Epigenetic modification

Related Terms

Biovular twins, conjoined twins, dichorionic diamniotic twins, dizygotic twins, epigenetic modification, fraternal twins, identical twins, monochorionic diamniotic twins, monochorionic monoamniotic twins, monozygotic twins, multiple births, multiple pregnancy, MZ twins, non-identical twins.

Background

Two children resulting from the same pregnancy are referred to as twins. Twinning refers to the development and occurrence of twins. Identical twins, also called monozygotic twins or MZ twins, develop when one fertilized egg splits into two embryos at the stage of splitting. Identical twins have the same chromosomes, so they are of the same sex and are highly similar, although usually not identical in appearance. Fraternal twins, also called dizygotic twins or DZ twins, occur when two separate eggs are fertilized by two different sperm cells. Fraternal twins share about 50% of their chromosomes, so they can be of different sexes and do not look any more alike than brothers or sisters born from different pregnancies. Fraternal twins are more common than identical twins, one of the reasons being that fertility drugs can cause production of more than one egg at a time.
MZ births are the only instance in which humans share virtually identical genes. Although MZ twins have virtually identical DNA, environmental factors throughout life can influence which genes are switched on or off. This is called epigenetic modification and denotes influencing factors on genes that are not genetic.
There are four types of MZ twin pairs: Twins with separate chorions (outer layer of the amniotic sac), amnions (inner membrane enclosing the embryo) and placentas; twins with separate chorions and amnions and fused placentas; twins with separate amnions and shared chorions and placentas; and twins with shared chorions, amnions, and placentas. There are two types of DZ twin pairs: Twins with separate chorions, amnions, and placentas; and twins with separate chorions and amnions and fused placentas.
The overall frequency of both MZ and DZ twin births is between 1% and 1.5%. The birth rate for DZ twins is about 32.2 per 1,000, while the birth rate for MZ twins is about four per 1,000. In the United States the Hispanic twinning rate (20.1 per 1,000 births) is substantially lower than the rate for non-Hispanic whites (31.5 per 1,000 births) and that for non-Hispanic blacks (32.1 per 1,000 births). Roughly 1 in 80 Caucasian births is a twin, and 30% of these are MZ twins. However, the chance of having MZ twins is usually a random event not influenced by the mother's age, race, or country of residence.
The likelihood of DZ twins is influenced by environmental and genetic factors. DZ twins occur from the release of several eggs at the same time, an event controlled by the level of follicle-stimulating hormone (FSH) in the mother. FSH is the central hormone in human reproduction and is necessary for egg production. The likelihood of bearing DZ twins increases in women who are well-nourished, significantly increases in obese women, and declines with malnutrition. DZ twins tend to run in families. Twinning is passed on as a dominant genetic trait in women, with the trait skipping a generation. The likelihood of having twins is 1.7% higher for sisters of mothers of DZ twins, and 2.5% higher for children of female DZ twins compared with women who have no family history of twins. A woman with a mother who bore DZ twins has an increased chance of having DZ twins. The woman's brother would not have an increased chance of DZ twins, although the trait may be passed on to his daughters, who would then have an increased chance of having DZ twins. More DZ twins are conceived in July and the fewest are conceived in January, possibly due to the impact of daylight duration on FSH secretion. The pineal gland perceives changes in daylight via feedback from the retina, leading to signaling of the pituitary gland and changes in FSH output.

Methods

The two main types of twins are identical twins, also called monozygotic or MZ twins, and fraternal twins, also called dizygotic or DZ twins. Several objective methods can be used to determine whether twins are MZ or DZ. These include a comparison of the genotypes and known polymorphisms (genetic variations) between the twins, with high degrees of similarity suggesting MZ, comparison of fingerprint patterns or ridges, and comparison of blood samples. Questionnaires asking about eye color, hair color and texture, height, weight, body build, and how often the person is mistaken for their twin by parents, friends, and acquaintances have also been used. However, a visual comparison of twins is almost as accurate as the more elaborate methods.
Fertility treatments primarily affect the rate of DZ twins due to the forced production of multiple eggs. The number of twin births increased by two-thirds (66%) between 1980 and 2003. About one-third of the increase is due to more women over age 30 having babies. The rest of this increase is due to the use of fertility-stimulating drugs and assisted reproductive techniques (ART). The two most common fertility treatments are ART, in which both eggs and sperm are handled in the laboratory to establish a pregnancy, and controlled ovarian hyperstimulation (COH), in which injectable drugs are used to stimulate a woman's ovaries to accelerate egg growth and maturity.
In in vitro fertilization (IVF), a type of ART, eggs are removed from the mother, fertilized in a laboratory dish, and then transferred into the uterus. About 45% of ART pregnancies result in twins. ART babies account for about 1% of all births in the United States every year. COH is used alone or with intrauterine insemination ("artificial insemination"), in which a sperm sample is placed directly into the uterus. ART and COH often lead to multiple births, including twins. In 2002, more than one-third of ART births and an unknown proportion of COH births were multiple births.
Twin studies have been a valuable source of information about the genetic basis of complex traits. Large, worldwide registers of data on twins and their relatives have been established to maximize the potential of twin studies.

Research

General: The two main types of twins are identical twins, also called monozygotic or MZ twins, and fraternal twins, also called dizygotic or DZ twins. Twin studies are research studies that compare DZ with MZ twins, or twins raised apart with twins raised in the same home. Twin studies are an extremely valuable tool to help separate the influence of genetics, environment, and the interactive effect of genetics and environment on a multitude of disease conditions, behavioral disorders, and personality traits.
Immune response to vaccine: Studies of twins in the development of vaccines helps determine the role of genetics and environment in differences in immune response to vaccination, side effects from vaccination, and the occurrence of diseases preventable with vaccines.
Genetic influences on brain structure: Brain imaging studies involving twins help provide a better understanding of the genetic influences on human brain structure. Data from twin studies suggest that differences in brain volume are genetically influenced, with inherited effects being most pronounced in the volumes of the frontal lobe, which is involved in impulse control, delayed gratification, long-term planning, and the hippocampus, which is involved in memory. Environmental factors influence the volume of several areas in the interior of the brain.
Fetal origin of adult disease: A negative influence on the developing fetus may have lasting or lifelong effects on the person, and the fetal origins of adult disease have been evaluated in twin studies. Although people with lower birth weights have a higher risk of cardiovascular disease as adults, the reason for this is uncertain. Twin studies allow the opportunity to compare shared factors with factors affecting the individual fetus. Comparison of findings in MZ (identical genes) versus DZ (some gene overlap) twins may shed light on the role of genetic factors in the development of cardiovascular disease.
Individual differences in disease risk: Family, twin, and adoption studies can provide evidence for family and genetic influences on individual differences in disease risk and behavior. Studies attempting to find individual genes have been only modestly helpful, and known genes account for only a small percentage of the heritability of most traits and diseases. Ongoing research involving twin and twin-family studies (twins reared apart) will allow a more detailed understanding of the interaction between genes and environmental conditions. These studies will provide a more detailed understanding of how disease and behavioral risk factors develop, especially with regard to mental illness and substance abuse.
Type 1 diabetes: Because type 1 (childhood-onset) diabetes is caused by multiple factors, twin studies can help define the contribution of genetic and non-genetic factors to the development of this disease. The immune system is now believed to play a prominent role in the development of this disease. Preliminary work suggests that the persistence and magnitude of abnormal immune responses in cells and surrounding cells are significant disease predictors and can also identify twins who have protective factors from a disease.

Implications

Many research studies on disease causation attempt to "match" the study subjects on as many characteristics as possible. These studies are called matched control studies. In the study of human behavior, twins, especially monozygotic (MZ) twins, represent the ultimate matched control, and twin studies are a common research tool because they allow the investigator to separate the environmental and genetic influences on many traits, including aggression, intelligence, schizophrenia, and alcohol dependence. These results can help tailor interventions, education, and prevention initiatives.
Because of the presumed contribution of inherited and environmental factors in the development of behavioral and psychological disorders, psychiatric conditions lend themselves well to twin studies. Twin research has shown a strong genetic contribution to Alzheimer's disease, bipolar disorder, schizophrenia, and childhood autism. Studies have also found a weaker genetic contribution to depression, anxiety, psychosomatic disorders (conditions with no apparent biological cause), and alcohol abuse.
Data from registers of twin studies can be used to obtain insights into the genetic epidemiology of complex traits and diseases; to study the interaction of genotype with sex, age, and lifestyle factors; and to study the causes of co-occurrence between traits and diseases.

Limitations

The two main types of twins are identical twins, also called monozygotic or MZ twins, and fraternal twins, also called dizygotic or DZ twins. Twins may not be representative of a typical singleton (a single birth) pregnancy. MZ twinning itself appears to be an abnormality and is associated with an increased number of spontaneous abortions and structural birth defects. Also, both MZ and DZ twins have growth rates that slow at 30 weeks in the uterus and might be programmed earlier in pregnancy to have different responses during and after birth compared with singletons.
The assumptions that underlie twin studies, especially the assumption that DZ and MZ twins raised in the same home experience the same environment, have been questioned by some researchers. There is some evidence suggesting that parents, teachers, peers, and others may treat identical twins more similarly than fraternal twins.
Results from different twin studies have, in some cases, not been in agreement. Some of these differences may be due to developmental differences in the cause of the disease or condition being studied, and measurement issues.

Future research

The two main types of twins are identical twins, also called monozygotic or MZ twins, and fraternal twins, also called dizygotic or DZ twins.
Research designs and methods that study twins are valuable tools to examine how genetics and environment influence the behavioral and medical characteristics of a person. Twin studies have already provided valuable information on learning disabilities, personality and temperament, attitudes, mental illness, and social behavior. Future research will increase the understanding of these complex characteristics.
Monochorionic DZ (MC DZ) twins are very rare in natural pregnancy. Monochorionic means that the twins share one fetal membrane or chorion. Large-scale research on the prevalence of MC DZ twins associated with assisted reproduction techniques, and long-term follow up of these twins are essential to understand this condition.
The zona pellucida (ZP) is the outer coating of the human egg. The role played by the ZP in the development of some cases of human twinning is not completely understood. However, an association has been proposed between ZP manipulation through in vitro fertilization and the incidence MZ twins. Future research will provide more information on this relationship.
The completion of the Human Genome Project and the innovations introduced in biotechnology research are changing how twins will be studied. The use of microarrays, an orderly arrangement of high numbers of probes (DNA, RNA, or proteins) immobilized onto a matrix, allows a global analysis of gene expression and therefore might point out the molecular mechanisms of differences between MZ twins, such as non-genetic factors influencing genes. The application of microarrays to twin studies will help define the role of genes and environment in the development of human diseases, in turn suggesting new diagnostic and therapeutic approaches.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

American College of Obstetricians and Gynecologists. .
American Society for Reproductive Medicine. .
California State University at Fullerton. .
Hoekstra C, Zhao ZZ, Lambalk CB, et al. Dizygotic twinning. Hum Reprod Update. 2008 Jan-Feb;14(1):37-47. .
Jacobson RM, Ovsyannikova IG, Targonski PV, et al. Studies of twins in vaccinology. Vaccine. 2007 Apr 20;25(16):3160-4. .
Kaprio J, Pulkkinen L, Rose RJ. Genetic and environmental factors in health-related behaviors: studies on Finnish twins and twin families. Twin Res. 2002 Oct;5(5):366-71. .
Morley R, Dwyer T. Studies of twins: what can they tell us about the fetal origins of adult disease? Paediatr Perinat Epidemiol. 2005 Jan;19 Suppl 1:2-7. .
National Vital Statistics Reports. .
Natural Standard: The Authority on Integrative Medicine. .
Peakman M, Leslie RD, Vergani D, et al. Immunological studies on type 1 diabetes in identical twins. Arch Dis Child. 1993 Jul;69(1):97-9. .
Peper JS, Brouwer RM, Boomsma DI, et al. Genetic influences on human brain structure: a review of brain imaging studies in twins. Hum Brain Mapp. 2007 Jun;28(6):464-73. .
Rebar RW, DeCherney AH. Assisted reproductive technology in the United States. N Engl J Med. 2004 Apr 15;350(16):1603-4. .
Reddy UM, Branum AM, Klebanoff MA. Relationship of maternal body mass index and height to twinning. Obstet Gynecol. 2005 Mar;105(3):593-7. .
World Health Organization (WHO). .