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Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson's disease in Black South African and Nigerian patients.

التفاصيل البيبلوغرافية
العنوان: Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson's disease in Black South African and Nigerian patients.
المؤلفون: Oluwole OG; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa., Kuivaniemi H; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa., Abrahams S; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa., Haylett WL; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.; Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Vorster AA; DNA Sequencing Unit, Central Analytical Facility, Stellenbosch University, Stellenbosch, South Africa., van Heerden CJ; DNA Sequencing Unit, Central Analytical Facility, Stellenbosch University, Stellenbosch, South Africa., Kenyon CP; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.; Bioinformatics Unit, South African Tuberculosis Bioinformatics Initiative, Stellenbosch University, Cape Town, South Africa.; DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.; South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa., Tabb DL; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.; Bioinformatics Unit, South African Tuberculosis Bioinformatics Initiative, Stellenbosch University, Cape Town, South Africa.; DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.; South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.; Centre for Bioinformatics and Computational Biology, Stellenbosch University, Stellenbosch, South Africa., Fawale MB; Neurology Unit, Department of Medicine, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria., Sunmonu TA; Neurology Unit, Department of Medicine, Federal Medical Centre, Owo, Nigeria., Ajose A; Department of Chemical Pathology, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria., Olaogun MO; Department of Medical Rehabilitation, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria., Rossouw AC; Division of Neurology, Department of Medicine, Faculty of Health Sciences, Walter Sisulu University, East London, South Africa., van Hillegondsberg LS; Division of Neurology, Department of Medicine, Faculty of Health Sciences, Walter Sisulu University, East London, South Africa.; Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Carr J; Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Ross OA; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.; Department of Clinical Genomics, Mayo Clinic College of Medicine, Jacksonville, Florida, USA., Komolafe MA; Neurology Unit, Department of Medicine, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria., Tromp G; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa. gctromp@sun.ac.za.; Bioinformatics Unit, South African Tuberculosis Bioinformatics Initiative, Stellenbosch University, Cape Town, South Africa. gctromp@sun.ac.za.; DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa. gctromp@sun.ac.za.; South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa. gctromp@sun.ac.za.; Centre for Bioinformatics and Computational Biology, Stellenbosch University, Stellenbosch, South Africa. gctromp@sun.ac.za., Bardien S; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa. sbardien@sun.ac.za.
المصدر: BMC medical genetics [BMC Med Genet] 2020 Feb 04; Vol. 21 (1), pp. 23. Date of Electronic Publication: 2020 Feb 04.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 100968552 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2350 (Electronic) Linking ISSN: 14712350 NLM ISO Abbreviation: BMC Med Genet Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2000-
مواضيع طبية MeSH: Genetic Predisposition to Disease* , High-Throughput Nucleotide Sequencing*, Parkinson Disease/*genetics , Proton-Translocating ATPases/*genetics, Adult ; Aged ; Aged, 80 and over ; Black People/genetics ; Female ; Gene Frequency ; Genetic Association Studies ; Humans ; Male ; Middle Aged ; Molecular Sequence Annotation ; Mutation, Missense ; Nigeria/epidemiology ; Parkinson Disease/epidemiology ; Parkinson Disease/pathology ; Point Mutation ; South Africa/epidemiology
مستخلص: Background: The prevalence of Parkinson's disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients.
Methods: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2's protein structure was investigated by molecular modelling.
Results: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein.
Conclusions: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry.
References: Front Mol Neurosci. 2014 May 27;7:48. (PMID: 24904274)
Mov Disord. 2014 Nov;29(13):1583-90. (PMID: 24976103)
Mol Cell Probes. 2016 Dec;30(6):386-396. (PMID: 27818248)
J Mov Disord. 2018 May;11(2):53-64. (PMID: 29860783)
BMC Public Health. 2014 Jun 26;14:653. (PMID: 24969686)
J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):368-76. (PMID: 18344392)
Curr Opin Struct Biol. 2013 Aug;23(4):507-14. (PMID: 23871101)
Biochim Biophys Acta. 2009 Jun;1793(6):941-6. (PMID: 19010358)
Ann Neurol. 2015 Mar;77(3):458-68. (PMID: 25558820)
Lancet Neurol. 2017 Nov;16(11):877-897. (PMID: 28931491)
N Engl J Med. 2006 Sep 28;355(13):1345-56. (PMID: 17005952)
Parkinsonism Relat Disord. 2012 Jan;18(1):89-92. (PMID: 21996382)
PLoS One. 2008;3(10):e3421. (PMID: 18927607)
Nucleic Acids Res. 2006 Jan 1;34(Database issue):D302-5. (PMID: 16381872)
Nat Protoc. 2015 Jun;10(6):845-58. (PMID: 25950237)
Nature. 2015 Jan 15;517(7534):327-32. (PMID: 25470054)
Mol Diagn Ther. 2016 Oct;20(5):481-91. (PMID: 27294386)
Hum Mol Genet. 2014 Jun 1;23(11):2816-33. (PMID: 24603074)
JAMA Neurol. 2016 Jan;73(1):68-75. (PMID: 26595808)
Mov Disord. 2016 Apr;31(4):458-70. (PMID: 26899883)
Hum Genomics. 2011 Mar;5(3):156-69. (PMID: 21504867)
Hum Mol Genet. 2017 Oct 1;26(R2):R225-R236. (PMID: 28977439)
Mol Psychiatry. 2013 Oct;18(10):1077-89. (PMID: 23711981)
Neurobiol Dis. 2013 Sep;57:38-46. (PMID: 22776331)
J Neurol. 2009 Jan;256(1):115-20. (PMID: 19184162)
Parkinsonism Relat Disord. 2017 Aug;41:51-57. (PMID: 28551322)
J Neurol Sci. 2013 Dec 15;335(1-2):22-5. (PMID: 24079843)
Hum Mutat. 2009 May;30(5):734-40. (PMID: 19306334)
Cold Spring Harb Perspect Med. 2012 Jan;2(1):a008888. (PMID: 22315721)
Hum Mutat. 2016 Mar;37(3):235-41. (PMID: 26555599)
Parkinsons Dis. 2016;2016:6465793. (PMID: 26942037)
Front Cell Neurosci. 2015 Apr 10;9:124. (PMID: 25914621)
Neurobiol Aging. 2014 Feb;35(2):445.e1-3. (PMID: 24080171)
Curr Genomics. 2013 Dec;14(8):560-7. (PMID: 24532987)
Clin Sci (Lond). 2005 Oct;109(4):355-64. (PMID: 16171459)
Nature. 2004 Jul 29;430(6999):529-35. (PMID: 15229613)
معلومات مُعتمدة: P50 NS072187 United States NS NINDS NIH HHS; R21 NS098862 United States NS NINDS NIH HHS
فهرسة مساهمة: Keywords: Next-generation sequencing; Nigeria; Parkinson’s disease; Scoring of sequence variants; Sequence variants; South Africa; Sub-Saharan Africa
المشرفين على المادة: 0 (ATP13A2 protein, human)
EC 3.6.3.14 (Proton-Translocating ATPases)
تواريخ الأحداث: Date Created: 20200206 Date Completed: 20200303 Latest Revision: 20240329
رمز التحديث: 20240329
مُعرف محوري في PubMed: PMC7001245
DOI: 10.1186/s12881-020-0953-1
PMID: 32019516
قاعدة البيانات: MEDLINE
الوصف
تدمد:1471-2350
DOI:10.1186/s12881-020-0953-1