| 1. |
- Hibar, Derrek P., et al.
(författare)
-
Novel genetic loci associated with hippocampal volume
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
|
|
| 2. |
- Satizabal, Claudia L., et al.
(författare)
-
Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
-
Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
|
|
| 3. |
- Kalscheuer, Vera M, et al.
(författare)
-
Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation
- 2003
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 35:4, s. 313-315
-
Tidskriftsartikel (refereegranskat)abstract
- We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously been implicated in the pathogenesis of polyglutamine expansion diseases. Our findings link this gene to XLMR and shed more light on the pathogenesis of this common disorder.
|
|
| 4. |
- Brown, Matthew, et al.
(författare)
-
Effect of Surface Charge Density on the Affinity of Oxide Nanoparticles for the Vapor–Water Interface
- 2013
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 29:16, s. 5023-5029
-
Tidskriftsartikel (refereegranskat)abstract
- Using in-situ X-ray photoelectron spectroscopy at the vapor–water interface, the affinity of nanometer-sized silica colloids to adsorb at the interface is shown to depend on colloid surface charge density. In aqueous suspensions at pH 10 corrected Debye–Hückel theory for surface complexation calculations predict that smaller silica colloids have increased negative surface charge density that originates from enhanced screening of deprotonated silanol groups (≡Si–O–) by counterions in the condensed ion layer. The increased negative surface charge density results in an electrostatic repulsion from the vapor–water interface that is seen to a lesser extent for larger particles that have a reduced charge density in the XPS measurements. We compare the results and interpretation of the in-situ XPS and corrected Debye–Hückel theory for surface complexation calculations with traditional surface tension measurements. Our results show that controlling the surface charge density of colloid particles can regulate their adsorption to the interface between two dielectrics.
|
|
| 5. |
- Mansouri, Mahmoud R., 1975-
(författare)
-
Molecular Characterisation of Structural Chromosomal Abnormalities Associated with Congenital Disorders
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chromosomal abnormalities are defined as changes in the chromosome structure and fall in one of two categories. The first category is numerical alterations while the second category consists of structural abnormalities. Structural chromosomal abnormalities do not always interrupt genes in order to cause disease. They can also affect gene expression by separating a gene and its promoter element from distant regulatory elements. We have used characterisation of structural chromosomal abnormalities to identify the genetic bases for several congenital disorders.In papers I-III, we have applied molecular characterisation of chromosomal translocations in order to identify candidate genes involved in mental retardation, hypospadias and anal malformation and premature ovarian failure. In paper I, we localised the chromosome X translocation breakpoint in a t(X;15) to be in the immediate proximity of the gene ZDHHC15 in a patient with severe mental retardation. Subsequent experiments revealed loss of ZDHHC15 transcription in the patient which suggests this gene to be involved in the aetiology of the patient’s phenotype. In paper II, we show that a balanced translocation between chromosomes 6 and 17 in a patient with urogential malformation disrupts 2 genes, one at each translocation breakpoint. We also identified a fusion-gene as a result of the translocation. Our hypethesis is that the translocation together with its molecular consequences is important for the phenotype in the patient. Similarly, in paper III, we have used molecular characterisation of the breakpoints in a balanced translocation between chromosomes X and 11 in order to localise candidate genes in ovarian function. Our results indicate a number of genes affected by the translocation. In paper IV, we have used array-based comparative genomic hybridisation (array-CGH) in order to investigate a cohort of autistic sib-pairs for submicroscopic chromosomal alterations. We have identified several novel duplications and one novel deletion with strong association with autism.
|
|
| 6. |
|
|
| 7. |
- Ponjavic, Vesna, et al.
(författare)
-
Phenotype variation within a choroideremia family lacking the entire CHM gene
- 1995
-
Ingår i: Ophthalmic Genetics. - : Informa UK Limited. - 1744-5094 .- 1381-6810. ; 16:4, s. 143-150
-
Tidskriftsartikel (refereegranskat)abstract
- A Swedish family with choroideremia and a deletion of the CHM gene has been studied with ophthalmological examination, full-field electro-retinography, and DNA analysis in order to characterize the phenotype of the disease. Although all four patients studied had a complete deletion of the gene, they showed a considerable variability regarding the phenotype, including the electroretinogram tracings. Two of the affected males demonstrated a severe form of choroideremia with low or nondetectable ERG recordings, while the other two affected males showed a less severe phenotype with only a slight reduction of the ERG amplitudes. The variation of the clinical phenotype among family members carrying the same mutation indicates that the severity of choroideremia is not solely a function of the CHM gene.
|
|
| 8. |
- Sá, Jacinto, et al.
(författare)
-
Transient mid-IR study of electron dynamics in TiO2 conduction band.
- 2013
-
Ingår i: The Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 138:7, s. 1966-70
-
Tidskriftsartikel (refereegranskat)abstract
- The dynamics of TiO2 conduction band electrons were followed with a novel broadband synchrotron-based transient mid-IR spectroscopy setup. The lifetime of conduction band electrons was found to be dependent on the injection method used. Direct band gap excitation results in a lifetime of 2.5 ns, whereas indirect excitation at 532 nm via Ru-N719 dye followed by injection from the dye into TiO2 results in a lifetime of 5.9 ns.
|
|
| 9. |
|
|
