Introduction

Twin gestations still face greatest challenges in obstetric attention and foetal medical specialty today. Much is known about the diseases by analyzing the development of babies who have shared the same fetuss. Pregnancies happening with twins have a higher incidence of preterm labor. abortion and foetal decease when compared to individual gestations.Non-identical twins( dizygotic. binovular. fraternal. or dizygous ) consequence from the fertilisation of two independently released ova by two different sperm. Their familial make-up is every bit dissimilar as one would anticipate between siblings. All these twins possess separate amniotic sac pouch.

Whereas.indistinguishable twins ( monozygous. uniovulate. monozygotic ) arise from the splitting of a individual fertilized egg within the first 14 yearss after fertilisation. Monozygous twins. depending on the timing of embryologic cleavage. may be dichorionic diamniotic ( d1–3 ) . monochorionic diamniotic ( MCDA ) ( d3–8 ) . monochorionic monoamniotic ( d9–12 ) . or conjoined. when cleavage of the embryo occurs on twenty-four hours 12 or beyond ( Farah Siddiqui. 2007 ) . Monozygotic twins although. considered genetically indistinguishable. but there may be a important phenotypic discordance particularly in the psychiatric diseases like schizophrenic disorder and bipolar upset. ( Mario F. Fraga. 2004 )

The history behind utilizing Twinss to look into the function of heredity and environment in human life caputs back to 19^Thursdaycentury. Francis Galton. Charles Darwin cousin was the first research worker to believe of this. Since. so twins are been considered as facets of survey in biological science. medical specialty and psychological science.

Galton thought that since twin braces ( both indistinguishable and non-identical ) portion the same environment. there will be greater coordination of the familial factors in the disease in genetically indistinguishable twins compared to non indistinguishable twins. But. by contrast. similar coordination rates for a disease in twins braces ( both indistinguishable and non-identical ) . or differences between the indistinguishable twins. suggest that the disease is likely due to non-genetical factors.

Twin surveies have been many times used to gauge the impact of familial factors on the disease cause. It is believed that a familial consequence is suggested when the concordinance rate is indistinguishable twins exceeds that in nonidentical twins. The concordinance rate in the both indistinguishable and nonidentical twins in population based surveies suggested that in instance of multiple induration there is 27 % happening compared of the latter which is 3 % . Similarly. Rheumatoid arthritis happening in former in 12. 3 % compared to the latter which is 3. 5 % .

Whereas in systemic lupus erythematosus the harmony rate in nonidentical twin was nil compared to the indistinguishable twin. where the rate were 33 % ( Marco Salvetti. 2000 ) . Twin surveies besides have the possiblity of assesing other applications in the appraisal of facets of possible relevancy in the pathogenesis of autoimmune diseases. There are possible precipitating factors of autoimmune conditions that await definition including epigenetic effects due to DNA aor protein alterations. the accretion of bodily mitochondrial Deoxyribonucleic acid mutants. X chromosme incativation and the transcriptionally active endogeneous retroviral sequences presence ( Marco Salvetti. 2000 ) .

This part discusses the difference in the monozygous twins in which factors like the timings of monozygous duplicating. lingual differences and the familial mechanism are discussed. There are many differences observed among duplicate braces like mirror twinning. hair oculus. and finger prints etc. without any known grounds or in other word we have really limited apprehension of why these sort of differences arises? . In instance of mirror duplicating about 25 % of twins have differences and most common is handedness where both twin used different manus for peculiar intent. The difference due to any unknown mechanism is besides included.

The biggest challenge faced by research workers for measuring familial footing of complex disease is to place little figure of cistrons responsible for disease among 1000s of cistrons present in whole genome in add-on to that environmental consequence makes task more hard. Thus development of ideal theoretical account system to look into familial footing of disease becomes primary demands. In the following some of the instance surveies where twins were used as theoretical account system for explain familial bases of diseases are discussed including factors like unsusceptibility. leukaemia. infective and autoimmune diseases.

A `corpus`

Mechanisms for differences in monozygous twins:

In general perceptual experience Monozygous ( MZ ) twins are physically and genetically indistinguishable. Similarly. clinical finding of zygosity relies on the premise that any physical differences between a brace of twins imply they are dizygotic. As per the other perceptual experience dizygotic twins portion about 50 % of the same cistrons. whereas monozygous twins portion 100 % .

But promotion in molecular techniques and apprehension of genetic sciences of twins puts several inquiry Markss on above reference perceptual experience as there are many exclusion sing familial composing and physical visual aspect of glandular fever and dizygous twins. There are many Numberss of intrauterine effects and other mechanisms that may ensue in phenotypic. genotypic. and epigenetic differences between monozygous twins. Some of those mechanisms are as follows.

• Timing of monozygous twinning:

Monozygous ( MZ ) duplicating occurs when individual fertilized egg give rise to two separate embryos and timing of this separation decides the station zygotic differences in approaching twins. As early the separation there will be less similarity and late the separation there will be more similarity. During development if the two embryos are separated at latter portion most of the distinction processes completed before they separate and therefore both offspring have similar beginning.

The utmost illustration of late twining is twins holding common bodily organ ( Conjoined twins ) . While in instance of early separation the procedure of distinction occurs independently which leads to creative activity of differences among of springs. If twining occurs 8 yearss after the fertilisation and before 12^Thursdaytwenty-four hours the twins are rather indistinguishable to each other and called as monozygotic twins comprises of about 5 % of entire twins.

• Familial mechanisms:

It is widely believed that monozygotic twins are genetically indistinguishable and any differences among them are consequence of environmental influence. But there is an ever-growing organic structure of grounds that monozygotic twins are non ever genetically indistinguishable. A figure of phenotypic fluctuations in monozygotic twins have been demonstrated to be caused by familial differences entirely and non act upon by ante-natal environmental factors. In add-on epigenetic alterations in peculiar sets of cistron within a monozygotic twin brace leads to change look and therefore contribute towards differences. ( Paul Gringrasa. 2001 ) .

Genetically monozygotic twins can be different at the degree of chromosome ( figure or morphology of chromosome ) or DNA ( mutant. epigenetic alteration ) . At chromosome degree fluctuation classical illustration is gender difference and certain diseases like Turner syndrome ( XYY ) this is chiefly happened due to early station zygotic mitotic mistake. ensuing in heterokaryotic twining that involves nondisjunction or anaphase slowdown of the Y chromosome.

While at DNA degree there are chiefly three mechanisms by which differences arises for illustration differential methylation of CpG island leads to inactivation or activation of peculiar cistron and which contribute in doing differences among monozygotic twins. Not merely that. this procedure of methylation is cardinal factor for inactivation of whole X chromosome and many X-linked diseases like fragile-X. coloring material sightlessness. are consequence of this inactivation. Similarly station zygotic mutant leads to emergence of differences among monozygotic twins.

• Differences due to some unknown mechanism:

There are many differences observed among duplicate braces like mirror twinning. hair oculus. and finger prints etc. without any known grounds or in other words we have really limited apprehension of why these sorts of differences arises? In instance of mirror duplicating about 25 % of twins have differences and most common is handedness where both twin used different manus for peculiar intent.

The ground behind this was thought to be due to asymmetry of intellectual hemisphere laterality. Similarly. hair and oculus coloring materials were know to be the designation grade for dizygous twins but now it was realized the there are many cases where the differences were observed in MZ excessively. The ground behind these differences are non good understood and thought to be due to complex familial interaction and station zygotic mutant.

• Linguistic differences:

Twin based heritability estimations for linguistic communication seldom exceeds 0. 6 and for monozygotic twins in many cases they were found to be really different. In add-on to that it was found that MZ are more likely to endure lingual hold and damage than singletons. There are many factors which affect or create these differences like familial. epigenetic and antenatal environmental factors. Meta-analyzed information from about 100 duplicate surveies indicate that depending on what facet of linguistic communication is assessed. heritable factors account for between 1/2 to 2/3’s of the discrepancy in language- impaired twins’ lingual abilities and 1/4 to 1/2 of the discrepancy in normal twins’ lingual abilities.

These meta-analyses besides reveal that for both linguistic communications impaired and normal twins ( Stromswold. 2006 ) . The major contributory factors among perinatal environmental conditions are low birth weight. premature birth. Placental and amnionic complications. Intrauterine infections. neonatal hyperbilirubinea. encephalon hurts to linguistic communication country etc. likewise post natal factors includes linguistic communication input. parental function etc. There are no good documented familial factors act uponing the linguistic communication in isolation and ever studied in visible radiation of environmental influence.

Twinss and genetic sciences and diseases:

The biggest challenge faced by research workers for measuring familial footing of complex disease is to place little figure of cistrons responsible for disease among 1000s of cistrons present in whole genome in add-on to that environmental consequence makes task more hard. Thus development of ideal theoretical account system to look into familial footing of disease becomes primary demands. The survey of twins become cardinal phase for this sort of probe for illustration in instance of non-identical twins there are some similarity like age. household environment and background environmental fluctuation while they have different familial make-up. Provides first-class tool to determined consequence of familial make-up on diseases.

While in instance of indistinguishable twins. similarity in familial make-up provides research workers with ways to insulate the map of single cistrons involved in disease together with attacks to understanding how cistrons and the environment interact. Followings are some of the instance surveies where twins were used as theoretical account system for explain familial bases of diseases. ( Alex J. MacGregor. 2000 )

• Twinss and unsusceptibility:

Immunological upsets are some of the widely observed phenomenon and about 5 % of entire population is enduring from these upsets. including insulin-dependent diabetes mellitus ( IDDM ) . multiple induration ( MS ) . and arthritic arthritis ( RA ) . systemic lupus erythematosus ( SLE ) . ancylosing spondylitis ( AS ) and celiac disease. Strong correlativity between familial make-up and immunological upset were established based on assorted twins’ surveies.

Here in this peculiar instance the complexness of disease and engagement of familial every bit good as environmental factors makes duplicate surveies a right system for probe where research workers can repair one parametric quantity ( familial make-up in instance of indistinguishable twins ) and other variable to measure consequence of other factor ( i. e. environment ) . Initially familial and environmental factors are both thought to lend to the pathogenesis of immune-mediated diseases. But after employment of twins based survey strongly rejected the above statement and clearly demonstrated that environment is the major subscriber towards immune disease. Twins survey demonstrated that the bulk of indistinguishable twins with an autoimmune disease have an unaffected twin ( Table 1 ) .

Table 1. Harmony rates in indistinguishable and non-identical twin braces in population-based

Surveies of immune-mediated diseases

Disease	Identical twin braces ( % )	Non Identical twin braces
Multiple sclerosis	26. 7	3. 5
RA	12. 3	3. 5
Type i diabetes	13	2. 5
Systemic lupus erythematosus	33	0

( Marco Salvetti. 2000 )

In some instances ab initio unaffected twin may develop the clinical disease some old ages after the index twin. but that was non statistically important. As the bulk remain unaffected on prospective survey. But one should retrieve that even indistinguishable twins can differ genetically for illustration X-chromosome inactivation in females. And differential methylation of CpG Island leads to look of wholly different sets of cistrons.

Similarly there are several bodily rearrangement occurred during T cell receptor development and antibody production and therefore differential disease susceptibleness in indistinguishable twins may be due to consequence of non familial ( epigenetic ) factor on familial. Similarly. one should observe the fact that observed frequence of peculiar disease ( table1 ) found to be more in instance of indistinguishable twins compared to non indistinguishable twins clearly indicates function of familial factor. In decision for immune diseases environmental factors play major function in visible radiation of familial background.

• Twinss and Leukemia:

The first study of accordant leukaemia in duplicate kids appeared in the German literature in 1882 and so after many studies came in similar lines. Most of these surveies indicated that there is about 5-15 % harmony rate among monozygotic twins and there are important differences observed in instance of different type of leukaemia and age.

But surprisingly in instance of grownup twins the concordant was found to be less than 1 % which clearly indicated antenatal beginning of disease. The hazard appraisal of likelinesss of happening of disease in carbon monoxide twin is non rather accurate but they can be consider as sensible usher and nearing 100 % for baby while hazard of the order of 1 in 10 for older kids. This appraisal is valid for monozygotic twins and those who have monochrorionic placenta. ( Mel F. Greaves. 2003 )

• Twinss and infective diseases:

There are several observations that clearly indicate infective diseases have an familial component. and persons respond otherwise to peculiar infections. The behaviour of infective agents can change so greatly between strains that the effects of single Variation are best seen when the same strain of an being at the same time infects antecedently unexposed persons. Twin surveies have compared the disease position among indistinguishable and non-identical twins. with the outlook that disease harmony will be higher in indistinguishable twins for a disease with a genetically determined constituent. ( Table 3 ) .

Even though there are legion surveies carried out to place major cistron responsible for diseases susceptibleness there was no clear image appears for the same. The major part for diffrential suceptibility of infective disease came for fluctuation in HLA ( major histocompatibility composite ) . T cell recptor and diffrential V-D-J recombination among twins. The environmental factor here played really important function.

Table: 3 Table picturing the harmony of disease per centum in both Monozygotic and Dizygotic twins. conformity to the state. ( Hill. 2001 )

Disease	Concordance*
State	MZ ( % )	DZ ( % )
Tuberculosis	Germany USA United kingdom	65 62 32	25 18 14
Leprosy	India	52	22
Poliomyelitis	USA	36	6
Hepatitis B	Taiwan	35	4

Possibility of twins holding twins:

Birth of Identical or monozygotic twins dose non run in to the household but non identical of dizygous twins have some heridetory influence. Thyminehe chief ground behind this is monozygotic twins are developed from individual fertilized egg while non indistinguishable twins develop from two egges shed by ovary. The procedure of egg casting have familial manifestation and observed in adult female holding household history of twins. In decision. a female parent of fraternal twins is 3-4 times more likely to hold another set of fraternal twins. A adult female who is an indistinguishable twin is no more likely to hold twins compared to person else anticipating.

Decision:

Twinss were consider to be an ideal theoretical account system to understand influence of familial and environmental factors on assorted facet of human life including diseases susceptibleness. metamorphosis. societal behaviour. IQ. personality. lingual proficiency. Behavior etc. But the biggest challenges were to understand influence of single factors on overall development of twins.

In ideal status MZ twins considered to be genetically and physiologically indistinguishable but there are many exclusions and that is chiefly Due to post zygotic mutant and epigenetic influence along with good studied environmental factors. Similarly Immunity and disease susceptibleness is chiefly influence by environment and partially by familial factor. For certain diseases like malignant neoplastic disease. preventative steps should be taken in instance of one of the twin diagnosed with disease. as opportunities of outgrowth of same disease in co-twin are high.

If the potency of duplicate surveies is to be realized there should be strong coaction between clinician. scientist and information direction bureau. Till recent past the chief accent were given to familial and environmental factors for any differences among twins. But development of newer engineering based on molecular biological science alterations our perceptual experiences. The epigenetic factors emerge as cardinal subscriber towards oncoming of physiological alterations among twins at old age. Careful probe along with new engineering makes duplicate surveies more utile with conclusive reply of assorted jobs.

Bibliography

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Farah Siddiqui. A. M. ( 2007 ) . Twins. OBDTETRICS. GYNAECOLGY AND REPRODUCTIVE MEDICINE. 289-295.

Hill. G. S. ( 2001 ) . GENETICS OF SUSCEPTIBILITY TO HUMAN INFECTIOUS DISEASE. NATURE REVIEWS GENETICS. 967-977.

Marco Salvetti. G. R. ( 2000 ) . Twinss: mirrors of the immune system. IMMUNOLOGY TODAY.

Mario F. Fraga* . E. B. ( 2004 ) . Epigenetic differences arise during the life-time. Proceeding OF NATIONAL ACADEMY OF SCIENCES. 10604-10609.

Mel F. Greaves. A. T. ( 2003 ) . Leukemia in twins: lessons in natural history. BLOOD. 2321-2331.

Paul Gringrasa. . . W. ( 2001 ) . Mechanisms for differences in monozygous twins. Early HUMAN DEVELOPMENT. 105-117.

Stromswold. K. ( 2006 ) . Why aren’t indistinguishable twins linguistically indistinguishable? Genetic. prenatal and postpartum factors. COGNITION. 333-386.