Abstract
The completion of the Human Genome Project has advanced our understanding of the biological processes involved in health and disease. The increasing amount of whole-genome sequencing data becoming available from healthy and affected individuals has pinpointed variations in the DNA sequence, like single-nucleotide polymorphisms (SNPs), that may help to explain differences in phenotype, as well as in disease susceptibility and resistance. On the other hand, it is becoming increasingly apparent that the DNA-stored information alone cannot be the sole determinant of human variation and disease. The extreme phenotypic variability that characterizes the >250 different cell types in the human body, where all cells carry the same genetic information, as well as the high monozygotic discordance rates for human diseases clearly indicate so. Nowadays, it is well established that the epigenome exerts an additional layer of regulation on gene expression and can “manipulate” the same genetic code into producing distinct phenotypes. The epigenome shows far greater plasticity than the genome and contributes significantly to development and differentiation by responding to environmental stimuli. Errors in epigenetic programming caused by genetic defects and/or environmental factors have been directly implicated with human disease. In this chapter, we describe known epigenetic mechanisms and discuss the aberrant epigenetic patterns that characterize several human diseases.
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Abbreviations
- AID:
-
Autoimmune diseases
- ALL:
-
Acute lymphoblastic leukemia
- AML:
-
Acute myeloid leukemia
- BDNF :
-
Brain-derived neurotrophic factor
- CD:
-
Cluster of differentiation
- CDH3 :
-
Cadherin 3 type 1, P-cadherin
- CDKN2A :
-
Cyclin-dependent kinase inhibitor 2A
- ChIP:
-
Chromatin immunoprecipitation
- DLX5 :
-
Distal-less homeobox 5
- DLX6 :
-
Distal-less homeobox 6
- DNMT:
-
DNA methyltransferases
- DOT1L :
-
DOT1-like histone H3 methyltransferase
- GADD45a :
-
Growth arrest and DNA-damage-inducible protein alpha
- GSTP1 :
-
Glutathione S-transferase-π1
- HATs:
-
Histone acetyltransferases
- HDAC:
-
Histone deacetylases
- HDMs:
-
Histone demethylases
- HMT:
-
Histone methyltransferases
- Hoxa9 :
-
Homeobox A9
- IGF2 :
-
Insulin-like growth factor 2
- ITGAL :
-
Integrin alpha L
- LINEs:
-
Long interspersed nuclear elements
- LOI:
-
Loss of imprinting
- MBD:
-
Methyl-binding domain
- MDM2 :
-
Mdm2 p53 binding protein homolog
- MECP2 :
-
Methyl-CpG binding protein 2
- MGMT :
-
O-6-methylguanine-DNA methyltransferase
- MHC:
-
Major histocompatibility complex
- miRNAs:
-
MicroRNAs
- MLL1 :
-
Mixed-lineage leukemia 1 gene
- Mø:
-
Macrophages
- NLS:
-
Nuclear localization signal
- nt:
-
Nucleotides
- p53:
-
Tumor protein p53
- PDCD1 :
-
Programmed cell death 1
- Pol II:
-
RNA polymerase II
- PRF1 :
-
Perforin 1
- RISC:
-
RNA-induced silencing complex
- RTT:
-
Rett syndrome
- SLE:
-
Systemic lupus erythematosus
- SNPs:
-
Single-nucleotide polymorphisms
- SOX4 :
-
SRY (sex-determining region Y)-box 4
- TCR:
-
T cell antigen receptor
- TRD:
-
Transcriptional repression domain
- TSA:
-
Trichostatin A
- UBE3A :
-
Ubiquitin protein ligase E3A
- XCI:
-
X chromosome inactivation
- Xi:
-
X inactivation
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Magklara, A., Lomvardas, S. (2012). Epigenetics and Human Disease. In: Ahituv, N. (eds) Gene Regulatory Sequences and Human Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1683-8_12
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