Genetics of Twins: Dizygotic and Monozygotic Twins

In this article we will discuss about the dizygotic twins and monozygotic twins.

Twins can be either dizygotic (fraternal) or monozygotic (identical). Dizygotic twins are the result of two different ova fertilized by two different sperm. Monozygotic twins are the result of one ovum fertilized by one sperm that divides to form two embryos. In the past, the only way of differentiating between monozygotic and dizygotic twins at birth was their sex and appearance.

If the twins were of unlike sex, they are said to be dizygotic and if they were like-sexed and looked identical, they are said to be monozygotic. But this is not reliable. Today sex, placentation cord, blood type, HLA antigens and DNA fingerprinting are all used to differentiate between Monozygotic and Dizygotic twins.

However, DNA fingerprinting has become the only accurate method to dif­ferentiate between Monozygotic and Dizygotic twins. The monozygotic twins are genetically identical and any discordance between them is due to environmental influences whereas diffe­rences within dizygotic twin pairs are likely to be a combination of genetic and environmen­tal factors.

Both monozygotic and dizygotic twins are known to have an increased risk of structural defects compared to the singletons. Structural defects in monozygotic twins however, are three times more frequent than among dizy­gotic twins and approximately 2-3 times more frequent than in single-tones.

The incidence of monozygotic twins is thought to be constant throughout the world. By contrast, the incidence of dizygotic twins varies from population to population with a higher prevalence in some areas like Nigeria, and lower prevalence in other areas, as in Japan.

The prevalence of monozygotic twins in remarkably constant and has not been observed to be affected by environmental or maternal factors. Ultrasound studies done early in pregnancy have shown that at least 10% of twin pregnancies are either lost early in pregnancy by miscarriage or are reduced to singletons.

Several studies have confirmed that the number of twins at delivery is considerably less than the number of twins conceptions seen on ultrasound examinations in early preg­nancy. Some of the mechanism that have been suggested for the vanishing twin include vascular compromise, life threatening malfor­mations, or spontaneous mutations incompat­ible with life.

Dizygotic Twins:

Their gentic contribution is different since it comes from two diffe­rent ova and two different sperm. Dizygotic twining is a common occurrence in animals. Mammals are known to have sizable litters, generally due to poly-ovulation, making every member of a litter a dizygotic twin.

Dizygotic twins produced by the fertilization of multiple ova may be result of superfecundation and it occurs when two different ova are fertilized by two different sperm in more than one act of coitus, either during one ovarian cycle or in subsequent cycles. Dizygotic twins may also arise from superfetation. Superfetation occurs when a second fertilized ovum implants in a uterus already containing a pregnancy of at least one month.

Superfetation has been suggested in some cases in whom the twins are markedly discordant for birth weight sup­posedly due to different gestational ages. Polar body twins are other types of dizygotic twins, thought to arise from the simultane­ous fertilization of the meiotic product of the same primary oocyte—the oocyte and the polar body—by two different spermatozoa.

All most all dizygotic twins have two pla­centas, two chorions and two amnions, i.e., be diamniotic and di-chorionic. However these two may fuse and look like one. The highest dizygotic twining rate is seen in the black populations (Africans) and lowest in Asian populations. But dizygotic twining rate is closely related with maternal age, pari­ty, height, weight and also on gonadotropin levels.

Tall and heavy women are more likely to give birth to dizygotic twins than are short and thin women:

There are many reports of familial dizy­gotic twining and the female members of these families are thought to have an inherited pre­disposition to multiple ovulation and in turn have a higher number of dizygotic twin pairs when compared to general populations.

Monozygotic Twins:

These are also known as identical twins and are the result of the fertilization of one ovum by one sperm. The single fertilized ovum then divides into two embryos; both embryos are thought to have the same genetic contribution.

The major cause for the monozygotic twining in human is still unknown, however several mechanisms have been proposed, which are:

(1) Lack of O₂ prior to implantation which caused developmental arrest and splitting in the zygote

(2) Delayed implantation

(3) Disturbances in the developmental clocks

(4) Delayed fertilization

(5) Rupture of zona pellucida

(6) Congenital anomaly or an abnorma­lity in development

(7) Discordance in the expression of genetic information like X-inactivation’s, imprinting, uniparental disomy, changes in the chromosome number and also mitochondrial mutations.

The incidence of monozygotic twins is constant throughout the world and it is about 3-4/1000 births. The rate of monozygotic twining appears to be unaffected by maternal age, parity, height or weight. But a few families have been reported in which monozygotic twining occurs more frequently than expected. This has been termed as “Familial monozygotic twining” and it is generally inherited from both the maternal and paternal side of the family.

It has also been suggested that this is due to a single gene effect which is unaffected by the sex of the parent transmitting gene. Monozygotic twins are known to have a higher incidence of all types of congenital anomalies and some of them are very unique to the monozygotic twining process itself.

These anomalies are:

The sex ratio, i.e., the proportion of males to the combination of males and females—among monozygotic twins is lower than among dizygotic twins or singletons. Conjoined twins have an even lower sex ratio than that of monozygotic twins. Female con­ceptions may be at higher risk of late splitting of the embryo.

Twin Study and Multifactorial Inheri­tance:

Most quantitative traits behave in a more complex manner. The trait may be influenced not only by multiple genes but also by envi­ronmental factors. There may, in addition, be interactions among genes and between genes and the environment. How, then, can the con­tribution of genetic factors be dissected out? One of the most powerful tools for doing this is the twin study. Comparison of the concor­dance of a trait in identical twins with fraternal twins or full siblings is a powerful way to define the degree to which a trait is genetically deter­mined.

For a single gene trait with complete penetrance, identical twins will, of course, be fully concordant. Siblings will be concordant less often, depending on whether they both inherit the mutant gene. For a non-genetic trait, concordance will be the same in identical twins or in full siblings and will depend on the degree of similarity of their exposure to envi­ronmental or other factors that determine the trait.

For a multifactorial trait concordance in identical twins will be greater than for siblings but not to the extent of a single gene trait with complete penetrance. The degree of concor­dance in monozygotic twins versus dizygotic twins or full siblings provides a measure of the contribution of genetic factors to the trait.

Twin studies have helped to identify genetic contributions not only to congenital anomalies but also to common disorders such as hyper­tension, asthma and diabetes.

Some example of concordance rate for congenital common anomalies in identical and non-identical twins is given below:

Though powerful, twin studies are limited by the relative scarcity of identical twins who have a trait of interest, a problem that has been partly addressed through the develop­ment of twin registries. Another limitation is that twins share not only genetic identity but also some common environmental exposures, beginning with having developed in the same of identical twins.

These offspring are the uterine environment. Studies of twins separated at birth control for post-natal environmental effects but not for prenatal effects. Another environment, approach has been to compare the offspring Identical twins. These offspring are the equivalent of half siblings and share half their genes, yet they are born and raised in different environment.