Epigenetics in forensic science

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Epigenetics in forensic science is the application of epigenetics to solving crimes. [1] [2]

Contents

Forensic science has been using DNA as evidence since 1984, however this does not give information about any changes in the individual since birth and will not be useful in distinguishing identical siblings. The focus of epigenetics in the forensic field is on non-heritable changes such as aging and diseases. [2]

Epigenetics involves any changes to the DNA that does not affect the sequence, but instead affects the activity of the DNA, such as the level of transcription of a particular gene. These changes can be passed down transgenerationally through the germline or arise after birth from environmental factors. [3] [4] In humans and other mammals, CpG dinucleotides are the main sequence that develops methylation, and because of this most studies on try and find unique methylation sites. There are a few methylation sites that have been determined as a cause of environmental influences from age, lifestyle, or certain diseases.

DNA methylation

DNA methylation is a common epigenetic mark being studied as potential evidence in forensic science. [5] [6] Unlike DNA, realistic DNA methylation is less likely be planted at crime scenes.> [6] Current methods to fabricate DNA usually exclude important methylation marks found in biological tissues making this a way to confirm the identity of an individual when evidence is being assessed. [2]

Many different tissues can be used to analyze methylation.

Sample preservation

The effect of cryopreservation on epigenetic marks in tissues is a new area of study. The primary focus of this research is on oocytes and sperm for the purpose of assisted reproductive technology, however it can be useful in forensics for the preservation of evidence. [7] Methylation can be analyzed in fresh tissue that is cryo-preserved within 24 hours of death and it can then be analyzed in this tissue for up to 1 year. [8] If the tissue is formalin-fixed or putrefied, methylation analysis is much more difficult.

Aging

Although blood is the primary sample used in studies, most tissues consistently show that methylation increases early in life and slowly decreases, globally, throughout late adulthood. [9] This process is referred to as epigenetic drift.

The epigenetic clock refers to methylation sites that are highly associated with aging. [10] These sites consistently change across individuals and can therefore be used as age markers for an individual. There are some models that have been developed to predict ages for specific samples, such as saliva and buccal epithelial cells, blood, or semen, but others have been made to age any tissue. In 2011, three significant, hypermethylated CpG sites related to aging across all samples were found in the KCNQ1DN, NPTX2, and GRIA2 genes. [9] The age guess for over 700 samples had a mean absolute deviation from chronological age (MAD) of 11.4 years. Two years later, almost 8,000 samples were used in an elastic net regularized regression to create a new age predictive model. [9] This resulted in 353 CpG sites being chosen for the age prediction, and the model had a MAD of 3.6 years.

There is evidence for specific methylation sites to be associated with the circadian clock, meaning a sample could have a time of day associated with their death through methylation marks. In whole blood from humans, plasma homocysteine and global DNA methylation change in levels throughout the day. [11] Homocysteine levels peak in the evening and are at their lowest overnight while DNA methylation follows an inverse pattern. Other studies with rats found that expression of DNMT3B and other methylation enzymes oscillate with the circadian clock and may be regulated by the circadian clock. [11] Another methylation associated factor, MECP2, is phosphorylated by the superchiasmatic nucleus in response to light signaling. In a group of subjects that died from a variety of causes, there was partial methylation at the PER2, PER3, CRY1, and TIM promoters which are important genes in controlling the circadian clock. [8] The methylation of CRY1 varied within an individual's tissues and between two individuals, however the difference between individuals may have been due to methamphetamine exposure.

Teeth

An age model using dentin from teeth is currently being studied. [12] Over 300 genes have been found that are a part of odontogenesis and quite a few affect the epigenome. For example, JMJD3 is a histone demethylase that modifies the methylation of homeobox and bone morphogenetic proteins. [13] More studies are being done to differentiate genetic, epigenetic, and environmental factors on methylation in teeth so that aging algorithms are more accurate.

Previously, measuring differences in between sets of teeth was done with calipers, but 2D and 3D imaging has become more available and allows for better accuracy of measurements. New programs are being developed to analyze these images of teeth. [14] Mono-zygotic twin studies reveal 8-29% of changes between the twins' teeth is from the environment. Several studies of mono-zygotic twins have shown that when they have a tooth defect, such as congenitally missing or supernumerary teeth, the twins can share the same number or position of the defective tooth, but sometimes not both of these factors. [15]

Twin identification

Monozygotic twins provide information on epigenetic differences that are not from genetic factors. Epigenetic markers differ the most in monozygotic twins who spend time apart or have a very different medical history. As twins age, their methylation and acetylation of histone H3 and H4 increasingly vary. [16] These marks are specific to the environmental changes between the twins and not changes in methylation from general aging. The rate of disease discordance between monozygotic twins is usually over 50%, including heritable diseases. [17] This does not correlate to the disease prevalence rate.

There are more phenotypic methylation differences in twins discordant for bipolar, schizophrenia, or systemic lupus erythematosus than in unrelated cases. [17] There is no difference between twins discordant for rheumatoid arthritis or dermatomyositis. A limitation to the current studies on twin disease discordance is the lack of a baseline epigenetic profile of the twins before they develop the disease. [17] This baseline will be used to distinguish the environmental changes between the twins to narrow down the methylation sites related to the disease. Several studies are obtaining newborn epigenetic profiles for long-term research.

Related Research Articles

<span class="mw-page-title-main">Epigenetics</span> Study of DNA modifications that do not change its sequence

In biology, epigenetics are stable heritable traits that cannot be explained by changes in DNA sequence, and the study of a type of stable change in cell function that does not involve a change to the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic mechanism of inheritance. Epigenetics usually involves a change that is not erased by cell division, and affects the regulation of gene expression. Such effects on cellular and physiological phenotypic traits may result from environmental factors, or be part of normal development. They can lead to cancer.

<span class="mw-page-title-main">5-Methylcytosine</span> Chemical compound which is a modified DNA base

5-Methylcytosine is a methylated form of the DNA base cytosine (C) that regulates gene transcription and takes several other biological roles. When cytosine is methylated, the DNA maintains the same sequence, but the expression of methylated genes can be altered. 5-Methylcytosine is incorporated in the nucleoside 5-methylcytidine.

<span class="mw-page-title-main">DNA methylation</span> Biological process

DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis.

<span class="mw-page-title-main">Neoplasm</span> Abnormal mass of tissue as a result of abnormal growth or division of cells

A neoplasm is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumour or tumor.

A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase and is synchronized with solar time.

<span class="mw-page-title-main">Transgenerational epigenetic inheritance</span> Epigenetic transmission without DNA primary structure alteration

Transgenerational epigenetic inheritance is the transmission of epigenetic markers and modifications from one generation to multiple subsequent generations without altering the primary structure of DNA. Thus, the regulation of genes via epigenetic mechanisms can be heritable; the amount of transcripts and proteins produced can be altered by inherited epigenetic changes. In order for epigenetic marks to be heritable, however, they must occur in the gametes in animals, but since plants lack a definitive germline and can propagate, epigenetic marks in any tissue can be heritable.

The Epigenomics database at the National Center for Biotechnology Information was a database for whole-genome epigenetics data sets. It was retired on 1 June 2016.

<span class="mw-page-title-main">Biomarkers of aging</span> Type of biomarkers

Biomarkers of aging are biomarkers that could predict functional capacity at some later age better than chronological age. Stated another way, biomarkers of aging would give the true "biological age", which may be different from the chronological age.

Behavioral epigenetics is the field of study examining the role of epigenetics in shaping animal and human behavior. It seeks to explain how nurture shapes nature, where nature refers to biological heredity and nurture refers to virtually everything that occurs during the life-span. Behavioral epigenetics attempts to provide a framework for understanding how the expression of genes is influenced by experiences and the environment to produce individual differences in behaviour, cognition, personality, and mental health.

The epigenetics of schizophrenia is the study of how inherited epigenetic changes are regulated and modified by the environment and external factors and how these changes influence the onset and development of, and vulnerability to, schizophrenia. Epigenetics concerns the heritability of those changes, too. Schizophrenia is a debilitating and often misunderstood disorder that affects up to 1% of the world's population. Although schizophrenia is a heavily studied disorder, it has remained largely impervious to scientific understanding; epigenetics offers a new avenue for research, understanding, and treatment.

An epigenetic clock is a biochemical test that can be used to measure age. The test is based on DNA methylation levels, measuring the accumulation of methyl groups to one's DNA molecules.

Epigenetic regulation of neurogenesis is the role that epigenetics plays in the regulation of neurogenesis.

Epigenetic therapy is the use of drugs or other epigenome-influencing techniques to treat medical conditions. Many diseases, including cancer, heart disease, diabetes, and mental illnesses are influenced by epigenetic mechanisms. Epigenetic therapy offers a potential way to influence those pathways directly.

Epigenetics of physical exercise is the study of epigenetic modifications to the cell genome resulting from physical exercise. Environmental factors, including physical exercise, have been shown to have a beneficial influence on epigenetic modifications. Generally, it has been shown that acute and long-term exercise has a significant effect on DNA methylation, an important aspect of epigenetic modifications.

<span class="mw-page-title-main">Epigenetics of neurodegenerative diseases</span> Field of study

Neurodegenerative diseases are a heterogeneous group of complex disorders linked by the degeneration of neurons in either the peripheral nervous system or the central nervous system. Their underlying causes are extremely variable and complicated by various genetic and/or environmental factors. These diseases cause progressive deterioration of the neuron resulting in decreased signal transduction and in some cases even neuronal death. Peripheral nervous system diseases may be further categorized by the type of nerve cell affected by the disorder. Effective treatment of these diseases is often prevented by lack of understanding of the underlying molecular and genetic pathology. Epigenetic therapy is being investigated as a method of correcting the expression levels of misregulated genes in neurodegenerative diseases.

Neuroepigenetics is the study of how epigenetic changes to genes affect the nervous system. These changes may effect underlying conditions such as addiction, cognition, and neurological development.

<span class="mw-page-title-main">Epigenome-wide association study</span>

An epigenome-wide association study (EWAS) is an examination of a genome-wide set of quantifiable epigenetic marks, such as DNA methylation, in different individuals to derive associations between epigenetic variation and a particular identifiable phenotype/trait. When patterns change such as DNA methylation at specific loci, discriminating the phenotypically affected cases from control individuals, this is considered an indication that epigenetic perturbation has taken place that is associated, causally or consequentially, with the phenotype.

<span class="mw-page-title-main">Steve Horvath</span> German–American aging researcher, geneticist and biostatistician

Steve Horvath is a German–American aging researcher, geneticist, and biostatistician. He is a professor at the University of California, Los Angeles known for developing the Horvath aging clock, which is a highly accurate molecular biomarker of aging, and for developing weighted correlation network analysis. His work on the genomic biomarkers of aging, the aging process, and many age related diseases/conditions has earned him several research awards. Horvath is a principal investigator at the anti-aging startup Altos Labs and co-founder of nonprofit Clock Foundation.

Epigenetics of anxiety and stress–related disorders is the field studying the relationship between epigenetic modifications of genes and anxiety and stress-related disorders, including mental health disorders such as generalized anxiety disorder (GAD), post-traumatic stress disorder, obsessive-compulsive disorder (OCD), and more. These change can lead to transgenerational stress inheritance.

Sleep epigenetics is the field of how epigenetics affects sleep.

References

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