caa a22 4500 445376155 CHVBK 20180317143003.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00702-011-0591-z doi (NATIONALLICENCE)springer-10.1007/s00702-011-0591-z Identification of Parkinson's disease candidate genes using CAESAR and screening of MAPT and SNCAIP in South African Parkinson's disease patients [Elektronische Daten] [Rowena Keyser, Ekow Oppon, Jonathan Carr, Soraya Bardien] Assuming that a significant cause of Parkinson's disease (PD) is genetic, genetic factors have been shown to account for <10% of all PD cases to date, and it is therefore necessary to identify novel genes. The aim of the present study was to identify PD candidate genes using a bioinformatic approach and to screen them for possible PD-causing mutations. The CAESAR (CAndidatE Search And Rank) program was used in the present study to identify and prioritize PD candidate genes. CAESAR ranks annotated human genes as candidates by using ontologies to semantically map natural language descriptions of the trait under investigation to gene-centric databases. Two of the candidates were selected and screened for mutations in 202 South African PD patients using the High-Resolution Melt (HRM) method. Samples exhibiting altered HRM profiles were sequenced. CAESAR generated a prioritized list of candidates including both known and novel PD genes. The MAPT and SNCAIP genes were selected for mutation screening from the list of ten highest scoring genes. Two novel missense (A91V and V635I), four synonymous and three intronic sequence variants were identified in MAPT. For SNCAIP, three novel missense (T383N, R606Q, N906H), one known (E709Q), four synonymous and one intronic sequence variant were found. A bioinformatic approach was used to aid in the identification and selection of PD candidate genes in a group of South African patients. Mutation screening of MAPT and SNCAIP identified novel sequence variants in both genes and further studies are necessary to determine their possible functional consequences. Springer-Verlag, 2011 Parkinson's disease nationallicence CAESAR nationallicence Bioinformatic tools nationallicence MAPT nationallicence SNCAIP nationallicence Keyser Rowena Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, University of Stellenbosch, P.O. Box 19063, 7505, Tygerberg, Cape Town, South Africa aut Oppon Ekow The South African National Bioinformatics Institute (SANBI), University of the Western Cape, Cape Town, South Africa aut Carr Jonathan Division of Neurology, Faculty of Health Sciences, University of Stellenbosch, Cape Town, South Africa aut Bardien Soraya Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, University of Stellenbosch, P.O. Box 19063, 7505, Tygerberg, Cape Town, South Africa aut Journal of Neural Transmission Springer Vienna 118/6(2011-06-01), 889-897 0300-9564 118:6<889 2011 118 702 https://doi.org/10.1007/s00702-011-0591-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-011-0591-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Keyser Rowena Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, University of Stellenbosch, P.O. Box 19063, 7505, Tygerberg, Cape Town, South Africa aut NATIONALLICENCE 700 1- Oppon Ekow The South African National Bioinformatics Institute (SANBI), University of the Western Cape, Cape Town, South Africa aut NATIONALLICENCE 700 1- Carr Jonathan Division of Neurology, Faculty of Health Sciences, University of Stellenbosch, Cape Town, South Africa aut NATIONALLICENCE 700 1- Bardien Soraya Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, University of Stellenbosch, P.O. Box 19063, 7505, Tygerberg, Cape Town, South Africa aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/6(2011-06-01), 889-897 0300-9564 118:6<889 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer