| 1. |
- Thomassen, Mads, et al.
(författare)
-
Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants : Application of a points-based ACMG/AMP approach
- 2022
-
Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 43:12, s. 1921-1944
-
Tidskriftsartikel (refereegranskat)abstract
- Skipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples. ∆E3 was measured using quantitative analysis. A mouse embryonic stem cell (mESC) based assay was used to determine the impact of 18 variants on mRNA splicing and protein function. For each variant, population frequency, bioinformatic predictions, clinical data, and existing mRNA splicing and functional results were collated. Variant class was assigned using a gene-specific adaptation of ACMG/AMP guidelines, following a recently proposed points-based system. mRNA and mESC analysis combined identified six variants with transcript and/or functional profiles interpreted as loss of function. Cryptic splice site use for acceptor site variants generated a transcript encoding a shorter protein that retains activity. Overall, 69/85 (81%) variants were classified using the points-based approach. Our analysis shows the value of applying gene-specific ACMG/AMP guidelines using a points-based approach and highlights the consideration of cryptic splice site usage to appropriately assign PVS1 code strength.
|
|
| 2. |
- Gasol, Josep M., et al.
(författare)
-
Mesopelagic prokaryotic bulk and single-cell heterotrophic activity and community composition in the NW Africa-Canary Islands coastal-transition zone
- 2009
-
Ingår i: Progress in Oceanography. - : Elsevier BV. - 0079-6611 .- 1873-4472. ; 83, s. 189-196
-
Tidskriftsartikel (refereegranskat)abstract
- Mesopelagic prokaryotic communities have often been assumed to be relatively inactive in comparison to those from epipelagic waters, and therefore unresponsive to the presence of nearby upwelled waters. We have studied the zonal (shelf-ocean), latitudinal, and depth (epipelagic-mesopelagic) variability of microbial assemblages in the NW Africa-Canary Islands coastal-transition zone (CTZ). Vertical profiles of bacterial bulk and single-cell activity through the epi- and mesopelagic waters were combined with point measurements of bacterial respiration, leucine-to-carbon conversion factors and leucine-to-thymidine incorporation ratios. The overall picture that emerges from our study is that prokaryotes in the mesopelagic zone of this area are less abundant than in the epipelagic but have comparable levels of activity. The relationship between prokaryotes and heterotrophic nanoflagellates, their main predators, remains constant throughout the water column, further contradicting the assumption that deep ocean bacterial communities are mostly inactive. Both bulk and single-cell activity showed clear differences between stations, with higher mesopelagic activities closer to the shelf or affected by upwelling features. We also tested whether differences in microbial function between stations could be related to differences in bacterial community structure, and conclude that bacterial communities are very similar at similar depths in the deep ocean, even if the stations present order-of-magnitude differences in bacterial function.
|
|
