-is still the gold standard, it often needs to be complemented with other methods to increase resolution. To evaluate the feasibility and applicability of mate pair whole genome sequencing (MP-WGS) to detect structural chromosomal rearrangements in the diagnostic setting, we sequenced ten bone marrow samples from leukemia patients with recurrent rearrangements.

Impact on affected families and society of severe rotavirus infections in Swedish children assessed in a prospective cohort study.

Background: Few prospective cohort studies have estimated the overall impact of severe rotavirus gastroenteritis (RVGE) leading to hospitalization on families and society. We assessed human and economic resources needed to care for an affected average child aged <5 years in Sweden.

Methods: The study was conducted in Astrid Lindgren Children's Hospital which serves approximately 14% of all Swedish children <5 years of age.

MYC-dependent downregulation of telomerase by FLT3 inhibitors is required for their therapeutic efficacy on acute myeloid leukemia.

The somatic mutation of FLT3 occurs in 30% of acute myeloid leukemia (AML), with the majority of mutations exhibiting internal tandem duplication (ITD). On the other hand, the induction of telomerase reverse transcriptase (hTERT) and the activation of telomerase is a key step in AML development. Here, we sought to determine whether FLT3ITD regulates hTERT expression in AML cells and whether hTERT expression affects FLT3 inhibitors' therapeutic efficacy on AML.

Detailed gene dose analysis reveals recurrent focal gene deletions in pediatric B-cell precursor acute lymphoblastic leukemia.

To identify copy number alterations (CNAs) in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL), array comparative genomic hybridization was performed on 50 cases; detected CNAs were validated in a cohort of 191 cases analyzed by single nucleotide polymorphism arrays. Apart from CNAs involving leukemia-associated genes, recurrent deletions targeting genes not previously implicated in BCP ALL, e.g.

Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden.

Background: The aim of this prospective cohort study was to estimate the burden of severe disease caused by rotavirus-induced gastroenteritis in Swedish children aged < 5 y.

Methods: Rotavirus-positive children admitted to hospitals serving 3 geographical regions with 155,838 children aged < 5 y, were offered inclusion in this 1-year study. Rotavirus strains identified were genotyped using multiplex PCR.

DNPTrapper: an assembly editing tool for finishing and analysis of complex repeat regions.

Background: Many genome projects are left unfinished due to complex, repeated regions. Finishing is the most time consuming step in sequencing and current finishing tools are not designed with particular attention to the repeat problem.

Results: We have developed DNPTrapper, a shotgun sequence finishing tool, specifically designed to address the problems posed by the presence of repeated regions in the target sequence.

The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease.

Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T.

Comparative genomics of trypanosomatid parasitic protozoa.

A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite.

Trypanothione synthetase locus in Trypanosoma cruzi CL Brener strain shows an extensive allelic divergence.

The protozoan parasite Trypanosoma cruzi, agent of Chagas' disease, displays an extensive genetic heterogeneity among strains and isolates. It is, therefore, important to determine the degree of polymorphism in potential candidates for drug design. Our studies on the organisation of the locus containing the gene encoding trypanothione synthetase (TcTRS) (an enzyme involved in the unique trypanothione pathway and hence a promising drug target) revealed a high degree of sequence polymorphism between the two alleles in the T.