BACKGROUND
The 1000 Genomes Project provides a database of genomic variants from whole genome sequencing of 2504 individuals across five continental superpopulations. This database can enrich our background knowledge of worldwide blood group variant geographic distribution and identify novel variants of potential clinical significance.
STUDY DESIGN AND METHODS
The 1000 Genomes database was analyzed to 1) expand knowledge about continental distributions of known blood group variants, 2) identify novel variants with antigenic potential and their geographic association, and 3) establish a baseline scaffold of chromosomal coordinates to translate next‐generation sequencing output files into a predicted red blood cell (RBC) phenotype.
RESULTS
Forty‐two genes were investigated. A total of 604 known variants were mapped to the GRCh37 assembly; 120 of these were reported by 1000 Genomes in at least one superpopulation. All queried variants, including the ACKR1 promoter silencing mutation, are located within exon pull‐down boundaries. The analysis yielded 41 novel population distributions for 34 known variants, as well as 12 novel blood group variants that warrant further validation and study. Four prediction algorithms collectively flagged 79 of 109 (72%) known antigenic or enzymatically detrimental blood group variants, while 4 of 12 variants that do not result in an altered RBC phenotype were flagged as deleterious.
CONCLUSION
Next‐generation sequencing has known potential for high‐throughput and extended RBC phenotype prediction; a database of GRCh37 and GRCh38 chromosomal coordinates for 120 worldwide blood group variants is provided as a basis for this clinical application.
IWS1 is an RNA-polymerase II (RNAPII)-associated transcription elongation factor whose biological functions are poorly characterized. To shed some light on the function of this protein at the organismal level, we performed a systematic tissue analysis of its expression and generated Iws1-deficient mice. A thorough immunohistochemical characterization shows that IWS1 protein is present in the nucleus of all cells in most of the examined tissues, with few notable exceptions. We also report that ablation of Iws1 consistently causes lethality at the pre-implantation stage with high expression of the gene in fertilized oocytes. In summary, we are providing evidence that Iws1 is expressed in all adult organs and it is an essential gene for mouse embryonic development.
Bronchiolitis Obliterans Syndrome (BOS) complicates the course of many lung transplant recipients. It carries significant risk of morbidity and mortality, but its course is difficult to characterize. We evaluated the prognostic utility of the 6min walk test (6MWT) obtained after the onset of BOS in 42 patients. This was compared to the prognostic significance of changes in the FEV(1). The median time between the onset of BOS and the 6MWT was 109 days. The median decline in the FEV(1) from baseline to BOS onset was 25.7%, while the median change over the ensuing 3 months was 12.5%. Neither of these was predictive of subsequent mortality. The 6MWT yielded averages in the resting saturation, lowest saturation, distance walked and maximal Borg scores of 97%, 90.2%, 323m and 2.35, respectively. The best of these parameters in discriminating survival was the distance. Patients who walked further than 330m had a median survival of 1178 days versus 263 days for those who walked less (p<0.0001). We conclude that the 6MWT provides important prognostic information in patients with BOS and might perform better than spirometry. Use of this test might allow different clinical phenotypes to be discerned.
Maintaining an in-compliance clinical laboratory takes continuous awareness and review of standards, regulations, and best practices. A strong quality assurance program and well informed leaders who maintain professional networks can aid in this necessary task. This article will discuss a process that laboratories can follow to interpret, understand, and comply with the rules and standards set by laboratory accreditation bodies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.