Shayla McCafferyMay 27, 2015ANTH311.A01_1153Term Paper

Epigenetics Studies and Twins

Epigenetics is the modern versions of the theories about DNA that

Lamarck originally presented. Focusing on genetic changes due to the envi-

ronment in which an individual lives. Changes than occur outside of the DNA

sequence, but are passed down to the next generation. The changes are

seen expressed in the genotypes and phenotype of an individual. Twins are

either eternal where two separate eggs are fertilized at one time, these twins

are more like siblings. The second type of twin is an identical twin, this is

where egg divides early and both parts of the egg continue to grow as their

own fetus. These two eggs then share identical DNA (UCSB). Twins allow sci-

entist to study epigenetics and gain a greater understanding about genetics

because their are two set of identical DNA looks different than the twins. The

different influences of the twins environment affect what genes will be ex-

pressed. This paper will describe the study of epigenetics. This paper will

also discuss and explain example of how epigenetics and twins are related.

Epigenetics is furthering the understanding of genetics and how and why ill-

ness and disease occur. This paper will look at research that has been done

on Huntington’s Disease, spinocerebellar ataxias (SCAs), and dominant forms

of Alzheimer’s disease (AD). Lastly, this paper will discuss other types of re-

search that is being conducted using epigenetics.

What is Epigenetics?

Lamarck believed that the acquisitions or losses were preserved by re-

production (inherited). Lastly, Lamarck believed that spontaneous generation

of simple forms would exist. In epigenetic, generation of simple forms is con-

sidered mutations in DNA. Lamarck’s theory was proven wrong when epige-

netics was proven. Epigenetics prove that there are no “internal forces” to

use or to disuse, but rather there are environmental forces. Secondly, there

are genes that are not always passed on when the environmental stress acts

on the sex cells. This would cause change in the next generation. Twins have

been the focus of Epigenetics and comparing the two types of twins. Identi-

cal twins are called monozygotic twins and Fraternal twins are considered

dizygotic twins in all research that will be presented. According to: Why

aren’t identical twins linguistically identical? Genetic, prenatal and postnatal

factors: “By the 1990s, microbiologists had discovered that micro-RNA (which

regulates gene expression at the mRNA level by splicing exons, silencing

genes, and editing proteins) and other epigenetic processes (e.g., methyla-

tion, phosphorylation, glycosylation, acetylation, imprinting, X chromosome

inactivation) could alter gene expression without changing the underlying

genomic sequence. In addition to playing a crucial role in early development,

these epigenetic processes can occur at any point in development as random

events or in response to environmental factors (Jaenisch & Bird, 2003), and

Fraga et al. (2005) recently reported that epigenetic differences between MZ

cotwins increase with age” (Stromswold, 2006). Knowing how the environ-

ment affects gene expression is important when improving the health of gen-

erations to come.

Epigenetics is also explained by Epigenetic regulation of gene expres-

sion: how the genome integrates intrinsic and environmental signals: “The

term 'epigenetics', which literally means 'outside conventional genetics', is

now used to describe the study of stable alterations in gene expression po-

tential that arise during development and cell proliferation. This has effec-

tively replaced an earlier usage, which referred to the study of 'epigenesis',

meaning interpretation of the genotype during development to give the phe-

notype” (Jaenisch & Bird, 2003). Additional research explains epigenetic and

its scientific impact as “Monozygous twins share a common genotype. How-

ever, most monozygotic twin pairs are not identical; several types of pheno-

typic discordance may be observed, such as differences in suscep- tibilities

to disease and a wide range of anthropomorphic features. There are several

possible explanations for these observations, but one is the existence of epi-

genetic differences. To address this issue, we examined the global and locus-

specific differences in DNA methylation and histone acetylation of a large co-

hort of monozy- gotic twins. We found that, although twins are epigenetically

indistinguishable during the early years of life, older monozygous twins ex-

hibited remarkable differences in their overall content and genomic distribu-

tion of 5-methylcytosine DNA and histone acety- lation, affecting their gene-

expression portrait. These findings indicate how an appreciation of epigenet-

ics is missing from our understanding of how different phenotypes can be

originated from the same genotype" (Fraga et al. (2005)). Epigenetics is al-

lowing scientific researchers to identify small differences in DNA and how

events in one’s life influence DNA ( Petronis, 2004). Comparing twins allows

scientist to see how DNA is affected and how diseases are affected under

different environmental pressures and conditions.

Epigenetic Research Findings

Researchers have studied different affect of environmental factors on a

person’s DNA. The first research I will explain was conducted by Ketelaar ME,

Hofstra RMW, Hayden MR: What monozygotic twins discordant for phenotype

illustrate about mechanisms influencing genetic forms of neurodegeneration.

These researchers first bring up the fact that both types of twins, even iden-

tical ones can vary both genetically and epigenetically. “Screening MZ (iden-

tical) twins for genetic and/or epigenetic differences could be a useful and

novel approach to identify modifying factors influencing phenotypic expres-

sion of disease. MZ twins that are phenotypically discordant for monogenic

diseases are of special interest” (Ketelaar, Hofstra, Hayden. 2011). Diseases

like Huntington’s disease, spinocerebellar ataxias and Alzheimer’s disease.

Comparing identical twins that are phenotypically discordant, crucial factors

influencing the phenotypic expression of the disease could be identified.

These influences are important in order to understand disease and variability

in disease and phenotypes (Ketelaar, Hofstra, Hayden. 2011). This study

compares identical twins who are suffering from Huntington’s disease (HD),

spinocerebellar ataxias (SCAs), or dominant forms of Alzheimer’s disease

(AD), discordance in identical twins.

Huntington’s disease is where there is progressive neurodegeneration

and there is degeneration of the striatum and cerebral cortex, which pro-

duces motor, cognitive, and psychiatric symptoms. Huntington’s disease is a

mutation of a CAG coded chain. This is where there is a repeated elongation

in the HTT gene. This is where chromosome. 4 is found. Normally, the longer

the CAG track (35 or more) shows the that this is where the expression varia-

tions come from. The longer the tracks, the earlier the onset. According to

Ketelaar, Hofstra, Hayden; “some studies indicate that only 70% of the vari-

ance in AO can be explained by CAG tract size, leaving ∼30% to be ex-

plained by modifying factors other than the causative gene (7). It has been

estimated that 10–20% of the difference in AO might be explained by ‘herita-

ble factors, including non-CAG genetic modifiers’ and the remaining 10%

might be environmental. MZ twins that are discordant for HD phenotype, al-

though rare, have been described (14–23) and may be useful to determine

crucial modifiers in the development of HD” (2011.)

This research discovered that identical twins with Huntington’s disease

patients affected by the disease and who are identical twins have reported

many different symptoms of the disease that are different then the other

twin’s symptoms. The symptoms have been reported to be different both

neurologically and affected motor skills (Ketelaar, Hofstra, Hayden. 2011).

These changes occur during the transcription process of DNA creation and

duplication. This is where the changes in identical twins occur, and we can

see different genetic factors that influence or modify disease. According to

the article: it is useful to use identical twins concordant for HD allowing sci-

entist to see the difference between acquired pathogenic difference from

non-pathogenic ones. The article slows shows that this evidence is sparse

because of the lack of twins with Huntington’s, although older reports also

support the evidence that possible epigenetic differences can show underly-

ing disease discordance that can exist in DNA and can be better identified in

singletons (humans without identical or fraternal twins (Ketelaar, Hofstra,

Hayden. 2011).

Ketelaar, Hofstra, Hayden, also studied the difference in identical twins

who suffer from Spinocerebellar ataxias. This is an inherited condition, that

causes “atrophy in cerebellar and spinal tissue, resulting in motor symptoms

such as unsteady gait, clumsiness and dysarthria, and by neurological symp-

toms including pyramidal signs, ophthalmoplegia, and cognitive impairment”

(Ketelaar, Hofstra, Hayden. 2011). Even when both parents have been domi-

nate for the gene there has been significant differences in phenotype expres-

sions that are seen in people who suffer from Spinocerebellar ataxias. Genet-

ically they can be identified and grouped in different coding groups: CAG-ex-

pansion forms, non-coding expansion SCAs or conventional mutation SCAs,

SCA1-3 is the most common form of the disease found (Ketelaar, Hofstra,

Hayden. 2011). Studying twins also the CAG expansion forms for disease to

identified for diseases and what factors are modifying them. This is how the

science is applied to twins are both diseases discussed thus far. The length

of the non-mutated allele is show to influence the gene expression variabil-

ity. Ketelaar, Hofstra, Hayden stated that showing cis and trans acting ge-

netic factors need to be considered in CAG expansion disorders. Twins allow

these coded CAG chains to be examined and investigate the discordant of

Identical twins.

Ketelaar, Hofstra, Hayden research also studied Alzheimer’s disease.

Alzheimer’s disease is the most common type of neurodegenerative disorder.

This disease causes dementia as an elderly person. According to the article;

“43% of persons above 85 years suffer from AD, and AD comprises between

60% and 80% of all prevalent dementia cases” (Ketelaar, Hofstra, Hayden.

2011). This disease is characterized by cognitive decline, accumulation of

beta- amyloid deposited and neurofibrillary triangles in the brains. Most

cases are consider LOAD meaning late onset this is over the age of 60. Ac-

cording to Ketelaar, Hofstra, Hayden, 95% of cases where polygenetic and

environmental factors influence the disease (2011).

Ketelaar, Hofstra, Hayden found that identical twins with discordant for

Alzheimer’s disease, their phenotype can be valuable while finding crucial

modifiers among potential candidates. For those who are affected by the

early onset version of the disease (LOAD) there is a lower rate of discor-

dance in identical twins. This occurs in the inherited forms of the disease.

This information is also sparse because there have been only 3 set of identi-

cal twins who have reported having the EOFAD (the most common type),

This research is important to discovering crucial factors influencing the

pathogenesis of Alzheimer’s and know more about the different kinds of

Alzheimer’s. According to the article: “Overall, cases discordant for strongly

inherited forms

of AD show that also in familial AD other factors than the causative gene

may play a significant role in disease development” (Ketelaar, Hofstra,

Hayden, 2011). According to Ketelaar, Hofstra, Hayden, “MZ (identical) twins

can differ in the epigenetic status of their genome. Several studies have

identified epigenetic differences either at selected genes of MZ twins on the

overall epigenome . In general, the term epigenetics refers to ‘modifications

of gene expression that are controlled by heritable factors other than DNA

sequence, and are potentially reversible. Epigenetic mechanisms are dy-

namic processes that are influenced by developmental stage, tissue type,

environmental and stochastic factors. Typical examples of epigenetic mecha-

nisms include DNA methylation and histone modifications, but also comprise

other mechanisms including ATP-based chromatin remodeling, non-coding

RNA-mediated gene silencing and transcription factor-binding mechanisms.

Histone modifications and DNA methylation particularly have been linked to

phenotypic outcome, through altering transcription and genomic stability.

Epigenetic modifications have been found relevant for human disease, in-

cluding many neurodegenerative disorders such as Parkinson disease, AD

and HD” (Ketelaar, Hofstra, Hayden, 2011). Differences in epigenetic modifi-

cations can influence the phenotypic expression of disease. This could also

form an explanation for variable disease phenotypes that exist in identical

twins and can even identify modifications that will also affect singletons.

Other uses for Epigenetic Studies on Twins

Not only is testing twins and their epigenetics beneficial for identifying

disease, but it is being used in sociological research as well. Epigenetic stud-

ies on twins are occurring for identifying elements of criminology. According

to ABANDON TWIN RESEARCH? EMBRACE, EPIGENETIC RESEARCH? PREMA-

TURE ADVICE FOR

CRIMINOLOGISTS: by Terrie E. Moffitt and Amber Beckley; “Twin discordance

can be studied for most of the leading causal variables in criminology. Crim-

inogenic experiences unique to the individual and not shared with his or her

sibling include being the target of child sexual abuse, falling in with a gang of

delinquent friends, dropping out of high school, sustaining a head injury, de-

veloping an addiction, or

suffering long-term unemployment. To date, discordant twin designs in de-

velopmental

criminology have been limited mainly to studying childhood aggression.

However,

enough twin samples have reached adulthood that it is now possible to apply

the discordant twin design to testing causes of adult crime and causes of de-

sistance from crime. Imagine testing whether prison causes crime by com-

paring twin siblings who go to prison against their co-twins who do not. Re-

search attempting to test the iatrogenic influence of incarceration on post re-

lease criminal recidivism is bedeviled by the possibility that longer prison

sentences might selectively be given to individuals carrying greater criminal

propensity (Nagin and Snodgrass, 2013)” (Beckley, Moffitt, 2015). Beckley

and Moffitt also explain that this is a very new area of study and that crimi-

nologist must be very careful about the research that they take at full value.

Conclusion

In conclusion, epigenetics allows scientific researchers to identify cer-

tain phenotype variations and disease mutations that exists. In order to pre-

form more inclusive testing, scientist have been studying twins for a better

idea of how the same set of DNA can be expressed differently. This is impor-

tant when identifying what codon chains order or length are associated with

diseases. These variations are due to environmental influences. Epigenetic

studies preformed on twins are beneficial for diseases like Huntington’s Dis-

ease, spinocerebellar ataxias (SCAs), and dominant forms of Alzheimer’s dis-

ease (AD). In addition, epigenetic studies on twins are also beginning to be

used in the sociology field. Epigenetic studies are proving to be helpful and

may be a key to predicting deadly disease before they happen, or possibly

improving the changes of finding cures for diseases that are affecting our so-

ciety.

Sources:

1. Jaenisch, R., & Bird, A. (n.d.). Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals. Nat Genet Nature Genetics, 245-254.

2. Ketelaar, M., Hofstra, R., & Hayden, M. (2011). What monozygotic twins discordant for phenotype illustrate about mechanisms influencing genetic forms of neurodegeneration. Clinical Genetics, 325-333.

3. Moffitt, T., & Beckley, A. (n.d.). Abandon Twin Research? Embrace Epige-netic Research? Premature Advice For Criminologists. Criminology, 121-126.

4. Petronis, A. (2004). The origin of schizophrenia: Genetic thesis, epigenetic antithesis, and resolving synthesis. Biological Psychiatry, 965-970.

5. Scherer, S. (2005). Faculty of 1000 evaluation for Epigenetic differences arise during the lifetime of monozygotic twins. F1000 - Post-publication Peer Review of the Biomedical Literature.

6. Stromswold, K. (2006). Why aren’t identical twins linguistically identical? Genetic, prenatal and postnatal factors. Cognition, 333-384.

7. UCSB Science Line." UCSB Science Line. Web. 28 May 2015.