Plantar pressures in identical and non-identical twins

Identifying environmental risk factors for musculoskeletal disorders is challenging due to the number of potential confounders. Twins are of particular interest for researchers interested in studying these types of problems due to their inherent control for the influence of genetic factors. In twin studies, this population can allow environmental risk factors to be more easily identified, and this type of study design may allow the role of biomechanics in injury and disease to be further explored. At present, it is unclear if foot function displays more similarity between certain types of twins. In this study, we hypothesized that the plantar pressures of monozygotic (identical) twins would be more similar between pairs than dizygotic (non-identical) twins. We measured static and dynamic plantar pressures from five pairs of each twin type. Statistical parametric modeling was used to compare pressure distributions at the sensor level. For >80% of stance phase, the pixel level analysis indicated that monozygotic twins had less variation in plantar pressure between pairs. The average z-statistic across the entire trial was 0.88 for the monozygotic group and 1.13 for the dizygotic group. In this study we provide evidence of greater similarity of plantar pressures in monozygotic twin pairs compared to dizygotic twins. This finding supports the use of co-twin studies investigating potentially modifiable environmental and biomechanical risk factors for musculoskeletal conditions that affect the foot and ankle.     

Genetic determination of the human EEG

Summary In this article, we have discussed recent progress in quantifying the genetically determined component of the resting EEG. This progress has been made possible in particular by the application of advanced information processing techniques such as supervised learning, and the development of a problem-oriented similarity concept. Our work aimed at modeling previous findings regarding the distinct individuality of human brain-wave patterns, the high similarity between the EEGs of monozygotic twins, and the average within-pair similarity of dizygotic twins. Thus, we had three objectives: First, we wanted to improve the quantification of EEG characteristics with respect to reproducibility and specificity by means of adaptive procedures and repeated measurements. Second, we wanted to compare the typical within-subject EEG similarity with the typical within-pair EEG similarity of monozygotic and dizygotic twins brought up together. Finally, we were interested in the degree to which environmental factors affect the characteristics of human brain-wave patterns. Our investigations were based on the empirical data derived from five different populations: (1) 81 healthy subjects, (2) 24 pairs of monozygotic twins brought up together, (3) 25 pairs of dizygotic twins brought up together, (4) 28 pairs of monozygotic twins reared apart, and (5) 21 pairs of dizygotic twins reared apart. Following our similarity conception, repeated measurements on the set of 81 individuals were used as design samples, and new registrations from the same individuals taken 14 days later were referred to as test samples in order to develop the appropriate method and to determine all required calibration parameters. This specific approach allowed us to construct EEG spectral patterns which, with a specificity and reproductibility of>90% each, largely met the requirements of genetic EEG studies. Hence, we were able systematically to investigate the within-pair EEG similarity of our twin samples. Our results provided ample evidence that the individual characteristics of the resting EEG are primarily determined by genetic factors: (1) There exists an almost perfect one-to-one mapping between each individual and his EEG; (2) monozygotic twins proved, with respect to their resting EEGs, to be only slightly less like one another (if there is any difference at all) than each person is to himself over time; (3) the average within-pair EEG similarity estimated from a sufficiently representative sample of dizygotic twins is significantly above the inter-individual EEG similarity between unrelated persons (this finding holds true for both samples of dizygotic twins brought up together and reared apart, and there is also no statistically significant difference in the resting EEG between these two samples) and, (4) the EEGs of monozygotic twins reared apart are obviously as similar to each other as are the EEGs of the same person over time, and there is no statistically significant difference in the resting EEG between the two populations of monozygotic twins brought up together and monozygotic zygotic twins reared apart.     

The Development of Francis Galton's Ideas on the Mechanism of Heredity

Galton greeted Darwin's theory of pangenesis with enthusiasm, and tried to test the assumption that the hereditary particles circulate in the blood by transfusion experiments on rabbits. The failure of these experiments led him to reject this assumption, and in the 1870s he developed an alternative theory of heredity, which incorporated those parts of Darwin's theory that did not involve the transportation of hereditary particles throughout the system. He supposed that the fertilized ovum contains a large number of hereditary elements, which he collectively called the “stirp,” a few of which are patent, developing into particular cell types, while the rest remain latent; the latent elements can be transmitted to the next generation, while the patent elements, with rare exceptions, cannot since they have developed into cells. The problem with this theory is that it does not explain the similarity between parent and child unless there is a high correlation between latent and patent elements. Galton probably came to realize this problem during his subsequent statistical work on heredity, and he quietly dropped the idea that patent elements are not transmitted in Natural Inheritance (1889). Galton thought that brothers and sisters had identical stirps, and he attributed differences between them to variability in the choice of patent elements from the stirp, that is to say to developmental variability. He attributed the likeness of monozygotic twins to the similarity of their developmental environment. Galton's twin method was to track the life history changes of twins to see whether twins who were similar at birth diverged in dissimilar environments or whether twins who were dissimilar at birth converged in similar environments. It is quite different from the modern twin method of comparing the similarities between monozygotic and dizygotic twins, on the assumption that monozygotic twins are genetically identical whereas dizygotic twins are not. It has been argued that Galton foreshadowed Weismann's theory of the continuity of the germ-plasm, but this is only true in a weak sense. They both believed that the inheritance of acquired characters was either rare or impossible, but Galton did not forestall the essential part of Weismann's theory, that the germ-plasm of the zygote is doubled, with one part being reserved for the formation of the germ-cells. This revised version was published online in July 2006 with corrections to the Cover Date.     

The color and structure of the human iris. 2. Studies of 200 twins]

Subject of the present report is an investigation of the heredity of 30 iris characteristics. The material basis of this sample of twins (100 monozygotic and 100 dizygotic pairs), the largest ever taken as a basis for the purpose of iris research, consists of standardized colour photographs of the examined persons' irises and iris-microscopic observations. The pairs of twins are compared to 100 non-related casual pairs in order to render a better estimation of the degree of heredity of the features possible. On every occasion several classes were constituted for the concordance verification. These classes result from the number of the classes of the forms of markedness and present different levels of similarity. The different distribution of the twin pairs and the control pairs on the concordance classes are always examined for their statistical significance, and for each group of pairs a concordance value is computed. The intervals between the concordance values of the monozygotic and dizygotic pairs and the control pairs indicate the degree of heredity of the investigated feature. Taking all the compiled factors and conditions into consideration, an evaluation of the features as heredity features is made. Though a hereditary component can be observed for all iris characteristics, only about a third could be called heredity features. Quantity of pigment and the hitherto undescribed limiting layer folds were evaluated as "very good", whereas pigment colour in the fine analysis, quality of the anterior stroma leaf, frequency of iris crypts and iris frill position were judged as "good". Tone of blue, markedness of Woelfflin nodules, quantity and markedness of contractional rings could be evaluated as "moderately good" as to their heredity. On the basis of the prior concordance investigations for each of the 300 pairs, a "similarity index" and a "concordance index" were computed in order to arrive at evidence as to the degree of similarity of the single pairs; i.e. in order to detect the limits of the similarity between non-identical twins and the dissimilarity between identical twins. This concluding investigations lead to the question of the possibility of a diagnosis of genetic identicalness solely on the basis of the comparison of irises.     

X-ray anatomic features of the skeletons of twin children

The size of right and left middle phalanges in the II-V fingers and the III finger have been studied in 108 pairs of monozygotic and dizygotic twins at 8--19 years of age and in 60 paris (pedagogical experiment) of separated twins (from the same pair), schoolchildren of the 2d--5th forms trained according different programs of physical culture. A great similarity of osteometric signs has been stated in monozygotic twins. As to local (intradigital) differences, a prevalence of the IIId finger should be mentioned. Maximum of genetic determination is evident for transversal growth--under high mechanical loadings on the bones, for longitudinal--under low mechanical loadings. The data of the pedagogical experiment demonstrate that increased mechanical loading on the hand bones activates osteogenesis. According to the majority of indices the main is the "radial" (II--III fingers) type.     

The potential use of artificially produced monozygotic twins for comparative experiments

The uniformity of twins has been examined by assembling estimates of the intraclass correlation coefficient (rho(I)) available in the literature for a variety of parameters studied in cattle monozygotic twins and human dizygotic and monozygotic twins. The values of rho(I) vary considerably between parameters. In human monozygotic twins rho(I) is always larger compared to that found in dizygotic twins. There is insufficient evidence to determine whether artificial monozygotic twins are more uniform than natural monozygotic twins. A new measure of twin uniformity, given by T (3) = 1 (1-rho (I)) , is introduced. In practice 2T(3) gives the number of animals chosen at random that one member of a twin pair can replace without loss of statistical efficiency. A useful class of experimental designs for the exploitation of twin uniformity is incomplete block designs. These designs are defined by (v, k, b), where v is the number of treatments to be compared, k = 2, and b is the number of twin pairs. Each design has an associated efficiency (E). Provided rho(I)>1-E, an incomplete block design will be advantageous. In general, when only a few twin pairs are available, this relation will only hold for monozygotic and not dizygotic twins. Suitable arrangements of treatment comparisons for designs (3,2,8), (4,2,9), (5,2,10), (6,2,11) are presented.     

Familial monozygotic twinning: report of an extended multi-generation family.

Thirteen sets of monozygotic (MZ) twins from an extended multi-generation family are reported. Zygosity was determined by interviewing families for overall physical similarity and by assessment of facial photographs. A hypothetical gene was traced back five generations to a common grandfather. Familial monozygotic twinning in this pedigree is compatible with autosomal dominant inheritance with reduced penetrance. Other plausible mechanisms of inheritance are discussed.     

Zygosity misclassification of twins at birth in Japan.

Though twinning rates have been rapidly increasing in Japan, the problem of zygosity misclassification at birth has been paid little attention. By analyzing four independent samples, the authors found that at a constant rate about 25-30% of monozygotic twins were misclassified as dizygotic twins at birth. This percentage is in very good accordance with that of monozygotic twins having dizygous placenta. Generally the obstetricians informed twins' parents about their children's zygosity. The number of placentas, as informed by obstetricians, was very strongly associated with zygosity. Concluding, even now many monozygotic twins in Japan may be misclassified as dizygotic at birth by obstetricians based solely on the number of placenta.     

Intra-Monozygotic Twin Pair Discordance and Longitudinal Variation of Whole-Genome Scale DNA Methylation in Adults

Monozygotic twins share identical genomic DNA and are indistinguishable using conventional genetic markers. Increasing evidence indicates that monozygotic twins are epigenetically distinct, suggesting that a comparison between DNA methylation patterns might be useful to approach this forensic problem. However, the extent of epigenetic discordance between healthy adult monozygotic twins and the stability of CpG loci within the same individual over a short time span at the whole-genome scale are not well understood. Here, we used Infinium HumanMethylation450 Beadchips to compare DNA methylation profiles using blood collected from 10 pairs of monozygotic twins and 8 individuals sampled at 0, 3, 6, and 9 months. Using an effective and unbiased method for calling differentially methylated (DM) CpG sites, we showed that 0.087%–1.530% of the CpG sites exhibit differential methylation in monozygotic twin pairs. We further demonstrated that, on whole-genome level, there has been no significant epigenetic drift within the same individuals for up to 9 months, including one monozygotic twin pair. However, we did identify a subset of CpG sites that vary in DNA methylation over the 9-month period. The magnitude of the intra-pair or longitudinal methylation discordance of the CpG sites inside the CpG islands is greater than those outside the CpG islands. The CpG sites located on shores appear to be more suitable for distinguishing between MZ twins.     

Twin births to mothers who are twins: a registry based study.

OBJECTIVES: To estimate the risk of having twin infants for mothers who are twins; to investigate the genetic influence on twinning. DESIGN: Retrospective study of multiple births in two nationwide registries. SETTING: Sweden. SUBJECTS: Multiple births among 31,586 deliveries between 1973 and 1991 to women who were twins. MAIN OUTCOME MEASURES: Numbers of monozygotic and dizygotic twin births expected and estimated. RESULTS: Women who are dizygotic twins have a moderately increased risk of having twins (relative risk 1.30, 95% confidence interval 1.14 to 1.49) which seems to be completely the result of dizygotic twinning. When a mother is a monozygotic twin, her risk of having twins of the same sex is significantly increased (1.47; 1.10 to 1.97). This is the result of an excess of monozygotic twins (39 pairs estimated, 18 expected). CONCLUSIONS: Women who are twins have an increased risk of giving birth to twins. Genetic components of monozygotic and dizygotic twinning seem to be independent.     

A study of the occurrence of monochorionic and monozygotic twinning in the pig

In humans as well as in most farm animals, monozygotic twins have been described. Nevertheless, only a few reports of twinning in the pig have been published. It has been suggested that monozygotic twins are formed during the first 14 days of pregnancy. This monozygotic twin study includes the investigation of porcine monochorionic embryos from 76 sows at days 26–29 post-insemination (p.i.), as well as an examination of 10 whole litters at days 21–22 p.i. In the former group, 29% of the sows carried monochorionic embryos. Based on DNA profiling using microsatellite markers, one monozygotic twin pair was found among these embryos. In the latter group, three monozygotic twin pairs were identified. Thus, it can be concluded that although the occurrence of monozygotic twins in pigs is a sporadic event, the fusion of extra-embryonic membranes is relatively common.     

Twins and the paradox of dental-age estimations: A caution for researchers and clinicians

The biological age difference among twins is frequently an issue in studies of genetic influence on various dental features, particularly dental development. The timing of dental development is a crucial issue also for many clinicians and researchers. The aim of this study was therefore to verify within groups of twins how dental development differs, by applying Demirjian's method, Mincer's charts of development of third molars and two of Cameriere's methods for dental age estimation, which are among the most popular methods both in the clinical and the forensic scenario. The sample consisted of 64 twin pairs: 21 monozygotic, 30 dizygotic same-sex and 13 dizygotic opposite-sex with an age range between 5.8 and 22.6 years. Dental age was determined from radiographs using the mentioned methods. Results showed that dental age of monozygotic twins is not identical even if they share all their genes. The mean intra-pair difference of monozygotic pairs was low and similar to the difference in dizygotic same-sex twins; the maximum difference between monozygotic twins, however, was surprisingly large (nearly two years). This should lead to some circumspection in the interpretation of systematic estimations of dental age both in the clinical and forensic scenario.     

Steady-state plasma levels of nortriptyline in twins: Influence of genetic factors and drug therapy

Nineteen identical (monozygotic) and 20 fraternal (dizygotic) sets of twins between 45 and 51 years of age were given nortriptyline orally in doses of 0·2 mg./kg. body weight three times daily for eight days. The steady-state plasma concentrations of nortriptyline were calculated from the mean of the determinations for days 6, 7, and 8. Identical twins, not treated with other drugs, achieved similar steady-state plasma concentrations of nortriptyline in contrast to fraternal twins who were not given other drugs. The intrapair similarity in steady-state plasma concentrations was not found in identical twins simultaneously treated with various drugs during the experiment. Identical and fraternal twins treated with drugs containing barbiturates had considerably lower steady-state plasma concentrations of nortriptyline compared with untreated twins.It is concluded that most of the variability in nor-triptyline steady-state plasma concentration between persons who have not received drugs is genetically determined. Exposure to other drugs also influences the steady-state plasma concentration of nortriptyline, which in a given patient may therefore be determined by a resultant of genetic and environmental factors.     

Does higher concordance in monozygotic twins than in dizygotic twins suggest a genetic component?

It is widely regarded that twins can be used as a natural experiment to subject hypotheses to empirical testing regarding the contributions of genetic factors to phenotypic variability in human traits, especially behavioral traits. In genetic epidemiology, a higher concordance rate in monozygotic (MZ) twins than in dizygotic (DZ) twins is often taken as prima facie evidence for a genetic component. While twins studies have been used to estimate the contributions of genetic factors to phenotypic variability in human traits, the corresponding methodology that allows the estimation entails several crucial assumptions. The most critical is that MZ and DZ twins are equally similar environmentally. Although MZ twins are genetically more similar than DZ twins, they are often environmentally more similar. This paper demonstrates that, even in the complete absence of any genetic factor and of any biases, the greater environmental similarity alone in MZ twins can result in higher concordance rate in MZ twins than in DZ twins. This is especially true when there are multiple environmental factors, which may have multiple exposure levels and/or interact strongly, although each of them may be of low risk. This may serve as a sobering antidote to the uncritical reliance on twin studies without examining the validity of the underlying assumptions.     

Relation of the individual specificity of emotional autoregulation controlled by EEG feedback to the influence of a genetic factor as revealed by a twin study

On the model of biofeedback connection by the given parameters of the EEG alpha-rhythm the dynamics of bioelectrical and vegetative characteristics and correlative connections between them were compared in the pairs of mono- and dizygotic twins. More likeness in the dynamics of the studied parameters was found in the pairs of genetically identical monozygotic twins. There was a maximum increase of the objective similarity characteristics in the moment of activity realization, judging by the change of alpha-rhythm parameters. The obtained results testify to genetic determination of individual specific styles in organization of complex integrative processes of the higher nervous activity.     

Retrospective determination of chorion type in twins using a simple questionnaire.

This study investigates the validity of retrospective determination of chorion type by asking the question to the mother about the number of placentas. In the "East Flanders Prospective Twin Survey" (EFPTS), accurate information on the placentation and zygosity of the multiples was collected prospectively. The mothers of 231 monozygotic (95 dichorionic and 136 monochorionic) twins and 255 dizygotic twins were asked to fill in a simple questionnaire regarding 1). the zygosity and 2). the number of placentas of their twins. The accuracy of the response to the question on "the number of placentas" was 60% for monozygotic twins and 37% for dizygotic twins. The accuracy of the response to the question on the zygosity of the twins was 93% for monozygotic and 95% for dizygotic twins. If the questionnaire was used for the determination of chorion type, a total of 31 monozygotic twins (13%) should have been assigned as dichorionic on the fact that there were two separate placentas. Of these, 10 (32%) are monochorionic and 12 (39%) were falsely reported as having two placentas. We conclude from these findings that this simple questionnaire method is unreliable for the retrospective determination of the chorion type.     

The effects of chorion type on variation in IQ in the NCPP twin population.

The 7-year IQ scores (WISC) of 116 white and 143 black nonmalformed twins of known zygosity and placental type were ascertained from the NINCDS Collaborative Perinatal Project (NCPP). The type of chorion and zygosity had no significant effect on the mean IQ or among-pair variation. In white monozygotic twins, however, analysis of variance revealed a significantly greater within-pair mean square for dichorionic twins than monochorionic twins. On the other hand, the white dichorionic monozygotic (MZ) and dizygotic (DZ) within-pair mean squares were quite similar. These findings were not evident in blacks for either of the within-pair comparisons. In addition, estimates of genetic variance were dependent upon MZ chorion type in both races. These data suggest to us that (1) in white twin pairs dichorionic placentas are of greater influence than the similarity or dissimilarity of genomes with regard to intrapair IQ development, and (2) failure to consider chorion type may introduce a serious bias in the interpretation of genetic variance estimates of IQ variability.     

Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles

The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant or discordant phenotype by using two platforms for genome-wide CNV analyses and showed that CNVs exist within pairs in both groups. These findings have an impact on our views of genotypic and phenotypic diversity in monozygotic twins and suggest that CNV analysis in phenotypically discordant monozygotic twins may provide a powerful tool for identifying disease-predisposition loci. Our results also imply that caution should be exercised when interpreting disease causality of de novo CNVs found in patients based on analysis of a single tissue in routine disease-related DNA diagnostics.