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Epigenetics and Human Disease

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Gene Regulatory Sequences and Human Disease

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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Authors and Affiliations

  1. Department of Anatomy, University of California San Francisco, 1550 4th St., Rock Hall #348D, San Francisco, CA, 94158, USA

    Angeliki Magklara & Stavros Lomvardas

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  1. Angeliki Magklara
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  2. Stavros Lomvardas
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Correspondence to Stavros Lomvardas .

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  1. Institute for Human Genetics, 513 Parnassus Ave., San Francisco, 94143, USA

    Nadav Ahituv

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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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