Spectrum of free fatty acids of DU145 cells after SCD inhibition. DU145 cells were treated with SCD inhibitors (100nM) or solvent (DMSO) for 48hrs in medium with low serum or supplemented with BSA or BSA-coupled oleic acid (BSA-oleate). (a) Amounts of different FFA species. (b) Amounts of selected saturated and mono-unsaturated FFAs. (c) Relative contribution of FFA species to total FFA pool. (d) Relative contribution of selected saturated and mono-unsaturated FFA species to total FFA pool. Data represent mean ÂąSEM of three independent biological replicates. Statistical comparisons were performed using Student t-test (*pâ¤0.05). (PDF 648 kb

Barrie Peck (3418217)

Zachary Schug (3418208)

Qifeng Zhang (116382)

Beatrice Dankworth (3418235)

Dylan Jones (3418223)

Elizabeth Smethurst (644355)

Rachana Patel (839101)

Susan Mason (2963952)

Ming Jiang (11433)

Rebecca Saunders (3418229)

Michael Howell (228756)

Richard Mitter (132333)

Bradley Spencer-Dene (1085)

Gordon Stamp (55542)

Lynn McGarry (3418214)

Daniel James (325064)

Emma Shanks (3418226)

Eric Aboagye (3418220)

Susan Critchlow (2093512)

Hing Leung (425854)

Adrian Harris (94740)

Michael Wakelam (3418232)

Eyal Gottlieb (206953)

Almut Schulze (3418211)

Abstract: Background and Aim. Osteogenesis imperfecta (OI), also called brittle bone disease, is a clinically and genetically heterogeneous disorder characterized by decreased bone density. Autosomal dominant forms result from mutations in either the COL1A1 (collagen type I alpha-1 chain) or COL1A2 (collagen type I alpha-2 chain) genes encoding the type I collagen. The aim of this study was to identify mutations and allelic variants of the COL1A1 gene in patients with osteogenesis imperfecta (OI). Methods and Results: Molecular genetic analysis of the COL1A1 gene was performed in a cohort of 34 patients with OI. The DNA samples were analysed by PCR and Sanger sequencing. DNA changes in coding sequences of the gene were compared with Type 1 Collagen Mutation Database. Genetic variants resulting in either quantitatively or structurally defective protein production were found in 6 unrelated patients. Four identified mutations are connected to decreased protein production (Tyr47X, Arg131X, Arg415X, Gln1341X), 2 result in amino acid substitution (Cys61Phe, Pro1186Ala) and the last affects splicing (c.1057-1G>T). Further, one silent mutation (Gly794Gly) was detected. No protein analysis was performed. Conclusion: Of the 8 identified mutations, 5 were novel and have not been reported before. Only one causes substitution of glycine located within the Gly-X-Y triplets in the triple helical domain. Two mutations are located in major ligand binding regions (MLBR) which are important for bone strength and flexibility. Although the genotype-phenotype correlation is still unclear, our findings should contribute to elucidating this relationship in patients diagnosed with OI

Hruskova, Lucie

Fija\u142kowski, Igor

Van Hul, Wim

Marik, Ivo

Mortier, Geert

Martasek, Pavel

Mazura, Ivan

Institutional Repository Universiteit Antwerpen

Eight mutations including 5 novel ones in the COL1A1 gene in Czech patients with osteogenesis imperfecta

Background and Aim. Osteogenesis innperfecta (OI), also called brittle bone disease, is a clinically and genetically heterogeneous disorder characterized by decreased bone density. Autosonnal dominant forms result from mutations in either the COL1A1 (collagen type I alpha-1 chain) or COL1A2 (collagen type I alpha-2 chain) genes encoding the type I collagen. The aim of this study was to identify mutations and allelic variants of the COL1A1 gene in patients with osteogenesis innperfecta (OI).

Methods and Results. Molecular genetic analysis of the COL1A1 gene was performed in a cohort of 34 patients with 01. The DNA samples were analysed by PCR and Sanger sequencing. DNA changes in coding sequences of the gene were compared with Type 1 Collagen Mutation Database. Genetic variants resulting in either quantitatively or structurally defective protein production were found in 6 unrelated patients. Four identified mutations are connected to decreased protein production (Tyr47X, Arg131 X, Arg415X, Glnl 341X), 2 result in amino acid substitution (Cys61Phe, Pro1186Ala) and the last affects splicing (c.1057-1G>T). Further, one silent mutation (Gly794Gly) was detected. No protein analysis was performed.

Conclusion. Of the 8 identified mutations, 5 were novel and have not been reported before. Only one causes substitution of glycine located within the Gly-X-Y triplets in the triple helical domain. Two mutations are located in major ligand binding regions (MLBR) which are important for bone strength and flexibility. Although the genotype-phenotype correlation is still unclear, our findings should contribute to elucidating this relationship in patients diagnosed with OI

Hruskova, L

Fijalkowski, Igor

Van Hul, W

Marik, I

Mortier, G

Martasek, P

Mazura, I

Ghent University Academic Bibliography

English

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