Academic journal article International Journal of Child Health and Human Development

Stress, Genetics, and Epigenetics Related to Abuse and Maltreatment

Academic journal article International Journal of Child Health and Human Development

Stress, Genetics, and Epigenetics Related to Abuse and Maltreatment

Article excerpt

Introduction

In the 21st century, it remains the case that the maltreatment of children represents a major public health concern worldwide (1), with some 700,000 reports in the US alone each year (2). A steadily growing number of studies have linked this maltreatment with poor health outcomes, including hypertension, diabetes, asthma, heart disease, inflammation, and obesity (3-6). Early life stress is associated with an increased susceptibility to major psychiatric disorders including major depression, bipolar disorder, post-traumatic stress disorder (PTSD), alcohol and drug abuse, and schizophrenia (7). By cataloging the biological markers that accumulate as a result of these traumas, specific understanding in the underlying bases for these health problems can be gathered and treatments devised.

How can traumatic events early in childhood, including physical and mental abuse and malnutrition, underlie increased incidence of disease later in life? How does our environment affect our genome, sometimes in a heritable way? Why can twins with identical DNA sequences display different features? Why does Mendelian genetics alone fall short of describing a number of afflictions, including cancer and mental retardation? To appreciate some of the answers to these questions, we must not only understand the most basic aspects of genetics, but also a rapidly emerging field of study called epigenetics. There is now a convincing body of evidence that connects epigenetics to the underlying bases for changes in DNA expression changes in response to early life experiences (8).

Our genome in a modern perspective

For much of the 20th century, our understanding of biology and its most fundamental tenets were guided by the seminal contributions of figures such as Gregor Mendel and Charles Darwin, which include the concepts of traits, heredity, and evolution. Preceding the Nobel-prize winning work of the team of Francis Crick, James Watson, Maurice Wilkins, and Rosalind Franklin in the 1950s (9,10) was a growing body of evidence supplied by geneticists that it was deoxyribonucleic acid (DNA) and not the protein in chromosomes that was responsible for heredity among species. The work of this quartet of scientists ultimately illuminated the molecular basis of these heritable units in 1953 with their discovery of the double-helix structure of DNA using X-ray crystallography. At its most basic level, DNA is seemingly simple: a polymer comprised of four chemical bases (adenine (A), thymine (T), guanine (G), and cytosine (C)) (see Figure 1). Between the strands of the DNA double-helix, adenine only pairs with thymine and guanine only pairs with cytosine, creating a base pair between two strands. However, the potential information content across the entire DNA content of a cell is expansive. A genome is the complete set of DNA found within the cell of an organism. In the nuclei of each of the ~1013 cells in the human body, the approximately three billion pairs of DNA of the human genome reside across 23 pairs of chromosomes. In typewritten form, the sequence of the human genome would occupy some one million pages. Contained within the genome are units of sequences called genes which encode for biopolymers called proteins. The basic building blocks of proteins are called amino acids, of which twenty naturally occurring units are known. Proteins in turn serve a variety of chemical and structural roles that underlie basic cellular functions. The term "proteome" refers to the entire collection of proteins that can exist within a cell during its lifetime.

In its fully-extended form, the DNA of one cell is approximately a meter in length, yet tightly packaged into a cellular compartment (the nucleus) of a cell with a diameter of ~10 microns. How is this feat accomplished? Within the cell, DNA is tight wound around an octet of small proteins known as histones, creating what appears to be a node on a string. Each of these nodes is what is called a nucleosome, which wraps around -165 base pairs (bps) of DNA. …

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