Prioritization of genes driving congenital phenotypes of patients with de novo genomic structural variants.
Authors of this article are:
Middelkamp S, Vlaar JM, Giltay J, Korzelius J, Besselink N, Boymans S, Janssen R, de la Fonteijne L, van Binsbergen E, van Roosmalen MJ, Hochstenbach R, Giachino D, Talkowski ME, Kloosterman WP, Cuppen E.
A summary of the article is shown below:
BACKGROUND: Genomic structural variants (SVs) can affect many genes and regulatory elements. Therefore, the molecular mechanisms driving the phenotypes of patients carrying de novo SVs are frequently unknown.METHODS: We applied a combination of systematic experimental and bioinformatic methods to improve the molecular diagnosis of 39 patients with multiple congenital abnormalities and/or intellectual disability harboring apparent de novo SVs, most with an inconclusive diagnosis after regular genetic testing.RESULTS: In 7 of these cases (18%), whole-genome sequencing analysis revealed disease-relevant complexities of the SVs missed in routine microarray-based analyses. We developed a computational tool to predict the effects on genes directly affected by SVs and on genes indirectly affected likely due to the changes in chromatin organization and impact on regulatory mechanisms. By combining these functional predictions with extensive phenotype information, candidate driver genes were identified in 16/39 (41%) patients. In 8 cases, evidence was found for the involvement of multiple candidate drivers contributing to different parts of the phenotypes. Subsequently, we applied this computational method to two cohorts containing a total of 379 patients with previously detected and classified de novo SVs and identified candidate driver genes in 189 cases (50%), including 40 cases whose SVs were previously not classified as pathogenic. Pathogenic position effects were predicted in 28% of all studied cases with balanced SVs and in 11% of the cases with copy number variants.CONCLUSIONS: These results demonstrate an integrated computational and experimental approach to predict driver genes based on analyses of WGS data with phenotype association and chromatin organization datasets. These analyses nominate new pathogenic loci and have strong potential to improve the molecular diagnosis of patients with de novo SVs.
Check out the article’s website on Pubmed for more information:
This article is a good source of information and a good way to become familiar with topics such as: Copy number variants; Driver genes; Intellectual disability; Multiple congenital anomalies; Neurodevelopmental disorders; Position effects; Structural variation; Topologically associating domains; Transcriptome sequencing; Whole-genome sequencing.
NativeFolder: The Only Bacterial Culture Medium for the Expression of Soluble Proteins
-
- Sale!
- Molecular Biology, Research Kits
NativeFolder Bacterial Culture Medium
- $350.00 – $19,500.00
- Select options
Interference Test Kit for Assay Validation
-
- Sale!
- Interference, Research Kits
Interference Test Kit
- Original price was: $595.00.$395.00Current price is: $395.00.
- Add to cart
Rheumatoid Factor Interference Blocker
-
- Sale!
- Antibodies, Interference
Rheumatoid Factor Interference Blocker
- Original price was: $595.00.$395.00Current price is: $395.00.
- Add to cart
New Antibodies from MOLECULAR DEPOT
-
- Sale!
- Antibodies
Antibody to Thyroxine T4 Monoclonal
- Original price was: $995.00.$495.00Current price is: $495.00.
- Add to cart
-
- Antibodies
SAA Antibody Monoclonal Anti-Serum Amyloid A
- $350.00 – $1,550.00
- Select options
-
- Antibodies
Valproic Acid Antibody (Mouse Monoclonal)
- $250.00 – $1,095.00
- Select options
-
- Antibodies
Phenytoin Antibody (Mouse Monoclonal)
- $350.00 – $1,450.00
- Select options
-
- Sale!
- Antibodies
Anti Sheep IgG (H+L) Rabbit Polyclonal
- $250.00 – $1,495.00
- Select options
-
- Sale!
- Antibodies
Anti Human IgM Antibody Polyclonal
- Original price was: $595.00.$295.00Current price is: $295.00.
- Add to cart
-
- Sale!
- Antibodies
Myoglobin Antibody (Human Affinity Purified)
- Original price was: $650.00.$350.00Current price is: $350.00.
- Add to cart
-
- Sale!
- Antibodies, Interference
Rheumatoid Factor Interference Blocker
- Original price was: $595.00.$395.00Current price is: $395.00.
- Add to cart
-
- Sale!
- Antibodies, Interference
HAMA Blocking Reagent (Affinity Purified)
- Original price was: $895.00.$450.00Current price is: $450.00.
- Add to cart
New Proteins from MOLECULAR DEPOT
-
- Sale!
- Proteins, Conjugates
Tacrolimus BSA Conjugate Solution
- Original price was: $695.00.$495.00Current price is: $495.00.
- Add to cart
-
- Sale!
- Enzymes, Proteins
Cholesterol Oxidase from Streptomyces sp.
- Original price was: $595.00.$295.00Current price is: $295.00.
- Add to cart
-
- Sale!
- Proteins
Aprotinin from Bovine Lung (Lyophilized powder)
- Original price was: $450.00.$250.00Current price is: $250.00.
- Add to cart
-
- Sale!
- Proteins, Enzymes
Beta-galactosidase Enzyme Donor
- Original price was: $795.00.$450.00Current price is: $450.00.
- Add to cart
-
- Sale!
- Proteins, Enzymes
Beta-galactosidase Enzyme Acceptor
- Original price was: $795.00.$375.00Current price is: $375.00.
- Add to cart
-
- Sale!
- Enzymes, Proteins
Xanthine Oxidase Grade II (Lyophilized Powder)
- Original price was: $695.00.$395.00Current price is: $395.00.
- Add to cart
-
- Sale!
- Proteins, Enzymes
Ascorbate Oxidase (Lyophilized Powder)
- Original price was: $350.00.$250.00Current price is: $250.00.
- Add to cart
-
- Sale!
- Proteins
Silk Fibroin (Bombyx Mori Silkworm)
- Original price was: $595.00.$295.00Current price is: $295.00.
- Add to cart
-
- Sale!
- Proteins
Fibrinogen from Bovine Plasma Lyophilized
- Original price was: $595.00.$295.00Current price is: $295.00.
- Add to cart
-
- Sale!
- Proteins, Enzymes
Horseradish Peroxidase Biotinylated
- Original price was: $595.00.$295.00Current price is: $295.00.
- Add to cart
New Chemicals from MOLECULAR DEPOT
-
- Sale!
- Chemicals, Interference, Lipids
Triglyceride Mix for Interference Testing
- Original price was: $495.00.$295.00Current price is: $295.00.
- Add to cart
-
- Sale!
- Chemicals
Microparticle Stabilizer Solution
- Original price was: $595.00.$295.00Current price is: $295.00.
- Add to cart
-
- Sale!
- Buffers & Solutions, Chemicals
Enzyme Acceptor Stabilization Buffer
- Original price was: $495.00.$250.00Current price is: $250.00.
- Add to cart
-
- Sale!
- Buffers & Solutions, Chemicals
Enzyme Donor Stabilization Buffer
- Original price was: $495.00.$250.00Current price is: $250.00.
- Add to cart
-
- Sale!
- Chemicals, Conjugates
Progesterone Biotin Conjugate Solution
- Original price was: $650.00.$350.00Current price is: $350.00.
- Add to cart
-
- Sale!
- Buffers & Solutions, Chemicals
Microparticle Activation Buffer
- Original price was: $595.00.$295.00Current price is: $295.00.
- Add to cart
-
- Sale!
- Buffers & Solutions, Chemicals
Microparticle Washing Buffer
- Original price was: $595.00.$295.00Current price is: $295.00.
- Add to cart
-
- Sale!
- Buffers & Solutions, Chemicals
Microparticle Blocking Buffer
- Original price was: $650.00.$350.00Current price is: $350.00.
- Add to cart
-
- Sale!
- Buffers & Solutions, Chemicals
Microparticle Anti Aggregation Agent
- Original price was: $595.00.$295.00Current price is: $295.00.
- Add to cart
-
- Sale!
- Chemicals
CPRG (Chlorophenol red-β-D-galactopyranoside)
- Original price was: $850.00.$395.00Current price is: $395.00.
- Add to cart