The Host Genotype and Environment Affect Strain Types of Bifidobacterium longum subsp. longum Inhabiting the Intestinal Tracts of Twins

To investigate the influences of host genotype and environment on Bifidobacterium longum subsp. longum inhabiting human intestines at the strain level, six pairs of twins, divided into two groups (children and adults), were recruited. Each group consisted of two monozygotic (MZ) twin pairs and one dizygotic (DZ) twin pair. Child twins had been living together from birth, while adult twins had been living separately for 5 to 10 years. A total of 345 B. longum subsp. longum isolates obtained from 60 fecal samples from these twins were analyzed by multilocus sequence typing (MLST), and 35 sequence types (STs) were finally acquired. Comparison of strains within and between the twin pairs showed that no strains with identical STs were observed between unrelated individuals or within adult DZ twin pairs. Eight STs were found to be monophyletic, existing within MZ twins and child DZ twins. The similarity of strain types within child cotwins was significantly higher than that within adult cotwins, which indicated that environment was one of the important determinants in B. longum subsp. longum strain types inhabiting human intestines. However, although these differences between MZ and DZ twins were observed, it is still difficult to reach an exact conclusion about the impact of host genotype. This is mainly because of the limited number of subjects tested in the present study and the lack of strain types tracing in the same twin pairs from birth until adulthood.     

“14 and 6/sec positive spikes” im Schlaf-EEG von jugendlichen ein- und zweieiigen Zwillingen

Among 67 monozygotic twin pairs, 14 and 6 per second positive spikes were found concordantly in the sleeping EEG of 15 pairs, whereas 52 pairs showed negative concordance. Among 62 dizygotic twin pairs positive concordance could only be found in 3 pairs, while 44 pairs showed negative concordance, and 15 pairs were discordant.

---

---

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Genetic,Maternal and Placental Factors in the Association between Birth Weight and Physical Fitness: A Longitudinal Twin Study

Background

Adult cardiorespiratory fitness and muscle strength are related to all-cause and cardiovascular mortality. Both are possibly related to birth weight, but it is unclear what the importance is of genetic, maternal and placental factors in these associations.

Design

Peak oxygen uptake and measures of strength, flexibility and balance were obtained yearly during adolescence (10–18 years) in 114 twin pairs in the Leuven Longitudinal Twin Study. Their birth weights had been collected prospectively within the East Flanders Prospective Twin Survey.

Results

We identified linear associations between birth weight and adolescent vertical jump (b = 1.96 cm per kg birth weight, P = 0.02), arm pull (b = 1.85 kg per kg birth weight P = 0.03) and flamingo balance (b = −1.82 attempts to stand one minute per kg birth weight, P = 0.03). Maximum oxygen uptake appeared to have a U-shaped association with birth weight (the smallest and largest children had the lowest uptake, P = 0.01), but this association was no longer significant after adjustment for parental BMI. Using the individual twin’s deviation from his own twin pair’s average birth weight, we found positive associations between birth weight and adolescent vertical jump (b = 3.49, P = 0.0007) and arm pull (b = 3.44, P = 0.02). Δ scores were calculated within the twin pairs as first born twin minus second born twin. Δ birth weight was associated with Δ vertical jump within MZ twin pairs only (b = 2.63, P = 0.009), which indicates importance of placental factors.

Conclusions

We found evidence for an association between adolescent physical performance (strength, balance and possibly peak oxygen uptake) and birth weight. The associations with vertical jump and arm pull were likely based on individual, more specifically placental (in the case of vertical jump) factors. Our results should be viewed as hypothesis-generating and need confirmation, but potentially support preventive strategies to optimize birth weight, for example via placental function, to target later fitness and health.     

HLA and genomewide allele sharing in dizygotic twins

Gametic selection during fertilization or the effects of specific genotypes on the viability of embryos may cause a skewed transmission of chromosomes to surviving offspring. A recent analysis of transmission distortion in humans reported significant excess sharing among full siblings. Dizygotic (DZ) twin pairs are a special case of the simultaneous survival of two genotypes, and there have been reports of DZ pairs with excess allele sharing around the HLA locus, a candidate locus for embryo survival. We performed an allele-sharing study of 1,592 DZ twin pairs from two independent Australian cohorts, of which 1,561 pairs were informative for linkage on chromosome 6. We also analyzed allele sharing in 336 DZ twin pairs from The Netherlands. We found no evidence of excess allele sharing, either at the HLA locus or in the rest of the genome. In contrast, we found evidence of a small but significant (P=.003 for the Australian sample) genomewide deficit in the proportion of two alleles shared identical by descent among DZ twin pairs. We reconciled conflicting evidence in the literature for excess genomewide allele sharing by performing a simulation study that shows how undetected genotyping errors can lead to an apparent deficit or excess of allele sharing among sibling pairs, dependent on whether parental genotypes are known. Our results imply that gene-mapping studies based on affected sibling pairs that include DZ pairs will not suffer from false-positive results due to loci involved in embryo survival.     

Microbiota conservation and BMI signatures in adult monozygotic twins

The human gastrointestinal (GI) tract microbiota acts like a virtual organ and is suggested to be of great importance in human energy balance and weight control. This study included 40 monozygotic (MZ) twin pairs to investigate the influence of the human genotype on GI microbiota structure as well as microbial signatures for differences in body mass index (BMI). Phylogenetic microarraying based on 16S rRNA genes demonstrated that MZ twins have more similar microbiotas compared with unrelated subjects (P<0.001), which allowed the identification of 35 genus-like microbial groups that are more conserved between MZ twins. Half of the twin pairs were selected on discordance in terms of BMI, which revealed an inverse correlation between Clostridium cluster IV diversity and BMI. Furthermore, relatives of Eubacterium ventriosum and Roseburia intestinalis were positively correlated to BMI differences, and relatives of Oscillospira guillermondii were negatively correlated to BMI differences. Lower BMI was associated with a more abundant network of primary fiber degraders, while a network of butyrate producers was more prominent in subjects with higher BMI. Combined with higher butyrate and valerate contents in the fecal matter of higher BMI subjects, the difference in microbial networks suggests a shift in fermentation patterns at the end of the colon, which could affect human energy homeostasis.     

A comparison of the proliferative and replicative life span kinetics of cell cultures derived from monozygotic twins

Summary We have compared the growth rates, kinetics of cell aging, and replicative life spans of skin fibroblast cell cultures derived from three pairs of monozygotic twins of similar ages. The results of these studies indicated no significant differences in the cell densities 7 days after inoculation or replicative life spans within each twin pair but highly significant differences among each twin pair. The kinetics by which each culture aged ([³H]thymidine-labeled nuclei) were compared within and among the twin cell cultures. Although the slopes of each regression line were not significantly different, comparisons of the elevations of each line supported the conclusion that the aging of monozygotic twin cell cultures is similar within the twin pairs but differs among the twin pairs. This research was supported by IIT Research Institute.     

Estimating Modifying Effect of Age on Genetic and Environmental Variance Components in Twin Models

Twin studies have been adopted for decades to disentangle the relative genetic and environmental contributions for a wide range of traits. However, heritability estimation based on the classical twin models does not take into account dynamic behavior of the variance components over age. Varying variance of the genetic component over age can imply the existence of gene–environment (G × E) interactions that general genome-wide association studies (GWAS) fail to capture, which may lead to the inconsistency of heritability estimates between twin design and GWAS. Existing parametric G × E interaction models for twin studies are limited by assuming a linear or quadratic form of the variance curves with respect to a moderator that can, however, be overly restricted in reality. Here we propose spline-based approaches to explore the variance curves of the genetic and environmental components. We choose the additive genetic, common, and unique environmental variance components (ACE) model as the starting point. We treat the component variances as variance functions with respect to age modeled by B-splines or P-splines. We develop an empirical Bayes method to estimate the variance curves together with their confidence bands and provide an R package for public use. Our simulations demonstrate that the proposed methods accurately capture dynamic behavior of the component variances in terms of mean square errors with a data set of >10,000 twin pairs. Using the proposed methods as an alternative and major extension to the classical twin models, our analyses with a large-scale Finnish twin data set (19,510 MZ twins and 27,312 DZ same-sex twins) discover that the variances of the A, C, and E components for body mass index (BMI) change substantially across life span in different patterns and the heritability of BMI drops to ∼50% after middle age. The results further indicate that the decline of heritability is due to increasing unique environmental variance, which provides more insights into age-specific heritability of BMI and evidence of G × E interactions. These findings highlight the fundamental importance and implication of the proposed models in facilitating twin studies to investigate the heritability specific to age and other modifying factors.     

Variations in genome-wide gene expression in identical twins – a study of primary osteoblast-like culture from female twins discordant for osteoporosis

Background  

Monozygotic twin pairs who are genetically identical would be potentially useful in gene expression study for specific traits as cases and controls, because there would be much less gene expression variation within pairs compared to two unrelated individuals. However the twin pair has to be discordant for the particular trait or phenotype excluding those resulting from known confounders. Such discordant monozygotic twin pairs are rare and very few studies have explored the potential usefulness of this approach.     

Genetic and environmental effects on age at menarche,and its relationship with reproductive health in twins

INTRODUCTION:

Menarche or first menstrual period is a landmark in reproductive life span and it is the most prominent change of puberty. The timing of menarche can be under the influence of genes as well as individual environmental factors interacting with genetic factors.

OBJECTIVE:

Our study objectives were (a) to investigate the heritability of age of menarche in twins, (b) to obtain the association between age of menarche and childhood factors, and reproductive events/behavior, (c) to examine whether or not having a male co-twin affects early/late menarche.

METHODOLOGY:

A group of female-female identical (n = 108, 54 pairs), non-identical twins (n = 68, 34 pairs) and 17 females from opposite-sex twin sets were identified from twin registries of Malaysia and Iran. Genetic analysis was performed via two methods of Falconers’ formula and maximum likelihood.

RESULTS:

Heritability was found to be 66% using Falconers’ formula and 15% using univariate twin analysis. Model analysis revealed that shared environmental factors have a major contribution in determining the age of menarche (82%) followed by non-shared environment (18%).

DISCUSSION:

Result of this study is consistent with that of the literature. Timing of menarche could be under the influence of shared and non-shared environmental effects. Hirsutism was found to have a higher frequency among subjects with late menarche. There was no significant difference in age of menarche between females of opposite-sex twins and females of same-sex twins.

CONCLUSION:

It is concluded that twin models provide a powerful means of examining the total genetic contribution to age of menarche. Longitudinal studies of twins may clarify the type of environmental effects that determine the age of menarche.     

Heritability of Antibody Isotype and Subclass Responses to Plasmodium falciparum Antigens

Background

It is important to understand the extent to which genetic factors regulate acquired immunity to common infections. A classical twin study design is useful to estimate the heritable component of variation in measurable immune parameters.

Methodology/Principal Findings

This study assessed the relative heritability of different plasma antibody isotypes and subclasses (IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE) naturally acquired to P. falciparum blood stage antigens AMA1, MSP1-19, MSP2 (two allelic types) and MSP3 (two allelic types). Separate analyses were performed on plasma from 213 pairs of Gambian adult twins, 199 child twin pairs sampled in a dry season when there was little malaria transmission, and another set of 107 child twin pairs sampled at the end of the annual wet season when malaria was common. There were significantly positive heritability (h ²) estimates for 48% (20/42) of the specific antibody assays (for the seven isotypes and subclasses to the six antigens tested) among the adults, 48% (20/42) among the children in the dry season and 31% (13/42) among the children in the wet season. In children, there were significant heritability estimates for IgG4 reactivity against each of the antigens, and this subclass had higher heritability than the other subclasses and isotypes. In adults, 75% (15/20) of the significantly heritable antigen-specific isotype responses were attributable to non-HLA class II genetic variation, whereas none showed a significant HLA contribution.

Significance

Genome-wide approaches are now warranted to map the major genetic determinants of variable antibody isotype and subclass responses to malaria, alongside evaluation of their impact on infection and disease. Although plasma levels of IgG4 to malaria antigens are generally low, the exceptionally high heritability of levels of this subclass in children deserves particular investigation.     

Absence of HLA association or linkage for variations in sensitivity to the odor of androstenone

Sensitivity to the odor of 5-androst-16-en-3-one (androstenone), a testosterone metabolite, shows wide variations among unrelated individuals. Analysis of correlations in sensitivity between monozygotic twin pairs, dizygotic twin pairs, and nontwin sib pairs now shows that at least a portion of this variation is genetically determined. However, although data from some mouse studies have suggested a relationship between olfaction and the murine histocompatibility system (H-2), we were unable to demonstrate any role of the human HLA system in explaining the wide individual variations in human sensitivity to androstenone. An additional analysis of HLA antigens among 61 human mating pairs also provided no evidence that HLA phenotypes play a role in human mating preference. These data fail to support a role for the human HLA system in the recognition of an odorant of potential biological significance.     

Development of the Preterm Gut Microbiome in Twins at Risk of Necrotising Enterocolitis and Sepsis

The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae.This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics.     

Differential infant carrying in captive and wild common marmosets (Callithrix jacchus)

Callitrichids are communal breeders that lack sexual dimorphism, and only a few studies have examined behavioral gender differences among them. The purpose of this study was to investigate gender differences in infant carrying in 16 captive and seven wild common marmoset groups. Our results showed that female–female twin pairs were carried significantly more often by fathers than were male–male and male–female pairs both in the wild and in captivity. We suggest these differences may be related to different reproductive potentials of male and female Callithrix jacchus and possibly to future breeding competition among females.     

Education in Time: Cohort Differences in Educational Attainment in African-American Twins

Objectives

Educational opportunities for African-Americans expanded throughout the 20^th century. Twin pairs are an informative population in which to examine changes in educational attainment because each twin has the same parents and childhood socioeconomic status. We hypothesized that correlation in educational attainment of older twin pairs would be higher compared to younger twin pairs reflecting changes in educational access over time and potentially reflecting a “ceiling effect” associated with Jim Crow laws and discrimination.

Methodology and Principal Findings

We used data from 211 same-sex twin pairs (98 identical, 113 fraternal) in the Carolina African-American Twin Study of Aging who were identified through birth records. Participants completed an in-person interview. The twins were predominantly female (61%), with a mean age of 50 years (SD = 0.5). We found that older age groups had a stronger intra-twin correlation of attained educational level. Further analysis across strata revealed a trend across zygosity, with identical twins demonstrating more similar educational attainment levels than did their fraternal twin counterparts, suggesting a genetic influence.

Discussion

These findings suggest that as educational opportunities broadened in the 20th century, African-Americans gained access to educational opportunities that better matched their individual abilities.     

Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

Background

Although genetic variation is believed to contribute to an individual’s susceptibility to major depressive disorder, genome-wide association studies have not yet identified associations that could explain the full etiology of the disease. Epigenetics is increasingly believed to play a major role in the development of common clinical phenotypes, including major depressive disorder.

Results

Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder.

Conclusions

Our results suggest that aberrant methylation profiles affecting the hippocampus are associated with major depressive disorder and show the potential of the epigenetic twin model in neuro-psychiatric disease.     

Heritability of Attractiveness to Mosquitoes

Female mosquitoes display preferences for certain individuals over others, which is determined by differences in volatile chemicals produced by the human body and detected by mosquitoes. Body odour can be controlled genetically but the existence of a genetic basis for differential attraction to insects has never been formally demonstrated. This study investigated heritability of attractiveness to mosquitoes by evaluating the response of Aedes aegypti (=Stegomyia aegypti) mosquitoes to odours from the hands of identical and non-identical twins in a dual-choice assay. Volatiles from individuals in an identical twin pair showed a high correlation in attractiveness to mosquitoes, while non-identical twin pairs showed a significantly lower correlation. Overall, there was a strong narrow-sense heritability of 0.62 (SE 0.124) for relative attraction and 0.67 (0.354) for flight activity based on the average of ten measurements. The results demonstrate an underlying genetic component detectable by mosquitoes through olfaction. Understanding the genetic basis for attractiveness could create a more informed approach to repellent development.     

Three twinning types in mink (<Emphasis Type="Italic">Mustela vison</Emphasis>) embryogenesis

The frequency of occurrence of monochorionic twins in the postimplantational embryogenesis of the American mink and their karyotypes were studied. Monochorionic twin pairs were found in which embryos had different chromosome sets: 2n, XX and 2n, XY or 2n and 3n. This fact contradicts the idea that monochorionic twins should be monozygotic and genetically identical but confirms our earlier hypothesis that a third twinning type exists in mink: monozygotic but genetically different. The mechanism of the emergence of this twinning type in mammals is discussed. It is suggested that the high (up to 4.5%) frequency of its emergence in the American mink is related to obligate embryonic diapause, causing abnormal fertilization.     

Contribution of familial factors to the occurrence of cancer before old age in twin veterans

In an earlier report, we evaluated familial factors in deaths from all causes before age 62 among the 31,848 white male twin veterans who were followed during 1946–1978 through the National Academy of Sciences-National Research Council Twin Registry. We now report data for this group on twin concordances and heritabilities of cancer recorded on the death certificate as an underlying or associated cause. The study subjects have a mortality from cancer 0.88 times, and one from all causes 0.84 times, that of U.S. white males [12], but this is very similar to the mortality of other U.S. veterans [9].

Among 11,350 monozygotic (MZ) and 14,450 dizygotic (DZ) individuals in twin pairs alive on January 1, 1946, 1,162 MZ and 1,646 DZ individuals died before January 1, 1979. Cancer was diagnosed for 223 MZ and 323 DZ twins as an underlying or associated cause of death. Among the latter were 176 MZ and 274 DZ pairs with the only death in the pair a cancer death, 10 MZ and eight DZ pairs concordant for cancer, and 12 MZ and 14 DZ pairs in which the first death in the pair from cancer was followed by death of the other twin from another cause. When account is taken of the three MZ and two DZ pairs concordant for lung cancer, most likely related to cigarette smoking, the twin cancer death concordance rates are very low, and they are not appreciably different between the two zygosity groups.

Genetic factors may be important in some specific forms of cancer. However, these data suggest that genetic factors and early familial environment, generally shared by twin-pair members, do not contribute much to mortality from most cancers between 30 and 60 years of age.