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Clinical applicability of methylome sequencing in a pilot study of ischemic stroke individuals

Ziemann, Mark, Harikrishnan, K. N., Khurana, Ishant, Kaspi, Antony, Keating, Samuel T., De Silva, Deidre Anne, Moe, Kyaw Thu and El-Osta, Assam 2015, Clinical applicability of methylome sequencing in a pilot study of ischemic stroke individuals, Methods in Next Generation Sequencing, vol. 2, no. 1, pp. 11-22, doi: 10.1515/mngs-2015-0002.

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Title Clinical applicability of methylome sequencing in a pilot study of ischemic stroke individuals
Author(s) Ziemann, MarkORCID iD for Ziemann, Mark orcid.org/0000-0002-7688-6974
Harikrishnan, K. N.
Khurana, Ishant
Kaspi, Antony
Keating, Samuel T.
De Silva, Deidre Anne
Moe, Kyaw Thu
El-Osta, Assam
Journal name Methods in Next Generation Sequencing
Volume number 2
Issue number 1
Start page 11
End page 22
Total pages 12
Publisher De Gruyter Open
Place of publication Berlin, Germany
Publication date 2015-11-05
ISSN 2084-7173
Keyword(s) homocysteine
DNA methylation
epigenetics
one-carbon metabolism
hypertension
Summary Despite recent progress in screening for genetic causes of cardiovascular disease using genome-wide association studies, identifying causative polymorphisms has not met initial expectations. This has led to interestin exploring the contribution of non-genetic factors in disease etiology. Elevated plasma homocysteine is an independent risk factor for cardiovascular disease but the mechanism for increased risk remains poorly understood. This study evaluates the clinical applicability of screeningfor genome-wide CpG methylation differences using methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq). Peripheral blood genomic DNA methylation in 8 Singaporean-Chinese ischemic stroke patients (4 male, 4 female) was profiled. Differential methylation of genes implicated in hyperhomocysteinemia was observed in males correlating withhomocysteine; namely CBS (cystathionine-beta-synthase) and MTHFR (methylenetetrahydrofolate reductase). In females, hypomethylation of the LDLR (low density lipoprotein receptor) and CELSR1 (cadherin, EGF LAGseven-pass G-type receptor 1) genes were observed in the hypertensive group (2 normal and 2 hypertensive individuals). While the number of clinical samples analysed is small, the findings of this evaluation suggest that MBD-seq is a suitable and sufficiently sensitive technology to determine methylation variability. The results presented warrant an expanded case-control study to determine the pathophysiological implications of DNA methylation for hyper-homocysteinemia.
Language eng
DOI 10.1515/mngs-2015-0002
Indigenous content off
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2015, The Authors
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30141378

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.