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Sample records for discordant monozygotic twins

  1. Monozygotic twins discordant for sex.

    PubMed Central

    Schmidt, R; Sobel, E H; Nitowsky, H M; Dar, H; Allen, F H

    1976-01-01

    A pair of monozygotic, adolescent twins is discordant for sex. The phenotypic female twin has chromosome constitution of 46, XY/45, X. She displays many signs of Turner's syndrome, including typical facies, webbed neck, malformed left kidney, high plasma gonadotropins, and streak ovaries. However, her height is 154 cm which exceeds the height usually reported in Turner's syndrome. The male twin has a karyotype of 46, XY and normal sexual development. Only two other reports of pairs of monozygotic twins of opposite sex have been published. Images PMID:944787

  2. Monozygotic twins with trisomy 18: a report of discordant phenotype.

    PubMed Central

    Schlessel, J S; Brown, W T; Lysikiewicz, A; Schiff, R; Zaslav, A L

    1990-01-01

    The predicted incidence of liveborn monozygotic trisomy 18 twins is one per million births. The first case of liveborn monozygotic trisomy 18 twins was reported in 1989 and we report a second case in which striking phenotypic discordance existed. The probability of monozygotic trisomy 18 twinning and the mechanisms for phenotypic discordance in trisomic twins is discussed. Images PMID:2246775

  3. Monozygotic twins discordant for body stalk anomaly.

    PubMed

    Daskalakis, G J; Nicolaides, K H

    2002-07-01

    We report on two cases of monozygotic twins discordant for body stalk anomaly, diagnosed prenatally in a multicenter ultrasound screening study at 10-14 weeks of gestation. Ultrasound showed a large abdominal wall defect with most of the abdominal contents and almost half of the body in the celomic cavity, in association with severe kyphoscoliosis and a very short umbilical cord. Both pregnancies were managed expectantly and delivered by Cesarean section. The abnormal babies died soon after birth and autopsy confirmed the sonographic diagnosis. Body stalk anomaly in twins is extremely rare. These are, to our knowledge, the first cases reported on monozygotic twins discordant for this anomaly, indicating that the incomplete twinning theory cannot uniformly explain the pathogenesis of the body stalk in twins.

  4. Monozygotic twins discordant for fibular aplasia.

    PubMed

    Halal, F

    1991-12-15

    We report on monozygotic (MZ) twins, one with the fibular aplasia developmental field defect, and the other with ectrosyndactyly of the hand. This may represent a coincidental occurrence of two sporadic events, or syndromal fibular aplasia.

  5. Monozygotic twins discordant for Aicardi syndrome.

    PubMed Central

    Costa, T; Greer, W; Rysiecki, G; Buncic, J R; Ray, P N

    1997-01-01

    Aicardi syndrome is a developmental disorder characterised by agenesis of the corpus callosum, retinal lacunae, seizures, and developmental delay. It is believed to be X linked with lethality in males. We report a set of monozygotic female twins one of whom is healthy and intellectually normal while the other has the classical Aicardi phenotype with profound retardation. Family history is negative. Both had normal karyotypes. Monozygosity was established by blood grouping, chromosomal heteromorphisms, and DNA analysis using six hypervariable probes (five autosomal and one X linked) and three X linked RFLP probes. We tested the hypothesis that preferential inactivation of a different X chromosome had occurred in each girl. Methylation sensitive RFLP analysis of DNA from EBV transformed B lymphocytes and cultured skin fibroblasts using MspI/HpaII digestion and probing with M27 beta showed a very similar pattern of X inactivation in both twins with no evidence of preferential expression of one particular X chromosome. We conclude that the abnormalities in the affected twin are probably the consequence of a postzygotic mutation in early embryonic development. Images PMID:9279766

  6. Methylomic analysis of monozygotic twins discordant for childhood psychotic symptoms.

    PubMed

    Fisher, Helen L; Murphy, Therese M; Arseneault, Louise; Caspi, Avshalom; Moffitt, Terrie E; Viana, Joana; Hannon, Eilis; Pidsley, Ruth; Burrage, Joe; Dempster, Emma L; Wong, Chloe C Y; Pariante, Carmine M; Mill, Jonathan

    2015-01-01

    Childhood psychotic symptoms are associated with increased rates of schizophrenia, other psychiatric disorders, and suicide attempts in adulthood; thus, elucidating early risk indicators is crucial to target prevention efforts. There is considerable discordance for psychotic symptoms between monozygotic twins, indicating that child-specific non-genetic factors must be involved. Epigenetic processes may constitute one of these factors and have not yet been investigated in relation to childhood psychotic symptoms. Therefore, this study explored whether differences in DNA methylation at age 10 were associated with monozygotic twin discordance for psychotic symptoms at age 12. The Environmental Risk (E-Risk) Longitudinal Twin Study cohort of 2,232 children (1,116 twin pairs) was assessed for age-12 psychotic symptoms and 24 monozygotic twin pairs discordant for symptoms were identified for methylomic comparison. Children provided buccal samples at ages 5 and 10. DNA was bisulfite modified and DNA methylation was quantified using the Infinium HumanMethylation450 array. Differentially methylated positions (DMPs) associated with psychotic symptoms were subsequently tested in post-mortem prefrontal cortex tissue from adult schizophrenia patients and age-matched controls. Site-specific DNA methylation differences were observed at age 10 between monozygotic twins discordant for age-12 psychotic symptoms. Similar DMPs were not found at age 5. The top-ranked psychosis-associated DMP (cg23933044), located in the promoter of the C5ORF42 gene, was also hypomethylated in post-mortem prefrontal cortex brain tissue from schizophrenia patients compared to unaffected controls. These data tentatively suggest that epigenetic variation in peripheral tissue is associated with childhood psychotic symptoms and may indicate susceptibility to schizophrenia and other mental health problems.

  7. Risk factors for myopia in a discordant monozygotic twin study.

    PubMed

    Ramessur, Rishi; Williams, Katie M; Hammond, Christopher J

    2015-11-01

    Monozygotic (MZ) twin pairs discordant for disease allow careful examination of environmental factors whilst controlling for genetic variation. The purpose of this study was to examine differences in environmental risk factors in MZ twins discordant for myopia. Sixty four MZ twin pairs discordant for refractive error were interviewed. Discordant twins were selected from 1326 MZ twin pairs from the TwinsUK adult twin registry with non-cycloplegic autorefraction. Discordancy was defined as ≥ 2 Dioptres (D) difference in spherical equivalent (SphE) and discordant for class of refractive error. In a 35-item telephone questionnaire twins were separately asked (and scored) about the risk factors urban/rural residence, occupational status and highest educational level. They responded with more (1), less (-1) or the same (0) as their twin on time spent outside, playing outdoor sport, and on close work aged <16 and 16-25 years. The lower SphE twin's score was subtracted from the higher SphE twin's score, and mean values of the difference calculated for each variable. Sixty four twin pairs were included (mean age 56, range 30-79 years; mean difference in refraction 3.35 D, S.D. 1.55 D, median difference 2.78 D). Within discordant MZ twin pairs, the more myopic twin was associated with having a higher occupational status (mean score between 16 and 25 years -0.11; 95% CI -0.19 to -0.04; mean score aged >25 years -0.23, 95% CI -0.28 to -0.17), being resident in urban area (mean score -0.26; 95% CI -0.33 to -0.18) and performing more close work (mean score <16 years -0.11; 95% CI -0.18 to -0.05; mean score aged 16-25 years -0.17, 95% CI -0.24 to -0.10) than their twin. The twins who spent more time outdoors (mean score <16 years 0.09; 95% CI 0.03-0.15; mean score aged 16-25 years 0.28, 95% CI 0.15-0.41) or performed more outdoors sports (mean score <16 years 0.13; 95% CI 0.04-0.21; mean score aged 16-25 years 0.23, 95% CI 0.10-0.36) were less likely to be myopic than their

  8. Mitochondrial DNA Copy Number in Sleep Duration Discordant Monozygotic Twins.

    PubMed

    Wrede, Joanna E; Mengel-From, Jonas; Buchwald, Dedra; Vitiello, Michael V; Bamshad, Michael; Noonan, Carolyn; Christiansen, Lene; Christensen, Kaare; Watson, Nathaniel F

    2015-10-01

    Mitochondrial DNA (mtDNA) copy number is an important component of mitochondrial function and varies with age, disease, and environmental factors. We aimed to determine whether mtDNA copy number varies with habitual differences in sleep duration within pairs of monozygotic twins. Academic clinical research center. 15 sleep duration discordant monozygotic twin pairs (30 twins, 80% female; mean age 42.1 years [SD 15.0]). Sleep duration was phenotyped with wrist actigraphy. Each twin pair included a "normal" (7-9 h/24) and "short" (< 7 h/24) sleeping twin. Fasting peripheral blood leukocyte DNA was assessed for mtDNA copy number via the n-fold difference between qPCR measured mtDNA and nuclear DNA creating an mtDNA measure without absolute units. We used generalized estimating equation linear regression models accounting for the correlated data structure to assess within-pair effects of sleep duration on mtDNA copy number. Mean within-pair sleep duration difference per 24 hours was 94.3 minutes (SD 62.6 min). We found reduced sleep duration (β = 0.06; 95% CI 0.004, 0.12; P < 0.05) and sleep efficiency (β = 0.51; 95% CI 0.06, 0.95; P < 0.05) were significantly associated with reduced mtDNA copy number within twin pairs. Thus every 1-minute decrease in actigraphy-defined sleep duration was associated with a decrease in mtDNA copy number of 0.06. Likewise, a 1% decrease in actigraphy-defined sleep efficiency was associated with a decrease in mtDNA copy number of 0.51. Reduced sleep duration and sleep efficiency were associated with reduced mitochondrial DNA copy number in sleep duration discordant monozygotic twins offering a potential mechanism whereby short sleep impairs health and longevity through mitochondrial stress. © 2015 Associated Professional Sleep Societies, LLC.

  9. Mitochondrial DNA Copy Number in Sleep Duration Discordant Monozygotic Twins

    PubMed Central

    Wrede, Joanna E.; Mengel-From, Jonas; Buchwald, Dedra; Vitiello, Michael V.; Bamshad, Michael; Noonan, Carolyn; Christiansen, Lene; Christensen, Kaare; Watson, Nathaniel F.

    2015-01-01

    Study Objectives: Mitochondrial DNA (mtDNA) copy number is an important component of mitochondrial function and varies with age, disease, and environmental factors. We aimed to determine whether mtDNA copy number varies with habitual differences in sleep duration within pairs of monozygotic twins. Setting: Academic clinical research center. Participants: 15 sleep duration discordant monozygotic twin pairs (30 twins, 80% female; mean age 42.1 years [SD 15.0]). Design: Sleep duration was phenotyped with wrist actigraphy. Each twin pair included a “normal” (7–9 h/24) and “short” (< 7 h/24) sleeping twin. Fasting peripheral blood leukocyte DNA was assessed for mtDNA copy number via the n-fold difference between qPCR measured mtDNA and nuclear DNA creating an mtDNA measure without absolute units. We used generalized estimating equation linear regression models accounting for the correlated data structure to assess within-pair effects of sleep duration on mtDNA copy number. Measurements and Results: Mean within-pair sleep duration difference per 24 hours was 94.3 minutes (SD 62.6 min). We found reduced sleep duration (β = 0.06; 95% CI 0.004, 0.12; P < 0.05) and sleep efficiency (β = 0.51; 95% CI 0.06, 0.95; P < 0.05) were significantly associated with reduced mtDNA copy number within twin pairs. Thus every 1-minute decrease in actigraphy-defined sleep duration was associated with a decrease in mtDNA copy number of 0.06. Likewise, a 1% decrease in actigraphy-defined sleep efficiency was associated with a decrease in mtDNA copy number of 0.51. Conclusions: Reduced sleep duration and sleep efficiency were associated with reduced mitochondrial DNA copy number in sleep duration discordant monozygotic twins offering a potential mechanism whereby short sleep impairs health and longevity through mitochondrial stress. Citation: Wrede JE, Mengel-From J, Buchwald D, Vitiello MV, Bamshad M, Noonan C, Christiansen L, Christensen K, Watson NF. Mitochondrial DNA copy number

  10. mtDNA Heteroplasmy in Monozygotic Twins Discordant for Schizophrenia.

    PubMed

    Li, Hong; Bi, Rui; Fan, Yu; Wu, Yong; Tang, Yanqing; Li, Zongchang; He, Ying; Zhou, Jun; Tang, Jinsong; Chen, Xiaogang; Yao, Yong-Gang

    2017-08-01

    Although monozygotic (MZ) twins have theoretically identical nuclear DNA sequences, there may be phenotypic differences between them caused by somatic mutations and epigenetic changes affecting each genome. In this study, we collected eight families of MZ twins discordant for schizophrenia with the aim of investigating the potential role of mitochondrial DNA (mtDNA) heteroplasmy in causing the phenotypic differences between the twin pairs. Next-generation sequencing (NGS) technology was used to screen the whole mitochondrial genome of the twin pairs and their parents. The mtDNA heteroplasmy level was found to be nearly identical between the twin pairs but was distinctly different between each mother and their offspring. These results suggest that the discordance of schizophrenia between MZ twins may not be attributable to the difference in mtDNA heteroplasmy, and the high concordance of mtDNA heteroplasmy between MZ twins may indicate the relatively equal distribution of mtDNA during embryo separation of MZ twins and/or the modulation effect from the same nuclear genetic background. Furthermore, we observed an overrepresentation of heteroplasmy in noncoding regions and an elevated ratio of nonsynonymous heteroplasmy, suggesting the possible effects of a purifying selection in shaping the pattern of mtDNA heteroplasmy.

  11. Adult glucose metabolism in extremely birthweight-discordant monozygotic twins.

    PubMed

    Frost, M; Petersen, I; Brixen, K; Beck-Nielsen, H; Holst, J J; Christiansen, L; Højlund, K; Christensen, K

    2012-12-01

    Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment. Among 77,885 twins in the Danish Twin Registry, 155 of the most BW-discordant MZ twin pairs (median BW difference 0.5 kg) were assessed using a 2 h oral glucose tolerance test with sampling of plasma (p-)glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. HOMA for beta cell function (HOMA-β) and insulin resistance (HOMA-IR), and also insulin sensitivity index (BIGTT-SI) and acute insulin response (BIGTT-AIR), were calculated. Subgroup analyses were performed in those with: (1) double verification of BW difference; (2) difference in BW >0.5 kg; and (3) no overt metabolic disease (type 2 diabetes, hyperlipidaemia or thyroid disease). No intra-pair differences in p-glucose, insulin, C-peptide, incretin hormones, HOMA-β, HOMA-IR or BIGTT-SI were identified. p-Glucose at 120 min was higher in the twins with the highest BW without metabolic disease, and BIGTT-AIR was higher in those with the highest BW although not in pairs with a BW difference of >0.5 kg. BW-discordant MZ twins provide no evidence for a detrimental effect of low BW on glucose metabolism in adulthood once genetic factors and rearing environment are controlled for.

  12. Learning and memory in monozygotic twins discordant for schizophrenia.

    PubMed

    Goldberg, T E; Torrey, E F; Gold, J M; Ragland, J D; Bigelow, L B; Weinberger, D R

    1993-02-01

    Learning and memory were assessed in 24 monozygotic (MZ) pairs of individuals discordant for schizophrenia or delusional disorder and seven normal pairs of MZ twins. On declarative memory tasks, the affected group displayed a pattern that might best be characterized as dysmnesic in that they performed significantly worse than the discordant unaffected group on story recall, paired associated learning, and visual recall of designs, but they learned over time, had relatively preserved recognition memory, and did not show profoundly accelerated rates of forgetting. Effortful, volitional retrieval from the lexicon, measured by verbal fluency, was also compromised in the affected group. On the other hand, procedural learning of the motor skill in a pursuit rotor task was relatively intact in the affected group. Comparisons of the normal group and unaffected group indicated that the latter group had very mild impairments in some aspects of episodic memory, namely, immediate and delayed recall of stories and delayed recall of designs. It is highly unlikely that the impairments observed in the affected group can be attributed to differences in genome, family environment, socioeconomic circumstance, or educational opportunity, as all of these were controlled by the twin paradigm. Rather, the impairments appear to be related to the intercession of disease. The neuropsychological profile is consistent with frontal lobe and medial temporal lobe dysfunction, as noted in this sample as well as other samples of schizophrenic singletons. Significant correlations between many measures of memory and global level of social and vocational functioning within the discordant group were also found. Thus difficulties in rapidly acquiring new information and propitiously retrieving old information may burden patients with schizophrenia in many of the transactions of everyday life.

  13. DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks.

    PubMed

    Castellani, Christina A; Laufer, Benjamin I; Melka, Melkaye G; Diehl, Eric J; O'Reilly, Richard L; Singh, Shiva M

    2015-05-06

    Despite their singular origin, monozygotic twin pairs often display discordance for complex disorders including schizophrenia. It is a common (1%) and often familial disease with a discordance rate of ~50% in monozygotic twins. This high discordance is often explained by the role of yet unknown environmental, random, and epigenetic factors. The involvement of DNA methylation in this disease appears logical, but remains to be established. We have used blood DNA from two pairs of monozygotic twins discordant for schizophrenia and their parents in order to assess genome-wide methylation using a NimbleGen Methylation Promoter Microarray. The genome-wide results show that differentially methylated regions (DMRs) exist between members representing discordant monozygotic twins. Some DMRs are shared with parent(s) and others appear to be de novo. We found twenty-seven genes affected by DMR changes that were shared in the affected member of two discordant monozygotic pairs from unrelated families. Interestingly, the genes affected by pair specific DMRs share specific networks. Specifically, this study has identified two networks; "cell death and survival" and a "cellular movement and immune cell trafficking". These two networks and the genes affected have been previously implicated in the aetiology of schizophrenia. The results are compatible with the suggestion that DNA methylation may contribute to the discordance of monozygotic twins for schizophrenia. Also, this may be accomplished by the direct effect of gene specific methylation changes on specific biological networks rather than individual genes. It supports the extensive genetic, epigenetic and phenotypic heterogeneity implicated in schizophrenia.

  14. SEARCH FOR GENOMIC ALTERATIONS IN MONOZYGOTIC TWINS DISCORDANT FOR CLEFT LIP AND/OR PALATE

    PubMed Central

    Kimani, Jane W.; Yoshiura, Koh-ichiro; Shi, Min; Jugessur, Astanand; Moretti-Ferreira, Danilo; Christensen, Kaare; Murray, Jeffrey C.

    2010-01-01

    Phenotypically discordant monozygotic twins offer the possibility of gene discovery through delineation of molecular abnormalities in one member of the twin pair. One proposed mechanism of discordance is postzygotically occurring genomic alterations resulting from mitotic recombination and other somatic changes. Detection of altered genomic fragments can reveal candidate gene loci that can be verified through additional analyses. We investigated this hypothesis using array comparative genomic hybridization; the 50K and 250K Affymetrix GeneChip® SNP arrays and an Illumina custom array consisting of 1,536 SNPs, to scan for genomic alterations in a sample of monozygotic twin pairs with discordant cleft lip and/or palate phenotypes. Paired analysis for deletions, amplifications and loss of heterozygosity, along with sequence verification of SNPs with discordant genotype calls did not reveal any genomic discordance between twin pairs in lymphocyte DNA samples. Our results demonstrate that postzygotic genomic alterations are not a common cause of monozygotic twin discordance for isolated cleft lip and/or palate. However, rare or balanced genomic alterations, tissue-specific events and small aberrations beyond the detection level of our experimental approach cannot be ruled out. The stability of genomes we observed in our study samples also suggests that detection of discordant events in other monozygotic twin pairs would be remarkable and of potential disease significance. PMID:19803774

  15. Monozygotic twin discordant for Down syndrome: mos 47,XX,+21/46,XX and 46,XX.

    PubMed

    Choi, Sun Ah; Ko, Jung Min; Shin, Choong Ho; Yang, Sei Won; Choi, Jin Sun; Oh, Sun Kyung

    2013-08-01

    Monozygotic twins, developed from a single zygote, are almost identical in clinical phenotype and concordant karyotypes. Monozygotic twins with discordant karyotypes are thought to be quite rare. Here, we report monochorionic-diamniotic twins discordant for Down syndrome. On findings of prenatal ultrasonography, nuchal translucency thickness was different between twins, and suggested that one of the twins was at high risk for having chromosomal abnormalities including Down syndrome. The twins were monochorionic-diamniotic; therefore, chorionic villi sampling of the common placenta was performed. The karyotype of the chorionic villi cells was 46,XX, and pregnancy was maintained. After delivery, dysmorphic clinical features suggesting Down syndrome were found in one of the twins, while the other twin showed a morphologically normal appearance. Karyotypes of peripheral blood leukocytes were repeatedly normal in the dysmorphic twin; however, the karyotype of skin fibroblasts from the dysmorphic twin indicated Down syndrome mosaicism; 47,XX,+21[99]/46,XX[2]. The karyotype of skin fibroblasts from the morphologically normal twin was 46,XX. Monozygosity of the twins was confirmed by a short tandem repeat analysis using 16 polymorphic markers. A mitotic nondisjunction followed by the twinning would explain the discordant karyotypes between monozygotic twins.

  16. Copy number variation distribution in six monozygotic twin pairs discordant for schizophrenia.

    PubMed

    Castellani, Christina A; Awamleh, Zain; Melka, Melkaye G; O'Reilly, Richard L; Singh, Shiva M

    2014-04-01

    We have evaluated copy number variants (CNVs) in six monozygotic twin pairs discordant for schizophrenia. The data from Affymetrix® Human SNP 6.0 arrays™ were analyzed using Affymetrix® Genotyping Console™, Partek® Genomics Suite™, PennCNV, and Golden Helix SVS™. This yielded both program-specific and overlapping results. Only CNVs called by Affymetrix Genotyping Console, Partek Genomics Suite, and PennCNV were used in further analysis. This analysis included an assessment of calls in each of the six twin pairs towards identification of unique CNVs in affected and unaffected co-twins. Real time polymerase chain reaction (PCR) experiments confirmed one CNV loss at 7q11.21 that was found in the affected patient but not in the unaffected twin. The results identified CNVs and genes that were previously implicated in mental abnormalities in four of the six twin pairs. It included PYY (twin pairs 1 and 5), EPHA3 (twin pair 3), KIAA1211L (twin pair 4), and GPR139 (twin pair 5). They represent likely candidate genes and CNVs for the discordance of four of the six monozygotic twin pairs for this heterogeneous neurodevelopmental disorder. An explanation for these differences is ontogenetic de novo events that differentiate in the monozygotic twins during development.

  17. Is there a genetic basis for Fuchs' heterochromic uveitis? Discordance in monozygotic twins.

    PubMed Central

    Jones, N P; Read, A P

    1992-01-01

    One pair, and probably two pairs, of monozygotic twins are reported with discordance for Fuchs' heterochromic uveitis (FHU). Regular Mendelian inheritance of this disease is now proved to be impossible. The heritability of FHU is low and may be zero. The possibility of any genetic predisposition to the disease and its association with 'simple' heterochromia are discussed. Images PMID:1739686

  18. Fasting plasma total ghrelin concentrations in monozygotic twins discordant for obesity.

    PubMed

    Leskelä, Piia; Ukkola, Olavi; Vartiainen, Johanna; Rönnemaa, Tapani; Kaprio, Jaakko; Bouchard, Claude; Kesäniemi, Y Antero

    2009-02-01

    Ghrelin is a hormone that is involved in the regulation of food intake. Neuronal, endocrine, and genetic factors have been shown to regulate plasma ghrelin levels; but the determinants of fasting ghrelin concentrations are not yet fully understood. The main aim was to explore the roles of adiposity and genetic differences in determining fasting plasma total ghrelin levels. We measured total ghrelin levels in a population of 23 monozygotic twin pairs discordant for obesity. In addition, 2 variants of ghrelin gene, namely, Arg51Gln and Leu72Met, were genotyped in 3 populations of monozygotic twin pairs: 23 obesity-discordant, 43 lean-concordant, and 46 obesity-concordant twin pairs. In discordant twins, lean co-twins had higher fasting plasma total ghrelin levels (950 pg/mL, SD = 328 pg/mL) than obese twins (720 pg/mL, SD = 143 pg/mL; P = .003). Arg51Gln-polymorphism of the ghrelin gene was equally distributed between the twin groups. However, there were significant differences in genotype frequencies at the Leu72Met polymorphism between the discordant and obese-concordant groups (P = .003) and between the discordant and lean-concordant groups (P = .011), but not between the 2 concordant groups. In the discordant group, there were fewer Met carriers (4%) than among the obese (17%) or the lean-concordant groups (15%). Plasma total ghrelin levels are affected by acquired obesity independent of genetic background. The Leu72 allele is particularly common among monozygotic twins discordant for obesity, suggesting that this ghrelin allele is more permissive in the regulation of energy balance. The ghrelin gene may thus play a role in the regulation of variability of body weight, such that Leu72 allele carriers are more prone to weight variability in response to environmental factors.

  19. Intrapair differences in hippocampal volume in monozygotic twins discordant for the risk for anxiety and depression.

    PubMed

    de Geus, Eco J C; van't Ent, Dennis; Wolfensberger, Saskia P A; Heutink, Peter; Hoogendijk, Witte J G; Boomsma, Dorret I; Veltman, Dick J

    2007-05-01

    Current biological psychiatric models assume that genetic and environmental risk factors for anxiety and depression act on the same brain structures. To test this assumption, we assessed brain anatomy by using optimized voxel-based morphometry on magnetic resonance images obtained in monozygotic twin pairs who were discordant for the risk of anxiety and depression (n = 10 pairs) and in monozygotic twin pairs who were concordant for high (n = 7 pairs) or low (n = 15 pairs) risk for anxiety and depression. We observed volume reductions in the temporal lobe, most notably in the left posterior hippocampal region in subjects at high risk for anxiety and depression, but exclusively in the intrapair comparison of discordant monozygotic twins. Because monozygotic twins are genetically identical, any discordance in their risk for anxiety and depression and hippocampal volume must arise from differential exposure to environmental influences. A group comparison between pairs concordant for low or high risk, which is more likely to reflect differences in genetic vulnerability, did not show reduced temporal-lobe and posterior hippocampal volumes in the pairs at high risk for anxiety and depression. This pattern of results suggests that damage to temporal-lobe structures may be specific to an environmentally driven etiology of anxiety and depression.

  20. Discordant sex in monozygotic XXY/XX twins: a case report.

    PubMed

    Tachon, G; Lefort, G; Puechberty, J; Schneider, A; Jeandel, C; Boulot, P; Prodhomme, O; Meyer, P; Taviaux, S; Touitou, I; Pellestor, F; Geneviève, D; Gatinois, V

    2014-12-01

    We report a case of discordant phenotypic sex in monozygotic twins mosaic 47,XXY/46,XX: monozygotic heterokaryotypic twins. The twins presented with cognitive and comprehension delay, behavioural and language disorders, all symptoms frequently reported in Klinefelter syndrome. Molecular zygosity analysis with several markers confirmed that the twins are in effect monozygotic (MZ). Array comparative genomic hybridization found no evidence for the implication of copy number variation in the phenotypes. Ultrasound scans of the reproductive organs revealed no abnormalities. Endocrine tests showed a low testosterone level in Twin 1 (male phenotype) and a low gonadotrophin level in Twin 2 (female phenotype) which, combined with the results from ultrasound examination, provided useful information for potentially predicting the future fertility potential of the twins. Blood karyotypes revealed the presence of a normal 46,XX cell line and an aneuploïd 47,XXY cell line in both patients. Examination of the chromosome constitutions of various tissues such as blood, buccal smear and urinary sediment not surprisingly showed different proportions for the 46,XX and 47,XXY cell lines, which most likely explains the discordant phenotypic sex and mild Klinefelter features. The most plausible underlying biological mechanism is a post-zygotic loss of the Y chromosome in an initially 47,XXY zygote. This would result in an embryo with both 46,XX and 47,XXY cells lines which could subsequently divide into two monozygotic embryos through a twinning process. The two cell lines would then be distributed differently between tissues which could result in phenotypic discordances in the twins. These observations emphasize the importance of regular paediatric evaluations to determine the optimal timing for fertility preservation measures and to detect new Klinefelter features which could appear throughout childhood in the two subjects.

  1. Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome

    PubMed Central

    Kunio, Miyake; Yang, Chunshu; Minakuchi, Yohei; Ohori, Kenta; Soutome, Masaki; Hirasawa, Takae; Kazuki, Yasuhiro; Adachi, Noboru; Suzuki, Seiko; Itoh, Masayuki; Goto, Yu-ichi; Andoh, Tomoko; Kurosawa, Hiroshi; Akamatsu, Wado; Ohyama, Manabu; Okano, Hideyuki; Oshimura, Mitsuo; Sasaki, Masayuki; Toyoda, Atsushi; Kubota, Takeo

    2013-01-01

    Monozygotic (identical) twins have been widely used in genetic studies to determine the relative contributions of heredity and the environment in human diseases. Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different patterns of X chromosome inactivation (XCI). However, recent studies have identified genetic and epigenetic differences between monozygotic twins, thereby challenging the accepted experimental model for distinguishing the effects of nature and nurture. Here, we report the genomic and epigenomic sequences in skin fibroblasts of a discordant monozygotic twin pair with Rett syndrome, an X-linked neurodevelopmental disorder characterized by autistic features, epileptic seizures, gait ataxia and stereotypical hand movements. The twins shared the same de novo mutation in exon 4 of the MECP2 gene (G269AfsX288), which was paternal in origin and occurred during spermatogenesis. The XCI patterns in the twins did not differ in lymphocytes, skin fibroblasts, and hair cells (which originate from ectoderm as does neuronal tissue). No reproducible differences were detected between the twins in single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (indels), or copy number variations. Differences in DNA methylation between the twins were detected in fibroblasts in the upstream regions of genes involved in brain function and skeletal tissues such as Mohawk Homeobox (MKX), Brain-type Creatine Kinase (CKB), and FYN Tyrosine Kinase Protooncogene (FYN). The level of methylation in these upstream regions was inversely correlated with the level of gene expression. Thus, differences in DNA methylation patterns likely underlie the discordance in Rett phenotypes between the twins. PMID:23805272

  2. Epigenetic Differences in Cortical Neurons from a Pair of Monozygotic Twins Discordant for Alzheimer's Disease

    PubMed Central

    Mastroeni, Diego; McKee, Ann; Grover, Andrew; Rogers, Joseph; Coleman, Paul D.

    2009-01-01

    DNA methylation [1], [2] is capable of modulating coordinate expression of large numbers of genes across many different pathways, and may therefore warrant investigation for their potential role between genes and disease phenotype. In a rare set of monozygotic twins discordant for Alzheimer's disease (AD), significantly reduced levels of DNA methylation were observed in temporal neocortex neuronal nuclei of the AD twin. These findings are consistent with the hypothesis that epigenetic mechanisms may mediate at the molecular level the effects of life events on AD risk, and provide, for the first time, a potential explanation for AD discordance despite genetic similarities. PMID:19672297

  3. Neuroanatomic, epigenetic and genetic differences in monozygotic twins discordant for attention deficit hyperactivity disorder.

    PubMed

    Chen, Y-C; Sudre, G; Sharp, W; Donovan, F; Chandrasekharappa, S C; Hansen, N; Elnitski, L; Shaw, P

    2017-03-21

    The study of monozygotic twins discordant for attention deficit hyperactivity disorder can elucidate mechanisms that contribute to the disorder, which affects ~7% of children. First, using in vivo neuroanatomic imaging on 14 pairs of monozygotic twins (mean age 9.7, s.d. 1.9 years), we found that discordance for the disorder is mirrored by differing dimensions of deep brain structures (the striatum and cerebellum), but not the cerebral cortex. Next, using whole-blood DNA from the same twins, we found a significant enrichment of epigenetic differences in genes expressed in these 'discordant' brain structures. Specifically, there is differential methylation of probes lying in the shore and shelf and enhancer regions of striatal and cerebellar genes. Notably, gene sets pertaining to the cerebral cortex (which did not differ in volume between affected and unaffected twins) were not enriched by differentially methylated probes. Genotypic differences between the twin pairs-such as copy number and rare, single-nucleotide variants-did not contribute to phenotypic discordance. Pathway analyses of the genes implicated by the most differentially methylated probes implicated γ-aminobutyric acid (GABA), dopamine and serotonin neurotransmitter systems. The study illustrates how neuroimaging can help guide the search for epigenomic mechanisms in neurodevelopmental disorders.Molecular Psychiatry advance online publication, 21 March 2017; doi:10.1038/mp.2017.45.

  4. Metabolome and fecal microbiota in monozygotic twin pairs discordant for weight: a Big Mac challenge.

    PubMed

    Bondia-Pons, Isabel; Maukonen, Johanna; Mattila, Ismo; Rissanen, Aila; Saarela, Maria; Kaprio, Jaakko; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Hyötyläinen, Tuulia; Pietiläinen, Kirsi H; Orešič, Matej

    2014-09-01

    Postprandial responses to food are complex, involving both genetic and environmental factors. We studied postprandial responses to a Big Mac meal challenge in monozygotic co-twins highly discordant for body weight. This unique design allows assessment of the contribution of obesity, independent of genetic liability. Comprehensive metabolic profiling using 3 analytical platforms was applied to fasting and postprandial serum samples from 16 healthy monozygotic twin pairs discordant for weight (body mass index difference >3 kg/m(2)). Nine concordant monozygotic pairs were examined as control pairs. Fecal samples were analyzed to assess diversity of the major bacterial groups by using 5 different validated bacterial group specific denaturing gradient gel electrophoresis methods. No differences in fecal bacterial diversity were detected when comparing co-twins discordant for weight (ANOVA, P<0.05). We found that within-pair similarity is a dominant factor in the metabolic postprandial response, independent of acquired obesity. Branched chain amino acids were increased in heavier as compared with leaner co-twins in the fasting state, but their levels converged postprandially (paired t tests, FDR q<0.05). We also found that specific bacterial groups were associated with postprandial changes of specific metabolites. Our findings underline important roles of genetic and early life factors in the regulation of postprandial metabolite levels.

  5. Environmental Factors in Obsessive-Compulsive Behavior: Evidence from Discordant and Concordant Monozygotic Twins

    PubMed Central

    van Grootheest, Daniel S.; Willemsen, Gonneke; van Oppen, Patricia; Boomsma, Dorret I.

    2008-01-01

    To investigate environmental factors that protect against or exacerbate obsessive-compulsive (OC) symptoms, we selected 25 monozygotic (MZ) twin pairs discordant, 17 MZ twin pairs concordant high and 34 MZ pairs concordant low on OC symptoms from a large longitudinal Dutch sample of adult twin pairs and their family members, applying stringent criteria for OC symptomatology. Data were collected on psychopathology, family structure, health, lifestyle, birth complications and life events. Unique environmental factors were studied using within-discordant MZ pair comparisons, whereas between-concordant MZ pair comparisons were used to study environmental factors that are shared by the twins of an MZ pair. The high-scoring MZ twins of the discordant group reported more life events (especially sexual abuse) than their low-scoring twin-siblings. The between-pair comparisons showed lower birth weight in the discordant MZ pairs than in the concordant MZ pairs. Further, the concordant high MZ pairs as well as their spouses had a lower educational level than the two other groups. On scale scores of anxious-depression, neuroticism, and somatic complaints, concordant high MZ pairs showed highest scores, and the discordant MZ pairs scored intermediate, except for neuroticism, on which the high-scoring twins of discordant MZ pairs were equal to the concordant high pairs. Discordance on psychological scale scores between the concordant MZ pairs was evident from 1991 onward, and within the discordant MZ pairs from 1997 onward, confirming previous reports of an association of early-onset OC symptoms with higher genetic load. Parent scores of OC symptoms and anxious-depression suggested intermediate genetic load in the discordant MZ group. In conclusion, this study reports on both unique and shared environmental factors associated with OC symptomatology. Whether these factors operate in addition to or in interaction with genetic disposition is to be elucidated in future studies

  6. X chromosome gene methylation in peripheral lymphocytes from monozygotic twins discordant for scleroderma

    PubMed Central

    Selmi, C; Feghali-Bostwick, C A; Lleo, A; Lombardi, S A; De Santis, M; Cavaciocchi, F; Zammataro, L; Mitchell, M M; LaSalle, J M; Medsger Jr, T; Gershwin, M E

    2012-01-01

    Scleroderma (SSc) is a rare connective tissue disease characterized by fibrosis, microvasculopathy and autoimmune features. The role of genetics is limited in SSc, as suggested by similar concordance rates in monozygotic and dizygotic twin pairs, while environmental factors may act through epigenetic changes, as demonstrated for specific genes. Further, sex chromosome changes have been reported in SSc and may explain the female preponderance. In the present study we compared the methylation profile of all X chromosome genes in peripheral blood mononuclear cells from monozygotic twins discordant (n = 7) and concordant (n = 1) for SSc. Methylated DNA immunoprecipitations from each discordant twin pair were hybridized to a custom-designed array included 998 sites encompassing promoters of all X chromosome genes and randomly chosen autosomal genes. Biostatistical tools identified sites with an elevated probability to be consistently hypermethylated (n = 18) or hypomethylated (n = 25) in affected twins. Identified genes include transcription factors (ARX, HSFX1, ZBED1, ZNF41) and surface antigens (IL1RAPL2, PGRMC1), and pathway analysis suggests their involvement in cell proliferation (PGK1, SMS, UTP14A, SSR4), apoptosis (MTM1), inflammation (ARAF) and oxidative stress (ENOX2). In conclusion, we propose that X chromosome genes with different methylation profiles in monozygotic twin pairs may constitute candidates for SSc susceptibility. PMID:22861365

  7. Monozygotic Monochorionic Twins Discordant for Trisomy 21: A Reason to Evaluate Both Fetuses: A Case Report.

    PubMed

    Macatangga, Monica; De la Calle, Maria; Torres, Maria Luisa; Bartha, Jose Luis

    2016-01-01

    The occurrence of a discordant chromosomal abnormality in monozygotic twins is an extremely rare condition. We report the prenatal sonographic findings and cytogenetic studies in a monochorionic twin pregnancy discordant for severe fetal anomalies. Amniocentesis was normal for both twins. The pregnancy was managed conservatively, resulting in the delivery of discordant twins at 28 weeks. Cytogenetic analysis performed on cultured lymphocytes from peripheral blood revealed a mosaic 47XY+21 (in 2% of the cells)/46XY (in 98%) in the structurally normal twin, and a mosaic 47XY+21 (4%)/46XY (96%) for the abnormal twin. The abnormal neonate died shortly after delivery. The structurally normal twin survived without sequelae and had a normal karyotype 2 years later. This report adds to the literature a case of a monochorionic twin pregnancy with a mosaic fetus who gives his co-twin trisomic cells through placental vascular anastomoses, this twin being a chimera, highlighting the necessity of performing molecular genetics with polymorphic DNA markers to differentiate chimerism from mosaicism and define the origin of cell lines.

  8. Prenatal diagnosis of female monozygotic twins discordant for Turner syndrome: implications for prenatal genetic counselling.

    PubMed

    Gilbert, B; Yardin, C; Briault, S; Belin, V; Lienhardt, A; Aubard, Y; Battin, J; Servaud, M; Philippe, H J; Lacombe, D

    2002-08-01

    We describe a set of monozygotic (MZ) female twins, one of whom presented with a typical Turner syndrome (TS) phenotype and the other a normal female phenotype. Prenatal fetal ultrasonographic examination showed a monochorial diamniotic pregnancy with a hygroma colli and growth delay in Twin A and no anomalies in Twin B. Karyotypic analysis performed on fetal blood samples demonstrated a 46,XX/45,X (23/2) mosaicism in Twin A and a normal 46,XX chromosome constitution in Twin B. At birth, Twin A presented with a typical TS and Twin B had a normal female phenotype. Postnatal cytogenetic investigation of blood lymphocytes showed the same 46,XX/45,X mosaicism in both twins: 46,XX/45,X (40/7) in Twin A and 46,XX/45,X (40/5) in Twin B. Further investigations at the age of 10 months showed in Twin A a 46,XX/45,X (98/2) mosaicism in lymphocytes and 100% of 45,X (50 analysed cells) in fibroblasts, and in Twin B a normal 46,XX (100 analysed cells) chromosome constitution in lymphocytes but a mild 46,XX/45,X (78/2) mosaicism in fibroblasts. Monozygosity was confirmed by molecular analysis. To our knowledge, this is the first report of prenatal diagnosis of MZ female twins discordant for TS. Review of reported sets of MZ female twins (eight cases) or triplets (one case) discordant for TS shows, as in the present case, that the phenotype correlates better with the chromosomal distribution of mosaicism in fibroblasts than in lymphocytes. In the blood of MZ twins chimerism may modify the initial allocation of the mosaicism. These results suggest that, in cases of prenatal diagnosis of MZ female twins discordant for TS, the phenotype of each twin would be better predicted from karyotype analysis of cells from amniotic fluid than from fetal blood.

  9. Monozygotic twins with discordant karyotypes following preimplantation genetic screening and single embryo transfer: case report

    PubMed Central

    Gaillyova, Renata; Travnik, Pavel; Oracova, Eva; Vesela, Katerina; Hromadova, Lenka; Vesely, Jan; Musilova, Petra; Rubes, Jiri; Kadlecova, Jitka; Slamova, Iva; Makaturova, Eva; Vranova, Vladimira

    2010-01-01

    Purpose To report a case of monozygotic monochorial diamniotic twins with discordant karyotypes. Methods and results The pregnancy was achieved following a treatment cycle with intracytoplasmic sperm injection (ICSI) and preimplantation genetic screening (PGS) for chromosomes X, Y, 13, 16, 18, 21, 22. One embryo euploid for studied chromosomes was transferred. Prenatal ultrasonography revealed monozygotic twins. One fetus had growth retardation, multiple organ abnormalities and polyhydramnion. The other twin had normal ultrasound appearance. Delivery on week 29 of gestation resulted in the birth of two females, a stillborn twin with karyotype 45,XX,-13[12]/46,XX,r(13)[3] and a healthy twin with normal karyotype. Conclusions The discordance in the twins’ karyotypes originated from a mosaic embryo. Structural chromosomal abnormality of the affected twin could not be revealed using standard PGS investigation. Embryo splitting occurred probably due to apoptotic process in an early stage of embryo development. Apoptosis represents one of the possible mechanisms which can explain the embryo twinning process globally. PMID:20700760

  10. DNA Methylation Changes in the IGF1R Gene in Birth Weight Discordant Adult Monozygotic Twins.

    PubMed

    Tsai, Pei-Chien; Van Dongen, Jenny; Tan, Qihua; Willemsen, Gonneke; Christiansen, Lene; Boomsma, Dorret I; Spector, Tim D; Valdes, Ana M; Bell, Jordana T

    2015-12-01

    Low birth weight (LBW) can have an impact on health outcomes in later life, especially in relation to pre-disposition to metabolic disease. Several studies suggest that LBW resulting from restricted intrauterine growth leaves a footprint on DNA methylation in utero, and this influence likely persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg12562232, p = 2.62 × 10(-8)), was significantly associated with birth weight discordance at a genome-wide false-discovery rate (FDR) of 0.05. We pursued replication in three additional independent datasets of birth weight discordant MZ pairs and observed the same direction of association, but the results were not significant. However, a meta-analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect was particularly pronounced in older twins (random-effects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent of genetic effects.

  11. Attention Problems and Attention-Deficit/Hyperactivity Disorder in Discordant and Concordant Monozygotic Twins: Evidence of Environmental Mediators

    ERIC Educational Resources Information Center

    Lehn, Hanne; Derks, Eske M.; Hudziak, James J.; Heutink, Peter; van Beijsterveldt, Toos; Boomsma, Dorret I.

    2007-01-01

    Objective: To study familial and nonfamilial environmental influences on attention problems and attention-deficit/hyperactivity disorder (ADHD) in monozygotic twins discordant and concordant-high and low for these traits. Method: Ninety-five twin pairs from The Netherlands Twin Register were selected. Longitudinal survey data were collected at 1,…

  12. Attention Problems and Attention-Deficit/Hyperactivity Disorder in Discordant and Concordant Monozygotic Twins: Evidence of Environmental Mediators

    ERIC Educational Resources Information Center

    Lehn, Hanne; Derks, Eske M.; Hudziak, James J.; Heutink, Peter; van Beijsterveldt, Toos; Boomsma, Dorret I.

    2007-01-01

    Objective: To study familial and nonfamilial environmental influences on attention problems and attention-deficit/hyperactivity disorder (ADHD) in monozygotic twins discordant and concordant-high and low for these traits. Method: Ninety-five twin pairs from The Netherlands Twin Register were selected. Longitudinal survey data were collected at 1,…

  13. Monozygotic twins with 45,X/46,XY mosaicism discordant for phenotypic sex.

    PubMed

    Costa, T; Lambert, M; Teshima, I; Ray, P N; Richer, C L; Dallaire, L

    1998-01-06

    We report on two sets of monozygotic twins (MZTs) discordant for phenotypic sex ascertained at birth when the female twin was noted to have signs of the Ullrich-Turner syndrome. Cytogenetic investigations on the female of the first pair showed 45,X/46,XY mosaicism in lymphocytes but fibroblasts grown from two skin biopsies at separate sites and from gonadal tissue showed only 45,X cells. The male showed mosaicism in both blood lymphocytes and skin fibroblasts. In the second family, both twins also showed mosaicism in lymphocytes. The female had a 45,X karyotype in fibroblasts from skin and gonadal tissue, but in contrast to the first family, the male twin had a normal male karyotype in fibroblasts from skin biopsy and from connective tissue adjacent to the vas deferens. Discordant phenotypic sex in monozygotic twins is rare. As in our cases, the nine previously reported sets of MZTs all had mosaicism for sex chromosome abnormalities. A mitotic error leading to the loss of a Y chromosome prior to, accompanying, or following the twinning process would account for the reported combinations of karyotypes.

  14. Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences

    PubMed Central

    2012-01-01

    Genetic-epidemiological studies on monozygotic (MZ) twins have been used for decades to tease out the relative contributions of genes and the environment to a trait. Phenotypic discordance in MZ twins has traditionally been ascribed to non-shared environmental factors acting after birth, however recent data indicate that this explanation is far too simple. In this paper, we review other reasons for discordance, including differences in the in utero environment, genetic mosaicism, and stochastic factors, focusing particularly on epigenetic discordance. Epigenetic differences are gaining increasing recognition. Although it is clear that in specific cases epigenetic alterations provide a causal factor in disease etiology, the overall significance of epigenetics in twin discordance remains unclear. It is also challenging to determine the causality and relative contributions of environmental, genetic, and stochastic factors to epigenetic variability. Epigenomic profiling studies have recently shed more light on the dynamics of temporal methylation change and methylome heritability, yet have not given a definite answer regarding their relevance to disease, because of limitations in establishing causality. Here, we explore the subject of epigenetics as another component in human phenotypic variability and its links to disease focusing particularly on evidence from MZ twin studies. PMID:22898292

  15. Proteomic analysis of lymphoblastoid cells derived from monozygotic twins discordant for bipolar disorder: a preliminary study.

    PubMed

    Kazuno, An-a; Ohtawa, Kenji; Otsuki, Kaori; Usui, Masaya; Sugawara, Hiroko; Okazaki, Yuji; Kato, Tadafumi

    2013-01-01

    Bipolar disorder is a severe mental illness characterized by recurrent manic and depressive episodes. In bipolar disorder, family and twin studies suggest contributions from genetic and environmental factors; however, the detailed molecular pathogenesis is yet unknown. Thus, identification of biomarkers may contribute to the clinical diagnosis of bipolar disorder. Monozygotic twins discordant for bipolar disorder are relatively rare but have been reported. Here we performed a comparative proteomic analysis of whole cell lysate derived from lymphoblastoid cells of monozygotic twins discordant for bipolar disorder by using two-dimensional differential in-gel electrophoresis (2D-DIGE). We found approximately 200 protein spots to be significantly differentially expressed between the patient and the co-twin (t test, p<0.05). Some of the proteins were subsequently identified by liquid chromatography tandem mass spectrometry and included proteins involved in cell death and glycolysis. To examine whether these proteins could serve as biomarkers of bipolar disorder, we performed Western blot analysis using case-control samples. Expression of phosphoglycerate mutase 1 (PGAM1), which is involved in glycolysis, was significantly up-regulated in patients with bipolar disorder (t test, p<0.05). Although PGAM1 cannot be regarded as a qualified biomarker of bipolar disorder from this preliminary finding, it could be one of the candidates for further study to identify biomarkers of bipolar disorder.

  16. Differential DNA Methylation in Monozygotic Twins Discordant for Female Sexual Functioning.

    PubMed

    Burri, Andrea; Leupin, Myriam; Spector, Timothy; Marinova, Zoya

    2017-09-27

    Research has repeatedly suggested genetic and environmental factors in the etiology underlying female sexual dysfunction (FSD). Because sexual functioning is a highly variable trait, epigenetics could provide a promising approach to tackle the origins of FSD and consequently offer a step-change in our understanding of these problems. To identify differentially methylated CpG positions for sexual functioning in a sample of monozygotic twin pairs discordant for sexual functioning. The sample consisted of 33 trait-discordant monozygotic twin pairs (mean age = 54.1 years, SD = 9.05) from the Twins UK Registry. Phenotypic data on sexual desire, arousal, lubrication, orgasm, satisfaction, and pain were collected using the Female Sexual Function Index-Lifelong (FSFI-LL). The Illumina Infinium HumanMethylation 450 DNA BeadChip was used for epigenome-wide analyses of DNA methylation in whole-blood samples. Comparison of DNA methylation patterns associated with the FSFI-LL total score and its six subdomains. Two differentially methylated CpG positions (cg09580409 and cg14734994) reaching experiment-wide statistical significance were found for overall sexual functioning, mapping to MGC45800 and the threonine synthase-like 2 gene (THNSL2), respectively. Furthermore, potential biologically relevant candidates for sexual desire (CUB and zona pellucida-like domains 1, CUZD1) and satisfaction (solute carrier family 6 member 19, SLC6A19) were identified. THNSL2 and SLC6A19, which have been linked to weight and adiposity, might represent novel candidates for sexual problems in women. This is the first study to investigate epigenetic mechanisms underlying FSD. The study used a relative small sample of monozygotic female twins. The cutoff to determine discordance in sexual problems was chosen based on a 10% FSFI score difference. Therefore, the results have to be interpreted with caution and need replication in larger clinical samples. Understanding how genes and environment

  17. The corpus callosum in monozygotic twins concordant and discordant for handedness and language dominance.

    PubMed

    Häberling, Isabelle S; Badzakova-Trajkov, Gjurgjica; Corballis, Michael C

    2012-10-01

    We used diffusion tensor imaging to assess callosal morphology in 35 pairs of monozygotic twins, of which 17 pairs were concordant for handedness and 18 pairs were discordant for handedness. Functional hemispheric language dominance was established for each twin member using fMRI, resulting in 26 twin pairs concordant and 9 twin pairs discordant for language dominance. On the basis of genetic models of handedness and language dominance, which assume one "right shift" (RS) gene with two alleles, an RS+ allele biasing toward right-handedness and left cerebral language dominance and an RS- allele leaving both asymmetries to chance, all twins were classified according to their putative genotypes, and the possible effects of the gene on callosal morphology was assessed. Whereas callosal size was under a high genetic control that was independent of handedness and language dominance, twin pairs with a high probability of carrying the putative RS+ allele showed a connectivity pattern characterized by a genetically controlled, low anisotropic diffusion over the whole corpus callosum. In contrast, the high connectivity pattern exhibited by twin pairs more likely to lack the RS+ allele was under significantly less genetic influence. The data suggest that handedness and hemispheric dominance for speech production might be at least partly dependent on genetically controlled processes of axonal pruning in the corpus callosum.

  18. Influence of acquired obesity on coronary vessel wall late gadolinium enhancement in discordant monozygote twins.

    PubMed

    Makowski, Marcus R; Jansen, Christian H P; Ebersberger, Ullrich; Schaeffter, Tobias; Razavi, Reza; Mangino, Massimo; Spector, Tim D; Botnar, Rene M; Greil, Gerald F

    2016-10-14

    The aim of this study was to investigate the impact of BMI on late gadolinium enhancement (LGE) of the coronary artery wall in identical monozygous twins discordant for BMI. Coronary LGE represents a useful parameter for the detection and quantification of atherosclerotic coronary vessel wall disease. Thirteen monozygote female twin pairs (n = 26) with significantly different BMIs (>1.6 kg/m2) were recruited out of >10,000 twin pairs (TwinsUK Registry). A coronary 3D-T2prep-TFE MR angiogram and 3D-IR-TFE vessel wall scan were performed prior to and following the administration of 0.2 mmol/kg of Gd-DTPA on a 1.5 T MR scanner. The number of enhancing coronary segments and contrast to noise ratios (CNRs) of the coronary wall were quantified. An increase in BMI was associated with an increased number of enhancing coronary segments (5.3 ± 1.5 vs. 3.5 ± 1.6, p < 0.0001) and increased coronary wall enhancement (6.1 ± 1.1 vs. 4.8 ± 0.9, p = 0.0027) compared to matched twins with lower BMI. This study in monozygous twins indicates that acquired factors predisposing to obesity, including lifestyle and environmental factors, result in increased LGE of the coronary arteries, potentially reflecting an increase in coronary atherosclerosis in this female study population. • BMI-discordant twins allow the investigation of the influence of lifestyle factors independent from genetic confounders. • Only thirteen obesity-discordant twins were identified underlining the strong genetic component of BMI. • In female twins, a BMI increase is associated with increased coronary late gadolinium enhancement. • Increased late gadolinium enhancement in the coronary vessel wall potentially reflects increased atherosclerosis.

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

    PubMed Central

    Zhang, Su-Hua; Chen, Jinzhong; Lu, Daru; Shen, Min; Li, Chengtao

    2015-01-01

    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. PMID:26248206

  20. Genome-Wide DNA Methylation and Gene Expression Analyses of Monozygotic Twins Discordant for Intelligence Levels

    PubMed Central

    Kobayashi, Kazuhiro; Shikishima, Chizuru; Cha, Pei-Chieng; Sese, Jun; Sugawara, Hiroko; Iwamoto, Kazuya; Kato, Tadafumi; Ando, Juko; Toda, Tatsushi

    2012-01-01

    Human intelligence, as measured by intelligence quotient (IQ) tests, demonstrates one of the highest heritabilities among human quantitative traits. Nevertheless, studies to identify quantitative trait loci responsible for intelligence face challenges because of the small effect sizes of individual genes. Phenotypically discordant monozygotic (MZ) twins provide a feasible way to minimize the effects of irrelevant genetic and environmental factors, and should yield more interpretable results by finding epigenetic or gene expression differences between twins. Here we conducted array-based genome-wide DNA methylation and gene expression analyses using 17 pairs of healthy MZ twins discordant intelligently. ARHGAP18, related to Rho GTPase, was identified in pair-wise methylation status analysis and validated via direct bisulfite sequencing and quantitative RT-PCR. To perform expression profile analysis, gene set enrichment analysis (GSEA) between the groups of twins with higher IQ and their co-twins revealed up-regulated expression of several ribosome-related genes and DNA replication-related genes in the group with higher IQ. To focus more on individual pairs, we conducted pair-wise GSEA and leading edge analysis, which indicated up-regulated expression of several ion channel-related genes in twins with lower IQ. Our findings implied that these groups of genes may be related to IQ and should shed light on the mechanism underlying human intelligence. PMID:23082141

  1. Two pairs of proven monozygotic twins discordant for familial amyloid neuropathy (FAP) TTR Met 30

    PubMed Central

    Munar-Ques, M.; Pedrosa, J.; Coelho, T.; Gusmao, L.; Seruca, R.; Amorim, A.; Sequeiros, J.

    1999-01-01

    Twin studies are an important tool in medical genetics for the evaluation of the relative roles of genetic and non-genetic factors in several diseases. Familial amyloidotic polyneuropathy type I (FAP-I), TTR Met 30, was present in two sets of proven monozygotic (MZ) twins, one from Majorca and the other from Portugal. Monozygosity was established by analysis of DNA polymorphisms. Both pairs were discordant for age at onset and some clinical manifestations of FAP-I. We reviewed the differences in age at onset and clinical features in both sets and in two other pairs of presumed MZ twins with FAP-I and compared them with those in MZ twin pairs with other Mendelian disorders, such as neurofibromatosis type 1, Huntington's disease, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. We conclude that, in addition to the postulated modifying genes, there must be a significant contribution from non-genetic factors to the phenotypic variability of FAP-I (age at onset and clinical expression), either because of enviromental differences or stochastic events during (or after) the twinning process.


Keywords: hereditary amyloidosis; discordant MZ twins; non-genetic factors; stochastic process PMID:10465115

  2. Psychiatric outcomes of bullying victimization: A study of discordant monozygotic twins

    PubMed Central

    Silberg, Judy L.; Copeland, William; Linker, Julie; Moore, Ashlee A.; Roberson-Nay, Roxann; York, Timothy P.

    2016-01-01

    Background Bullying victimization in childhood is associated with a broad array of serious mental health disturbances, including anxiety, depression, and suicidal ideation and behavior. The key goal of this study was to evaluate whether bullying victimization is a true environmental risk factor for psychiatric disturbance using data from 145 bully-discordant monozygotic (MZ) juvenile twin pairs from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and their follow-up into young adulthood. Method Since MZ twins share an identical genotype and familial environment, a higher rate of psychiatric disturbance in a bullied MZ twin compared to their non-bullied MZ co-twin would be evidence of an environmental impact of bullying victimization. Environmental correlations between being bullied and the different psychiatric traits were estimated by fitting structural equation models to the full sample of MZ and DZ twins (N = 2824). Environmental associations were further explored using the longitudinal data on the bullying-discordant MZ twins. Results Being bullied was associated with a wide range of psychiatric disorders in both children and young adults. The analysis of data on the MZ-discordant twins supports a genuine environmental impact of bullying victimization on childhood social anxiety [odds ratio (OR) 1.7], separation anxiety (OR 1.9), and young adult suicidal ideation (OR 1.3). There was a shared genetic influence on social anxiety and bullying victimization, consistent with social anxiety being both an antecedent and consequence of being bullied. Conclusion Bullying victimization in childhood is a significant environmental trauma and should be included in any mental health assessment of children and young adults. PMID:26979565

  3. Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders.

    PubMed

    Kato, T; Iwamoto, K; Kakiuchi, C; Kuratomi, G; Okazaki, Y

    2005-07-01

    Classical twin research focused on differentiating genetic factors from environmental factors by comparing the concordance rate between monozygotic (MZ) and dizygotic twins. On the other hand, recent twin research tries to identify genetic or epigenetic differences between MZ twins discordant for mental disorders. There are a number of reports of MZ twins discordant for genetic disorders caused by genetic or epigenetic differences of known pathogenic genes. In the case of mental disorder research, for which the causative gene has not been established yet, we are trying to identify the 'pathogenic gene' by comprehensive analysis of genetic or epigenetic difference between discordant MZ twins. To date, no compelling evidence suggesting such difference between MZ twins has been reported. However, if the genetic or epigenetic difference responsible for the discordant phenotype is found, it will have impact on the biology of mental disorder, in which few conclusive molecular genetic evidences have been obtained.

  4. Novel epigenetic changes unveiled by monozygotic twins discordant for smoking habits.

    PubMed

    Allione, Alessandra; Marcon, Francesca; Fiorito, Giovanni; Guarrera, Simonetta; Siniscalchi, Ester; Zijno, Andrea; Crebelli, Riccardo; Matullo, Giuseppe

    2015-01-01

    Exposure to cigarette smoking affects the epigenome and could increase the risk of developing diseases such as cancer and cardiovascular disorders. Changes in DNA methylation associated with smoking may help to identify molecular pathways that contribute to disease etiology. Previous studies are not completely concordant in the identification of differentially methylated regions in the DNA of smokers. We performed an epigenome-wide DNA methylation study in a group of monozygotic (MZ) twins discordant for smoking habits to determine the effect of smoking on DNA methylation. As MZ twins are considered genetically identical, this model allowed us to identify smoking-related DNA methylation changes independent from genetic components. We investigated the whole blood genome-wide DNA methylation profiles in 20 MZ twin pairs discordant for smoking habits by using the Illumina HumanMethylation450 BeadChip. We identified 22 CpG sites that were differentially methylated between smoker and non-smoker MZ twins by intra-pair analysis. We confirmed eight loci already described by other groups, located in AHRR, F2RL3, MYOG1 genes, at 2q37.1 and 6p21.33 regions, and also identified several new loci. Moreover, pathway analysis showed an enrichment of genes involved in GTPase regulatory activity. Our study confirmed the evidence of smoking-related DNA methylation changes, emphasizing that well-designed MZ twin models can aid the discovery of novel DNA methylation signals, even in a limited sample population.

  5. Discordant Growth of Monozygotic Twins Starts at the Blastocyst Stage: A Case Study

    PubMed Central

    Noli, Laila; Capalbo, Antonio; Ogilvie, Caroline; Khalaf, Yacoub; Ilic, Dusko

    2015-01-01

    Summary Discordant growth is a common complication of monochorionic/diamniotic pregnancies; in approximately 50% of cases, the cause is unknown. The case presented here suggests that discordant growth of monozygotic twins could start during preimplantation development. Two inner cell masses (ICMs) within the same blastocyst may originate in uneven splitting of a single “parental” ICM, or the two ICMs may be formed independently de novo. We studied the transcriptomes of two morphologically distinct ICMs within a single blastocyst using high-resolution RNA sequencing. The data indicated that the two ICM were at different stages of development; one was in the earliest stages of lineage commitment, while the other had already differentiated into epiblast and primitive endoderm. IGF1-mediated signaling is likely to play a key role in ICM growth and to be the major driver behind these differences. PMID:26584541

  6. Genomic and epigenomic analyses of monozygotic twins discordant for congenital renal agenesis.

    PubMed

    Jin, Meiling; Zhu, Shida; Hu, Panpan; Liu, Dongbing; Li, Qinggang; Li, Zuoxiang; Zhang, Xueguang; Xie, Yuansheng; Chen, Xiangmei

    2014-07-01

    Monozygotic twins have been widely studied to distinguish genetic and environmental factors in the pathogenesis of human diseases. For renal agenesis, the one-sided absence of renal tissue, the relative contributions of genetic and environmental factors to its pathogenesis are still unclear. In this study of a pair of monozygotic twins discordant for congenital renal agenesis, the genomic profile was analyzed from a set of blood samples using high-throughput exome-capture sequencing to detect single-nucleotide polymorphisms (SNPs), copy number variations (CNVs), and insertions and deletions (indels). Also, an epigenomic analysis used reduced-representation bisulfite sequencing to detect differentially methylated regions (DMRs). No discordant SNPs, CNVs, or indels were confirmed, but 514 DMRs were detected. KEGG analysis indicated the DMRs localized to 10 signaling pathways and 25 genes, including the mitogen-activated protein kinase pathway and 6 genes (FGF18, FGF12, PDGFRA, MAPK11, AMH, CTBP1) involved in organ development. Although methylation results from our adult patient and her sister may not represent the pattern that was present during kidney development, we could at least confirm a lack of obvious differences at the genome level, which suggests that nongenetic factors may be involved in the pathogenesis of renal agenesis.

  7. Discordance of oral-facial-digital syndrome type 1 in monozygotic twin girls.

    PubMed

    Shotelersuk, V; Tifft, C J; Vacha, S; Peters, K F; Biesecker, L G

    1999-09-17

    The oral-facial-digital syndrome type 1 (OFD1) includes limb, facial, intraoral malformations and the gene for the disorder was recently mapped to Xp22.3-p22.2. We report on monozygotic twin girls discordant for OFD1. Monozygosity is supported by placental pathology (monochorionic diamniotic) and molecular studies with probability of dizygosity <1 x 10(-6). The affected twin has oral cavity abnormalities including median cleft lip, cleft palate, lobulated hamartomatous tongue, aberrant hyperplastic oral frenula, alveolar notches, and absent lateral incisors. Facial manifestations include telecanthus, hypoplastic alae nasi, and transient neonatal facial milia. The patient also has short and deviated fingers with partial cutaneous syndactyly. At 10 years, she has not had central nervous system or kidney problems. X-inactivation study revealed similar X-inactivation patterns in the lymphoblasts of both twins. We conclude that skewed X-inactivation is an unlikely cause for the discordance, which is more likely due to a postzygotic mutation in the affected twin. Copyright 1999 Wiley-Liss, Inc.

  8. Discordant tooth agenesis and peg-shaped in a pair of monozygotic twins: Clinical and molecular study.

    PubMed

    Antunes, Lívia Azeredo Alves; Küchler, Erika Calvano; Costa, Marcelo de Castro; Antunes, Leonardo Santos; Granjeiro, José Mauro

    2013-11-01

    The present report aimed to study an uncommon case of a pair of twins that presented a discordant dental phenotype. Family investigation, clinical, radiographic examination and molecular analysis were performed in both girls. Molecular analysis confirmed the monozygosity by deoxyribonucleic acid chip technology. One twin presented tooth agenesis in left upper lateral incisor and peg-shaped on the contra lateral side while the other twin had no dental alterations. The dental casts study employed digital caliper to compare morphological dimensions and showed alteration only in peg-shaped tooth. In conclusion, this study provide support that one or more mutated gene could cause discordances in dental phenotype in these monozygotic twins.

  9. Hypomethylation within Gene Promoter Regions and Type 1 Diabetes in Discordant Monozygotic Twins

    PubMed Central

    Elboudwarej, Emon; Cole, Michael; Briggs, Farren B.S.; Fouts, Alexandra; Fain, Pamela R.; Quach, Hong; Quach, Diana; Sinclair, Elizabeth; Criswell, Lindsey A.; Lane, Julie A.; Steck, Andrea K.; Barcellos, Lisa F.; Noble, Janelle A.

    2016-01-01

    Genetic susceptibility to type 1 diabetes (T1D) is well supported by epidemiologic evidence; however, disease risk cannot be entirely explained by established genetic variants identified so far. This study addresses the question of whether epigenetic modification of the inherited DNA sequence may contribute to T1D susceptibility. Using the Infinium HumanMethylation450 BeadChip array (450k), a total of seven long-term disease-discordant monozygotic (MZ) twin pairs and five pairs of HLA-identical, disease-discordant non-twin siblings (NTS) were examined for associations between DNA methylation (DNAm) and T1D. Strong evidence for global hypomethylation of CpG sites within promoter regions in MZ twins with TID compared to twins without T1D was observed. DNA methylation data were then grouped into three categories of CpG sites for further analysis, including those within: 1) the major histocompatibility complex (MHC) region, 2) non-MHC genes with reported T1D association through genome wide association studies (GWAS), and 3) the epigenome, or remainder of sites that did not include MHC and T1D associated genes. Initial results showed modest methylation differences between discordant MZ twins for the MHC region and T1D-associated CpG sites, BACH2, INS-IGF2, and CLEC16A (DNAm difference range: 2.2% – 5.0%). In the epigenome CpG set, the greatest methylation differences were observed in MAGI2, FANCC, and PCDHB16, (DNAm difference range: 6.9% – 16.1%). These findings were not observed in the HLA-identical NTS pairs. Targeted pyrosequencing of five candidate CpG loci identified using the 450k array in the original discordant MZ twins produced similar results using control DNA samples, indicating strong agreement between the two DNA methylation profiling platforms. However, findings for the top five candidate CpG loci were not replicated in six additional T1D-discordant MZ twin pairs. Our results indicate global DNA hypomethylation within gene promoter regions may

  10. Hypomethylation within gene promoter regions and type 1 diabetes in discordant monozygotic twins.

    PubMed

    Elboudwarej, Emon; Cole, Michael; Briggs, Farren B S; Fouts, Alexandra; Fain, Pamela R; Quach, Hong; Quach, Diana; Sinclair, Elizabeth; Criswell, Lindsey A; Lane, Julie A; Steck, Andrea K; Barcellos, Lisa F; Noble, Janelle A

    2016-04-01

    Genetic susceptibility to type 1 diabetes (T1D) is well supported by epidemiologic evidence; however, disease risk cannot be entirely explained by established genetic variants identified so far. This study addresses the question of whether epigenetic modification of the inherited DNA sequence may contribute to T1D susceptibility. Using the Infinium HumanMethylation450 BeadChip array (450k), a total of seven long-term disease-discordant monozygotic (MZ) twin pairs and five pairs of HLA-identical, disease-discordant non-twin siblings (NTS) were examined for associations between DNA methylation (DNAm) and T1D. Strong evidence for global hypomethylation of CpG sites within promoter regions in MZ twins with TID compared to twins without T1D was observed. DNA methylation data were then grouped into three categories of CpG sites for further analysis, including those within: 1) the major histocompatibility complex (MHC) region, 2) non-MHC genes with reported T1D association through genome wide association studies (GWAS), and 3) the epigenome, or remainder of sites that did not include MHC and T1D associated genes. Initial results showed modest methylation differences between discordant MZ twins for the MHC region and T1D-associated CpG sites, BACH2, INS-IGF2, and CLEC16A (DNAm difference range: 2.2%-5.0%). In the epigenome CpG set, the greatest methylation differences were observed in MAGI2, FANCC, and PCDHB16, (DNAm difference range: 6.9%-16.1%). These findings were not observed in the HLA-identical NTS pairs. Targeted pyrosequencing of five candidate CpG loci identified using the 450k array in the original discordant MZ twins produced similar results using control DNA samples, indicating strong agreement between the two DNA methylation profiling platforms. However, findings for the top five candidate CpG loci were not replicated in six additional T1D-discordant MZ twin pairs. Our results indicate global DNA hypomethylation within gene promoter regions may contribute to T

  11. Monozygotic twins are discordant for chronic periodontitis: white blood cell counts and cytokine production after ex vivo stimulation.

    PubMed

    Torres de Heens, Gaudy L; Loos, Bruno G; van der Velden, Ubele

    2010-02-01

    The aim of this study was to investigate the extent of concordance in the number of leucocytes and their cytokine secretion after ex vivo stimulation in a twin population discordant for the amount of periodontal breakdown. Venous blood was collected from 18 adult twin pairs (10 monozygotic and eight dizygotic twins). Each twin pair consisted of a diseased twin (proband) and his/her co-twin. In venous blood, leucocytes were counted. The cytokines interleukin (IL)-1beta, IL-6, IL-8, IL-10 and IL-12p40 were assessed after stimulation of monocytic cells, while IL-13 and interferon (IFN)-gamma were determined after lymphocytic stimulation. In the study population as a whole, probands showed higher total numbers of leucocytes and lower IL-12p40 levels compared with their co-twins. In monozygotic twins, no difference was found in the leucocyte counts, but probands secreted more IL-6 than their co-twins; an opposite trend was found for IL-12p40. The results suggest that the observed discordance in periodontal breakdown in the studied monozygotic twin population may be related to the relatively high levels of IL-6 and the low levels of IL-12p40 secretion after ex vivo stimulation of whole-blood cell cultures. This cytokine secretion profile may be regarded as a risk indicator of periodontitis.

  12. Discordant Type I Preaxial Polydactyly in Monozygotic Twins on the Same Hand: A Case Report.

    PubMed

    Ng, Zhi Yang; Sau, Po Yi; Lim, Gale Jue-Shuang

    2015-10-01

    There are 4 types of preaxial polydactyly (PPD), and type I (PPD-I), also known as thumb duplication, is the most common. This frequently encountered condition has since been further described and classified by Wassel based on the level of duplication of skeletal anatomy. Genetic studies have localized possible candidate gene(s) for PPD types II to IV to the chromosomal region 7q36 but the current literature attributes PPD-I to isolated, spontaneous mutations typically with unilateral involvement only. Recent epidemiological studies have also suggested nongenetic causes for PPD-I including social and environmental factors. Herein, we would like to present a case of discordant PPD-I expression affecting the same hand in a pair of monozygotic twins and suggest possible reasons for this presentation because previous similar reports only had involvement of 1 child.

  13. Xenotropic Murine Leukemia Virus-Related Virus in Monozygotic Twins Discordant for Chronic Fatigue Syndrome

    PubMed Central

    Jerome, Keith R.; Diem, Kurt; Huang, Meei-Li; Selke, Stacy; Corey, Lawrence; Buchwald, Dedra

    2011-01-01

    A recent report suggested an association between xenotropic murine leukemia virus-related virus (XMRV) and chronic fatigue syndrome (CFS). If confirmed, this would suggest that antiretroviral therapy might benefit patients suffering from CFS. We validated a set of assays for XMRV, and evaluated the prevalence of XMRV in a cohort of monozygotic twins discordant for CFS. Stored PBMC were tested with 3 separate PCR assays (one of which was nested) for XMRV DNA, and serum/plasma was tested for XMRV RNA by reverse transcription (RT)-PCR. None of the PBMC samples from the twins with CFS or their unaffected co-twins were positive for XMRV, by any of the assays. One plasma sample, from an unaffected co-twin, was reproducibly positive by RT-PCR. However, serum from the same day was negative, as was a followup plasma sample obtained 2 days after the positive specimen. These data do not support an association of XMRV with CFS. PMID:21795004

  14. Increased Expression and Altered Methylation of HERVWE1 in the Human Placentas of Smaller Fetuses from Monozygotic, Dichorionic, Discordant Twins

    PubMed Central

    Wang, Zilian; Luo, Yanmin; Sun, Hongyu; Zhou, Yi; Huang, Linhuan; Li, Manchao; Fang, Qun; Jiang, Shiwen

    2012-01-01

    Background The human endogenous retroviral family W, Env(C7), member 1 gene (HERVWE1) is thought to participate in trophoblast cell fusion, and its expression is diminished in the placentas of singleton intrauterine growth-retarded pregnancies. However, there is limited information about the role of HERVWE1 in discordant fetal growth in twins. This study was to compare HERVWE1 gene expression between the placentas of discordant monozygotic twins and to identify its regulation by methylation. Methodology/Principal Findings Fetuses from twenty-one pairs of monozygotic, dichorionic, discordant twins were marked as “smaller” or “larger” according to birth weight. Placental HERVWE1 mRNA and protein expression profiles were analyzed using quantitative RT-PCR and immunohistochemistry (IHC) staining. Methylation profiles of the HERVWE1 promoter region were analyzed using a pyrosequencing assay. DNA methyltransferase (DNMT) transcript levels were analyzed by RT-PCR. 5-methyl cytosine (5-MC) was stained using an immunohistochemical assay. There was a significant negative correlation between HERVWE1 mRNA levels and birth weight in twins (P<0.01). Whereas the mean methylation level of the HERVWE1 promoter region was diminished in the smaller group in discordant twins(P<0.01), increased mRNA and protein levels of HERVWE1 were found in smaller fetuses compared with larger fetuses in discordant twins(P<0.01). There was no significant difference in 5-MC staining intensity between discordant twins (P>0.05). The DNMT3b3 mRNA levels in the smaller group were significantly downregulated compared with the larger group in discordant twins(P<0.05), whereas the DNMT3b7 mRNA levels in the smaller group were significantly upregulated compared with the larger group in discordant twins(P<0.05). Conclusions/Significance In discordant, monozygotic, dichorionic twins, HERVWE1 expression was higher in smaller fetuses and lower in larger fetuses. Methylation of the HERVWE1 gene promoter

  15. Transcriptional and epigenetic phenomena in peripheral blood cells of monozygotic twins discordant for alzheimer's disease, a case report.

    PubMed

    D'Addario, Claudio; Candia, Sussy Bastias; Arosio, Beatrice; Di Bartolomeo, Martina; Abbate, Carlo; Casè, Alessandra; Candeletti, Sanzio; Romualdi, Patrizia; Damanti, Sarah; Maccarrone, Mauro; Bergamaschini, Luigi; Mari, Daniela

    2017-01-15

    Target genes in Alzheimer's disease (AD) have been identified. In monozygotic twins discordant for AD we analysed the expression of selected genes, and their possible regulation by epigenetic mechanisms in peripheral blood mononuclear cells, possibly useful to discover biomarkers. Amyloid precursor protein, sirtuin 1 and peptidyl prolyl isomerase 1 gene expressions were highly up-regulated in the AD twin versus the healthy one. Consistently with sirtuin 1 role in controlling acetylation status, we observed a substantial reduction of the acetylation on histone 3 lysine 9, associated with gene transcription in the AD twin. Noteworthy in the AD twin we also observed an increased gene expression in two histone deacetylases (HDACs) isoforms: HDAC2 and HDAC9. A general DNA hypomethylation of all gene promoters studied was also observed in both twins. Our results unravel transcriptional and epigenetic differences potentially helpful to better understand environmental factors and phenotypic differences in monozygotic twins.

  16. Differential Response to High Glucose in Skin Fibroblasts of Monozygotic Twins Discordant for Type 1 Diabetes.

    PubMed

    Caramori, M Luiza; Kim, Youngki; Natarajan, Rama; Moore, Jason H; Rich, Stephen S; Mychaleckyj, Josyf C; Kuriyama, Ryoko; Kirkpatrick, David; Mauer, Michael

    2015-06-01

    Most epigenetic studies in diabetes compare normal cells in "high glucose" (HG) to cells in "normal glucose" (NG) and cells returned from HG to NG. Here we challenge this approach. The objective was to determine whether there were differences in gene expression in skin fibroblasts of monozygotic twins (MZT) discordant for type 1 diabetes (T1D). Skin fibroblasts were grown in NG (5.5 mmol/L) and HG (25 mmol/L) for multiple passages. This study was conducted at the University of Minnesota. Patients were nine MZT pairs discordant for T1D. Gene expression was assessed by mRNA-Seq, using the Illumina HiSeq 2000 instrument. Pathway analysis tested directionally consistent group differences within the Kyoto Encyclopedia of Genes and Genomes pathways. A total of 3308 genes were differentially expressed between NG and HG in T1D MZT vs 889 in non-T1D twins. DNA replication, proteasome, cell cycle, base excision repair, homologous recombination, pyrimidine metabolism, and spliceosome pathways had overrepresented genes with increased expression in T1D twins with P values ranging from 7.21 × 10(-10) to 1.39 × 10(-4). In a companion article, we demonstrate that these pathway changes are related to diabetic nephropathy risk. There were no pathways statistically significant differently expressed in nondiabetic twins in HG vs NG. In vivo exposure to diabetes alters cells in a manner that markedly changes their in vitro responses to HG. These results highlight the importance of using cells directly derived from diabetic patients for studies examining the effects of HG in diabetes.

  17. Genome, Epigenome and RNA sequences of Monozygotic Twins Discordant for Multiple Sclerosis

    SciTech Connect

    Miller, Neil

    2010-06-02

    Neil Miller, Deputy Director of Software Engineering at the National Center for Genome Resources, discusses a monozygotic twin study on June 2, 2010 at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM

  18. Global Transcript Profiles of Fat in Monozygotic Twins Discordant for BMI: Pathways behind Acquired Obesity

    PubMed Central

    Rissanen, Aila; Saharinen, Juha; Ellonen, Pekka; Keränen, Heli; Suomalainen, Anu; Götz, Alexandra; Suortti, Tapani; Yki-Järvinen, Hannele; Orešič, Matej; Kaprio, Jaakko; Peltonen, Leena

    2008-01-01

    Background The acquired component of complex traits is difficult to dissect in humans. Obesity represents such a trait, in which the metabolic and molecular consequences emerge from complex interactions of genes and environment. With the substantial morbidity associated with obesity, a deeper understanding of the concurrent metabolic changes is of considerable importance. The goal of this study was to investigate this important acquired component and expose obesity-induced changes in biological pathways in an identical genetic background. Methods and Findings We used a special study design of “clonal controls,” rare monozygotic twins discordant for obesity identified through a national registry of 2,453 young, healthy twin pairs. A total of 14 pairs were studied (eight male, six female; white), with a mean ± standard deviation (SD) age 25.8 ± 1.4 y and a body mass index (BMI) difference 5.2 ± 1.8 kg/m2. Sequence analyses of mitochondrial DNA (mtDNA) in subcutaneous fat and peripheral leukocytes revealed no aberrant heteroplasmy between the co-twins. However, mtDNA copy number was reduced by 47% in the obese co-twin's fat. In addition, novel pathway analyses of the adipose tissue transcription profiles exposed significant down-regulation of mitochondrial branched-chain amino acid (BCAA) catabolism (p < 0.0001). In line with this finding, serum levels of insulin secretion-enhancing BCAAs were increased in obese male co-twins (9% increase, p = 0.025). Lending clinical relevance to the findings, in both sexes the observed aberrations in mitochondrial amino acid metabolism pathways in fat correlated closely with liver fat accumulation, insulin resistance, and hyperinsulinemia, early aberrations of acquired obesity in these healthy young adults. Conclusions Our findings emphasize a substantial role of mitochondrial energy- and amino acid metabolism in obesity and development of insulin resistance. PMID:18336063

  19. A pair of monozygotic twins discordant for homosexuality: sex-dimorphic behavior and penile volume responses.

    PubMed

    McConaghy, N; Blaszczynski, A

    1980-04-01

    In reports of identical twins discordant for homosexuality, the homosexual twins showed the effeminacy syndrome in childhood. This has been considered evidence that the homosexuality comes from the twin himself. The possibility that the heterosexual twin was denying homosexuality has never been excluded. A pair of identical male twins discordant for homosexuality are reported. They showed significant differences in their penile volume responses to moving pictures of male and female nudes indicative of sexual orientations consistent with their statements. The homosexual twin showed the effeminacy syndrome. Aspects of the syndrome can be induced in mammals by altering their hormonal environment during some critical period in their intrauterine development. Discordance for homosexuality in identical twins could be due to one's being exposed to a different hormonal level during such a critical period.

  20. Expression discordance of monozygotic twins at birth: effect of intrauterine environment and a possible mechanism for fetal programming.

    PubMed

    Gordon, Lavinia; Joo, Ji-Hoon E; Andronikos, Roberta; Ollikainen, Miina; Wallace, Euan M; Umstad, Mark P; Permezel, Michael; Oshlack, Alicia; Morley, Ruth; Carlin, John B; Saffery, Richard; Smyth, Gordon K; Craig, Jeffrey M

    2011-05-01

    Within-pair comparison of monozygotic (MZ) twins provides an ideal model for studying factors that regulate epigenetic profile, by controlling for genetic variation. Previous reports have demonstrated epigenetic variability within MZ pairs, but the contribution of early life exposures to this variation remains unclear. As epigenetic marks govern gene expression, we have used gene expression discordance as a proxy measure of epigenetic discordance in MZ twins at birth in two cell types. We found strong evidence of expression discordance at birth in both cell types and some evidence for higher discordance in twin pairs with separate placentas. Genes previously defined as being involved in response to the external environment showed the most variable expression within pairs, independent of cell type, supporting the idea that even slight differences in intrauterine environment can influence expression profile. Focusing on birthweight, previously identified as a predisposing factor for cardiovascular, metabolic and other complex diseases, and using a statistical model that estimated association based on within-pair variation of expression and birthweight, we found some association between birthweight and expression of genes involved in metabolism and cardiovascular function. This study is the first to examine expression discordance in newborn twins. It provides evidence of a link between birthweight and activity of specific cellular pathways and, as evidence points to gene expression profiles being maintained through cell division by epigenetic factors, provides a plausible biological mechanism for the previously described link between low birthweight and increased risk of later complex disease.

  1. Non-random X chromosome inactivation in an affected twin in a monozygotic twin pair discordant for Wiedemann-Beckwith syndrome

    SciTech Connect

    Oestavik, R.E.; Eiklid, K.; Oerstavik, K.H.

    1995-03-27

    Wiedemann-Beckwith syndrome (WBS) is a syndrome including exomphalos, macroglossia, and generalized overgrowth. The locus has been assigned to 11p15, and genomic imprinting may play a part in the expression of one or more genes involved. Most cases are sporadic. An excess of female monozygotic twins discordant for WBS have been reported, and it has been proposed that this excess could be related to the process of X chromosome inactivation. We have therefore studied X chromosome inactivation in 13-year-old monozygotic twin girls who were discordant for WBS. In addition, both twins had Tourette syndrome. The twins were monochorionic and therefore the result of a late twinning process. This has also been the case in previously reported discordant twin pairs with information on placentation. X chromosome inactivation was determined in DNA from peripheral blood cells by PCR analysis at the androgen receptor locus. The affected twin had a completely skewed X inactivation, where the paternal allele was on the active X chromosome in all cells. The unaffected twin had a moderately skewed X inactivation in the same direction, whereas the mother had a random pattern. Further studies are necessary to establish a possible association between the expression of WBS and X chromosome inactivation. 18 refs., 2 figs., 1 tab.

  2. Incomplete penetrance of susceptibility genes for MHC-determined immunoglobulin deficiencies in monozygotic twins discordant for type 1 diabetes

    PubMed Central

    Alper, Chester A.; Husain, Zaheed; Larsen, Charles E.; Dubey, Devendra P.; Stein, Rosanne; Day, Caitlin; Baker, Alissa; Beyan, Huriya; Hawa, Mohammed; Ola, Thomas O.; Leslie, R. David

    2006-01-01

    Incomplete intrinsic penetrance is the failure of some genetically susceptible individuals (e.g., monozygotic twins of those who have a trait) to exhibit that trait. For the first time, we examine penetrance of susceptibility genes for multiple MHC gene-determined traits in the same subjects. Serum levels of IgA, IgD, IgG3, but not IgG4, in 50 pairs of monozygotic twins discordant for type 1 diabetes (T1D) correlated more closely in the twins than in random paired controls. The frequencies of subjects deficient in IgA (6%), IgD (33%) and IgG4 (12%), but not in IgG3, were higher in the twins than in controls. We postulate that this was because the MHC haplotypes (and possible non-MHC genes) that predispose to T1D also carry susceptibility genes for certain immunoglobulin deficiencies. Immunoglobulin deficiencies were not associated with T1D. Pairwise concordance for the deficiencies in the twins was 50% for IgA, 57% for IgD and 50% for IgG4. There were no significant associations among the specific immunoglobulin deficiencies except that all IgA-deficient subjects had IgD deficiency. Thus, intrinsic penetrance is a random process independently affecting different MHC susceptibility genes. Because multiple different external triggers would be required to explain the results, differential environmental determinants appear unlikely. PMID:17029885

  3. Monozygotic female twins discordant for Silver-Russell syndrome and hypomethylation of the H19-DMR.

    PubMed

    Yamazawa, Kazuki; Kagami, Masayo; Fukami, Maki; Matsubara, Keiko; Ogata, Tsutomu

    2008-01-01

    Silver-Russell syndrome (SRS) is characterized by growth failure and dysmorphic features, and is frequently caused by hypomethylation of the paternally derived H19-DMR (epimutation). We observed 5 8/12-year-old female twins discordant for SRS. One twin exhibited SRS-compatible features, such as pre- and postnatal growth failure, relative macrocephaly, triangular face, left hemihypotrophy, and bilateral fifth finger clinodactyly, whereas the other twin showed apparently normal phenotype. Microsatellite analysis for 26 loci on multiple chromosomes showed monozygosity. Methylation analysis for the H19-DMR indicated epimutation in roughly half of cells in the affected twin and normal patterns in the unaffected twin and the parents. X-inactivation analysis revealed random X-inactivation with a nearly identical pattern between the twins. The discordant methylation pattern of the H19-DMR may primarily be due to a failure to maintain the DNA methyltransferase-1-dependent methylation imprint around the pre-implantation S phase, because such failure would result in the production of two different cell clones, one with normally methylated DMR and the other with demethylated DMR, leading to the separation of cells with different characters and resultant twinning.

  4. DNA methylation and gene expression patterns in adipose tissue differ significantly within young adult monozygotic BMI-discordant twin pairs.

    PubMed

    Pietiläinen, K H; Ismail, K; Järvinen, E; Heinonen, S; Tummers, M; Bollepalli, S; Lyle, R; Muniandy, M; Moilanen, E; Hakkarainen, A; Lundbom, J; Lundbom, N; Rissanen, A; Kaprio, J; Ollikainen, M

    2016-04-01

    Little is known about epigenetic alterations associated with subcutaneous adipose tissue (SAT) in obesity. Our aim was to study genome-wide DNA methylation and gene expression differences in SAT in monozygotic (MZ) twin pairs who are discordant for body mass index (BMI). This design completely matches lean and obese groups for genetic background, age, gender and shared environment. 14We analyzed DNA methylome and gene expression from SAT, together with body composition (magnetic resonance imaging/spectroscopy) and glucose tolerance test, lipids and C-reactive protein from 26 rare BMI-discordant (intrapair difference in BMI ⩾3 kg m(-2)) MZ twin pairs identified from 10 birth cohorts of young adult Finnish twins. We found 17 novel obesity-associated genes that were differentially methylated across the genome between heavy and lean co-twins. Nine of them were also differentially expressed. Pathway analyses indicated that dysregulation of SAT in obesity includes a paradoxical downregulation of lipo/adipogenesis and upregulation of inflammation and extracellular matrix remodeling. Furthermore, CpG sites whose methylation correlated with metabolically harmful fat depots (intra-abdominal and liver fat) also correlated with measures of insulin resistance, dyslipidemia and low-grade inflammation, thus suggesting that epigenetic alterations in SAT are associated with the development of unhealthy obesity. This is the first study in BMI-discordant MZ twin pairs reporting genome-wide DNA methylation and expression profiles in SAT. We found a number of novel genes and pathways whose methylation and expression patterns differ within the twin pairs, suggesting that the pathological adaptation of SAT to obesity is, at least in part, epigenetically regulated.

  5. Plasma proteomic profiles from disease-discordant monozygotic twins suggest that molecular pathways are shared in multiple systemic autoimmune diseases*

    PubMed Central

    2011-01-01

    Introduction Although systemic autoimmune diseases (SAID) share many clinical and laboratory features, whether they also share some common features of pathogenesis remains unclear. We assessed plasma proteomic profiles among different SAID for evidence of common molecular pathways that could provide insights into pathogenic mechanisms shared by these diseases. Methods Differential quantitative proteomic analyses (one-dimensional reverse-phase liquid chromatography-mass spectrometry) were performed to assess patterns of plasma protein expression. Monozygotic twins (four pairs discordant for systemic lupus erythematosus, four pairs discordant for juvenile idiopathic arthritis and two pairs discordant for juvenile dermatomyositis) were studied to minimize polymorphic gene effects. Comparisons were also made to 10 unrelated, matched controls. Results Multiple plasma proteins, including acute phase reactants, structural proteins, immune response proteins, coagulation and transcriptional factors, were differentially expressed similarly among the different SAID studied. Multivariate Random Forest modeling identified seven proteins whose combined altered expression levels effectively segregated affected vs. unaffected twins. Among these seven proteins, four were also identified in univariate analyses of proteomic data (syntaxin 17, α-glucosidase, paraoxonase 1, and the sixth component of complement). Molecular pathway modeling indicated that these factors may be integrated through interactions with a candidate plasma biomarker, PON1 and the pro-inflammatory cytokine IL-6. Conclusions Together, these data suggest that different SAID may share common alterations of plasma protein expression and molecular pathways. An understanding of the mechanisms leading to the altered plasma proteomes common among these SAID may provide useful insights into their pathogeneses. PMID:22044644

  6. Monozygotic triplets: concordance and discordance for cleft lip and palate / twin research reviews: depression in mothers of multiples; depression in mothers and fathers of ART conceived multiples; epigenetic differences in monozygotic twins; congenital anomalies in surviving twins / headlines x two: twin Chefs; the world's largest twin registry; twin table tennis champions.

    PubMed

    Segal, Nancy L

    2009-08-01

    A review of twin research on cleft lip and palate is presented. This information is accompanied by a look at the lives of young monozygotic (MZ) male triplets concordant for cleft lip, but discordant for the type and placement of the cleft and for the presence of cleft palate. Research on depression in mothers and fathers of twins conceived naturally and by artificial reproductive techniques follows. Current findings and implications of epigenetic differences in MZ twins are also summarized. Interesting life history events surrounding MZ twin chefs and table tennis players, as well as plans to construct the world's largest twin registry, are presented in the final section.

  7. The Relationship Between Help-Seeking Attitudes and Masculine Norms Among Monozygotic Male-Twins Discordant for Sexual Orientation

    PubMed Central

    Sánchez, Francisco J.; Bocklandt, Sven; Vilain, Eric

    2014-01-01

    Objective In general, heterosexual men are less favorable to asking for help compared to women and gay men. This can be problematic if a man avoids professional help when he is experiencing significant psychological distress. Yet, it is unclear to what degree such attitudes among men are due to innate differences or social environments. Studying twins provides one avenue for teasing apart these relationships. Methods We recruited 38 pairs of monozygotic male-twins (MAge 35.87; SD = 9.52) raised together and who were discordant for sexual orientation. They completed a measure of psychological distress (Symptom–Checklist–90–Revised), positive attitudes towards psychological help-seeking behavior, and emphasis with fulfilling traditional masculine norms. Results Contrary to predictions, the heterosexual twins expressed more symptoms of specific distress—Hostility (r = .30), Paranoid Ideation (r = .26), and Psychoticism (r = .24)—compared to their gay co-twins. As predicted, heterosexual men were less favorable to seeking help (r = .25) and expressed greater emphasis on masculine norms (r = .26) compared to their co-twins. Within each group of men, unique aspects of masculine norms were significantly related to attitudes towards psychological help-seeking behavior. Conclusion The findings lend credence to the hypothesis that social environments influence attitudes and behaviors that are stereotypically masculine and potentially detrimental to men’s health. PMID:23025300

  8. Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles

    PubMed Central

    2013-01-01

    Background Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intra-uterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. To address this, we acquire genome-wide DNA methylation profiles from saliva DNA in a unique cohort of 17 monozygotic monochorionic female twins very discordant for birth weight. We examine if adverse prenatal growth conditions experienced by the smaller co-twins lead to long-lasting DNA methylation changes. Results Overall, co-twins show very similar genome-wide DNA methylation profiles. Since observed differences are almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3,153 are differentially methylated between the heavy and light co-twins at nominal significance, of which 45 show sensible absolute mean β-value differences. Deep bisulfite sequencing of eight such loci reveals that differences remain in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicates no significant intra-pair differences. Conclusions Severe intra-uterine growth differences observed within these monozygotic twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies. PMID:23706164

  9. Generalized Arterial Calcification in a Recipient Twin: Discordant Fetal Hemodynamics Result in Differing Phenotypes in Monozygotic Twins with an ABCC6 Mutation.

    PubMed

    Votava-Smith, Jodie K; Pitukcheewanont, Pisit; Randolph, Linda M; Chmait, Ramen H

    2017-01-01

    Recipients of the twin-twin transfusion syndrome (TTTS) often develop cardiac manifestations, but arterial calcification has rarely been reported. Generalized arterial calcification of infancy (GACI) is a genetic disorder with high infantile mortality. We report the case of a TTTS recipient with moderate cardiomyopathy at diagnosis who developed progressive calcification of the pulmonary arteries and aorta after successful in utero laser therapy. Postnatally, both twins were diagnosed with a heterozygous ABCC6 gene mutation associated with GACI. The recipient had progressive supravalvular pulmonary and aortic stenosis, was treated with bisphosphonate therapy, and successfully underwent cardiac surgery at 4 months of age. The donor twin with the same mutation remained phenotypically normal at 15 months of age. This case illustrates monozygotic fetuses with discordant in utero hemodynamics, with subsequent development of phenotypic differences. TTTS recipients with arterial calcifications should undergo genetic testing for GACI. © 2016 S. Karger AG, Basel.

  10. Gene expression profiles from discordant monozygotic twins suggest that molecular pathways are shared among multiple systemic autoimmune diseases

    PubMed Central

    2011-01-01

    Introduction The objective of this study is to determine if multiple systemic autoimmune diseases (SAID) share gene expression pathways that could provide insights into pathogenic mechanisms common to these disorders. Methods RNA microarray analyses (Agilent Human 1A(V2) 20K oligo arrays) were used to quantify gene expression in peripheral blood cells from 20 monozygotic (MZ) twin pairs discordant for SAID. Six affected probands with systemic lupus erythematosus (SLE), six with rheumatoid arthritis (RA), eight with idiopathic inflammatory myopathies (IIM), and their same-gendered unaffected twins, were enrolled. Comparisons were made between discordant twin pairs and these were also each compared to 40 unrelated control subjects (matched 2:1 to each twin by age, gender and ethnicity) using statistical and molecular pathway analyses. Relative quantitative PCR was used to verify independently measures of differential gene expression assessed by microarray analysis. Results Probands and unrelated, matched controls differed significantly in gene expression for 104 probes corresponding to 92 identifiable genes (multiple-comparison adjusted P values < 0.1). Differentially expressed genes involved several overlapping pathways including immune responses (16%), signaling pathways (24%), transcription/translation regulators (26%), and metabolic functions (15%). Interferon (IFN)-response genes (IFI27, OASF, PLSCR1, EIF2AK2, TNFAIP6, and TNFSF10) were up-regulated in probands compared to unrelated controls. Many of the abnormally expressed genes played regulatory roles in multiple cellular pathways. We did not detect any probes expressed differentially in comparisons among the three SAID phenotypes. Similarly, we found no significant differences in gene expression when comparing probands to unaffected twins or unaffected twins to unrelated controls. Gene expression levels for unaffected twins appeared intermediate between that of probands and unrelated controls for 6535 probes

  11. The relationship between help-seeking attitudes and masculine norms among monozygotic male twins discordant for sexual orientation.

    PubMed

    Sánchez, Francisco J; Bocklandt, Sven; Vilain, Eric

    2013-01-01

    In general, heterosexual men are less favorable to asking for help compared to women and gay men. This can be problematic if a man avoids professional help when he is experiencing significant psychological distress. Yet, it is unclear to what degree such attitudes among men are due to innate differences or social environments. Studying twins provides one avenue for teasing apart these relationships. We recruited 38 pairs of monozygotic male twins (Mage = 35.87 years, SD = 9.52) raised together and who were discordant for sexual orientation. They completed measures of psychological distress (Symptom Checklist-90-Revised), positive attitudes toward psychological help-seeking behavior, and emphasis with fulfilling traditional masculine norms. Contrary to predictions, the heterosexual twins expressed more symptoms of specific distress-hostility (r = .30), paranoid ideation (r = .26), and psychoticism (r = .24)-than their gay cotwins. As predicted, heterosexual men were less favorable to seeking help (r = .25) and expressed greater emphasis on masculine norms (r = .26) than their cotwins. Within each group of men, unique aspects of masculine norms were significantly related to attitudes toward psychological help-seeking behavior. The findings lend credence to the hypothesis that social environments influence attitudes and behaviors that are stereotypically masculine and potentially detrimental to men's health. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  12. Higher dietary flavonoid intakes are associated with lower objectively measured body composition in women: evidence from discordant monozygotic twins.

    PubMed

    Jennings, Amy; MacGregor, Alex; Spector, Tim; Cassidy, Aedín

    2017-03-01

    Background: Although dietary flavonoid intake has been associated with less weight gain, there are limited data on its impact on fat mass, and to our knowledge, the contribution of genetic factors to this relation has not previously been assessed.Objective: We examined the associations between flavonoid intakes and fat mass.Design: In a study of 2734 healthy, female twins aged 18-83 y from the TwinsUK registry, intakes of total flavonoids and 7 subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymers, and proanthocyanidins) were calculated with the use of food-frequency questionnaires. Measures of dual-energy X-ray absorptiometry-derived fat mass included the limb-to-trunk fat mass ratio (FMR), fat mass index, and central fat mass index.Results: In cross-sectional multivariable analyses, higher intake of anthocyanins, flavonols, and proanthocyanidins were associated with a lower FMR with mean ± SE differences between extreme quintiles of -0.03 ± 0.02 (P-trend = 0.02), -0.03 ± 0.02 (P-trend = 0.03), and -0.05 ± 0.02 (P-trend < 0.01), respectively. These associations were not markedly changed after further adjustment for fiber and total fruit and vegetable intakes. In monozygotic, intake-discordant twin pairs, twins with higher intakes of flavan-3-ols (n = 154, P = 0.03), flavonols (n = 173, P = 0.03), and proanthocyanidins (n = 172, P < 0.01) had a significantly lower FMR than that of their co-twins with within-pair differences of 3-4%. Furthermore, in confirmatory food-based analyses, twins with higher intakes of flavonol-rich foods (onions, tea, and pears; P = 0.01) and proanthocyanidin-rich foods (apples and cocoa drinks; P = 0.04) and, in younger participants (aged <50 y) only, of anthocyanin-rich foods (berries, pears, grapes, and wine; P = 0.01) had a 3-9% lower FMR than that of their co-twins.Conclusions: These data suggest that higher habitual intake of a number of flavonoids, including anthocyanins, flavan-3-ols, flavonols, and

  13. Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21.

    PubMed

    Hibaoui, Youssef; Grad, Iwona; Letourneau, Audrey; Sailani, M Reza; Dahoun, Sophie; Santoni, Federico A; Gimelli, Stefania; Guipponi, Michel; Pelte, Marie Francoise; Béna, Frédérique; Antonarakis, Stylianos E; Feki, Anis

    2014-02-01

    Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD-SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) on chromosome 21 likely contributes to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects.

  14. Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21

    PubMed Central

    Hibaoui, Youssef; Grad, Iwona; Letourneau, Audrey; Sailani, M Reza; Dahoun, Sophie; Santoni, Federico A; Gimelli, Stefania; Guipponi, Michel; Pelte, Marie Françoise; Béna, Frédérique; Antonarakis, Stylianos E; Feki, Anis

    2014-01-01

    Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD-SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A ( DYRK1A) on chromosome 21 likely contributes to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects. PMID:24375627

  15. A Novel Model of Schizophrenia Age-of-Onset Data Challenges the Conventional Interpretations of the Discordance in Monozygote Twin Studies.

    PubMed

    Kramer, Ivan; Hong, L Elliot

    2013-01-01

    The relative importance of genetics and the environment in causing schizophrenia is still being debated. Although the high proportion of monozygote cotwins of schizophrenia patients who are discordant suggests that there may be a significant environmental contribution to the development of schizophrenia, this discordance is predicted by an accumulative multimutation model of schizophrenia onset constructed here implying a genetic origin of schizophrenia. In this model, schizophrenics are viewed as having been born with the genetic susceptibility to develop schizophrenia. As susceptible gene carriers age, they randomly accumulate the necessary mutations to cause schizophrenia, the last needed mutation coinciding with disease onset. The mutation model predicts that the concordance rate in monozygote twin studies will monotonically increase with age, theoretically approaching 100% given sufficient longevity. In dizygote cotwins of schizophrenia patients, the model predicts that at least 71% of cotwins are incapable of developing schizophrenia even though every cotwin and their schizophrenic twin shared a similar early environment. The multimutation model is shown to fit all of the monozygote and dizygote concordance rate data of the principle classical twin studies completed before 1970 considered in this paper. Thus, the genetic hypothesis of schizophrenia can be tested by bringing these studies up to date.

  16. A Novel Model of Schizophrenia Age-of-Onset Data Challenges the Conventional Interpretations of the Discordance in Monozygote Twin Studies

    PubMed Central

    Hong, L. Elliot

    2013-01-01

    The relative importance of genetics and the environment in causing schizophrenia is still being debated. Although the high proportion of monozygote cotwins of schizophrenia patients who are discordant suggests that there may be a significant environmental contribution to the development of schizophrenia, this discordance is predicted by an accumulative multimutation model of schizophrenia onset constructed here implying a genetic origin of schizophrenia. In this model, schizophrenics are viewed as having been born with the genetic susceptibility to develop schizophrenia. As susceptible gene carriers age, they randomly accumulate the necessary mutations to cause schizophrenia, the last needed mutation coinciding with disease onset. The mutation model predicts that the concordance rate in monozygote twin studies will monotonically increase with age, theoretically approaching 100% given sufficient longevity. In dizygote cotwins of schizophrenia patients, the model predicts that at least 71% of cotwins are incapable of developing schizophrenia even though every cotwin and their schizophrenic twin shared a similar early environment. The multimutation model is shown to fit all of the monozygote and dizygote concordance rate data of the principle classical twin studies completed before 1970 considered in this paper. Thus, the genetic hypothesis of schizophrenia can be tested by bringing these studies up to date. PMID:24027651

  17. The occurrence of gonadal dysgenesis in association with monozygotic twinning.

    PubMed Central

    Karp, L; Bryant, J I; Tagatz, G; Giblett, E; Fialkow, P J

    1975-01-01

    A case is presented of a monozygotic twin pair, discordant for phenotypic sex, in which the female member showed gonadal dysgenesis and chromosomal mosaicism. Review of the pertinent literature reveals that in monozygotic twin pairs, phenotypic and karyotypic concordance is the usual occurrence for Down's and Klinefelter's syndromes, whereas discordance often accompanies gonadal dysgenesis. Mosaicism is a frequent concomitant of gonadal dysgenesis in monozygotic twins. Our case strengthens the probability of a real association between mosaicism and monozygotic twinning in gonadal dysgenesis. Images PMID:1121022

  18. Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins

    PubMed Central

    Ouellet-Morin, I.; Wong, C. C. Y.; Danese, A.; Pariante, C. M.; Papadopoulos, A. S.; Mill, J.; Arseneault, L.

    2014-01-01

    Background Childhood adverse experiences are known to induce persistent changes in the hypothalamic–pituitary–adrenal (HPA) axis reactivity to stress. However, the mechanisms by which these experiences shape the neuroendocrine response to stress remain unclear. Method We tested whether bullying victimization influenced serotonin transporter gene (SERT) DNA methylation using a discordant monozygotic (MZ) twin design. A subsample of 28 MZ twin pairs discordant for bullying victimization, with data on cortisol and DNA methylation, were identified in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994–1995 cohort of families with twins. Results Bullied twins had higher SERT DNA methylation at the age of 10 years compared with their non-bullied MZ co-twins. This group difference cannot be attributed to the children’s genetic makeup or their shared familial environments because of the study design. Bullied twins also showed increasing methylation levels between the age of 5 years, prior to bullying victimization, and the age of 10 years whereas no such increase was detected in non-bullied twins across time. Moreover, children with higher SERT methylation levels had blunted cortisol responses to stress. Conclusions Our study extends findings drawn from animal models, supports the hypothesis that early-life stress modifies DNA methylation at a specific cytosine–phosphate–guanine (CpG) site in the SERT promoter and HPA functioning and suggests that these two systems may be functionally associated. PMID:23217646

  19. Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins.

    PubMed

    Ouellet-Morin, I; Wong, C C Y; Danese, A; Pariante, C M; Papadopoulos, A S; Mill, J; Arseneault, L

    2013-09-01

    Childhood adverse experiences are known to induce persistent changes in the hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress. However, the mechanisms by which these experiences shape the neuroendocrine response to stress remain unclear. Method We tested whether bullying victimization influenced serotonin transporter gene (SERT) DNA methylation using a discordant monozygotic (MZ) twin design. A subsample of 28 MZ twin pairs discordant for bullying victimization, with data on cortisol and DNA methylation, were identified in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994-1995 cohort of families with twins. Bullied twins had higher SERT DNA methylation at the age of 10 years compared with their non-bullied MZ co-twins. This group difference cannot be attributed to the children's genetic makeup or their shared familial environments because of the study design. Bullied twins also showed increasing methylation levels between the age of 5 years, prior to bullying victimization, and the age of 10 years whereas no such increase was detected in non-bullied twins across time. Moreover, children with higher SERT methylation levels had blunted cortisol responses to stress. Our study extends findings drawn from animal models, supports the hypothesis that early-life stress modifies DNA methylation at a specific cytosine-phosphate-guanine (CpG) site in the SERT promoter and HPA functioning and suggests that these two systems may be functionally associated.

  20. Genetic and Epigenetic Differences in Monozygotic Twins with NF1

    DTIC Science & Technology

    2011-10-01

    in Monozygotic Twins with NF1 PRINCIPAL INVESTIGATOR: Elizabeth K. Schorry, M.D...Differences in Monozygotic Twins with NF1 5b. GRANT NUMBER W81XWH-10-1-0867 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER... monozygotic (MZ) twins with NF1 who are discordant for various NF complications, and assessed for differences in copy number variations (CNV) in their

  1. Genome-wide blood DNA methylation alterations at regulatory elements and heterochromatic regions in monozygotic twins discordant for obesity and liver fat.

    PubMed

    Ollikainen, Miina; Ismail, Khadeeja; Gervin, Kristina; Kyllönen, Anjuska; Hakkarainen, Antti; Lundbom, Jesper; Järvinen, Elina A; Harris, Jennifer R; Lundbom, Nina; Rissanen, Aila; Lyle, Robert; Pietiläinen, Kirsi H; Kaprio, Jaakko

    2015-01-01

    The current epidemic of obesity and associated diseases calls for swift actions to better understand the mechanisms by which genetics and environmental factors affect metabolic health in humans. Monozygotic (MZ) twin pairs showing discordance for obesity suggest that epigenetic influences represent one such mechanism. We studied genome-wide leukocyte DNA methylation variation in 30 clinically healthy young adult MZ twin pairs discordant for body mass index (BMI; average within-pair BMI difference: 5.4 ± 2.0 kg/m(2)). There were no differentially methylated cytosine-guanine (CpG) sites between the co-twins discordant for BMI. However, stratification of the twin pairs based on the level of liver fat accumulation revealed two epigenetically highly different groups. Significant DNA methylation differences (n = 1,236 CpG sites (CpGs)) between the co-twins were only observed if the heavier co-twins had excessive liver fat (n = 13 twin pairs). This unhealthy pattern of obesity was coupled with insulin resistance and low-grade inflammation. The differentially methylated CpGs included 23 genes known to be associated with obesity, liver fat, type 2 diabetes mellitus (T2DM) and metabolic syndrome, and potential novel metabolic genes. Differentially methylated CpG sites were overrepresented at promoters, insulators, and heterochromatic and repressed regions. Based on predictions by overlapping histone marks, repressed and weakly transcribed sites were significantly more often hypomethylated, whereas sites with strong enhancers and active promoters were hypermethylated. Further, significant clustering of differentially methylated genes in vitamin, amino acid, fatty acid, sulfur, and renin-angiotensin metabolism pathways was observed. The methylome in leukocytes is altered in obesity associated with metabolic disturbances, and our findings indicate several novel candidate genes and pathways in obesity and obesity-related complications.

  2. Discordant sex in one of three monozygotic triplets.

    PubMed Central

    Dallapiccola, B; Stomeo, C; Ferranti, G; Di Lecce, A; Purpura, M

    1985-01-01

    A case is reported of monozygotic triplets, discordant for phenotypic sex, in which the female presented at birth with the features of Turner's syndrome. Chromosomal analyses showed homogeneous 46,XY karyotypes in the lymphocytes of the three sibs, while a 45,X non-mosaic chromosome constitution was detected in skin fibroblasts of the female triplet. It is suggested that mitotic non-disjunction or anaphase lag occurring early during embryonic development accounted for the occurrence of monosomy X in one cell line of the affected triplet. Previous observations of monozygotic twin pairs discordant for chromosome constitutions are reviewed. Images PMID:3856681

  3. Identification of genes modulated in rheumatoid arthritis using complementary DNA microarray analysis of lymphoblastoid B cell lines from disease-discordant monozygotic twins.

    PubMed

    Haas, Christian S; Creighton, Chad J; Pi, Xiujun; Maine, Ira; Koch, Alisa E; Haines, G Kenneth; Ling, Song; Chinnaiyan, Arul M; Holoshitz, Joseph

    2006-07-01

    To identify disease-specific gene expression profiles in patients with rheumatoid arthritis (RA), using complementary DNA (cDNA) microarray analyses on lymphoblastoid B cell lines (LCLs) derived from RA-discordant monozygotic (MZ) twins. The cDNA was prepared from LCLs derived from the peripheral blood of 11 pairs of RA-discordant MZ twins. The RA twin cDNA was labeled with cy5 fluorescent dye, and the cDNA of the healthy co-twin was labeled with cy3. To determine relative expression profiles, cDNA from each twin pair was combined and hybridized on 20,000-element microarray chips. Immunohistochemistry and real-time polymerase chain reaction were used to detect the expression of selected gene products in synovial tissue from patients with RA compared with patients with osteoarthritis and normal healthy controls. In RA twin LCLs compared with healthy co-twin LCLs, 1,163 transcripts were significantly differentially expressed. Of these, 747 were overexpressed and 416 were underexpressed. Gene ontology analysis revealed many genes known to play a role in apoptosis, angiogenesis, proteolysis, and signaling. The 3 most significantly overexpressed genes were laeverin (a novel enzyme with sequence homology to CD13), 11beta-hydroxysteroid dehydrogenase type 2 (a steroid pathway enzyme), and cysteine-rich, angiogenic inducer 61 (a known angiogenic factor). The products of these genes, heretofore uncharacterized in RA, were all abundantly expressed in RA synovial tissues. Microarray cDNA analysis of peripheral blood-derived LCLs from well-controlled patient populations is a useful tool to detect RA-relevant genes and could help in identifying novel therapeutic targets.

  4. Gene expression profile of subcutaneous adipose tissue in BMI-discordant monozygotic twin pairs unravels molecular and clinical changes associated with sub-types of obesity.

    PubMed

    Muniandy, M; Heinonen, S; Yki-Järvinen, H; Hakkarainen, A; Lundbom, J; Lundbom, N; Kaprio, J; Rissanen, A; Ollikainen, M; Pietiläinen, K H

    2017-08-01

    Subcutaneous adipose tissue (SAT) undergoes major changes in obesity, but little is known about the whole-genome scale patterns of these changes or about their variation between different obesity sub-groups. We sought to compare how transcriptomics profiles in SAT differ between monozygotic (MZ) co-twins who are discordant for body mass index (BMI), whether the profiles vary between twin pairs and whether the variation can be linked to clinical characteristics. We analysed the transcriptomics (Affymetrix U133 Plus 2.0) patterns of SAT in young MZ twin pairs (n=26, intra-pair difference in BMI >3 kg m(-2), aged 23-36), from 10 birth cohorts of adult Finnish twins. The clinical data included measurements of body composition, insulin resistance, lipids and adipokines. We found 2108 genes differentially expressed (false discovery rate (FDR)<0.05) in SAT of the BMI-discordant pairs. Pathway analyses of these genes revealed a significant downregulation of mitochondrial oxidative pathways (P<0.05) and upregulation of inflammation pathways (P<0.05). Hierarchical clustering of heavy/lean twin ratios, representing effects of acquired obesity in the transcriptomics data, revealed three sub-groups with different molecular profiles (FDR<0.05). Analyses comparing these sub-groups showed that, in the heavy co-twins, downregulation of the mitochondrial pathways, especially that of branched chain amino acid degradation was more evident in two clusters while and upregulation of the inflammatory response was most evident in the last, presumably the unhealthiest cluster. High-fasting insulin levels and large adipocyte diameter were the predominant clinical characteristic of the heavy co-twins in this cluster (Bonferroni-adjusted P<0.05). This is the first study in BMI-discordant MZ twin pairs reporting sub-types of obesity based on both SAT gene expression profiles and clinical traits. We conclude that a decrease in mitochondrial BCAA degradation and an increase in inflammation in

  5. Regulation of the Pituitary-Thyroid Axis in Adulthood Is Not Related to Birth Weight: Evidence from Extremely Birth Weight–Discordant Monozygotic Danish Twin Pairs

    PubMed Central

    Petersen, Inge; Hegedüs, Laszlo; Christiansen, Lene; Brix, Thomas; Christensen, Kaare

    2013-01-01

    Background Low birth weight has been linked with changes in thyroid function in adulthood, but it is unknown whether fetal programming or underlying genetic and environmental factors explains the association. We hypothesized that birth weight influences the pituitary-thyroid set point in adults. Methods A total of 152 birth weight–discordant monozygotic twin pairs with a median age of 57 years (interquartile range: 33–63) were ascertained from the Danish Twin Registry in 2010. Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and triiodothyronine (T3) levels were measured. Birth weights were retrieved from midwife records (individuals born before 1973) and the Danish Birth Record Registry (all other participants) Results Birth weight was inversely associated with serum levels of FT4 (β=−0.48 pmol/[L·kg], p=0.014) and serum T3 (β=−0.09 nmol/[L·kg], p=0.010), but not serum TSH after adjustment for age, sex, and current use of tobacco products, when the twins were investigated as singletons. Serum levels of TSH and T3 were similar in within twin-pair analyses, while serum FT4 was higher in twins with the lowest birth weight (median difference 0.3 mIU/L). When the analyses were repeated in twin pairs (n=46 pairs) characterized by extreme difference in birth weight (>0.5 kg), serum TSH, T3, and FT4 levels were similar in twins with high and low birth weight. The proportion of individuals with serum TSH level >4 mIU/L or <0.3 mIU/L was identical in both groups. Conclusions No overall evidence of an association between birth weight and adult pituitary-thyroid axis set point, after control for genetic and environmental factors, could be demonstrated. PMID:23308389

  6. Regulation of the pituitary-thyroid axis in adulthood is not related to birth weight: evidence from extremely birth weight-discordant monozygotic Danish twin pairs.

    PubMed

    Frost, Morten; Petersen, Inge; Hegedüs, Laszlo; Christiansen, Lene; Brix, Thomas; Christensen, Kaare

    2013-07-01

    Low birth weight has been linked with changes in thyroid function in adulthood, but it is unknown whether fetal programming or underlying genetic and environmental factors explains the association. We hypothesized that birth weight influences the pituitary-thyroid set point in adults. A total of 152 birth weight-discordant monozygotic twin pairs with a median age of 57 years (interquartile range: 33-63) were ascertained from the Danish Twin Registry in 2010. Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and triiodothyronine (T3) levels were measured. Birth weights were retrieved from midwife records (individuals born before 1973) and the Danish Birth Record Registry (all other participants) Birth weight was inversely associated with serum levels of FT4 (β=-0.48 pmol/[L·kg], p=0.014) and serum T3 (β=-0.09 nmol/[L·kg], p=0.010), but not serum TSH after adjustment for age, sex, and current use of tobacco products, when the twins were investigated as singletons. Serum levels of TSH and T3 were similar in within twin-pair analyses, while serum FT4 was higher in twins with the lowest birth weight (median difference 0.3 mIU/L). When the analyses were repeated in twin pairs (n=46 pairs) characterized by extreme difference in birth weight (>0.5 kg), serum TSH, T3, and FT4 levels were similar in twins with high and low birth weight. The proportion of individuals with serum TSH level >4 mIU/L or <0.3 mIU/L was identical in both groups. No overall evidence of an association between birth weight and adult pituitary-thyroid axis set point, after control for genetic and environmental factors, could be demonstrated.

  7. A multidisciplinary approach to study a couple of monozygotic twins discordant for the chronic fatigue syndrome: a focus on potential salivary biomarkers

    PubMed Central

    2013-01-01

    Background Chronic Fatigue Syndrome (CFS) is a severe, systemic illness characterized by persistent, debilitating and medically unexplained fatigue. The etiology and pathophysiology of CFS remains obscure, and diagnosis is formulated through the patient’s history and exclusion of other medical causes. Thereby, the availability of biomarkers for CFS could be useful for clinical research. In the present study, we used a proteomic approach to evaluate the global changes in the salivary profile in a couple of monozygotic twins who were discordant for CFS. The aim was to evaluate differences of salivary protein expression in the CFS patient in respect to his healthy twin. Methods Saliva samples were submitted to two-dimensional electrophoresis (2DE). The gels were stained with Sypro, and a comparison between CFS subject and the healthy one was performed by the software Progenesis Same Spot including the Analysis of variance (ANOVA test). The proteins spot found with a ≥2-fold spot quantity change and p<0.05 were identified by Nano-liquid chromatography electrospray ionization tandem mass spectrometry. To validate the expression changes found with 2DE of 5 proteins (14-3-3 protein zeta/delta, cyclophilin A, Cystatin-C, Protein S100-A7, and zinc-alpha-2-glycoprotein), we used the western blot analysis. Moreover, proteins differentially expressed were functionally analyzed using the Ingenuity Pathways Analysis software with the aim to determine the predominant canonical pathways and the interaction network involved. Results The analysis of the protein profiles allowed us to find 13 proteins with a different expression in CFS in respect to control. Nine spots were up-regulated in CFS and 4 down-regulated. These proteins belong to different functional classes, such as inflammatory response, immune system and metabolism. In particular, as shown by the pathway analysis, the network built with our proteins highlights the involvement of inflammatory response in CFS

  8. Monozygotic twinning: an evolutionary hypothesis.

    PubMed Central

    Gleeson, S K; Clark, A B; Dugatkin, L A

    1994-01-01

    Monozygotic twinning is rare within populations yet taxonomically widespread. We explore the evolution of monozygotic twinning by modeling an allele in a newly formed offspring that causes it to undergo mitosis and separation to form one or more clones (twins), potentially in conflict with the parents' best interest. The success of this twinning allele in our haploid models depends on the balance of the benefit of increased frequency in the clutch and the cost of reduced survival resulting from limited parental resources. The trait reaches high frequency in a broad range of plausible conditions but also fails to spread or is kept at low frequency in others when the survival cost is high (e.g., in small clutch sizes). Interestingly, there are two reasonable conditions that predict high frequency of the trait but low visibility: random parental abortion and selection for low penetrance. Thus our models suggest reasons why monozygotic twinning might be rare, or alternatively, be common yet appear rare. In addition, we discuss the implications for sex-linked twinning, dizygotic twinning, and twinning by gametes. Images PMID:7972065

  9. Effects of type II collagen epitope carbamylation and citrullination in human leucocyte antigen (HLA)-DR4(+) monozygotic twins discordant for rheumatoid arthritis.

    PubMed

    De Santis, M; Ceribelli, A; Cavaciocchi, F; Generali, E; Massarotti, M; Isailovic, N; Crotti, C; Scherer, H U; Montecucco, C; Selmi, C

    2016-09-01

    The aim of this study is to investigate the effect of the native, citrullinated or carbamylated type II human collagen T cell- and B cell-epitopes on the adaptive immune response in rheumatoid arthritis (RA). Peripheral blood T and B cells obtained from a human leucocyte D4-related (antigen DR4(-) HLA-DR4)(+) woman with early RA, her healthy monozygotic twin and an unrelated HLA-DR3(+) woman with early RA were analysed for activation (CD154/CD69), apoptosis (annexin/7-aminoactinomycin), cytokine production [interferon (IFN)γ/interleukin (IL)-17/IL-4/IL-10/IL-6] and functional phenotype (CD45Ra/CCR7) after stimulation with the collagen native T cell epitope (T261-273), the K264 carbamylated T cell epitope (carT261-273), the native B cell epitope (B359-369) or the R360 citrullinated B cell epitope (citB359-369), and the combinations of these. The T cell memory compartment was activated by T cell epitopes in both discordant DR4(+) twins, but not in the DR3(+) RA. The collagen-specific activation of CD4(+) T cells was induced with both the native and carbamylated T cell epitopes only in the RA twin. Both T cell epitopes also induced IL-17 production in the RA twin, but a greater IL-4 and IL-10 response in the healthy twin. The citrullinated B cell epitope, particularly when combined with the carbamylated T cell epitope, induced B cell activation and an increased IL-6/IL-10 ratio in the RA twin compared to a greater IL-10 production in the healthy twin. Our data suggest that circulating collagen-specific T and B cells are found in HLA-DR4(+) subjects, but only RA activated cells express co-stimulatory molecules and produce proinflammatory cytokines. Carbamylation and citrullination further modulate the activation and cytokine polarization of T and B cells. © 2016 British Society for Immunology.

  10. Blastocyst transfer and monozygotic twinning.

    PubMed

    Peramo, B; Ricciarelli, E; Cuadros-Fernández, J M; Huguet, E; Hernández, E R

    1999-12-01

    To report two cases of monozygotic twinning after IVF-blastocyst transfer. Case report. Private practice in an assisted reproductive technology clinic. Two women treated with IVF-ET at the blastocyst stage. Pituitary down-regulation with luteal leuprolide acetate, ovulation induction with gonadotropins, IVF, sequential culture, blastocyst transfer, and P for luteal support. Levels of hCG, pelvic ultrasound examination, amniocentesis, obstetric follow-up, and cesarean section. Two intrauterine monozygotic twin pregnancies occurred after IVF and blastocyst transfer. One of them was complicated by fetus-to-fetus transfusion syndrome and was delivered preterm by cesarean section; the other woman had a normal pregnancy and vaginal delivery. Monozygotic multiple gestations may be increased in IVF blastocyst transfers. The potential obstetric complications of this type of pregnancy should be discussed with patients.

  11. Isolated oligodontia in monozygotic twins

    PubMed Central

    Halicioglu, Koray; Sahin, Hakan; Corekci, Bayram; Irgin, Celal; Toptas, Orcun

    2013-01-01

    This case report defines a case of isolated oligodontia of 9 and 10 permanent teeth in 9-year-old monozygotic twin sisters and gives information about the possible genetic and environmental etiology, related dental anomalies and treatment options. The twins have a negative family history of hypodontia and oligodontia in their parents, as well as their paternal and maternal grandmothers and first cousins. No other dental anomalies could be detected in either of the twins. With the occurrence of similarly located tooth agenesis, except for one tooth, in monozygotic twins, one may consider the influence of genetic and/or environmental factors in their etiology. Hereditary relationships associated with oligodontia could help the clinicians to predict the possibility of its occurrence in other family members and in the next generations. However, clinicians should consider oligodontia when it is not hereditary. PMID:24966717

  12. Amino Acid Intakes Are Associated With Bone Mineral Density and Prevalence of Low Bone Mass in Women: Evidence From Discordant Monozygotic Twins.

    PubMed

    Jennings, Amy; MacGregor, Alexander; Spector, Tim; Cassidy, Aedín

    2016-02-01

    Although a higher protein intake, particularly from vegetable sources, has been shown to be associated with higher bone mineral density (BMD) the relative impact of specific amino acids on BMD and risk of osteoporosis remains to be determined. Mechanistic research suggests that a number of specific amino acids, including five nonessential amino acids--alanine, arginine, glutamic acid, glycine, and proline--may play a role in bone health, principally through improved production of insulin and insulin-like growth factor 1 and the synthesis of collagen and muscle protein. However to date, no previous studies have examined the associations between habitual intake of amino acids and direct measures of BMD and prevalence of osteoporosis or osteopenia, and no studies have examined this relationship in discordant identical twin-pairs. In these analyses of female monozygotic twin-pairs discordant for amino acid intake (n = 135), twins with higher intakes of alanine and glycine had significantly higher BMD at the spine than their co-twins with within-pair differences in spine-BMD of 0.012 g/cm(2) (SE 0.01; p = 0.039) and 0.014 g/cm(2) (SE 0.01; p = 0.026), respectively. Furthermore, in cross-sectional multivariable analyses of 3160 females aged 18 to 79 years, a higher intake of total protein was significantly associated with higher DXA-measured BMD at the spine (quartile Q4 to quartile Q1: 0.017 g/cm(2), SE 0.01, p = 0.035) and forearm (Q4 to Q1: 0.010 g/cm(2), SE 0.003, p = 0.002). Intake of six amino acids (alanine, arginine, glutamic acid, leucine, lysine, and proline) were associated with higher BMD at the spine and forearm with the strongest association observed for leucine (Q4 to Q1: 0.024 g/cm(2), SE 0.01, p = 0.007). When intakes were stratified by protein source, vegetable or animal, prevalence of osteoporosis or osteopenia was 13% to 19% lower comparing extreme quartiles of vegetable intake for five amino acids (not glutamic acid or proline). These data provide

  13. Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes

    PubMed Central

    Hu, Valerie W; Frank, Bryan C; Heine, Shannon; Lee, Norman H; Quackenbush, John

    2006-01-01

    Background The autism spectrum encompasses a set of complex multigenic developmental disorders that severely impact the development of language, non-verbal communication, and social skills, and are associated with odd, stereotyped, repetitive behavior and restricted interests. To date, diagnosis of these neurologically based disorders relies predominantly upon behavioral observations often prompted by delayed speech or aberrant behavior, and there are no known genes that can serve as definitive biomarkers for the disorders. Results Here we demonstrate, for the first time, that lymphoblastoid cell lines from monozygotic twins discordant with respect to severity of autism and/or language impairment exhibit differential gene expression patterns on DNA microarrays. Furthermore, we show that genes important to the development, structure, and/or function of the nervous system are among the most differentially expressed genes, and that many of these genes map closely in silico to chromosomal regions containing previously reported autism candidate genes or quantitative trait loci. Conclusion Our results provide evidence that novel candidate genes for autism may be differentially expressed in lymphoid cell lines from individuals with autism spectrum disorders. This finding further suggests the possibility of developing a molecular screen for autism based on expressed biomarkers in peripheral blood lymphocytes, an easily accessible tissue. In addition, gene networks are identified that may play a role in the pathophysiology of autism. PMID:16709250

  14. Mayer-Rokitansky-Küster-Hauser syndrome discordance in monozygotic twins: matrix metalloproteinase 14, low-density lipoprotein receptor-related protein 10, extracellular matrix, and neoangiogenesis genes identified as candidate genes in a tissue-specific mosaicism.

    PubMed

    Rall, Katharina; Eisenbeis, Simone; Barresi, Gianmaria; Rückner, Daniel; Walter, Michael; Poths, Sven; Wallwiener, Diethelm; Riess, Olaf; Bonin, Michael; Brucker, Sara

    2015-02-01

    To find a potential underlying cause for Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) discordance in monozygotic twins. Prospective comparative study. University hospital. Our study genetically analyzed 5 MRKHS-discordant monozygotic twin pairs with the unique opportunity to include saliva and rudimentary uterine tissue. Blood, saliva, or rudimentary uterine tissue from five MRKHS-discordant twins was analyzed and compared between twin pairs as well as within the same individual where applicable. We used copy number variations (CNVs) to identify differences. CNVs in blood, rudimentary uterine tissue, and saliva, network analysis, and review of the literature. One duplication found in the affected twin included two genes, matrix metalloproteinase 14 (MMP14) and low-density lipoprotein receptor-related protein 10 (LRP10), which have known functions in the embryonic development of the uterus and endometrium. The duplicated region was detected in rudimentary uterine tissue from the same individual but not in saliva, making a tissue-specific mosaicism a possible explanation for twin discordance. Additional network analysis revealed important connections to differentially expressed genes from previous studies. These genes encode several molecules involved in extracellular matrix (ECM) remodeling and neoangiogenesis. MMP-14, LRP-10, ECM, and neoangiogenesis genes are identified as candidate genes in a tissue-specific mosaicism. The detected clusters provide evidence of deficient vascularization during uterine development and/or disturbed reorganization of ECM components, potentially during müllerian duct elongation signaled by the embryologically relevant phosphatidylinositol 3-kinase/protein kinase B pathway. Therefore, we consider these genes to be new candidates in the manifestation of MRKHS. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Amino Acid Intakes Are Associated With Bone Mineral Density and Prevalence of Low Bone Mass in Women: Evidence From Discordant Monozygotic Twins

    PubMed Central

    Jennings, Amy; MacGregor, Alexander; Spector, Tim

    2015-01-01

    ABSTRACT Although a higher protein intake, particularly from vegetable sources, has been shown to be associated with higher bone mineral density (BMD) the relative impact of specific amino acids on BMD and risk of osteoporosis remains to be determined. Mechanistic research suggests that a number of specific amino acids, including five nonessential amino acids—alanine, arginine, glutamic acid, glycine, and proline—may play a role in bone health, principally through improved production of insulin and insulin‐like growth factor 1 and the synthesis of collagen and muscle protein. However to date, no previous studies have examined the associations between habitual intake of amino acids and direct measures of BMD and prevalence of osteoporosis or osteopenia, and no studies have examined this relationship in discordant identical twin‐pairs. In these analyses of female monozygotic twin‐pairs discordant for amino acid intake (n = 135), twins with higher intakes of alanine and glycine had significantly higher BMD at the spine than their co‐twins with within‐pair differences in spine‐BMD of 0.012 g/cm2 (SE 0.01; p = 0.039) and 0.014 g/cm2 (SE 0.01; p = 0.026), respectively. Furthermore, in cross‐sectional multivariable analyses of 3160 females aged 18 to 79 years, a higher intake of total protein was significantly associated with higher DXA‐measured BMD at the spine (quartile Q4 to quartile Q1: 0.017 g/cm2, SE 0.01, p = 0.035) and forearm (Q4 to Q1: 0.010 g/cm2, SE 0.003, p = 0.002). Intake of six amino acids (alanine, arginine, glutamic acid, leucine, lysine, and proline) were associated with higher BMD at the spine and forearm with the strongest association observed for leucine (Q4 to Q1: 0.024 g/cm2, SE 0.01, p = 0.007). When intakes were stratified by protein source, vegetable or animal, prevalence of osteoporosis or osteopenia was 13% to 19% lower comparing extreme quartiles of vegetable intake for five amino acids

  16. Multiple rectal carcinoid tumors in monozygotic twins.

    PubMed

    Doi, Momoko; Ikawa, Osamu; Taniguchi, Hiroki; Kawamura, Takuji; Katsura, Kanade

    2016-08-01

    We report multiple rectal carcinoid tumors in monozygotic twins who, respectively, had 42 and 36 carcinoid tumors in the lower rectum. This is the first report about carcinoid tumors in monozygotic twins. Both twins developed a similar number of rectal carcinoids with a similar distribution. Investigation of their genetic background may provide information about the origin of these tumors.

  17. Epigenetic discordance at imprinting control regions in twins.

    PubMed

    Ollikainen, Miina; Craig, Jeffrey M

    2011-06-01

    Imprinting control regions are differentially methylated in a parent-of-origin-dependent manner and this methylation state is inherited through the germline. These regions control parent-specific monoallelic expression of their target genes. Genetically identical organisms show considerable variation in their epigenomes owing to environmental and stochastic influences creating fluctuations in phenotype. Monozygotic twin pairs discordant for imprinting disorders due to epigenetic changes at imprinting control regions are an example of phenotypic variation caused by extreme variations of the epigenome. Here, we discuss the within-pair epigenetic discordance at imprinted loci, both in phenotypically concordant and discordant monozygotic twin pairs.

  18. Serum microRNAs explain discordance of non-alcoholic fatty liver disease in monozygotic and dizygotic twins: a prospective study

    PubMed Central

    Zarrinpar, Amir; Gupta, Shakti; Maurya, Mano R; Subramaniam, Shankar; Loomba, Rohit

    2016-01-01

    Objective In the setting where two individuals are genetically similar, epigenetic mechanisms could account for discordance in the presence or absence of nonalcoholic fatty liver disease (NAFLD). This study investigated if serum microRNAs (miRs) could explain discordance in NAFLD. Design This is a cross-sectional analysis of a prospective cohort study of 40 (n=80) twin-pairs residing in Southern California. All participants underwent a standardised research visit, liver MRI using proton-density fat fraction to quantify fat content and miR profiling of their serum. Results Among the 40 twin-pairs, there were 6 concordant for NAFLD, 28 were concordant for non-NAFLD and 6 were discordant for NAFLD. The prevalence of NAFLD was 22.5% (18/80). Within the six discordant twins, a panel of 10 miRs differentiated the twin with NAFLD from the one without. Two of these miRs, miR-331-3p and miR-30c, were also among the 21 miRs that were different between NAFLD and non-NAFLD groups (for miR-331-3p: 7.644±0.091 vs 8.057 ±0.071, respectively, p=0.004; for miR-30c: 10.013 ±0.126 vs 10.418±0.086, respectively, p=0.008). Both miRs were highly heritable (35.9% and 10.7%, respectively) and highly correlated with each other (R=0.90, p=2.2×10−16) suggesting involvement in a common mechanistic pathway. An interactome analysis of these two miRs showed seven common target genes. Conclusions Using a novel human twin-study design, we demonstrate that discordancy in liver fat content between the twins can be explained by miRs, and that they are heritable. PMID:26002934

  19. Fumarate hydratase deficiency in monozygotic twins.

    PubMed

    Phillips, Tonya M; Gibson, James B; Ellison, Dale A

    2006-08-01

    Monozygotic twins with fumarate hydratase deficiency presenting with profound hypotonia and developmental delay are reported. This rare organic aciduria has been previously described in random case reports, although, to our knowledge, these are the first reported monozygotic twins and gene testing revealed a novel mutation in both. During their course, one of the twins also developed acute pancreatitis, which has not been previously described in association with this particular organic aciduria.

  20. Huntington's disease in monozygotic twins reared apart.

    PubMed

    Sudarsky, L; Myers, R H; Walshe, T M

    1983-12-01

    Monozygotic twins, identical by serological studies, with Huntington's disease are described who were raised in separate households from birth. Age at onset, landmarks of the disease, and behavioural abnormalities were strikingly similar. Previously reported twin studies in Huntington's disease are reviewed. Twin data support the hypothesis that age at onset and several other clinical features of the illness are substantially determined by genetic mechanisms.

  1. Motor Disorder and Anxious and Depressive Symptomatology: A Monozygotic Co-Twin Control Approach

    ERIC Educational Resources Information Center

    Pearsall-Jones, Jillian G.; Piek, Jan P.; Rigoli, Daniela; Martin, Neilson C.; Levy, Florence

    2011-01-01

    The aim of this study was to investigate the relationship between poor motor ability and anxious and depressive symptomatology in child and adolescent monozygotic twins. The co-twin control design was used to explore these mental health issues in MZ twins concordant and discordant for a motor disorder, and controls. This methodology offers the…

  2. Motor Disorder and Anxious and Depressive Symptomatology: A Monozygotic Co-Twin Control Approach

    ERIC Educational Resources Information Center

    Pearsall-Jones, Jillian G.; Piek, Jan P.; Rigoli, Daniela; Martin, Neilson C.; Levy, Florence

    2011-01-01

    The aim of this study was to investigate the relationship between poor motor ability and anxious and depressive symptomatology in child and adolescent monozygotic twins. The co-twin control design was used to explore these mental health issues in MZ twins concordant and discordant for a motor disorder, and controls. This methodology offers the…

  3. Early Infantile Autism in Monozygotic Twins.

    ERIC Educational Resources Information Center

    Eshkevari, H. Salimi

    1979-01-01

    The article presents a case history of a pair of male monozygotic twins who both had autism. During pregnancy the mother suffered from severe toxemia, and delivery occurred 2 months before term. (Author/DLS)

  4. Nonshared Environmental Influences on Individual Differences in Early Behavioral Development: A Monozygotic Twin Differences Study.

    ERIC Educational Resources Information Center

    Asbury, Kathryn; Dunn, Judith F.; Pike, Alison; Plomin, Robert

    2003-01-01

    Examined nonshared environmental (NSE) influences on twin preschoolers' behavior independent of genetics. Found that within-pair parenting differences correlated with monozygotic differences in behavior. For the extreme 10 percent of the parenting-discordant and behavior-discordant distributions, average NSE effect size was 11 percent, suggesting…

  5. Spina bifida occulta and monozygotic twins.

    PubMed

    Spacca, Barbara; Buxton, Neil

    2008-10-01

    Central nervous system maldevelopment can have different presentations in twins. We report on a case of different presentations of spina bifida occulta in monozygotic twins. The first twin presented at birth with a lipomyelomeningocele; a tethered cord was diagnosed in the second twin at 2 years of age. Neural tube defects (NTDs) are a group of common congenital malformations of the brain and spine generated during neurulation. The genetic basis of this process is still not well known. Whenever an NTD is diagnosed in one of a pair of twins, the other twin should also be evaluated for NTDs.

  6. Monozygotic twins discordant for recessive dystrophic epidermolysis bullosa phenotype highlight the role of TGF-β signalling in modifying disease severity.

    PubMed

    Odorisio, Teresa; Di Salvio, Michela; Orecchia, Angela; Di Zenzo, Giovanni; Piccinni, Eugenia; Cianfarani, Francesca; Travaglione, Antonella; Uva, Paolo; Bellei, Barbara; Conti, Andrea; Zambruno, Giovanna; Castiglia, Daniele

    2014-08-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is a genodermatosis characterized by fragile skin forming blisters that heal invariably with scars. It is due to mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils connecting the cutaneous basement membrane to the dermis. Identical COL7A1 mutations often result in inter- and intra-familial disease variability, suggesting that additional modifiers contribute to RDEB course. Here, we studied a monozygotic twin pair with RDEB presenting markedly different phenotypic manifestations, while expressing similar amounts of collagen VII. Genome-wide expression analysis in twins' fibroblasts showed differential expression of genes associated with TGF-β pathway inhibition. In particular, decorin, a skin matrix component with anti-fibrotic properties, was found to be more expressed in the less affected twin. Accordingly, fibroblasts from the more affected sibling manifested a profibrotic and contractile phenotype characterized by enhanced α-smooth muscle actin and plasminogen activator inhibitor 1 expression, collagen I release and collagen lattice contraction. These cells also produced increased amounts of proinflammatory cytokines interleukin 6 and monocyte chemoattractant protein-1. Both TGF-β canonical (Smads) and non-canonical (MAPKs) pathways were basally more activated in the fibroblasts of the more affected twin. The profibrotic behaviour of these fibroblasts was suppressed by decorin delivery to cells. Our data show that the amount of type VII collagen is not the only determinant of RDEB clinical severity, and indicate an involvement of TGF-β pathways in modulating disease variability. Moreover, our findings identify decorin as a possible anti-fibrotic/inflammatory agent for RDEB therapeutic intervention.

  7. Huntington's disease in monozygotic twins reared apart.

    PubMed Central

    Sudarsky, L; Myers, R H; Walshe, T M

    1983-01-01

    Monozygotic twins, identical by serological studies, with Huntington's disease are described who were raised in separate households from birth. Age at onset, landmarks of the disease, and behavioural abnormalities were strikingly similar. Previously reported twin studies in Huntington's disease are reviewed. Twin data support the hypothesis that age at onset and several other clinical features of the illness are substantially determined by genetic mechanisms. PMID:6228662

  8. Monozygotic Twins with Asperger Syndrome: Differences in Behaviour Reflect Variations in Brain Structure and Function

    ERIC Educational Resources Information Center

    Belmonte, Matthew K.; Carper, Ruth A.

    2006-01-01

    A pair of monozygotic twins discordant for symptoms of Asperger syndrome was evaluated at the age of 13.45 years using psychometric, morphometric, behavioural, and functional imaging methods. The lower-functioning twin had a smaller brain overall, a smaller right cerebellum, and a disproportionately large left frontal lobe, and manifested almost…

  9. Monozygotic Twins with Asperger Syndrome: Differences in Behaviour Reflect Variations in Brain Structure and Function

    ERIC Educational Resources Information Center

    Belmonte, Matthew K.; Carper, Ruth A.

    2006-01-01

    A pair of monozygotic twins discordant for symptoms of Asperger syndrome was evaluated at the age of 13.45 years using psychometric, morphometric, behavioural, and functional imaging methods. The lower-functioning twin had a smaller brain overall, a smaller right cerebellum, and a disproportionately large left frontal lobe, and manifested almost…

  10. Creativity in Monozygotic and Dyzygotic Twins.

    ERIC Educational Resources Information Center

    Richmond, Bert O.

    The purpose of this study is to clarify further the relationships among creative, cognitive, and affective production of students. Thirteen pairs of twins, eight monozygotic (MZ), five dyzygotic (DZ), were administered the Torrance Tests of Creative Thinking, MMPI, and Revised Beta Examination. The F ratio for testing significance of within-set…

  11. Prenatal diagnosis of heterokaryotypic mosaic twins discordant for fetal sex.

    PubMed

    Schmid, O; Trautmann, U; Ashour, H; Ulmer, R; Pfeiffer, R A; Beinder, E

    2000-12-01

    The presence of a monozygotic twin gestation with discordant sex of the twins is a very rare constellation, which is referred to as heterokaryotypic monozygotic pregnancy. This constellation can develop either due to a chromosomal aberration after twinning or is - as in the following case - due to a mitotic error before twinning and an unequal distribution of mosaicism in both embryos. So far the diagnosis of heterokaryotypic monozygotic pregnancy has always been made postnatally, with only one exception (Gonsoulin et al., 1990). In this case we suspected the presence of monozygotic twins ultrasonically because of the chorionic and amniotic membrane characteristics. Surprisingly the sex of the fetuses was discrepant. As one of them had hydrops and a structural heart defect, we carried out an amniocentesis, which revealed mosaicism [45,X/46,X,i(Y)(p10)] of both fetuses. The female fetus with a predominant 45,X set of chromosomes and the typical intrauterine signs of the Ullrich-Turner syndrome (massive hygroma colli, hydrops fetalis and multiple cardiac defects) died during the 25th week of gestation due to cardiac decompensation. The other fetus appeared to be male with a predominance of a 46,X,i(Y)(p10) set of chromosomes and was born a few days after the intrauterine death of the hydropic fetus. In conclusion, our observation shows that ultrasonic evidence of discordant fetal sex in twins does not necessarily exclude monozygosity. Copyright 2000 John Wiley & Sons, Ltd.

  12. Coeliac disease in monozygotic twins

    PubMed Central

    Shale, Dennis J.; Hall, Reginald; Johnston, Desmond G.; Roberts, D. F.

    1982-01-01

    A case of concordance for coeliac disease in monozygous twins is reported. One presented with failure to enter puberty and responded to the exclusion of gluten from her diet. The other twin was asymptomatic. They represent a well documented example of monozygous twins with concordance for coeliac disease. PMID:6892062

  13. Ankylosing spondylitis in monozygotic twins: studies on immunological parameters

    PubMed Central

    Hohler, T.; Hug, R.; Schneider, P.; Krummenauer, F.; Gripenberg-Lerche, C.; Granfors, K.; Marker-Hermann, E.

    1999-01-01

    OBJECTIVE—To examine immunological parameters that might explain disease discordance in monozygotic twin pairs with ankylosing spondylitis (AS).
METHODS—11 monozygotic twin pairs (nine with AS, two with undifferentiated spondyloarthropathy) were investigated. The peripheral T cell receptor Vβ repertoire was investigated using FACS analysis and 14 different Vβ antibodies. In addition serum samples were tested for antibodies to Klebsiella pneumoniae, Streptococcus pyogenes, Candida albicans, Proteus mirabilis, and Escherichia coli. Peripheral blood lymphocyte reactivity against a number of bacteria was investigated by interferon γ ELISPOT assays.
RESULTS—Twins suffering from AS showed cellular hyporeactivity against K pneumoniae, S pyogenes, C albicans in the ELISPOT assays compared with healthy twins. In contrast with the antibody data, where no significant differences were observed between the two groups, AS concordant twins showed the most pronounced differences in their Vβ repertoire on CD4+ and CD8+ lymphocytes.
CONCLUSIONS—Cellular hyporeactivity of peripheral blood cells to bacterial antigens might reflect defective T cell responses allowing bacterial antigens to persist in diseased patients. There are probably other environmental factors that influence disease concordance.

 PMID:10381488

  14. Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition

    PubMed Central

    Rodríguez-Cortez, Virginia C.; del Pino-Molina, Lucia; Rodríguez-Ubreva, Javier; Ciudad, Laura; Gómez-Cabrero, David; Company, Carlos; Urquiza, José M.; Tegnér, Jesper; Rodríguez-Gallego, Carlos; López-Granados, Eduardo; Ballestar, Esteban

    2015-01-01

    Common variable immunodeficiency (CVID), the most frequent primary immunodeficiency characterized by loss of B-cell function, depends partly on genetic defects, and epigenetic changes are thought to contribute to its aetiology. Here we perform a high-throughput DNA methylation analysis of this disorder using a pair of CVID-discordant MZ twins and show predominant gain of DNA methylation in CVID B cells with respect to those from the healthy sibling in critical B lymphocyte genes, such as PIK3CD, BCL2L1, RPS6KB2, TCF3 and KCNN4. Individual analysis confirms hypermethylation of these genes. Analysis in naive, unswitched and switched memory B cells in a CVID patient cohort shows impaired ability to demethylate and upregulate these genes in transitioning from naive to memory cells in CVID. Our results not only indicate a role for epigenetic alterations in CVID but also identify relevant DNA methylation changes in B cells that could explain the clinical manifestations of CVID individuals. PMID:26081581

  15. Do MZ twins have discordant experiences of friendship? A qualitative hypothesis-generating MZ twin differences study.

    PubMed

    Asbury, Kathryn; Moran, Nicola; Plomin, Robert

    2017-01-01

    Using a qualitative monozygotic (MZ) twin differences design we explored whether adolescent MZ twins report discordant peer relationships and, if so, whether they perceive them as causes, consequences or correlates of discordant behaviour. We gathered free-response questionnaire data from 497 families and conducted in-depth telephone interviews with 97 of them. Within this dataset n = 112 families (23% of the sample) described discordant peer relationships. Six categories of discordance were identified (peer victimisation, peer rejection, fewer friends, different friends, different attitudes to friendship and dependence on co-twin). Participants described peer relationship discordance arising as a result of chance occurrences, enhanced vulnerability in one twin or discordant behaviour. Consequences of discordant peer relationships were seen as discordance in self-confidence, future plans, social isolation, mental health and interests. In all cases the twin with worse peer experiences was seen as having a worse outcome. Specific hypotheses are presented.

  16. Do MZ twins have discordant experiences of friendship? A qualitative hypothesis-generating MZ twin differences study

    PubMed Central

    Moran, Nicola; Plomin, Robert

    2017-01-01

    Using a qualitative monozygotic (MZ) twin differences design we explored whether adolescent MZ twins report discordant peer relationships and, if so, whether they perceive them as causes, consequences or correlates of discordant behaviour. We gathered free-response questionnaire data from 497 families and conducted in-depth telephone interviews with 97 of them. Within this dataset n = 112 families (23% of the sample) described discordant peer relationships. Six categories of discordance were identified (peer victimisation, peer rejection, fewer friends, different friends, different attitudes to friendship and dependence on co-twin). Participants described peer relationship discordance arising as a result of chance occurrences, enhanced vulnerability in one twin or discordant behaviour. Consequences of discordant peer relationships were seen as discordance in self-confidence, future plans, social isolation, mental health and interests. In all cases the twin with worse peer experiences was seen as having a worse outcome. Specific hypotheses are presented. PMID:28727730

  17. Infantile spasms syndrome in monozygotic twins.

    PubMed Central

    Pavone, L; Mollica, F; Incorpora, G; Pampiglione, G

    1980-01-01

    The infantile spasms syndrome appeared on the same day in a pair of monozygotic twins at age 6 months. Clinical, electroencephalographic, and neuroradiological findings during the development of the disease are reported. One of the twins was treated with ACTH and in his case clinical and electroencephalographic improvement was more rapid than in the other who was treated with clonazepam. While the computer tomography scan initially showed in each twin an area of low density in the right fronto-parietal region, this had disappeared in the tomograms obtained about 8 months later. PMID:6254446

  18. Infantile spasms syndrome in monozygotic twins.

    PubMed

    Pavone, L; Mollica, F; Incorpora, G; Pampiglione, G

    1980-11-01

    The infantile spasms syndrome appeared on the same day in a pair of monozygotic twins at age 6 months. Clinical, electroencephalographic, and neuroradiological findings during the development of the disease are reported. One of the twins was treated with ACTH and in his case clinical and electroencephalographic improvement was more rapid than in the other who was treated with clonazepam. While the computer tomography scan initially showed in each twin an area of low density in the right fronto-parietal region, this had disappeared in the tomograms obtained about 8 months later.

  19. The sex ratios of monozygotic and dizygotic twins.

    PubMed

    James, William H

    2010-08-01

    Fellman and Eriksson (2010) cited my suggestion that the sex ratio (proportion male) of monozygotic (MZ) twins is lower than that of dizygotic (DZ) twins (James 1975). Here I offer elaborations on and potential explanations for this.

  20. Differences of DNA methylation profiles between monozygotic twins' blood samples.

    PubMed

    Li, Chengtao; Zhao, Shumin; Zhang, Na; Zhang, Suhua; Hou, Yiping

    2013-09-01

    Monozygotic twins (MZs) share an identical genomic sequence, which makes it impossible to discriminate one another with conventional genetic markers like STRs. On the other hand, phenotypic discordance between MZs implies the existence of different epigenetic characteristics. DNA methylation, an essential epigenetic modification, however, might be a potential biomarker to solve the forensic puzzle. In this study, we examined 22 pairs of MZs with a methylation BeadChip including 27,578 CpG sites. The results suggested that MZs exhibited remarkable differences of genome-wide 5-methylcytosine. According to a set of criteria of selection, 92 CpG sites with significant differences of methylation status within MZs were identified from the global epigenome. In conclusion, this pilot study suggested that CpG methylation profile could be a useful biomarker in individual identification of MZs.

  1. Phenotypic variability in monozygotic twins with neurofibromatosis 2

    SciTech Connect

    Baser, M.E.; Ragge, N.K.; Riccardi, V.M.

    1996-09-06

    Mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene on chromosome 22q12 cause a clinically variable autosomal dominant syndrome characterized by bilateral vestibular schwannomas (VSs), other nervous system tumors, and early onset lenticular cataracts. We studied three pairs of monozygotic (MZ) twins with NF2, all with bilateral VSs, to separate genetic from nongenetic causes of clinical variability. The evaluation included gadolinium-enhanced high-resolution magnetic resonance imaging of the head and spine, neuro-ophthalmic examination with slit lamp, physical examination, and zygosity testing with microsatellite markers. Each MZ pair was concordant for general phenotypic subtype (mild or severe) and often for the affected organ systems. However, the MZ pairs were discordant for some features of disease presentation or progression. For example, all three pairs were discordant for presence or type of associated cranial tumors. We hypothesize that phenotypic differences between NF2 MZ twins are at least partly due to stochastic processes, such as the loss of the second NF2 allele or alleles of other genes. 42 refs., 1 tab.

  2. Oliver Sacks: Our Correspondence About Twins/Twin Research: Vanishing Twins Syndrome; Discordant Sex in MZ Twins; Pregnancy Outcomes in IVF and ICSI Conceived Twins/Print and Media: Superfetated Twins; Twins Discordant for Smoking; Twins in Fashion; Yale University Twin Hockey Players; Conjoined Twin-Visiting Professor.

    PubMed

    Segal, Nancy L

    2017-08-01

    The late neurologist and author, Oliver Sacks, published an insightful 1986 review of Marjorie Wallace's book, The Silent Twins, in the New York Times. Taking exception to his assertion about Sir Francis Galton, I wrote a letter to the Times' editor. The letter was unpublished, but it brought a wonderful response from Sacks himself that is reproduced and examined. Next, brief reviews of twin research concerning the vanishing twin syndrome (VTS), discordant sex in a monozygotic (MZ) twin pair, and multiple pregnancy outcomes from assisted reproductive technology (ART) are presented. This section is followed by popular coverage of superfetated twins, smoking-discordant co-twins, twins in fashion, Yale University twin hockey players, and a visiting professor who was a conjoined twin.

  3. Analysis of the T-cell receptor beta-chain variable-region (V beta) repertoire in monozygotic twins discordant for human immunodeficiency virus: evidence for perturbations of specific V beta segments in CD4+ T cells of the virus-positive twins.

    PubMed Central

    Rebai, N; Pantaleo, G; Demarest, J F; Ciurli, C; Soudeyns, H; Adelsberger, J W; Vaccarezza, M; Walker, R E; Sekaly, R P; Fauci, A S

    1994-01-01

    We analyzed the T-cell receptor (TCR) V beta repertoire in human immunodeficiency virus type 1 (HIV-1)-infected individuals at different stages of disease. To circumvent the effect of HLA and other loci on the expressed TCR repertoire, we compared the TCR repertoire in nine pairs of monozygotic twins who were discordant for HIV infection. A semiquantitative polymerase chain reaction (PCR) assay and flow cytometry enabled us to show distinct differences in the V beta repertoire in the HIV-positive twin compared with the HIV-negative twin. By combining PCR and cytofluorometry, these differences were restricted to a specific set of TCR V beta segments, with members of the V beta 13 family perturbed in six out of seven cases and those of the V beta 21 family perturbed in four out of seven cases studied. Most of the other V beta families remained unchanged. Our results provide direct evidence for a skewed TCR repertoire in HIV infection. Images PMID:7906416

  4. Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells from monozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine.

    PubMed

    Nakazawa, Takanobu; Kikuchi, Masataka; Ishikawa, Mitsuru; Yamamori, Hidenaga; Nagayasu, Kazuki; Matsumoto, Takuya; Fujimoto, Michiko; Yasuda, Yuka; Fujiwara, Mikiya; Okada, Shota; Matsumura, Kensuke; Kasai, Atsushi; Hayata-Takano, Atsuko; Shintani, Norihito; Numata, Shusuke; Takuma, Kazuhiro; Akamatsu, Wado; Okano, Hideyuki; Nakaya, Akihiro; Hashimoto, Hitoshi; Hashimoto, Ryota

    2017-03-01

    Schizophrenia is a chronic psychiatric disorder with complex genetic and environmental origins. While many antipsychotics have been demonstrated as effective in the treatment of schizophrenia, a substantial number of schizophrenia patients are partially or fully unresponsive to the treatment. Clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia; however, clozapine has rare but serious side-effects. Furthermore, there is inter-individual variability in the drug response to clozapine treatment. Therefore, the identification of the molecular mechanisms underlying the action of clozapine and drug response predictors is imperative. In the present study, we focused on a pair of monozygotic twin cases with treatment-resistant schizophrenia, in which one twin responded well to clozapine treatment and the other twin did not. Using induced pluripotent stem (iPS) cell-based technology, we generated neurons from iPS cells derived from these patients and subsequently performed RNA-sequencing to compare the transcriptome profiles of the mock or clozapine-treated neurons. Although, these iPS cells similarly differentiated into neurons, several genes encoding homophilic cell adhesion molecules, such as protocadherin genes, showed differential expression patterns between these two patients. These results, which contribute to the current understanding of the molecular mechanisms of clozapine action, establish a new strategy for the use of monozygotic twin studies in schizophrenia research.

  5. Identical Choroid Plexus Cysts in Monozygotic Monochorionic Twins.

    PubMed

    Qureshi, Adnan I; Degenhardt, Jan; Axt-Fliedner, Roland; Kohl, Thomas

    2016-01-01

    Choroid plexus cysts have been infrequently reported with chromosomal abnormalities.Isolated choroid plexus cysts in a monozygotic twin pair hints to a genetically determined pathway as a possible cause.

  6. Exploring Subclinical Phenotypic Features in Twin Pairs Discordant for Cleft Lip and Palate

    PubMed Central

    Leslie, Elizabeth J.; Carlson, Jenna C.; Cooper, Margaret E.; Christensen, Kaare; Weinberg, Seth M.; Marazita, Mary L.

    2016-01-01

    Objective Monozygotic twins of an individual with an orofacial cleft have a significantly elevated risk for orofacial cleft compared with the general population, but still the concordance rate for orofacial cleft in monozygotic twins is about 40% to 50%. The goal of this study was to determine whether unaffected cotwins have an increased frequency of orbicularis oris muscle defects, a subclinical form of orofacial cleft. The presence of such defects may reduce the overall rate of discordance. Method A total of 63 discordant monozygotic and dizygotic twin pairs, 262 unaffected nontwin siblings, and 543 controls with no history of orofacial clefts were assessed for orbicularis oris defects by high-resolution ultrasound. Frequencies were compared by the Fisher exact test. Results Unaffected cotwins from discordant monozygotic pairs had a higher frequency of defects (12.5%) than the other test groups (6.38% to 6.99%), but the difference was not statistically significant (P = .74). Conclusions In this study, orbicularis oris defects were not statistically significantly more common among the unaffected twins from orofacial cleft discordant twin pairs. The trends in the results warrant future studies with larger sample sizes and additional subclinical phenotypes. PMID:26882109

  7. Exploring Subclinical Phenotypic Features in Twin Pairs Discordant for Cleft Lip and Palate.

    PubMed

    Leslie, Elizabeth J; Carlson, Jenna C; Cooper, Margaret E; Christensen, Kaare; Weinberg, Seth M; Marazita, Mary L

    2017-01-01

    Monozygotic twins of an individual with an orofacial cleft have a significantly elevated risk for orofacial cleft compared with the general population, but still the concordance rate for orofacial cleft in monozygotic twins is about 40% to 50%. The goal of this study was to determine whether unaffected cotwins have an increased frequency of orbicularis oris muscle defects, a subclinical form of orofacial cleft. The presence of such defects may reduce the overall rate of discordance.   A total of 63 discordant monozygotic and dizygotic twin pairs, 262 unaffected nontwin siblings, and 543 controls with no history of orofacial clefts were assessed for orbicularis oris defects by high-resolution ultrasound. Frequencies were compared by the Fisher exact test.   Unaffected cotwins from discordant monozygotic pairs had a higher frequency of defects (12.5%) than the other test groups (6.38% to 6.99%), but the difference was not statistically significant (P = .74).   In this study, orbicularis oris defects were not statistically significantly more common among the unaffected twins from orofacial cleft discordant twin pairs. The trends in the results warrant future studies with larger sample sizes and additional subclinical phenotypes.

  8. Twin Legacies: Victor and Vincent McKusick/Twin Studies: Twinning Rates I; Twinning Rates II; MZ Twin Discordance for Russell-Silver Syndrome; Twins' Language Skills/Headlines: Babies Born to Identical Twin Couples; Identity Exchange; Death of Princess Ashraf (Twin); Yahoo CEO Delivers Identical Twins.

    PubMed

    Segal, Nancy L

    2016-04-01

    The lives of the illustrious monozygotic (MZ) twins, Victor A. and Vincent L. McKusick, are described. Victor earned the distinction as the 'Father of Medical Genetics', while Vincent was a legendary Chief Justice of the Maine Supreme Court. This dual biographical account is followed by two timely reports of twinning rates, a study of MZ twin discordance for Russell-Silver Syndrome (RSS) and a study of twins' language skills. Twin stories in the news include babies born to identical twin couples, a case of switched identity, the death of Princess Ashraf (Twin) and a new mother of twins who is also Yahoo's CEO.

  9. [Intrauterine growth characteristics of twins and those twins discordant birthweight].

    PubMed

    Han, Zhen-yan; Fang, Qun; Luo, Yan-min; Hou, Hong-ying; Chen, Min-ling; He, Zhi-ming; Song, Hua-lei

    2012-05-01

    To investigate the intrauterine growth characteristics of twins and birthweight discordant twins (discordant twins). Total of 1010 twin pregnancies (2020 fetuses) with complete delivery records from the Department of Obstetrics and Gynecology, the First and Third Affiliated Hospital of SUN Yat-sen University between January 1, 2000 and July 31, 2010 were studied retrospectively. One handred and ninteen cases (238 fetuses) with intrapair birthweight difference ≥ 25% were determined as the discordant twins group, and the other 891 cases (1782 fetuses) with intrapair birthweight difference < 25% were identified as the concordant twins group. The singleton control group included 4042 singleton pregnancies in the same period. (1) Comparison of clinical data between the twins groups: the birthweight of larger-twin, smaller-twin and intrapair birthweight difference in the discordant twins group and the concordant twins group were (2090 ± 827) g, (1392 ± 592) g, (33.9 ± 9.3)%, and (2408 ± 543) g, (2191 ± 505) g, (8.9 ± 6.5)%, respectively, with significant differences (P < 0.01). The incidence of discordant twins was 11.78% (119/1010). Compared with the concordant twins group, the discordant twins group had higher proportion of monochorionic twins, and higher prevalence of pregnancy complications such as late miscarriage, abnormal umbilical insertion, twin-twin transfusion syndrome and hypertensive disorders in pregnancy (P < 0.05). (2) The characteristics of twin birthweight distribution: 1) In all the 2020 twins, 80.05% (1617/2020) fetuses had birthweight below the 50(th) percentile of the singleton control group, while 23.71% (479/2020) feeuses got birthweight below the 10(th) percentile of the singleton control group. 2) After 19(th) gestational week, the 50(th) and 90(th) percentile of all twins' birthweight were lower than those of singletons. After 38(th) gestational week, the birthweight of singletons kept increasing and reached its peak at 41(th) week

  10. Sylvian fissure asymmetries in monozygotic twins: a test of laterality in schizophrenia.

    PubMed

    Bartley, A J; Jones, D W; Torrey, E F; Zigun, J R; Weinberger, D R

    1993-12-15

    To address prior reports that schizophrenia is associated with loss of normal brain asymmetry and that it might be linked to a defect of a gene controlling cerebral lateralization, we measured on three-dimensional cortical renderings from magnetic resonance imaging (MRI) scans the lengths and angles of the sylvian fissures in 10 normal monozygotic (MZ) twin pairs (n = 10 pairs) and in 10 MZ pairs discordant for schizophrenia (n = 10 pairs). We confirmed in both sets of twins the expected normal asymmetries of length and angle of the sylvian fissure. We also confirmed that the length asymmetry occurs solely in the region of the planum temporale. In the discordant twins, affected and unaffected twins did not differ in asymmetry measures, thus failing to support an association between illness per se and diminished asymmetry. Moreover, the discordant twins as a group did not differ from the normal twins as a group, thus failing to confirm the hypothesis of a genetic association with abnormal asymmetry. The implications of variations in methodology and patient samples are discussed.

  11. Symptomatic colloid cysts in the third ventricle of monozygotic twins

    PubMed Central

    Popek, Edith

    2015-01-01

    In this case report we describe colloid cysts in the third ventricles of monozygotic twin sisters. They were 26 years old when their condition was discovered. One woman was admitted to us on an emergency basis, with signs of high intracranial pressure such as unconsciousness and extension posturing. Her sister was also brought to the hospital since she had a history of attacks of headache. They were both operated with removal of the colloid cysts, and the clinical courses are described in the case report. In reviewing the literature another 30 familial cases were found. Of these were two pairs of monozygotic and one pair of dizygotic twins. PMID:25491677

  12. Asthma discordance in twins is linked to epigenetic modifications of T cells.

    PubMed

    Runyon, R Scott; Cachola, Leslie M; Rajeshuni, Nitya; Hunter, Tessa; Garcia, Marco; Ahn, Regina; Lurmann, Fred; Krasnow, Ruth; Jack, Lisa M; Miller, Rachel L; Swan, Gary E; Kohli, Arunima; Jacobson, Amanda C; Nadeau, Kari C

    2012-01-01

    T cells mediate the inflammatory responses observed in asthma among genetically susceptible individuals and have been suspected to be prone to epigenetic regulation. However, these relationships are not well established from past clinical studies that have had limited capacity to control for the effects of variable genetic predisposition and early environmental exposures. Relying on a cohort of monozygotic twins discordant for asthma we sought to determine if epigenetic modifications in T cells were associated with current asthma and explored whether such modifications were associated with second hand smoke exposures. Our study was conducted in a monozygotic twin cohort of adult twin pairs (n = 21) all discordant for asthma. Regulatory T cell (Treg) and effector T cell (Teff) subsets were assessed for levels of cellular function, protein expression, gene expression and CpG methylation within Forkhead box P3 (FOXP3) and interferon gamma-γ (IFNγ) loci. Comparisons by asthma and current report of exposure to second hand smoke were made. Treg from asthmatic discordant twins demonstrated decreased FOXP3 protein expression and impaired Treg function that was associated with increased levels of CpG methylation within the FOXP3 locus when compared to their non-asthmatic twin partner. In parallel, Teff from discordant asthmatic twins demonstrated increased methylation of the IFNγ locus, decreased IFNγ expression and reduced Teff function when compared to Teff from the non-asthmatic twin. Finally, report of current exposure to second hand smoke was associated with modifications in both Treg and Teff at the transcriptional level among asthmatics. The results of the current study provide evidence for differential function of T cell subsets in monozygotic twins discordant for asthma that are regulated by changes in DNA methylation. Our preliminary data suggest exposure to second hand smoke may augment the modified T cell responses associated with asthma.

  13. Spontaneous Remission of Congenital Complete Atrioventricular Block in Anti-Ro/La Antibody-Negative Monozygotic Twins: Case Report

    PubMed Central

    Kasar, Taner; Saygı, Murat; Özyılmaz, İsa; Ergül, Yakup

    2017-01-01

    Background: Congenital complete atrioventricular block without any structural heart disease and anti-Ro/La negativity is very rare. Discordant complete atrioventricular block, which is more frequently defined in the literature as an autoimmune mechanism, is much more rare in monozygotic twins. Case Report: The 26-year-old healthy mother had given birth in her first spontaneous, uneventful pregnancy to monozygotic twins at week 35. While the first twin’s physical examination proved her to be normal with a pulse rate consistent with her age, the second twin had a pulse rate of approximately 40 beats/minute.The patient was confirmed to have congenital complete atrioventricular block. Conclusion: Despite this case appears to be an isolated one, a discordant complete atrioventricular block regression without any autoimmune evidence should be included in the differential diagnosis of bradycardia in infants. PMID:28251027

  14. Gilles de la Tourette's syndrome in monozygotic twins

    PubMed Central

    Waserman, Jack; Lal, Samarthji; Gauthier, Serge

    1983-01-01

    Concordance is reported of Gilles de la Tourette syndrome in a male twin pair in whom phenotyping revealed a >98·7% probability that they were monozygotic. The development and extent of the illness differed markedly in the two subjects. Our findings are compatible with the view that there is a genetic form of Gilles de la Tourette syndrome. PMID:6573436

  15. College-age twins: university admission policies / twin research: birth weight and neuromotor performance; transfusion syndrome markers; vanishing twins and fetal sex determination; mz twin discordance for wilson's disease / media: big at birth; planned separation of conjoined twins; x factor twins; Cinema: the identical.

    PubMed

    Segal, Nancy L

    2014-12-01

    There is a lack of research findings addressing the unique college admissions issues faced by twins and other multiples. The advantages and disadvantage twins face, as reported by college administrators, twins and families are reviewed. Next, recent research addressing twins' birth weight and neuromotor performance, transfusion syndrome markers, the vanishing twin syndrome and monozygotic (MZ) twin discordance for Wilson's disease is described. News items concerning the birth of unusually large twins, the planned separation of conjoined twins, twin participants in the X Factor games and a film, The Identical, are also summarized.

  16. Unilateral primary pulmonary agenesis and hypoplasia in monozygotic twins.

    PubMed

    Alsaadi, Muslim; Al Muqhem, Badr; Boukai, A; Iqbal, Shaikh M

    2012-01-01

    We describe 10-month-old identical female twin infants, one with primary left-sided pulmonary agenesis and the other with primary left-sided pulmonary hypoplasia. They came to our outpatient clinic complaining of persistent dry cough. The clinical examination revealed decreased air entry over the left hemithorax. Chest x-rays showed complete left-sided radio-opacity in both the twins. The chest computed tomography scan with contrast confirmed the diagnoses of left-sided pulmonary agenesis (twin A) and left-sided hypoplasia (twin B). No other associated congenital anomaly was noted in either of the twins. To our knowledge, such a condition in live monozygotic twins has not been previously reported in published studies.

  17. Blood ties: chimerism can mask twin discordance in high-throughput sequencing.

    PubMed

    Erlich, Yaniv

    2011-04-01

    Twin studies have long provided a means to separate the contributions of genetic and environmental factors. A recent pioneering report by Baranzini et al. presented an analysis of the complete genomes and epigenomes of a monozygotic (MZ) twin pair discordant for multiple sclerosis. This failed to find any difference between the twins, raising doubts regarding the value of whole-genome twin studies for defining disease susceptibility alleles. However, the study was carried out with DNA extracted from blood. In many cases, the hematopoietic lineages of MZ twins are chimeric due to twin-to-twin exchange of hematopoietic stem cells during embryogenesis. We therefore wondered how chimerism might impact the ability to identify genetic differences. We inferred the blood chimerism rates and profiles of more than 30 discordant twin cases from a wide variety of medical conditions. We found that the genotype compositions of the twins were highly similar. We then benchmarked the performance of SNP callers to detect discordant variations using high-throughput sequencing data. Our analysis revealed that chimerism patterns, well within the range normally observed in MZ twins, greatly reduce the sensitivity of SNP calls. This raises questions regarding any conclusions of genomic homogeneity that might be drawn from studies of blood-derived twin DNA.

  18. Early onset alcohol use and self-harm: a discordant twin analysis.

    PubMed

    Few, Lauren R; Werner, Kimberly B; Sartor, Carolyn E; Grant, Julia D; Trull, Timothy J; Nock, Matthew K; Bucholz, Kathleen K; Deitz, Sarah K; Glowinski, Anne L; Martin, Nicholas G; Nelson, Elliot C; Statham, Dixie J; Madden, Pamela A F; Heath, Andrew C; Lynskey, Michael T; Agrawal, Arpana

    2015-11-01

    Self-harm has considerable societal and economic costs and has been extensively studied in relation to alcohol involvement. Although early onset alcohol use (EAU) has been causally linked to maladaptive clinical outcomes, its association with self-harm is less well characterized. This study aimed to further examine the link between EAU and both nonsuicidal self-injury (NSSI) and suicide attempt (SA), and elucidate shared familial and causal/individual-specific pathways that explain this co-occurrence. Using data from 6,082 Australian same-sex twin pairs (1,732 monozygotic [MZ] and 1,309 dizygotic [DZ]), ages 23 to 40, we examined prevalence rates of NSSI and SA among twin pairs concordant and discordant for EAU. Conditional logistic regression, controlling for early clinical covariates and the influence of zygosity on EAU, was used to examine the odds ratio (OR) of self-harm within twin pairs discordant for EAU. Prevalence rates of both NSSI and SA were highest among twin pairs concordant for EAU and for twins who reported EAU within discordant twin pairs. Results from discordant twin analyses revealed nearly 4-fold increased odds of SA for the twin who endorsed EAU, and this OR was equal across MZ and DZ twins. EAU also was associated with elevated odds of NSSI (OR = 7.62), although this was only the case for DZ twins in discordant pairs. The equivalent increase in odds of SA for both MZ and DZ twins suggests that causal or individual-specific influences explain the link between EAU and SA. For NSSI, elevated odds for DZ twins and nonsignificant findings for MZ twins implicate correlated genetic factors in the association between EAU and NSSI. Future studies should test mechanisms through which EAU may causally influence SA, as well as examine whether genetic risk for third variables (e.g., negative urgency, stress reactivity) may explain the genetic overlap between EAU and NSSI. Copyright © 2015 by the Research Society on Alcoholism.

  19. Family study of monozygotic twins affected by pemphigus vulgaris.

    PubMed

    Salathiel, Adriana Martinelli; Brochado, Maria José Franco; Kim, Olivia; Deghaide, Neifi Hassan Saloum; Donadi, Eduardo Antonio; Roselino, Ana Maria

    2016-07-01

    Rare are the family studies that include siblings affected by pemphigus vulgaris (PV) and in whom HLA class II alleles are related. HLA-DR and -DQ genotyping and profiling of antibodies against desmogleins (Dsg) 1 and Dsg3 were performed in ten members of a family including monozygotic twins affected by PV. The twin sisters were heterozygotes; they presented the haplotypes most commonly associated with increased susceptibility to PV (DRB1∗04:02-DQA1∗03:01-DQB1∗03:02 and DRB1∗14:04-DQA1∗01:01-DQB1∗05:03). Their parents and five siblings had only one or none of these two haplotypes in combination with the alleles or haplotypes associated with resistance to PV (DRB1∗07:01-DQA1∗02:01-DQB1∗02:02 and DRB1∗13:01-DQA1∗01:03-DQB1∗06:03). Only the monozygotic twins presented IgG antibodies against both Dsg1 and Dsg3. According to our knowledge based on a review of published literature on the topic, this is the first report of PV affecting monozygotic twins.

  20. Identical twin discordance for the Brachmann-de Lange syndrome revisited

    SciTech Connect

    Carakushansky, G.; Goncalves, M.R.; Kahn, E.

    1996-06-14

    The only known twin pair evidently discordantly affected for the BDLS (Brachmann-de Lange syndrome) and who had been considered monozygotic (MZ) based on blood analysis remained a problem because biological zygosity determination needed further typing. In this report we review the clinical findings of this pair of twins at the age of 20. The use of DNA fingerprinting with three multilocus probes, F10, DNT24, and 33.6, allowed us to present evidence of monozygosity with a high degree of certainty. The significance of this confirmation of discordance in determining the cause of BDLS is discussed. Intensive comparative genomic studies of the discordant twin sisters may be useful to unravel the molecular genetics of this enigmatic pattern of malformation. 21 refs., 2 figs.

  1. Graves’ disease in monozygotic twins – a case report

    PubMed Central

    2013-01-01

    Background Autoimmune thyroid diseases including Graves’ disease and Hashimoto’s thyroiditis are caused by immune response to self-thyroid antigens. The rare situation of hyperthyroidism with Graves’ disease in twins has been reported in a very few case reports in literature. Case presentation We present monozygotic female twins developing consecutively Graves’ disease within five years. One year before the diagnosis of Graves’ disease was established in the first twin, the mother developed a toxic thyroid nodule with hyperthyroidism leading to hemi thyroidectomy. Both the mother and the twins were cigarette smokers. The twins were treated with carbamizole and this therapy led to normalization of thyroid stimulating hormone and thyroxine. Conclusion This case report supports the hypothesis that a genetic factor as well as an environmental factor (cigarette smoking) might be of great importance in the aetiology of Graves’ disease. PMID:23705898

  2. Phenotypic extremes in liveborn monozygotic twins with mosaic Edwards syndrome.

    PubMed

    Bussmann, Neidin; Cunningham, Katie; Green, Andrew; Ryan, C Anthony

    2015-11-11

    Mosaic trisomy 18 (Edwards syndrome) in monozygotic diamniotic liveborn twins is rare. We describe such a case involving preterm male infants. Although both infants had a low percentage of trisomy 18 cells in peripheral blood leucocytes, their varied phenotypic presentation of mosaic trisomy 18 resulted in one twin surviving, with the other twin's demise at 1 month of age. Despite the presence of trisomy 18 in peripheral leucocytes, further analysis of a buccal smear and skin biopsy of the surviving twin did not show evidence of trisomy 18. Establishing such diagnoses in a timely manner is imperative for the child, parents and clinicians. The clinical course of these twins reflects the unpredictable prognosis associated with the diagnosis of mosaic trisomy 18, and emphasises the challenges that can be encountered when counselling parents.

  3. Discordance for Schimmelpenning-Feuerstein-Mims syndrome in monochorionic twins supports the concept of a postzygotic mutation.

    PubMed

    Rijntjes-Jacobs, Esther G J; Lopriore, Enrico; Steggerda, Sylke J; Kant, Sarina G; Walther, Frans J

    2010-11-01

    The Schimmelpenning-Feuerstein-Mims (SFM) syndrome comprises a craniofacial nevus sebaceus, seizures, developmental delay, ocular and skeletal abnormalities. It is a sporadic condition and hypothesized to result from mosaicism involving a lethal autosomal dominant gene. We report a second occurrence of discordant monozygotic (MZ) twins with severe SFM, supporting the concept of a postzygotic mutation. © 2010 Wiley-Liss, Inc.

  4. Longitudinal weight differences, gene expression, and blood biomarkers in BMI discordant identical twins

    PubMed Central

    van Dongen, Jenny; Willemsen, Gonneke; Heijmans, Bastiaan T.; Neuteboom, Jacoline; Kluft, Cornelis; Jansen, Rick; Penninx, Brenda W.J.; Slagboom, P. Eline; de Geus, Eco J.C.; Boomsma, Dorret I.

    2015-01-01

    Background BMI discordant monozygotic (MZ) twins allows an examination of the causes and consequences of adiposity in a genetically controlled design. Few studies have examined longitudinal BMI discordance in MZ pairs. Objectives To study the development over time of BMI discordance in adolescent and adult MZ twin pairs, and to examine lifestyle, metabolic, inflammatory, and gene expression differences associated with concurrent and long-term BMI discordance in MZ pairs. Subjects/Methods BMI data from 2775 MZ twin pairs, collected in eight longitudinal surveys and a biobank project between 1991 and 2011, were analyzed to characterize longitudinal discordance. Lifestyle characteristics were compared within discordant pairs (ΔBMI ≥ 3 kg/m2) and biomarkers (lipids, glucose, insulin, CRP, fibrinogen, IL-6, TNF-α and sIL-6R and liver enzymes AST, ALT and GGT) and gene expression were compared in peripheral blood from discordant pairs who participated in the NTR biobank project. Results The prevalence of discordance ranged from 3.2% in 1991 (mean age=17, SD=2.4) to 17.4% (N=202 pairs) in 2009 (mean age=35, SD=15), and was 16.5% (N=174) among pairs participating in the biobank project (mean age=35, SD=12). Of 699 MZ with BMI data from 3-5 time points, 17 pairs (2.4%) were long-term discordant (at all available time points; mean follow-up range=6.4 years). Concurrently discordant pairs showed significant differences in self-ratings of which twin eats most (p=2.3×10−13), but not in leisure time exercise activity (p=0.28) and smoking (p>0.05). Ten out of 14 biomarkers showed significantly more unfavorable levels in the heavier of twin of the discordant pairs (p-values < 0.001); most of these biomarker differences were largest in longitudinally discordant pairs. No significant gene expression differences were identified, although high ranking genes were enriched for Gene Ontology (GO) terms highlighting metabolic gene regulation and inflammation pathways. Conclusions

  5. Bilateral Mesiodens in Monozygotic Twins: 3D Diagnostic and Management

    PubMed Central

    Vecchione Gurgel, Carla; Soares Cota, Ana Lídia; Yuriko Kobayashi, Tatiana; Moura Bonifácio Silva, Salete; Aparecida Andrade Moreira Machado, Maria; Rios, Daniela; Garib, Daniela Gamba; Marchini Oliveira, Thais

    2013-01-01

    Mesiodens is the most frequent type of supernumerary tooth and may occur in several forms, causing different local disorders, such as impaction of the anterior permanent teeth. High-resolution three-dimensional (3D) images have improved the diagnosis and treatment plan of patients with impacted and supernumerary teeth. The purpose of this paper was to report a case of two mesiodens in monozygotic twin boys with appropriate 3D diagnostic and treatment plan. PMID:23533824

  6. Bilateral Mesiodens in Monozygotic Twins: 3D Diagnostic and Management.

    PubMed

    Vecchione Gurgel, Carla; Soares Cota, Ana Lídia; Yuriko Kobayashi, Tatiana; Moura Bonifácio Silva, Salete; Aparecida Andrade Moreira Machado, Maria; Rios, Daniela; Garib, Daniela Gamba; Marchini Oliveira, Thais

    2013-01-01

    Mesiodens is the most frequent type of supernumerary tooth and may occur in several forms, causing different local disorders, such as impaction of the anterior permanent teeth. High-resolution three-dimensional (3D) images have improved the diagnosis and treatment plan of patients with impacted and supernumerary teeth. The purpose of this paper was to report a case of two mesiodens in monozygotic twin boys with appropriate 3D diagnostic and treatment plan.

  7. Medical history of discordant twins and environmental etiologies of autism

    PubMed Central

    Willfors, C; Carlsson, T; Anderlid, B-M; Nordgren, A; Kostrzewa, E; Berggren, S; Ronald, A; Kuja-Halkola, R; Tammimies, K; Bölte, S

    2017-01-01

    The environmental contributions to autism spectrum disorder (ASD) and their informative content for diagnosing the condition are still largely unknown. The objective of this study was to investigate associations between early medical events and ASD, as well as autistic traits, in twins, to test the hypothesis of a cumulative environmental effect on ASD risk. A total of 80 monozygotic (MZ) twin pairs (including a rare sample of 13 twin pairs discordant for clinical ASD) and 46 dizygotic (DZ) twin pairs with varying autistic traits, were examined for intra-pair differences in early medical events (for example, obstetric and neonatal factors, first year infections). First, differences in early medical events were investigated using multisource medical records in pairs qualitatively discordant for ASD. The significant intra-pair differences identified were then tested in relation to autistic traits in the remaining sample of 100 pairs, applying generalized estimating equations analyses. Significant association of the intra-pair differences in the MZ pairs were found for the cumulative load of early medical events and clinical ASD (Z=−2.85, P=0.004) and autistic traits (β=78.18, P=0.002), as well as infant dysregulation (feeding, sleeping abnormalities, excessive crying and worriedness), when controlling for intelligence quotient and attention deficit hyperactivity disorder comorbidity. The cumulative load of early medical events in general, and infant dysregulation in particular, may index children at risk of ASD owing to non-shared environmental contributions. In clinical practice, these findings may facilitate screening and early detection of ASD. PMID:28140403

  8. Medical history of discordant twins and environmental etiologies of autism.

    PubMed

    Willfors, C; Carlsson, T; Anderlid, B-M; Nordgren, A; Kostrzewa, E; Berggren, S; Ronald, A; Kuja-Halkola, R; Tammimies, K; Bölte, S

    2017-01-31

    The environmental contributions to autism spectrum disorder (ASD) and their informative content for diagnosing the condition are still largely unknown. The objective of this study was to investigate associations between early medical events and ASD, as well as autistic traits, in twins, to test the hypothesis of a cumulative environmental effect on ASD risk. A total of 80 monozygotic (MZ) twin pairs (including a rare sample of 13 twin pairs discordant for clinical ASD) and 46 dizygotic (DZ) twin pairs with varying autistic traits, were examined for intra-pair differences in early medical events (for example, obstetric and neonatal factors, first year infections). First, differences in early medical events were investigated using multisource medical records in pairs qualitatively discordant for ASD. The significant intra-pair differences identified were then tested in relation to autistic traits in the remaining sample of 100 pairs, applying generalized estimating equations analyses. Significant association of the intra-pair differences in the MZ pairs were found for the cumulative load of early medical events and clinical ASD (Z=-2.85, P=0.004) and autistic traits (β=78.18, P=0.002), as well as infant dysregulation (feeding, sleeping abnormalities, excessive crying and worriedness), when controlling for intelligence quotient and attention deficit hyperactivity disorder comorbidity. The cumulative load of early medical events in general, and infant dysregulation in particular, may index children at risk of ASD owing to non-shared environmental contributions. In clinical practice, these findings may facilitate screening and early detection of ASD.

  9. Bidirectional Influences between Maternal Parenting and Children's Peer Problems: A Longitudinal Monozygotic Twin Difference Study

    ERIC Educational Resources Information Center

    Yamagata, Shinji; Takahashi, Yusuke; Ozaki, Koken; Fujisawa, Keiko K.; Nonaka, Koichi; Ando, Juko

    2013-01-01

    This twin study examined the bidirectional relationship between maternal parenting behaviors and children's peer problems that were not confounded by genetic and family environmental factors. Mothers of 259 monozygotic twin pairs reported parenting behaviors and peer problems when twins were 42 and 48 months. Path analyses on monozygotic twin…

  10. Bidirectional Influences between Maternal Parenting and Children's Peer Problems: A Longitudinal Monozygotic Twin Difference Study

    ERIC Educational Resources Information Center

    Yamagata, Shinji; Takahashi, Yusuke; Ozaki, Koken; Fujisawa, Keiko K.; Nonaka, Koichi; Ando, Juko

    2013-01-01

    This twin study examined the bidirectional relationship between maternal parenting behaviors and children's peer problems that were not confounded by genetic and family environmental factors. Mothers of 259 monozygotic twin pairs reported parenting behaviors and peer problems when twins were 42 and 48 months. Path analyses on monozygotic twin…

  11. Using epigenomic studies in monozygotic twins to improve our understanding of cancer.

    PubMed

    Roos, Leonie; Spector, Timothy D; Bell, Christopher G

    2014-06-01

    Cancer is a set of diseases that exhibit not only genetic mutations but also a profoundly distorted epigenetic landscape. Over the last two decades, great advances have been made in identifying these alterations and their importance in the initiation and progression of cancer. Epigenetic changes can be seen from the very early stages in tumorigenesis and dysregulation of the epigenome has an increasingly acknowledged pathogenic role. Epigenomic twin studies have great potential to contribute to our understanding of complex diseases, such as cancer. This is because the use of monozygotic twins discordant for cancer enables epigenetic variation analysis without the confounding influence of the constitutive genetic background, age or cohort effects. It therefore allows the identification of susceptibility loci that may be sensitive to modification by the environment. These studies into cancer etiology will potentially lead to robust epigenetic markers for the detection and risk assessment of cancer.

  12. Monozygotic twins of different apparent sex

    SciTech Connect

    Yokota, Yukifumi; Fujino, Nobuyuki; Sato, Yoshiaki; Matsunobu, Akira; Tadokoro, Mamoru; Akane, Atsushi; Matsuura, Nobuo; Maeda, Tohru; Nakahori, Yutaka; Nakagome, Yasuo

    1994-10-15

    We report on twins of unlike sex who shared a 45,X/46,X, +mar karyotype. The mar chromosome was found to be Yq- by DNA analysis. Marker studies, including 8 VNTR loci, yielded a probability of monozygosity of 0.99999996. 16 refs., 1 fig., 1 tab.

  13. [Pre-excitation syndrome in monozygotic twins].

    PubMed

    Mispireta, J L; Cárdenas, M; Attié, F; Martínez-Ríos, M A; Medrano, G A

    1976-01-01

    A family group of seven members is presented, two of which have pre-excitation syndrome. These subjects are identical twin brothers. One of them has the W-P-W syndrome tipe B, and the other has L-G-L syndrome. The latter had an associated atrial-septal defect, and the other twin had no associated cardiovascular lesions. Both underwent electrocardiographic and vectorcardiographic studies, as well as His bundle electrograms. In the case with W-P-W, the diagnosis was made by electrocardiography, and was confirmed by vertocardiography. The His bundle electrogram showed the habitual findings in this type of pre-excitation. The His bundle potential was preceded by the beginning of the delta wave. The patient with W-P-W had episodes of supraventricular paroxysmal tachycardia, some of these with antegrade conduction through the normal pathway, and others with conduction through the anomalous pathway. The other had a L-G-L syndrome, demonstrated by electrocardiography and vectorcardiography. During the register of the His bundle electrogram, he did not present pre-excitation, the tracings in basal conditions as well as during atrial stimulation were normal. The conclusion is that many factors exist which back up the hypothesis that the pre-excitation syndromes occur because of anomalous pathways, and that this type of alteration might have a sex linked genetic basis. This presumption appears to be confirmed by the presence of pre-excitation in identical twin brothers. Other possibilities are also discussed.

  14. Synesthesia in twins: incomplete concordance in monozygotes suggests extragenic factors.

    PubMed

    Bosley, Hannah G; Eagleman, David M

    2015-06-01

    Colored-sequence synesthesia (CSS) is a neurological condition in which sequential stimuli such as letters, numbers, or days of the week trigger simultaneous, involuntary color perception. Although the condition appears to run in families and several studies have sought a genetic link, the genetic contribution to synesthesia remains unclear. We conducted the first comparative twin study of CSS and found that CSS has a pairwise concordance of 73.9% in monozygotic twins, and a pairwise concordance of 36.4% in dizygotic twins. In line with previous studies, our results suggest a heritable element of synesthesia. However, consonant with the findings of previous single-pair case studies, our large sample size verifies that synesthesia is not completely conferred by genetics; if it were, monozygotic twins should have 100% concordance. These findings implicate a genetic mechanism of CSS that may work differently than previously thought: collectively, our data suggest that synesthesia is a heritable condition with incomplete penetrance that is substantially influenced by epigenetic and environmental factors. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Testing the face shape hypothesis in twins discordant for nonsyndromic orofacial clefting.

    PubMed

    Roosenboom, Jasmien; Indencleef, Karlijne; Hens, Greet; Peeters, Hilde; Christensen, Kaare; Marazita, Mary L; Claes, Peter; Leslie, Elizabeth J; Weinberg, Seth M

    2017-09-08

    Nonsyndromic orofacial clefts (OFCs) are complex traits characterized by multifactorial inheritance and wide phenotypic variability. Numerous studies have shown subtle differences in the faces of unaffected relatives from cleft families compared to controls, the implication being that such outward differences are an incomplete expression reflecting an underlying genetic predisposition. Twins discordant for OFCs provide a unique opportunity to further test this idea, as the unaffected co-twin shares on average 50% (for dizygotic twins) and 100% (for monozygotic twins) of the genetic risk factors as the affected twin. We used 3D surface imaging and spatially-dense morphometry to compare facial shape in a sample of 44 unaffected co-twins and age- and sex-matched unaffected controls (n = 241). Unaffected co-twins showed statistically significant differences in the midface, lateral upper face, and forehead regions, compared to controls. Furthermore, co-twins were characterized by a distinct pattern of midfacial retrusion, broader upper faces, and greater protrusion of the mandible and brow ridges. This same general facial pattern was shown in both unaffected monozygotic and dizygotic co-twin subsets. These results provide additional support that altered facial shape is a phenotypic marker for OFC susceptibility. © 2017 Wiley Periodicals, Inc.

  16. Gender identity disorder and anorexia nervosa in male monozygotic twins.

    PubMed

    Hepp, Urs; Milos, Gabriella; Braun-Scharm, Hellmuth

    2004-03-01

    Male identical twins with gender identity disorder (GID) in childhood and anorexia nervosa (AN) are presented. Etiologic aspects and the relationship among gender identity, sexual orientation, body dissatisfaction, and AN are discussed. Case reports and a review of the literature are reported. In childhood, both twins showed an atypical gender behavior. Whereas one of the twins later developed a transsexual gender identity and asked for sex reassignment, the other developed a male identity but his appearance and clothing are effeminate. According to their biologic sex, they are concordant in regard to their homosexual orientation. In adolescence, both developed AN. Monozygotism was proved by DNA analysis. GID in childhood could be at least partly hereditary, whereas the development of the later phenotype of the gender identification is more determined by environmental factors. GID might be a risk factor for the development of AN. Copyright 2004 by Wiley Periodicals, Inc. Int J Eat Disord 35: 239-243, 2004.

  17. Difficult diagnosis and management of an heterokaryotypic monochorionic twin pregnancy with discordant fetal sex and 45,X/47,XYY karyotypes.

    PubMed

    Bohec, Caroline; Douet-Guilbert, Nathalie; Basinko, Audrey; Le Bris, Marie-Josée; Marcorelles, Pascale; Audrézet, Marie-Pierre; Tetefort, Rémi; Bages, Karine; Collet, Michel; Morel, Frederic; De Braekeleer, Marc

    2010-01-01

    We report twins for whom ultrasound examinations revealed a Turner syndrome in the female fetus and a normal male fetus. A selective pregnancy termination was decided on the female fetus with hydrops. The death of both twins called in question the chorionic diagnosis. Amniotic fluid cytogenetic analysis revealed a 45,X karyotype in the female twin and a 47,XYY karyotype in the male twin. Molecular cytogenetic analysis on genital and renal cells showed different levels of 45,X/47,XYY mosaicism in both twins; molecular analysis on the amniocytes showed monozygosity. Monozygotic twins with discordant sex are very rare. This study showed the difficult diagnosis and management of a monochorionic twin pregnancy with discordant fetal sex.

  18. Somatosensory Brain Function and Gray Matter Regional Volumes Differ According to Exercise History: Evidence from Monozygotic Twins.

    PubMed

    Hautasaari, Pekka; Savić, Andrej M; Loberg, Otto; Niskanen, Eini; Kaprio, Jaakko; Kujala, Urho M; Tarkka, Ina M

    2017-01-01

    Associations between long-term physical activity and cortical function and brain structure are poorly known. Our aim was to assess whether brain functional and/or structural modulation associated with long-term physical activity is detectable using a discordant monozygotic male twin pair design. Nine monozygotic male twin pairs were carefully selected for an intrapair difference in their leisure-time physical activity of at least three years duration (mean age 34 ± 1 years). We registered somatosensory mismatch response (SMMR) in EEG to electrical stimulation of fingers and whole brain MR images. We obtained exercise history and measured physical fitness and body composition. Equivalent electrical dipole sources of SMMR as well as gray matter (GM) voxel counts in regions of interest indicated by source analysis were evaluated. SMMR dipolar source strengths differed between active and inactive twins within twin pairs in postcentral gyrus, medial frontal gyrus and superior temporal gyrus and in anterior cingulate (AC) GM voxel counts differed similarly. Compared to active twins, their inactive twin brothers showed greater dipole strengths in short periods of the deviant-elicited SMMR and larger AC GM voxel counts. Stronger activation in early unattended cortical processing of the deviant sensory signals in inactive co-twins may imply less effective gating of somatosensory information in inactive twins compared to their active brothers. Present findings indicate that already in 30's long-term physical activity pattern is linked with specific brain indices, both in functional and structural domains.

  19. Epigenetics of personality traits: an illustrative study of identical twins discordant for risk-taking behavior.

    PubMed

    Kaminsky, Zachary; Petronis, Arturas; Wang, Sun-Chong; Levine, Brian; Ghaffar, Omar; Floden, Darlene; Feinstein, Anthony

    2008-02-01

    DNA methylation differences between identical twins could account for phenotypic twin discordance of behavioral traits and diseases. High throughput epigenomic microarray profiling can be a strategy of choice for identification of epigenetic differences in phenotypically different monozygotic (MZ) twins. Epigenomic profiling of a pair of MZ twins with quantified measures of psychometric discordance identified several DNA methylation differences, some of which may have developmental and behavioral implications and are consistent with the contrasting psychometric profiles of the twins. In particular, differential methylation of CpG islands proximal to the homeobox DLX1 gene could modulate stress responses and risk taking behavior, and deserve further attention as a potential marker of aversion to danger. The epigenetic difference detected at DLX1 of approximately 1.2 fold change was used to evaluate experimental design issues such as the required numbers of technical replicates. It also enabled us to estimate the power this technique would have to detect a functionally relevant epigenetic difference given a range of 1 to 50 twin pairs. We found that use of epigenomic microarray profiling in a relatively small number (15-25) of phenotypically discordant twin pairs has sufficient power to detect 1.2 fold epigenetic changes.

  20. Monozygotic twins affected with major depressive disorder have greater variance in methylation than their unaffected co-twin.

    PubMed

    Byrne, E M; Carrillo-Roa, T; Henders, A K; Bowdler, L; McRae, A F; Heath, A C; Martin, N G; Montgomery, G W; Krause, L; Wray, N R

    2013-06-11

    Our understanding of major depressive disorder (MDD) has focused on the influence of genetic variation and environmental risk factors. Growing evidence suggests the additional role of epigenetic mechanisms influencing susceptibility for complex traits. DNA sequence within discordant monozygotic twin (MZT) pairs is virtually identical; thus, they represent a powerful design for studying the contribution of epigenetic factors to disease liability. The aim of this study was to investigate whether specific methylation profiles in white blood cells could contribute to the aetiology of MDD. Participants were drawn from the Queensland Twin Registry and comprised 12 MZT pairs discordant for MDD and 12 MZT pairs concordant for no MDD and low neuroticism. Bisulphite treatment and genome-wide interrogation of differentially methylated CpG sites using the Illumina Human Methylation 450 BeadChip were performed in WBC-derived DNA. No overall difference in mean global methylation between cases and their unaffected co-twins was found; however, the differences in females was significant (P=0.005). The difference in variance across all probes between affected and unaffected twins was highly significant (P<2.2 × 10⁻¹⁶), with 52.4% of probes having higher variance in cases (binomial P-value<2.2 × 10⁻¹⁶). No significant differences in methylation were observed between discordant MZT pairs and their matched concordant MZT (permutation minimum P=0.11) at any individual probe. Larger samples are likely to be needed to identify true associations between methylation differences at specific CpG sites.

  1. DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins

    PubMed Central

    Sailani, M. Reza; Santoni, Federico A.; Letourneau, Audrey; Borel, Christelle; Makrythanasis, Periklis; Hibaoui, Youssef; Popadin, Konstantin; Bonilla, Ximena; Guipponi, Michel; Gehrig, Corinne; Vannier, Anne; Carre-Pigeon, Frederique; Feki, Anis; Nizetic, Dean; Antonarakis, Stylianos E.

    2015-01-01

    DNA methylation is essential in mammalian development. We have hypothesized that methylation differences induced by trisomy 21 (T21) contribute to the phenotypic characteristics and heterogeneity in Down syndrome (DS). In order to determine the methylation differences in T21 without interference of the interindividual genomic variation, we have used fetal skin fibroblasts from monozygotic (MZ) twins discordant for T21. We also used skin fibroblasts from MZ twins concordant for T21, normal MZ twins without T21, and unrelated normal and T21 individuals. Reduced Representation Bisulfite Sequencing (RRBS) revealed 35 differentially methylated promoter regions (DMRs) (Absolute methylation differences = 25%, FDR < 0.001) in MZ twins discordant for T21 that have also been observed in comparison between unrelated normal and T21 individuals. The identified DMRs are enriched for genes involved in embryonic organ morphogenesis (FDR = 1.60 e -03) and include genes of the HOXB and HOXD clusters. These DMRs are maintained in iPS cells generated from this twin pair and are correlated with the gene expression changes. We have also observed an increase in DNA methylation level in the T21 methylome compared to the normal euploid methylome. This observation is concordant with the up regulation of DNA methyltransferase enzymes (DNMT3B and DNMT3L) and down regulation of DNA demethylation enzymes (TET2 and TET3) observed in the iPSC of the T21 versus normal twin. Altogether, the results of this study highlight the epigenetic effects of the extra chromosome 21 in T21 on loci outside of this chromosome that are relevant to DS associated phenotypes. PMID:26317209

  2. Lesch-Nyhan disease in a female with a clinically normal monozygotic twin.

    PubMed

    De Gregorio, Laura; Jinnah, H A; Harris, James C; Nyhan, William L; Schretlen, David J; Trombley, Lucy M; O'Neill, J Patrick

    2005-05-01

    Lesch-Nyhan disease (LND) is an inborn error of purine metabolism caused by defective activity of the enzyme hypoxanthine guanine phosphoribosyl transferase (HPRT, EC 2.4.2.8), resulting from mutation in the corresponding gene on the long arm of the X chromosome (Xq26). The classic phenotype occurs almost exclusively in males and is characterized by hyperuricemia, mental retardation, severe dystonia, and self-injurious behavior. Heterozygous carrier females are usually clinically normal. However, a small number of clinically affected females have been described. In all previous cases there was a mutation in one HPRT allele and non-random inactivation of the X chromosome carrying the normal HPRT gene. We have analyzed a female MZ twin pair discordant for Lesch-Nyhan disease. The mother and both twins are heterozygous carriers of a HPRT splicing mutation (IVS8 + 4A > G; c.609 + 4A > G) and all three express the mutant allele at similar frequencies in peripheral blood T cells. The mother and one sister are clinically normal. In the affected twin, the clinical phenotype is classical for Lesch-Nyhan disease, despite the fact that HPRT activity in the blood was also normal. X inactivation analysis showed a skewed pattern in the fibroblasts of the affected twin sister, with the X chromosome carrying the normal HPRT allele preferentially inactivated. As in many other reported cases of X-linked diseases, the discordant phenotype of the two monozygous twin sisters suggests that the process responsible for monozygotic twinning can trigger skewed X inactivation.

  3. Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis.

    PubMed

    Gan, Lu; O'Hanlon, Terrance P; Gordon, Aaron S; Rider, Lisa G; Miller, Frederick W; Burbelo, Peter D

    2014-03-06

    Studies of twin pairs discordant for autoimmune conditions provide a unique opportunity to explore contributing factors triggered by complex gene-environment interactions. In this cross-sectional study, thirty-one monozygotic or dizygotic twin pairs discordant for myositis or systemic lupus erythematosus (SLE), along with matched healthy controls were evaluated for antibodies against a panel of 21 autoantigens. Autoantibody profiling revealed that 42% of the affected twins showed significant seropositivity against autoantigens in the panel. In many of these affected twins, but none of healthy controls, there were high levels of autoantibodies detected against two or more autoantigens commonly seen in systemic autoimmune diseases including Ro52, Ro60, RNP-70 K and/or RNP-A. In contrast, only 10% (3/31) of the unaffected twins showed seropositivity and these immunoreactivities were against single autoantigens not seen in systemic autoimmune diseases. While no significant differences in autoantibodies were detected between the affected or unaffected twins against thyroid peroxidase, transglutaminase and several cytokines, 23% of the affected twins with myositis showed autoantibodies against the gastric ATPase. Analysis of the monozygotic twins separately also revealed a higher frequencies of autoantibodies in the affected twins compared to the unaffected twins (P = 0.046). Lastly, clinical analysis of both the affected monozygotic and dizygotic twins revealed that the autoantibody seropositive affected twins had a greater global disease activity score compared to seronegative affected twins (P = 0.019). The findings of significantly more autoantibodies in the affected twins with myositis and SLE compared to the unaffected twins are consistent with potential non-genetic factors playing a role in autoantibody production and pathogenesis of these autoimmune disorders.

  4. Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis

    PubMed Central

    2014-01-01

    Background Studies of twin pairs discordant for autoimmune conditions provide a unique opportunity to explore contributing factors triggered by complex gene-environment interactions. Methods In this cross-sectional study, thirty-one monozygotic or dizygotic twin pairs discordant for myositis or systemic lupus erythematosus (SLE), along with matched healthy controls were evaluated for antibodies against a panel of 21 autoantigens. Results Autoantibody profiling revealed that 42% of the affected twins showed significant seropositivity against autoantigens in the panel. In many of these affected twins, but none of healthy controls, there were high levels of autoantibodies detected against two or more autoantigens commonly seen in systemic autoimmune diseases including Ro52, Ro60, RNP-70 K and/or RNP-A. In contrast, only 10% (3/31) of the unaffected twins showed seropositivity and these immunoreactivities were against single autoantigens not seen in systemic autoimmune diseases. While no significant differences in autoantibodies were detected between the affected or unaffected twins against thyroid peroxidase, transglutaminase and several cytokines, 23% of the affected twins with myositis showed autoantibodies against the gastric ATPase. Analysis of the monozygotic twins separately also revealed a higher frequencies of autoantibodies in the affected twins compared to the unaffected twins (P = 0.046). Lastly, clinical analysis of both the affected monozygotic and dizygotic twins revealed that the autoantibody seropositive affected twins had a greater global disease activity score compared to seronegative affected twins (P = 0.019). Conclusion The findings of significantly more autoantibodies in the affected twins with myositis and SLE compared to the unaffected twins are consistent with potential non-genetic factors playing a role in autoantibody production and pathogenesis of these autoimmune disorders. PMID:24602337

  5. Anorectal malformation and Down's syndrome in monozygotic twins.

    PubMed

    de Buys Roessingh, Anthony S; Mueller, Claudia; Wiesenauer, Chad; Bensoussan, Arié L; Beaunoyer, Mona

    2009-02-01

    Anorectal malformation (ARM) can be divided in high, intermediate, and low forms according to the level of termination of the rectum in relation to the pubococcygeal and ischiatic lines. Patients with Down's syndrome have a high incidence of gastrointestinal anomalies, such as tracheoesophageal fistula, duodenal obstruction, annular pancreas, Hirschsprung's disease, and ARM. In these children, ARM is generally low with or without a fistula. The mode of inheritance of ARM and its genetic relation with Down's syndrome is not known, even if the association (ARM-Down's syndrome) seems not to be coincidental. We describe here a very rare case of monozygotic twins born with the association of ARM and Down's syndrome.

  6. Monozygotic twins with Alzheimer's disease treated with melatonin: Case report.

    PubMed

    Brusco, L I; Márquez, M; Cardinali, D P

    1998-12-01

    Monozygotic twins with Alzheimer's disease of 8 years duration were studied. The onset of the disease differed by about 6 months between twins and was characterized by a primary impairment of memory function. Clinical evaluation at the time of diagnosis indicated a similar cognitive and neuroimaging alteration in both patients, as well as a similar neuropsychologic impairment. A possible genetic origin of the disease was suggested by a similar disease suffered by the mother. Patients were initially treated with vitamin E (800 I.U./day). Starting at approximately the same time (about 3 years ago), they received 50 mg/day thioridazine because of the behavioral and sleep disorder. One of the patients was treated with melatonin (6 mg orally) at bed time daily for 36 months. Evolution of the disease in the melatonin-treated patient indicated a milder impairment of memory function, with substantial improvement of sleep quality and reduction of sundowning. This led to discontinuance (after 3 months) of thioridazine treatment. Present clinical evaluation indicated a difference in functional stage of the disease between the twins (Functional Assessment Tool For Alzheimer's Disease, FAST), with a score of 5 in the twin who received melatonin and of 7b in the twin who did not receive it. Since experimental data on melatonin in animals indicated its antioxidant, antiapoptotic, and beta-amyloid-decreasing activity, the hypothesis that melatonin has a beneficial effect in Alzheimer's disease patients should be considered.

  7. Late onset of familial neurogenic diabetes insipidus in monozygotic twins.

    PubMed

    Cizmarova, M; Nagyova, G; Janko, V; Pribilincova, Z; Virgova, D; Ilencikova, D; Kovacs, L

    2013-10-01

    Autosomal dominant familial diabetes insipidus (FNDI) is a rare disease characterized by polydipsia and polyuria due to deficiency of the antidiuretic hormone, arginine vasopressin (AVP). We report the first Slovak family with the disease. Noteworthy is the concordantly belated debut of the disease symptoms in two monozygotic twin proband girls in the age of 17 years. Because of inconclusive results of water deprivation test consistent with partial diabetes insipidus (DI), missing "bright spot" of posterior pituitary gland in T1-weighted magnetic resonance imaging and family occurrence of polyuria and polydipsia on anamnestic evaluation. Molecular genetic testing of the AVP gene was proceeded, because of the inconclusive results of water deprivation test consistent with partial diabetes insipidus, missing "bright spot" of posterior pituitary gland in T1-weighted magnetic resonance imaging and family occurrence of polyuria and polydipsia on anamnestic evaluation. Genetic analysis revealed a heterozygous g.279G>A substitution that predicts a p.Ala19Thr substitution in the signal peptide of the AVP prohormone. The wide intrafamiliar variations (3 to 17 years) in disease onset together with the concordantly delayed debut of polyuria in two monozygotic twin girls suggest that individual differences in genetic influences family environmental factors may modify the penetrance of the mutation of the AVP gene. The present paper supports the notion that molecular genetic evaluation should be performed in all patients with familial occurrence of DI regardless of the clinical results.

  8. Brain Structure and Function Differences in Monozygotic Twins: Possible Effects of Breast Cancer Chemotherapy

    PubMed Central

    Ferguson, Robert J.; McDonald, Brenna C.; Saykin, Andrew J.; Ahles, Tim A.

    2012-01-01

    Purpose Adjuvant chemotherapy has been associated with mild cognitive decline among a subset of breast cancer survivors. Late cognitive effects after chemotherapy can have a deleterious impact on survivor quality of life and functional health; however, the etiology of chemotherapy-related cognitive dysfunction remains unknown. Patients and Methods We present a case of monozygotic twins who are discordant for breast cancer and chemotherapy exposure (ie, one twin contracted breast cancer and underwent chemotherapy, and the other had no breast cancer). As part of a larger study, each was evaluated with standardized, self-report measures of cognitive function, standard neuropsychological tests, and structural and functional magnetic resonance imaging (MRI). Results Results indicated small differences in neuropsychological test performance but striking contrasts in self-reported cognitive complaints and structural and functional MRI images. Specifically, the twin who underwent chemotherapy had substantially more subjective cognitive complaints, more white matter hyperintensities on MRI, and an expanded spatial extent of brain activation during working memory processing than her nonaffected twin. Conclusion This case illustrates possible physiologic mechanisms that could produce long-term cognitive complaints among chemotherapy recipients and help formulate hypotheses for further empirical study in the area of chemotherapy-associated cognitive dysfunction. PMID:17761972

  9. Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus

    PubMed Central

    Javierre, Biola M.; Fernandez, Agustin F.; Richter, Julia; Al-Shahrour, Fatima; Martin-Subero, J. Ignacio; Rodriguez-Ubreva, Javier; Berdasco, Maria; Fraga, Mario F.; O'Hanlon, Terrance P.; Rider, Lisa G.; Jacinto, Filipe V.; Lopez-Longo, F. Javier; Dopazo, Joaquin; Forn, Marta; Peinado, Miguel A.; Carreño, Luis; Sawalha, Amr H.; Harley, John B.; Siebert, Reiner; Esteller, Manel; Miller, Frederick W.; Ballestar, Esteban

    2010-01-01

    Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis, and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Gene ontology analysis revealed enrichment in categories associated with immune function. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. These changes occurred in parallel with a global decrease in the 5-methylcytosine content that was concomitantly accompanied with changes in DNA methylation and expression levels of ribosomal RNA genes, although no changes in repetitive sequences were found. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease. PMID:20028698

  10. Epigenetic variation during the adult lifespan: cross-sectional and longitudinal data on monozygotic twin pairs

    PubMed Central

    Talens, Rudolf P; Christensen, Kaare; Putter, Hein; Willemsen, Gonneke; Christiansen, Lene; Kremer, Dennis; Suchiman, H Eka D; Slagboom, P Eline; Boomsma, Dorret I; Heijmans, Bastiaan T

    2012-01-01

    The accumulation of epigenetic changes was proposed to contribute to the age-related increase in the risk of most common diseases. In this study on 230 monozygotic twin pairs (MZ pairs), aged 18–89 years, we investigated the occurrence of epigenetic changes over the adult lifespan. Using mass spectrometry, we investigated variation in global (LINE1) DNA methylation and in DNA methylation at INS, KCNQ1OT1, IGF2, GNASAS, ABCA1, LEP, and CRH, candidate loci for common diseases. Except for KCNQ1OT1, interindividual variation in locus-specific DNA methylation was larger in old individuals than in young individuals, ranging from 1.2-fold larger at ABCA1 (P = 0.010) to 1.6-fold larger at INS (P = 3.7 × 10−07). Similarly, there was more within-MZ-pair discordance in old as compared with young MZ pairs, except for GNASAS, ranging from an 8% increase in discordance each decade at CRH (P = 8.9 × 10−06) to a 16% increase each decade at LEP (P = 2.0 × 10−08). Still, old MZ pairs with strikingly similar DNA methylation were also observed at these loci. After 10-year follow-up in elderly twins, the variation in DNA methylation showed a similar pattern of change as observed cross-sectionally. The age-related increase in methylation variation was generally attributable to unique environmental factors, except for CRH, for which familial factors may play a more important role. In conclusion, sustained epigenetic differences arise from early adulthood to old age and contribute to an increasing discordance of MZ twins during aging. PMID:22621408

  11. Investigating Unique Environmental Influences of Parenting Practices on Youth Anxiety: A Monozygotic Twin Differences Study

    ERIC Educational Resources Information Center

    Chen, Jie; Yu, Jing; Zhang, Jianxin

    2016-01-01

    The associations between parenting practices and adolescent anxiety symptoms were examined in both individual and monozygotic (MZ) twin differences levels. Participants were 804 pairs of Chinese MZ adolescent twins aged 10-18 years (M = 13.57, SD = 2.67, 52% females). Twins' anxiety symptoms were assessed by self- and parent-reports. Twins also…

  12. Investigating Unique Environmental Influences of Parenting Practices on Youth Anxiety: A Monozygotic Twin Differences Study

    ERIC Educational Resources Information Center

    Chen, Jie; Yu, Jing; Zhang, Jianxin

    2016-01-01

    The associations between parenting practices and adolescent anxiety symptoms were examined in both individual and monozygotic (MZ) twin differences levels. Participants were 804 pairs of Chinese MZ adolescent twins aged 10-18 years (M = 13.57, SD = 2.67, 52% females). Twins' anxiety symptoms were assessed by self- and parent-reports. Twins also…

  13. Heritability of thyroid peroxidase autoantibody levels in type 1 diabetes: evidence from discordant twin pairs.

    PubMed

    Wang, Bin; Hawa, Mohammed I; Rijsdijk, Frühling V; Fain, Pamela R; Paschou, Stavroula A; Boehm, Bernhard O; Steck, Andrea K; Snieder, Harold; Leslie, R David G

    2015-09-01

    The discordance status of (autoimmune) type 1 diabetes within monozygotic twin pairs points to the importance of environmental factors. The aim of this study was to investigate whether the environmental events causing type 1 diabetes influence thyroid autoimmunity. Monozygotic and dizygotic twins discordant for type 1 diabetes from the UK and USA were tested for thyroid peroxidase autoantibodies (TPOA) by radioimmunoassay. Using quantitative genetic model fitting of a liability-threshold model we estimated the contribution of genetic (heritability) and environmental factors to TPOA. TPOA positivity was higher in females than in males in both cohorts and was associated with later age at diagnosis in the UK and combined cohorts (p < 0.01). TPOA did not specifically segregate with type 1 diabetes in the twin pairs (p > 0.2 in all groups). The best-fitting models showed heritability (95% CI) estimates for TPOA of 63% (37%, 80%) for the UK and 80% (51%, 92%) for US twins, while the best-fitting meta-analysis model of the two twin cohorts combined included additive genetic and unique environmental factors with a heritability estimate of 69% (50%, 82%). Risk of thyroid autoimmunity, defined by TPOA, in the context of autoimmune diabetes is, substantially, genetically determined in discordant twin pairs. Environmental factors leading to type 1 diabetes were not the same as those involved with thyroid autoimmunity. It follows that it is as important to investigate for thyroid autoimmunity in relatives of type 1 diabetes patients as it is in the patients themselves.

  14. Dichorionic twin pregnancy discordant for fetal anencephaly: a case report.

    PubMed

    Taşcı, Yasemin; Karasu, Yetkin; Erten, Ozlem; Karadağ, Burak; Göktolga, Umit

    2012-01-01

    Dichorionic twin pregnancy discordant for fetal anencephaly is a serious condition that threatens the normal co-twin's life by causing polyhydramniosis, preterm labor and sudden death of one or both of the fetuses. We report a case of dichorionic twin pregnancy discordant for fetal anencephaly delivered at the 32(nd) week of gestation because of preterm labor and nonreassuring fetal monitoring. The aim of this case report is to summarize management options in this situation.

  15. Early onset alcohol use and self-harm: A discordant twin analysis

    PubMed Central

    Few, Lauren R.; Werner, Kimberly B.; Sartor, Carolyn E.; Trull, Timothy; Nock, Matthew K.; Bucholz, Kathleen K.; Deitz, Sarah K.; Glowinski, Anne L.; Martin, Nicholas G.; Nelson, Elliot C.; Statham, Dixie J.; Madden, Pamela A. F.; Heath, Andrew; Lynskey, Michael T.; Agrawal, Arpana

    2015-01-01

    Background Self-harm has considerable societal and economic costs and has been extensively studied in relation to alcohol involvement. Whereas early onset alcohol use (EAU) has been causally linked to maladaptive clinical outcomes, its association with self-harm is less well characterized. The current study aimed to further examine the link between EAU and both non-suicidal self-injury (NSSI) and suicide attempt (SA), and elucidate shared familial and causal/individual-specific pathways that explain this co-occurrence. Methods Using data from 6,082 Australian same-sex twin pairs (1,732 MZ and 1,309 DZ), ages 23-40, we examined prevalence rates of NSSI and SA among twin pairs concordant and discordant for EAU. Conditional logistic regression, controlling for early clinical covariates and the influence of zygosity on EAU, was used to examine the odds ratio (OR) of self-harm within twin pairs discordant for EAU. Results Prevalence rates of both NSSI and SA were highest among twin pairs concordant for EAU and for twins who reported EAU within discordant twin pairs. Results from discordant twin analyses revealed nearly four-fold increased odds of SA for the twin who endorsed EAU, and this OR was equal across monozygotic (MZ) and dizygotic (DZ) twins. EAU also was associated with elevated odds of NSSI (OR=7.62), although this was only the case for DZ twins in discordant pairs. Conclusions The equivalent increase in odds of SA for both MZ and DZ twins suggests that causal or individual-specific influences explain the link between EAU and SA. For NSSI, elevated odds for DZ twins and nonsignificant findings for MZ twins implicate correlated genetic factors in the association between EAU and NSSI. Future studies should test mechanisms through which EAU may causally influence SA, as well as examine whether genetic risk for third variables (e.g., negative urgency, stress reactivity) may explain the genetic overlap between EAU and NSSI. PMID:26463647

  16. Biotin-dependent functions in adiposity: a study of monozygotic twin pairs.

    PubMed

    Järvinen, E; Ismail, K; Muniandy, M; Bogl, L H; Heinonen, S; Tummers, M; Miettinen, S; Kaprio, J; Rissanen, A; Ollikainen, M; Pietiläinen, K H

    2016-05-01

    Biotin acts as a coenzyme for carboxylases regulating lipid and amino-acid metabolism. We investigated alterations of the biotin-dependent functions in obesity and the downstream effects of biotin restriction in adipocytes in vitro. Twenty-four monozygotic twin pairs discordant for body mass index (BMI). Mean within-pair difference (heavy-lean co-twin, Δ) of BMI was 6.0 kg m(-2) (range 3.1-15.2 kg m(-)(2)). Adipose tissue (AT) DNA methylation, gene expression of AT and adipocytes, and leukocytes (real-time quantitative PCR), serum biotin, C-reactive protein (CRP) and triglycerides were measured in the twins. Human adipocytes were cultured in low and control biotin concentrations and analyzed for lipid droplet content, mitochondrial morphology and mitochondrial respiration. The gene expression levels of carboxylases, PCCB and MCCC1, were upregulated in the heavier co-twins' leukocytes. ΔPCCB (r=0.91, P=0.0046) and ΔMCCC1 (r=0.79, P=0.036) correlated with ΔCRP within-pairs. Serum biotin levels were lower in the heavier (274 ng l(-1)) than in the lean co-twins (390 ng l(-1), P=0.034). ΔBiotin correlated negatively with Δtriglycerides (r=-0.56, P=0.045) within-pairs. In AT, HLCS and ACACB were hypermethylated and biotin cycle genes HLCS and BTD were downregulated (P<0.05). Biotin-dependent carboxylases were downregulated (ACACA, ACACB, PCCB, MCCC2 and PC; P<0.05) in both AT and adipocytes of the heavier co-twins. Adipocytes cultured in low biotin had decreased lipid accumulation, altered mitochondrial morphology and deficient mitochondrial respiration. Biotin-dependent functions are modified by adiposity independent of genetic effects, and correlate with inflammation and hypertriglyceridemia. Biotin restriction decreases lipid accumulation and respiration, and alters mitochondrial morphology in adipocytes.

  17. Multiple mitochondrial DNA deletions in monozygotic twins with OPMD.

    PubMed

    Muqit, M M K; Larner, A J; Sweeney, M G; Sewry, C; Stinton, V J; Davis, M B; Healy, D G; Payne, S J; Chotai, K; Wood, N W; Lane, R J M

    2008-01-01

    Oculopharyngeal muscular dystrophy (OPMD) is caused by expansions of the poly (A) binding protein 2 (PABP2) gene. Previous histological analyses have revealed mitochondrial abnormalities in the muscles of OPMD patients but their significance remains uncertain. We had the rare opportunity to study monozygotic twins with identical expansions of the PABP2 gene but with markedly different severities of OPMD. Both had histological features of mitochondrial myopathy. We determined whether mitochondrial DNA abnormalities underlay these changes. Clinical information was obtained by history and examination. Muscle biopsies were obtained from each subject and genetic analysis was performed using long-range PCR and Southern blotting. We demonstrate, for the first time, the presence of mitochondrial DNA (mtDNA) deletions by Southern blotting in individuals with OPMD. This correlates with the presence of mitochondrial myopathy in both twins. Moreover, both twins had different mtDNA deletions, which might explain their phenotypic differences. We hypothesise that mitochondrial dysfunction may occur as a consequence of PABP2 gene mutations, and that this dysfunction may affect the phenotypic manifestations of OPMD.

  18. An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins

    PubMed Central

    Yuan, Wei; Xia, Yudong; Bell, Christopher G.; Yet, Idil; Ferreira, Teresa; Ward, Kirsten J.; Gao, Fei; Loomis, A. Katrina; Hyde, Craig L.; Wu, Honglong; Lu, Hanlin; Liu, Yuan; Small, Kerrin S.; Viñuela, Ana; Morris, Andrew P.; Berdasco, María; Esteller, Manel; Brosnan, M. Julia; Deloukas, Panos; McCarthy, Mark I.; John, Sally L.; Bell, Jordana T.; Wang, Jun; Spector, Tim D.

    2014-01-01

    DNA methylation has a great potential for understanding the aetiology of common complex traits such as Type 2 diabetes (T2D). Here we perform genome-wide methylated DNA immunoprecipitation sequencing (MeDIP-seq) in whole-blood-derived DNA from 27 monozygotic twin pairs and follow up results with replication and integrated omics analyses. We identify predominately hypermethylated T2D-related differentially methylated regions (DMRs) and replicate the top signals in 42 unrelated T2D cases and 221 controls. The strongest signal is in the promoter of the MALT1 gene, involved in insulin and glycaemic pathways, and related to taurocholate levels in blood. Integrating the DNA methylome findings with T2D GWAS meta-analysis results reveals a strong enrichment for DMRs in T2D-susceptibility loci. We also detect signals specific to T2D-discordant twins in the GPR61 and PRKCB genes. These replicated T2D associations reflect both likely causal and consequential pathways of the disease. The analysis indicates how an integrated genomics and epigenomics approach, utilizing an MZ twin design, can provide pathogenic insights as well as potential drug targets and biomarkers for T2D and other complex traits. PMID:25502755

  19. An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins.

    PubMed

    Yuan, Wei; Xia, Yudong; Bell, Christopher G; Yet, Idil; Ferreira, Teresa; Ward, Kirsten J; Gao, Fei; Loomis, A Katrina; Hyde, Craig L; Wu, Honglong; Lu, Hanlin; Liu, Yuan; Small, Kerrin S; Viñuela, Ana; Morris, Andrew P; Berdasco, María; Esteller, Manel; Brosnan, M Julia; Deloukas, Panos; McCarthy, Mark I; John, Sally L; Bell, Jordana T; Wang, Jun; Spector, Tim D

    2014-12-12

    DNA methylation has a great potential for understanding the aetiology of common complex traits such as Type 2 diabetes (T2D). Here we perform genome-wide methylated DNA immunoprecipitation sequencing (MeDIP-seq) in whole-blood-derived DNA from 27 monozygotic twin pairs and follow up results with replication and integrated omics analyses. We identify predominately hypermethylated T2D-related differentially methylated regions (DMRs) and replicate the top signals in 42 unrelated T2D cases and 221 controls. The strongest signal is in the promoter of the MALT1 gene, involved in insulin and glycaemic pathways, and related to taurocholate levels in blood. Integrating the DNA methylome findings with T2D GWAS meta-analysis results reveals a strong enrichment for DMRs in T2D-susceptibility loci. We also detect signals specific to T2D-discordant twins in the GPR61 and PRKCB genes. These replicated T2D associations reflect both likely causal and consequential pathways of the disease. The analysis indicates how an integrated genomics and epigenomics approach, utilizing an MZ twin design, can provide pathogenic insights as well as potential drug targets and biomarkers for T2D and other complex traits.

  20. Monozygotic male twins concordant for Beckwith-Wiedemann syndrome

    SciTech Connect

    Clemens, M.; McPherson, E.; Sherer, C. |

    1994-09-01

    The Beckwith-Wiedemann syndrome (BWS) is a multiple congenital anomaly syndrome characterized by macrosomia, macro glossia, visceromegaly, characteristic facies, and in some cases omphalocele, hypoglycemia, hemihypertrophy, and risk of embryonal tumors. Most cases occur sporadically in chromosomally normal individuals, but a few BWS patients have anomalies of 11p and others have evidence of microduplications or paternal isodisomy in this region. In some families with autosomal dominant transmission, BWS maps to 11p15.5, but the mechanism of transmission is not fully understood. BWS has been reported in 11 sets of MZ twins, including 10 female pairs (9 discordant and 1 partially concordant) and one male pair concordant for both BWS & dup 15q11.2-q13. We report a pair of premature male MZ twins with macroglossia, postnatal overgrowth, characteristic BWS facies, and mild developmental delay. One twin had hypoglycemia, but neither had omphalocele or hemihypertrophy and serial abdominal ultrasounds have been normal. DNA fingerprinting confirmed monozygosity. Chromosome studies showed a marker 11p14.2 in one twin only, and molecular genetic studies of the 11p15.5 region showed no evidence of duplication or isodisomy in either twin.

  1. Situs Inversus Totalis in Twins: A Brief Review and a Life History / Twin Research: Twin Studies of Trisomy 21; Monozygotic Twin Concordance for Bilateral Coronoid Hyperplasia; Prenatal Hormonal Effects in Mixed-Sex Non-Human Primate Litters; Insurance Mandates and Twinning After In Vitro Fertilization / News Reports: First Report of Identical Twin Puppies; Twins Sisters Turn 100; Remembering an Identical Twin Production Designer; New York City Marathon Quadruplets.

    PubMed

    Segal, Nancy L

    2017-02-01

    The presence of situs inversus totalis (full reversal of internal organs) in twins is briefly reviewed. Information gathered from 35-year-old monozygotic (MZ) female twin pair discordant for this condition is presented. This is followed by summaries of research on the frequency of trisomy 21 (Down syndrome) in twins, the first case of MZ twin concordance for bilateral coronoid hyperplasia, prenatal hormonal effects in mixed-sex non-human primate litters, and links between insurance mandates and twinning following in vitro fertilization. The final section of this article describes twin-related events reported in the news, namely, the first recorded birth of identical twin puppies; the 100th birthday celebration of a pair of fraternal female twins, the passing of an award-winning identical twin production designer, and the first running of the New York City Marathon by a set of quadruplets.

  2. Early neonatal morbidity and mortality in growth-discordant twins.

    PubMed

    Alam Machado, Rita De Cássia; Brizot, Maria De Lourdes; Liao, Adolfo Wenjaw; Krebs, Vera Lucia Jornada; Zugaib, Marcelo

    2009-01-01

    To evaluate early neonatal morbidity and mortality in twin pregnancies with growth discordance. Retrospective study. Tertiary teaching hospital, Sao Paulo, Brazil. A total of 151 twin pregnancies managed and delivered at the Multiple Pregnancy Unit at Sao Paulo University Hospital between 1998 and 2004. METHODS; Comparison between twin pregnancies with weight discordance > or =20% and pregnancies concordant for fetal weight. Cases with fetal death, abnormalities, twin-to-twin transfusion and delivery before 26 weeks or in another hospital were excluded. Early neonatal morbidity (Apgar at 5 minutes <7, respiratory or neurological complications, infection, necrotizing enterocolitis, length of hospital stay) and mortality. Forty (26.5%) pregnancies presented discordance > or =20% and 111 (73.5%) were concordant. In the discordant group, 75% of pregnancies had at least one growth restricted fetus (<10th centile). In concordant twin pregnancies, monochorionic cases (22.5%) presented with lower gestational age (34.3 vs. 36.2 weeks), lower birthweight (2,067 vs. 2,334 g) and a longer period of hospital stay (5.5 vs. 3.0) compared to dichorionic concordant twins. No differences between monochorionic and dichorionic subgroups were observed in discordant twins. Pregnancies in which at least one baby was born with a birthweight below the 10th centile showed that discordant pregnancies had a lower gestational age at delivery (35.2 vs. 36.8 weeks) and a longer period of hospital stay (9 vs. 4 weeks) compared to concordant cases. Neonatal mortality was similar in discordant (3.7%) and concordant (4.5%) twins. Early perinatal morbidity is increased in twin pregnancies with birthweight discordance > or =20% only when associated with fetal growth restriction and low birthweight.

  3. A Monozygotic Twin Difference Study of Friends' Aggression and Children's Adjustment Problems

    ERIC Educational Resources Information Center

    Vitaro, Frank; Brendgen, Mara; Boivin, Michel; Cantin, Stephane; Dionne, Ginette; Tremblay, Richard E.; Girard, Alain; Perusse, Daniel

    2011-01-01

    This study used the monozygotic (MZ) twin difference method to examine whether differences in friends' aggression increased the differences in MZ twins' aggression and depressive symptoms from kindergarten to Grade 1 and whether perceived victimization by the friend played a mediating role in this context. Participants were 223 MZ twin pairs.…

  4. A Monozygotic Twin Difference Study of Friends' Aggression and Children's Adjustment Problems

    ERIC Educational Resources Information Center

    Vitaro, Frank; Brendgen, Mara; Boivin, Michel; Cantin, Stephane; Dionne, Ginette; Tremblay, Richard E.; Girard, Alain; Perusse, Daniel

    2011-01-01

    This study used the monozygotic (MZ) twin difference method to examine whether differences in friends' aggression increased the differences in MZ twins' aggression and depressive symptoms from kindergarten to Grade 1 and whether perceived victimization by the friend played a mediating role in this context. Participants were 223 MZ twin pairs.…

  5. The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium.

    PubMed

    Willemsen, Gonneke; Ward, Kirsten J; Bell, Christopher G; Christensen, Kaare; Bowden, Jocelyn; Dalgård, Christine; Harris, Jennifer R; Kaprio, Jaakko; Lyle, Robert; Magnusson, Patrik K E; Mather, Karen A; Ordoňana, Juan R; Perez-Riquelme, Francisco; Pedersen, Nancy L; Pietiläinen, Kirsi H; Sachdev, Perminder S; Boomsma, Dorret I; Spector, Tim

    2015-12-01

    Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many

  6. Heritability of changes in brain volume over time in twin pairs discordant for schizophrenia.

    PubMed

    Brans, Rachel G H; van Haren, Neeltje E M; van Baal, G Caroline M; Schnack, Hugo G; Kahn, René S; Hulshoff Pol, Hilleke E

    2008-11-01

    Structural brain abnormalities have consistently been found in schizophrenia, with increased familial risk for the disease associated with these abnormalities. Some brain volume changes are progressive over the course of the illness. Whether these progressive brain volume changes are mediated by genetic or disease-related factors is unknown. To investigate whether genetic and/or environmental factors are associated with progressive brain volume changes in schizophrenia. Longitudinal 5-year follow-up in monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for schizophrenia and healthy comparison twin pairs using brain magnetic resonance imaging. Participants were recruited from the twin pair cohort at the University Medical Center Utrecht. A total of 92 participants completed the study: 9 MZ and 10 DZ twin pairs discordant for schizophrenia and 14 MZ and 13 DZ healthy twin pairs. Percentage volume changes of the whole brain; cerebral gray and white matter of the frontal, temporal, parietal, and occipital lobes; cerebellum; and lateral and third ventricles over time between and within twin pairs were compared using repeated measures analysis of covariance. Structural equation modeling was applied to estimate contributions of additive genetic and common and unique environmental factors. Significant decreases over time in whole brain and frontal and temporal lobe volumes were found in patients with schizophrenia and their unaffected co-twins compared with control twins. Bivariate structural equation modeling using cross-trait/cross-twin correlations revealed significant additive genetic influences on the correlations between schizophrenia liability and progressive whole brain (66%; 95% confidence interval [CI], 51%-100%), frontal lobe (76%; 95% CI, 54%-100%), and temporal lobe (79%; CI, 56%-100%) volume change. The progressive brain volume loss found in patients with schizophrenia and their unaffected co-twins is at least partly attributable to genetic factors

  7. Phospholipids and insulin resistance in psychosis: a lipidomics study of twin pairs discordant for schizophrenia

    PubMed Central

    2012-01-01

    Background Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission. Methods Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 ± 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples. Results In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed. Conclusions Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins. PMID:22257447

  8. Two cases of mirror-image eye anomalies in monozygotic twins.

    PubMed

    Kim, Wook Kyum; Chung, Seung Ah; Lee, Jong Bok

    2010-10-01

    We report two cases of mirror image anomalies in two different pairs of monozygotic twins. In case 1, the twins exhibited mirroring of strabismus and refractive errors. Twin 1 had 35 prism diopters (PD) right intermittent exotropia at distant fixation and myopic anisometropia that was spherical 2.00 diopters more myopic in the right eye. Twin 2 had 35 PD left intermittent exotropia at distant fixation and her left eye was more myopic by - spherical 1.00 diopters. In case 2, the twins were diagnosed with infantile nystagmus with upbeat jerk. Twin 1 exhibited a habitual head turn of 30° to the left with dampening of her nystagmus in dextroversion. Twin 2 also exhibited abnormal head position, but in his case the habitual turn was 30° to the right. We believe that this is the first report describing mirror imaged intermittent exotropia with anisometropia and infantile nystagmus with opposite abnormal head positions in pairs of monozygotic twins.

  9. [Perinatal management of twins with discordant congenital defects].

    PubMed

    Yu, Hai-yan; Xing, Ai-yun; You, Yong; Liu, Xing-hui; Wang, Xiao-dong

    2014-11-01

    To review the outcomes of perinatal management of twins with discordant congenital defects. We retrospectively examined the cases of twins with discordant congenital defects treated in the West China Second University Hospital from December 2011 to December 2013. There were 26 cases of twins (14 dichorionic and 12 monochorionic) with one anomalous fetus. Of those twins, 16 were conceived by nature and 10 by in vitro fertilization and embryo tansfer (IVF-ET). Counselling services were offered to the parents by a multidisciplinary team about options of pregnancy. Termination of pregnancy was chosen on three monochorionic twins. Twelve pairs of twin were delivered at 26(+3)-37(+6) weeks gestation. One pair ended with neonatal death, and another one with gastroschisis was given intrapartum fetal operation. Selective termination was chosen on 11 cases using intracardiac injection of potassium chloride under ultrasonographic guidance (9 cases) or bipolar cord coagulation (2 cases). This resulted in ten live births delivered at 25(+5)-38(+4) gustation and one neonatal death. Early diagnosis of twins with discordant congenital defects is important. Multidisciplinary counselling services to parents are recommended for determination of options. Intensive prenatal care is essential in management of twins with discordant congenital defects.

  10. A pedigree analysis of familial hypercholesterolemia in monozygote twin brothers.

    PubMed

    Li, Jian-Jun; Chen, Ming-Zhe; Chen, Xin

    2003-01-01

    The current study was designed to investigate the features of a family with familial hypercholesterolemia (FH). Twenty members of 3 generations in a family with hypercholesterolemia were enrolled in the study. The data collected were from clinical observation and subjected to pedigree analysis. The proband was a 41-year-old male who suffered from angina pectoris with multi-vessel stenosis of coronary arteries at the age of 40. Among 20 members, 8 individuals had FH in this family with a total incidence of 40% (54.5% [6/11] in male and 22.2% [2/9] in female). The serum total cholesterol level was increased in childhood from 7.1 to 10.8 mmol/L and tended to increase with increasing age. In addition, the level of total cholesterol was increased in monozygote twin brothers and their offspring in the family. This pedigree analysis showed that FH appears to be a hereditary disease of autosomal dominance, and attention should be paid, especially in the only son or daughter society of China.

  11. Developmental origins and impact of BCR-ABL1 fusion and IKZF1 deletions in monozygotic twins with Ph+ acute lymphoblastic leukemia

    PubMed Central

    van Delft, Frederik W.; Lo Nigro, Luca; Ford, Anthony M.; Score, Joannah; Iacobucci, Ilaria; Mirabile, Elena; Taj, Mary; Colman, Susan M.; Biondi, Andrea

    2011-01-01

    The timing and developmental sequence of events for BCR-ABL1+ acute lymphoblastic leukemia (ALL), usually associated with IKAROS (IKZF1) deletions, are unknown. We assessed the status of BCR-ABL1 and IKZF1 genes in 2 pairs of monozygotic twins, one pair concordant, the other discordant for Philadelphia chromosome positive (Ph+) ALL. The twin pair concordant for ALL shared identical BCR-ABL1 genomic sequence indicative of monoclonal, in utero origin. One twin had IKZF1 deletion and died after transplantation. The other twin had hyperdiploidy, no IKZF1 deletion, and is still in remission 8 years after transplantation. In the twin pair discordant for ALL, neonatal blood spots from both twins harbored the same clonotypic BCR-ABL1 sequence. Low level BCR-ABL1+ cells were present in the healthy co-twin but lacked the IKZF1 deletion present in the other twin's leukemic cells. The twin with ALL relapsed and died after transplantation. The co-twin remains healthy and leukemia free. These data show that in childhood Ph+ ALL, BCR-ABL1 gene fusion can be a prenatal and possibly initiating genetic event. In the absence of additional, secondary changes, the leukemic clone remains clinically silent. IKZF1 is a secondary and probable postnatal mutation in these cases, and as a recurrent but alternative copy number change is associated with poor prognosis. PMID:21960589

  12. Hyperthyroid Graves' disease and primary hypothyroidism caused by TSH receptor antibodies in monozygotic twins: case reports.

    PubMed

    Tani, J; Yoshida, K; Fukazawa, H; Kiso, Y; Sayama, N; Mori, K; Aizawa, Y; Hori, H; Nakasato, N; Abe, K

    1998-02-01

    A 33-year-old woman with signs and symptoms of hypothyroidism, including increased thyroid stimulating blocking antibody (TSBAb) activity, was referred for treatment by her local physician. Her monozygote twin was treated for hyperthyroid Graves' disease 10 years earlier. This case of hyperthyroidism and hypothyroidism in identical twins suggests the involvement of environmental factors in the pathogenesis of autoimmune thyroid diseases.

  13. Rare case of monozygotic twins diagnosed with klinefelter syndrome during evaluation for infertility.

    PubMed

    Barazani, Yagil; Sabanegh, Edmund

    2015-01-01

    Although neither Klinefelter syndrome nor monozygotic twins are particularly rare (1/667 male births and 3-4/1000 live births, respectively), the occurrence of both in the same pregnancy (ie, identical twins with Klinefelter syndrome) is exceedingly rare and has only been reported three times previously in the literature. This report describes the fourth ever reported case of monozygotic twins with Klinefelter syndrome (who presented to our male fertility clinic with failure to conceive) and sheds interesting light on the reproductive concordance observed with this rare clinical entity. To our knowledge, this is the first reported case of monozygotic twins with Klinefelter syndrome that describes the infertility workup and outcomes of microsurgical testicular sperm extraction.

  14. From alcohol initiation to tolerance to problems: Discordant twin modeling of a developmental process.

    PubMed

    Deutsch, Arielle R; Slutske, Wendy S; Lynskey, Michael T; Bucholz, Kathleen K; Madden, Pamela A F; Heath, Andrew C; Martin, Nicholas G

    2017-08-01

    The current study examined a stage-based alcohol use trajectory model to test for potential causal effects of earlier drinking milestones on later drinking milestones in a combined sample of two cohorts of Australian monozygotic and same-sex dizygotic twins (N = 7,398, age M = 30.46, SD = 2.61, 61% male, 56% monozygotic twins). Ages of drinking, drunkenness, regular drinking, tolerance, first nontolerance alcohol use disorder symptom, and alcohol use disorder symptom onsets were assessed retrospectively. Ages of milestone attainment (i.e., age-of-onset) and time between milestones (i.e., time-to-event) were examined via frailty models within a multilevel discordant twin design. For age-of-onset models, earlier ages of onset of antecedent drinking milestones increased hazards for earlier ages of onset for more proximal subsequent drinking milestones. For the time-to-event models, however, earlier ages of onset for the "starting" milestone decreased risk for a shorter time period between the starting and the "ending" milestone. Earlier age of onset of intermediate milestones between starting and ending drinking milestones had the opposite effect, increasing risk for a shorter time period between the starting and ending milestones. These results are consistent with a causal effect of an earlier age of drinking milestone onset on temporally proximal subsequent drinking milestones.

  15. From alcohol initiation to tolerance to problems: Discordant twin modeling of a developmental process

    PubMed Central

    Deutsch, Arielle R.; Slutske, Wendy S.; Lynskey, Michael T.; Bucholz, Kathleen K.; Madden, Pamela A. F.; Heath, Andrew C.; Martin, Nicholas G.

    2017-01-01

    The current study examined a stage-based alcohol use trajectory model to test for potential causal effects of earlier drinking milestones on later drinking milestones in a combined sample of two cohorts of Australian monozygotic and same-sex dizygotic twins (N = 7,398, age M = 30.46, SD = 2.61, 61% mal 56% monozygotic twins). Ages of drinking, drunkenness, regular drinking, tolerance, first nontolerance alcohol use disorder symptom, and alcohol use disorder symptom onsets were assessed retrospectively. Ages of milestone attainment (i.e., age-of-onset) and time between milestones (i.e., time-to-even were examined via frailty models within a multilevel discordant twin design. For age-of-onset models, earlier ages of onset of antecedent drinking milestones increased hazards for earlier ages of onset for more proximal subsequent drinking milestones. For the time-to-event models, however, earlier ag of onset for the “starting” milestone decreased risk for a shorter time period between the starting and the “ending” milestone. Earlier age of onset of intermediate milestones between starting and ending drinking milestones had the opposite effect, increasing risk for a shorter time period between the starti and ending milestones. These results are consistent with a causal effect of an earlier age of drinking milestone onset on temporally proximal subsequent drinking milestones. PMID:27417028

  16. Confined blood chimerism in a monochorionic dizygotic sex discordant twin pregnancy conceived after induced ovulation.

    PubMed

    Mayeur Le Bras, Anne; Petit, François; Benachi, Alexandra; Bedel, Bettina; Oucherif, Salima; Martinovic, Jelena; Armanet, Narjes; Tosca, Lucie; Gautier, Valérie; Parisot, Frédéric; Labrune, Philippe; Tachdjian, Gérard; Brisset, Sophie

    2016-04-01

    Monochorionic twins are generally considered as a monozygotic twin pregnancy. However, several cases of monochorial dizygotic twin pregnancies have been reported. We report on a rare case of monochorionic dizygotic twin pregnancy conceived after induced ovulation in a 32-year-old woman. The diagnosis was made on morphological ultrasound examination at 18+4 weeks of gestation, showing two fetuses with discordant sex. The amniocentesis was declined by the patient. The monochorionic status was confirmed after a histopathalogical study of the placenta. At delivery, both a phenotypically normal boy and a phenotypically normal girl without sexual abnormality were observed. This analysis also revealed the presence of vascular anastomoses between both fetal circulations. Postnatal cytogenetic analyses indicated the presence of a chimerism in peripheral blood lymphocytes. This chimerism was not observed in cells obtained from a buccal swab. Molecular determination of zygosity confirmed the existence of the confined peripheral blood chimerism with the presence of four parental alleles. We report on a case of monochorionic dizygotic twin pregnancy. This observation underlies the need to carefully assess twin pregnancies, especially when obtained after assisted reproductive technology. © 2016 Wiley Periodicals, Inc.

  17. Functional and effective whole brain connectivity using magnetoencephalography to identify monozygotic twin pairs.

    PubMed

    Demuru, M; Gouw, A A; Hillebrand, A; Stam, C J; van Dijk, B W; Scheltens, P; Tijms, B M; Konijnenberg, E; Ten Kate, M; den Braber, A; Smit, D J A; Boomsma, D I; Visser, P J

    2017-08-29

    Resting-state functional connectivity patterns are highly stable over time within subjects. This suggests that such 'functional fingerprints' may have strong genetic component. We investigated whether the functional (FC) or effective (EC) connectivity patterns of one monozygotic twin could be used to identify the co-twin among a larger sample and determined the overlap in functional fingerprints within monozygotic (MZ) twin pairs using resting state magnetoencephalography (MEG). We included 32 cognitively normal MZ twin pairs from the Netherlands Twin Register who participate in the EMIF-AD preclinAD study (average age 68 years). Combining EC information across multiple frequency bands we obtained an identification rate over 75%. Since MZ twin pairs are genetically identical these results suggest a high genetic contribution to MEG-based EC patterns, leading to large similarities in brain connectivity patterns between two individuals even after 60 years of life or more.

  18. Ovarian Mature and Immature Teratomas in Monozygotic Twins: A Case Report of Simultaneous Presentation

    PubMed Central

    Kawai, Naoki; Takeshita, Toshiyuki

    2017-01-01

    Mature cystic teratoma is one of the most common kinds of ovarian tumor, and immature teratoma is a rare tumor, representing less than 1% of all ovarian teratomas. Although there are some reports about familial occurrences of ovarian tumors, literature concerning the clinical cases of monozygotic twins is rare. We report the 5-year clinical courses of a 12-year-old Japanese girl with a recurrent bilateral ovarian mature teratoma and her monozygotic twin with a unilateral ovarian mature teratoma and contralateral ovarian immature teratoma. This is the first clinical report on mature and immature teratomas of the ovary in monozygotic twins. Our cases support future clarification of the molecular mechanism and pathogenesis of teratoma. PMID:28293443

  19. Perinatal risk factors and neonatal complications in discordant twins admitted to the neonatal intensive care unit.

    PubMed

    Zhang, Xiao-rui; Liu, Jie; Zeng, Chao-mei

    2013-03-01

    Many studies have shown a relationship between birth weight discordance and adverse perinatal outcomes. This study aimed to investigate the perinatal risk factors and neonatal complications of discordant twins who are admitted to the neonatal intensive care unit. A total of 87 sets of twins were enrolled in this retrospective study, of which 22 sets were discordant twins and 65 sets were concordant twins. Binary Logistic regression analysis was used to identify the risk factors associated with the occurrence of discordant twins. The common neonatal complications of discordant twins were also investigated. Multivariate analysis showed that the use of assisted reproductive techniques, pregnancy-induced hypertension, and unequal placental sharing were risk factors for the occurrence of discordant twins. The incidence of small for gestational age infants and very low birth weight infants of discordant twins was significantly higher, while the birth weight of discordant twins was significantly lower than those of concordant twins. The duration of hospitalization of discordant twins was longer than that of concordant twins. The incidence of several neonatal complications, such as neonatal respiratory distress syndrome and intracranial hemorrhage, was higher in discordant twins than that in concordant twins. The percentage of those requiring pulmonary surfactant and mechanical ventilation was significantly higher in discordant twins than that in concordant twins. Use of assisted reproductive techniques, pregnancy-induced hypertension, and unequal placental sharing are perinatal risk factors of discordant twins who are admitted to the neonatal intensive care unit. These infants are also much more likely to suffer from various neonatal complications, especially respiratory and central nervous system diseases. It is important to prevent the occurrence of discordant twins by decreasing these risk factors and timely treatment should be given to discordant twins.

  20. Cerebral hemorrhage in monozygotic twins with hereditary hemorrhagic telangiectasia: case report and hemorrhagic risk evaluation.

    PubMed

    Rattani, Abbas; Dewan, Michael C; Hannig, Vickie; Naftel, Robert P; Wellons, John C; Jordan, Lori C

    2017-08-01

    The authors present a case of monozygotic twins with hereditary hemorrhagic telangiectasia (HHT) who experienced cerebral arteriovenous malformation (AVM) hemorrhage at a very young age. The clinical variables influencing HHT-related AVM rupture are discussed, and questions surrounding the timing of screening and intervention are explored. This is only the second known case of monozygotic HHT twins published in the medical literature, and the youngest pair of first-degree relatives to experience AVM-related cerebral hemorrhage. Evidence guiding the screening and management of familial HHT is lacking, and cases such as this underscore the need for objective and validated protocols.

  1. Managing twins discordant for fetal anomaly.

    PubMed

    Rustico, M A; Baietti, M G; Coviello, D; Orlandi, E; Nicolini, U

    2005-09-01

    An excess of structural anomalies is observed in twins compared to singletons. Approximately 1-2% of twin pregnancies may face the dilemma of expectant management versus selective termination following diagnosis of an anomaly affecting only one fetus. If the option of selective fetocide is considered, the main variable determining the technique to achieve this aim is chorionicity. In a dichorionic pregnancy, passage of substances from one twin into the circulation of the co-twin is unlikely due to the lack of placental anastomoses, hence KCl can be injected safely into the circulation of the affected twin to produce fetal asystole. In monochorionic twin pregnancies, selective termination needs to be performed by ensuring complete and permanent occlusion of both the arterial and venous flows in the umbilical cord of the affected twin, in order to avoid acute haemorrhage from the co-twin into the dying fetus, which may lead to death or organ damage. Bipolar cord coagulation under ultrasound guidance is associated with approximately 70-80% survival rates. 2005 John Wiley & Sons, Ltd.

  2. Dietary Intake at 9 Years and Subsequent Body Mass Index in Adolescent Boys and Girls: A Study of Monozygotic Twin Pairs.

    PubMed

    Dubois, Lise; Diasparra, Maikol; Bogl, Leonie-Helen; Fontaine-Bisson, Bénédicte; Bédard, Brigitte; Tremblay, Richard E; Kaprio, Jaakko; Boivin, Michel

    2016-02-01

    There is a lack of evidence pointing to specific dietary elements related to weight gain and obesity prevention in childhood and adulthood. Dietary intake and obesity are both inherited and culturally transmitted, but most prospective studies on the association between diet and weight status do not take genetics into consideration. The objective of this study was to document the association between dietary intake at 9 years and subsequent Body Mass Index (BMI) in adolescent monozygotic boy and girl twin pairs. This research used data from 152 twin pairs. Dietary data were collected from two 24-hour-recall interviews with a parent and the child aged 9 years. Height and weight were obtained when the twins were aged 9, 12, 13, and 14 years. Intrapair variability analysis was performed to identify dietary elements related to BMI changes in subsequent years. BMI-discordant monozygotic twin pairs were also identified to analyze the dietary constituents that may have generated the discordance. After eliminating potential confounding genetic factors, pre-adolescent boys who ate fewer grain products and fruit and consumed more high-fat meat and milk had higher BMIs during adolescence; pre-adolescent girls who consumed more grain products and high-fat meat and milk had higher BMIs during adolescence. Energy intake (EI) at 9 years was not related to BMI in subsequent years. Our study suggests that messages and interventions directed at obesity prevention could take advantage of sex-specific designs and' eventually' genetic information.

  3. Chromosomal Aberrations in Monozygotic and Dizygotic Twins Versus Singletons in Denmark During 1968-2009.

    PubMed

    Kroeldrup, Lone; Larsen, Lisbeth A; Fagerberg, Christina; Hertz, Jens M; Christensen, Kaare

    2017-06-01

    Hall (Embryologic development and monozygotic twinning. Acta Geneticae Medicae et Gemellologiae, Vol. 45, 1996, pp. 53-57) hypothesized that chromosomal aberrations can lead to monozygotic (MZ) twinning. However, twinning and chromosomal aberrations increase prenatal mortality and could reduce the prevalence of chromosomal aberrations in live-born twins. We compared prevalence proportion ratios (PPR) of chromosomal aberrations and trisomy 21 (T21) in live-born twins versus singletons born in Denmark during 1968-2009. We linked the Danish Twin Registry and a 5% random sample of all singletons to the Danish Cytogenetic Central Register and calculated PPR adjusted for maternal age for MZ, dizygotic (DZ), and all twins versus singletons. Zygosity was based on questionnaires or genetic markers. No overall difference in risk of chromosomal aberrations or T21 in twins versus singletons was found. PPR in MZ and DZ twins was 0.87 (95% CI [0.60, 1.27]) and 1.05 (95% CI [0.88, 1.27]), respectively. For T21 there was a tendency to a lower prevalence in MZ twins compared to singletons (PPR: 0.29, 95% CI [0.07, 1.14]), whereas PPR was significantly increased in DZ twins (1.62, 95% CI [1.20, 2.19]). The observed proportion of MZ twin pairs among twin pairs with aberrations (0.22, 95% CI [0.16, 0.28]) was significantly lower than the proportion expected from the Weinberg method (0.32, 95% CI [CI, 0.26, 0.39]). Based on databases providing complete national coverage on twins with chromosomal aberrations, we found no overall difference in risk of chromosomal aberrations or T21 in twins versus singletons. Around conception twins may have an increased risk of chromosomal aberrations, but loss of especially MZ embryos could lead to similar risk among live-born twins and singletons.

  4. Skeletal muscle magnesium content in identical twins, discordant for type 2 diabetes.

    PubMed

    Djurhuus, M S; Vaag, A; Altura, B M; Altura, B T; Klitgaard, N A H

    2002-06-01

    Low magnesium (Mg) status has been implied as a factor in the development of type 2 diabetes mellitus (DM) and its complications. We therefore studied Mg-status in identical twins, discordant for type 2 DM and in matched controls. Through correlation analysis, possible associations between Mg-status and glucose uptake were evaluated. Plasma Mg concentration was measured in 12 monozygote twin pairs, discordant for type 2 DM and in 12 matched controls. Muscle Mg content was measured in 10 persons from each group. An oral glucose tolerance test and a euglycaemic, hyperinsulinaemic clamp were utilized. Neither muscle Mg content nor plasma Mg concentration differed among groups. Plasma Mg concentration decreased during the euglycaemic, hyperinsulinaemic clamp. In the control group, muscle Mg content correlated positively with insulin stimulated glucose disposal rate (r=0.77, p<0.01) and negatively with two hour plasma glucose concentration during an oral glucose tolerance test (OGTT) (r=- 0.64, p<0.05). In the control group, the two hour plasma glucose concentration during an oral glucose tolerance test correlated with the decrease in plasma Mg concentration (r=- 0.80, p<0.002) and with the change in muscle Mg content (r=0.90, p<0.0005) induced by the clamp. None of these associations were found in the two twin groups. Normal plasma Mg concentration and muscle Mg content were found in persons with type 2 DM and in persons, who were heavily predisposed to the development of type 2 DM, indicating a normal whole-body Mg content. However, the missing associations between measures of glucose disposal and changes in both plasma Mg concentration and muscle Mg content in the two twin groups indicates, that physiological mechanisms, which partly regulates insulin sensitivity and Mg status in healthy individuals are either exhausted or fully utilized in both type 2 DM and in genetically identical twins without DM.

  5. Bidirectional influences between maternal parenting and children's peer problems: a longitudinal monozygotic twin difference study.

    PubMed

    Yamagata, Shinji; Takahashi, Yusuke; Ozaki, Koken; Fujisawa, Keiko K; Nonaka, Koichi; Ando, Juko

    2013-03-01

    This twin study examined the bidirectional relationship between maternal parenting behaviors and children's peer problems that were not confounded by genetic and family environmental factors. Mothers of 259 monozygotic twin pairs reported parenting behaviors and peer problems when twins were 42 and 48 months. Path analyses on monozygotic twin difference scores revealed that authoritative parenting (the presence of consistent discipline and lack of harsh parenting) and peer problems simultaneously influenced each other. Authoritative parenting reduced peer problems, and peer problems increased authoritative parenting. Neither consistent discipline nor harsh parenting alone was associated with peer problems. These results suggest that maternal authoritative parenting works protectively in regard to children's peer problems, and peer problems can evoke such effective parenting. © 2012 Blackwell Publishing Ltd.

  6. Sleep-EEG in dizygotic twins discordant for Williams syndrome.

    PubMed

    Bódizs, Róbert; Gombos, Ferenc; Szocs, Katalin; Réthelyi, János M; Gerván, Patrícia; Kovács, Ilona

    2014-01-30

    Reports on twin pairs concordant and discordant for Williams syndrome were published before, but no study unravelled sleep physiology in these cases yet. We aim to fill this gap by analyzing sleep records of a twin pair discordant for Williams syndrome extending our focus on presleep wakefulness and sleep spindling. We performed multiplex ligation-dependent probe amplification of the 7q11.23 region of a 17 years old dizygotic opposite-sex twin pair discordant for Williams syndrome. Polysomnography of laboratory sleep at this age was analyzed and followed-up after 1.5 years by ambulatory polysomnography. Sleep stages scoring, EEG power spectra and sleep spindle analyses were carried out. The twin brother showed reduced levels of amplification for all of the probes in the 7q11.23 region indicating a typical deletion spanning at least 1.038 Mb between FKBP6 and CLIP2. The results of the twin sister showed normal copy numbers in the investigated region. Lower sleep times and efficiencies, as well as higher slow wave sleep percents of the twin brother were evident during both recordings. Roughly equal NREM, Stage 2 and REM sleep percents were found. EEG analyses revealed state and derivation-independent decreases in alpha power, lack of an alpha spectral peak in presleep wakefulness, as well as higher NREM sleep sigma peak frequency in the twin brother. Faster sleep spindles with lower amplitude and shorter duration characterized the records of the twin brother. Spectra show a striking reliability and correspondence between the two situations (laboratory vs. home records). Alterations in sleep and specific neural oscillations including the alpha/sigma waves are inherent aspects of Williams syndrome.

  7. Nonshared environmental influences on sleep quality: a study of monozygotic twin differences.

    PubMed

    Barclay, Nicola L; Eley, Thalia C; Buysse, Daniel J; Maughan, Barbara; Gregory, Alice M

    2012-03-01

    Research has consistently demonstrated that environmental influences are important for explaining the variability in sleep quality observed in the general population. Although there is substantial evidence assessing associations between sleep quality and a host of environmental variables, it is possible that their effects are mediated by genetic influence. A monozygotic twin differences design was used to assess the specific contribution of nonshared environmental influences on sleep quality, whilst controlling for genetic and shared environmental effects in a sample of 380 monozygotic twins (mean age 19.8 years, SD = 1.26, range = 18-22 years). Participants completed the Pittsburgh Sleep Quality Index and questionnaires assessing several candidate "environmental" measures. When controlling for genetic and shared environmental effects, within monozygotic twin-pair differences in sleep quality were associated with within monozygotic twin-pair differences in general health for males (β = 1.56, p < 0.001) and relationship satisfaction for females (β = 1.01, p < 0.05). For the remaining environmental measures the results suggest that these seemingly "environmental" influences are actually in part dependent on genetics and/or the shared environment. These findings give insight into how specific environments affect sleep and the possible mechanisms behind these associations.

  8. Social Experiences in Kindergarten and Academic Achievement in Grade 1: A Monozygotic Twin Difference Study

    ERIC Educational Resources Information Center

    Vitaro, Frank; Boivin, Michel; Brendgen, Mara; Girard, Alain; Dionne, Ginette

    2012-01-01

    The goal of this study was to examine how different types of social experiences in kindergarten relate to Grade 1 academic achievement, while controlling for possible genetic and shared environmental influences through the use of the monozygotic (MZ) twin difference method. Social experiences in kindergarten included relationship quality with the…

  9. A Monozygotic Twin Differences Study of Nonshared Environmental Influence on Adolescent Depressive Symptoms

    ERIC Educational Resources Information Center

    Liang, Holan; Eley, Thalia C.

    2005-01-01

    The monozygotic (MZ) twin differences method was used to examine nonshared environmental aspects of the association of parenting (punitive and constructive discipline), negative life events (independent and dependent), and peers (antisocial and prosocial) with adolescent depressive symptoms in terms of sequelae, risk, and maintaining factors. Two…

  10. A nongenetic basis of cycle frequency in bipolar disorder: study of a monozygotic twin pair.

    PubMed Central

    Sharma, V; Ainsworth, P J; McCabe, S B; Persad, E; Kueneman, K M

    1997-01-01

    The authors describe a pair of monozygotic twins with bipolar disorder but with a different course of the illness including age of onset, sequence of episodes, and cycle length. Based on these findings, the clinical course of bipolar illness does not appear to be genetically determined. PMID:9074308

  11. Social Experiences in Kindergarten and Academic Achievement in Grade 1: A Monozygotic Twin Difference Study

    ERIC Educational Resources Information Center

    Vitaro, Frank; Boivin, Michel; Brendgen, Mara; Girard, Alain; Dionne, Ginette

    2012-01-01

    The goal of this study was to examine how different types of social experiences in kindergarten relate to Grade 1 academic achievement, while controlling for possible genetic and shared environmental influences through the use of the monozygotic (MZ) twin difference method. Social experiences in kindergarten included relationship quality with the…

  12. [Sturge-Weber-Krabbe syndrome. A severe form in a monozygote female twin].

    PubMed

    Pedailles, S; Martin, N; Launay, V; Sentias, C; Barre, M; Saintive, J P; Bessis, J L

    1993-01-01

    We report a severe case of Sturge-Weber syndrome in one of two monozygotic twins. This syndrome included a facial portwine stain over the trigeminal ophthalmic V1 area, and ipsilateral vascular anomalies of the eye and of the pia mater. CT scans and MRI were very informative. The cerebral regional blood flow, studied with SPECT, showed a paradoxically high rate.

  13. Sex ratios provide evidence for monozygotic twinning in the ring-tailed lemur, Lemur catta.

    PubMed

    St Clair, John; Campbell-Palmer, Roisin; Lathe, Richard

    2014-02-01

    Monozygotic (MZ) twinning is generally considered to be rare in species other than human. We inspected sex ratios in European zoo-bred ring-tailed lemurs (Lemur catta), revealing a significant excess of same-sex twins. Of 94 pairs, 60 (64%) were either both males or both females (p = .004). Application of the Weinberg differential rule argues that 27% of all twins in this species are MZ pairs. In this protected species, where twinning is commonplace (~50% of newborns are twins), the probable existence of frequent MZ twinning has ramifications for breeding programs aimed to maximize genetic diversity, and suggests that twin studies in a species other than human could have potential as a medical research tool.

  14. Discordant cerebral lateralisation for verbal fluency is not an artefact of attention: evidence from MzHd twins.

    PubMed

    Gurd, Jennifer M; Cowell, Patricia E

    2015-01-01

    The current study investigated how the brain structure-function relationships between covert and overt verbal fluency in monozygotic handedness discordant (MzHd) twins relates to broader attentional measures. Evidence presented here shows that the structure-function correlation demonstrated between functional cerebral lateralisation and corpus callosum widths 22-39, contiguous with Broca's area and the middle frontal gyri (Gurd et al. in Brain Struct Funct 218:491-509, 2013), is not an artefact of attention. Twenty-five pairs of female MzHd twins performed a verbal switching task titrated for number of switches. The paradigm permits calculation of switch rates and costs. The switch rate and cost varied as a function of number of switches (1, 2, 3). There were no differences in any measure in relation to right-left handedness in twin pairs. This was supported by large and significant within-twin pair correlations. Atypical functional lateralisation of inferior and middle frontal lobes does not appear to be associated with better or worse performance on verbal task-switching. Discordant lateralisation for verbal fluency does not predict behavioural performance profiles in MzHd twins. This evidence is compatible with a view that attentional components of verbal fluency task performance may have significant heritable components. It does not indicate that neural correlates of frontal cerebral laterality for verbal fluency in MzHd twins are significantly accountable for by heritable components.

  15. Kidney transplant from a living monozygotic twin donor with no maintenance immunosuppression.

    PubMed

    Sánchez-Escuredo, Ana; Barajas, Alberto; Revuelta, Ignacio; Blasco, Miquel; Cofan, Federic; Esforzado, Núria; Ricart, María José; Torregrosa, Vicens; Campistol, Josep Maria; Oppenheimer, Federic; Diekmann, Fritz

    2015-01-01

    From a theoretical point of view, an alloimmune response can not take place, still some type of standard immunosuppression is used in about 60% of patients receiving kidney grafts from their monozygotic twins. We aimed at assessing clinical response in patients receiving renal grafts from a living monozygotic twin donor when no immunosuppressive therapy is used. This is a retrospective observational study of patients receiving kidney grafts from their monozygotic twins from 1969 to 2013. The following data were recorded: age, renal graft recipient's primary disease, renal function, renal survival and overall survival. Immunosuppressive therapy included a single intraoperative dose of methylprednisolone 500 mg and no maintenance immunosuppression. Five patients with kidney grafts from their monozygotic twins were dentified in our centre. Mean age at transplantation was 33 years (27-39). One-year overall survival and graft survival were 100%. Mean creatinine level was 0.96 ± 0.2 one year after transplantation, and 1.2 ± 0.37 mg/dl at most recent follow-up. Two patients died with a functional graft more than 15 years after kidney transplantation (causes were melanoma and cardiovascular event respectively). Follow-up was lost in a patient one year after transplantation. Two patients are alive with a functioning graft at 18 months and 42.5 years after transplantation respectively. Kidney transplantation from a living monozygotic twin is associated to outstanding clinical outcomes. Immunossuppresive therapy to suppress alloimmune response in probably unnecessary 11 zygosity has been confirmed. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

  16. Increased physical activity decreases hepatic free fatty acid uptake: a study in human monozygotic twins

    PubMed Central

    Hannukainen, Jarna C; Nuutila, Pirjo; Ronald, Borra; Kaprio, Jaakko; Kujala, Urho M; Janatuinen, Tuula; Heinonen, Olli J; Kapanen, Jukka; Viljanen, Tapio; Haaparanta, Merja; Rönnemaa, Tapani; Parkkola, Riitta; Knuuti, Juhani; Kalliokoski, Kari K

    2007-01-01

    Exercise is considered to be beneficial for free fatty acid (FFA) metabolism, although reports of the effects of increased physical activity on FFA uptake and oxidation in different tissues in vivo in humans have been inconsistent. To investigate the heredity-independent effects of physical activity and fitness on FFA uptake in skeletal muscle, the myocardium, and liver we used positron emission tomography (PET) in nine healthy young male monozygotic twin pairs discordant for physical activity and fitness. The cotwins with higher physical activity constituting the more active group had a similar body mass index but less body fat and 18 ± 10% higher V˙O2,max (P < 0.001) compared to the less active brothers with lower physical activity. Low-intensity knee-extension exercise increased skeletal muscle FFA and oxygen uptake six to 10 times compared to resting values but no differences were observed between the groups at rest or during exercise. At rest the more active group had lower hepatic FFA uptake compared to the less active group (5.5 ± 4.3 versus 9.0 ± 6.1 μmol (100 ml)−1 min−1, P = 0.04). Hepatic FFA uptake associated significantly with body fat percentage (P = 0.05). Myocardial FFA uptake was similar between the groups. In conclusion, in the absence of the confounding effects of genetic factors, moderately increased physical activity and aerobic fitness decrease body adiposity even in normal-weighted healthy young adult men. Further, increased physical activity together with decreased intra-abdominal adiposity seems to decrease hepatic FFA uptake but has no effects on skeletal muscle or myocardial FFA uptake. PMID:17053033

  17. Intrapair differences in personality and cognitive ability among young monozygotic twins distinguished by chorion type.

    PubMed

    Sokol, D K; Moore, C A; Rose, R J; Williams, C J; Reed, T; Christian, J C

    1995-09-01

    We evaluated placentation effects on behavioral resemblance of 44 pairs of monozygotic (MZ) twin children. Tested at ages 4-6, the twins' zygosity and placental type had been determined at their delivery. The sample included 23 monochorionic (MC) and 21 dichorionic (DC) MZ twin pairs: DC-MZ twins result from separation of blastomeres within 72 h of ovulation; MC-MZ twins arise from later duplication of the inner cell mass. Twins were individually administered the McCarthy Scales of Cognitive Ability, while their mothers separately rated each cotwin on an individualized 280-item form of the Personality Inventory for Children (PIC). Absolute differences between MC-MZ cotwins were smaller than those between DC-MZ cotwins for all 20 PIC scales, significantly so for 3 of 4 factor scales, 8 of 12 clinical scales, and 2 of 4 validity/screening scales from the PIC; in contrast, no consistent differences in intrapair resemblance of mono- and dichorionic MZ twins were found for the McCarthy Scales. The chorion differences found in the PIC data cannot be due to genetic differences, because all pairs are monozygotes; nor are they associated with differences in parity, gestational age, birth weight, maternal education, palmar dermatoglyphic asymmetry, or maternal knowledge of chorion type. We interpret our findings as suggestive evidence that variation in timing of embryological division, with effects on MZ twins' placental vasculature, has significant consequences for some dimensions of their behavioral development, as well.

  18. A case report of monozygotic twins with Smith-Magenis syndrome.

    PubMed

    Hicks, Matthew; Ferguson, Susan; Bernier, Francois; Lemay, Jean-François

    2008-02-01

    Monozygotic 3.5-year-old twin boys presented for developmental assessment with a history of global developmental delay, behavioral issues including self-harm, and severe receptive and expressive language delays. Chromosome testing confirmed for both a 17p11.2 interstitial microdeletion commonly seen in Smith-Magenis syndrome (SMS), which is characterized by developmental delay, cognitive impairment, and facial and behavioral phenotype. To our knowledge, this is the first description in the literature of monozygotic twins with SMS. Despite their zygosity, the twins had marked differences in presentation including cardiac and renal anomalies, language development, and behavioral phenotype. Both twins displayed disordered speech development, impairments in social interaction, and stereotyped behaviors consistent with autism spectrum disorder, common in the vast majority of cases of SMS. Examining the differences in behavioral and clinical phenotype in monozygotic twins may lead to a better understanding of the cause of the clinical variability seen in SMS, as well as the natural history of this syndrome.

  19. A study of genetic and environmental contributions to structural brain changes over time in twins concordant and discordant for bipolar disorder.

    PubMed

    Bootsman, F; Brouwer, R M; Schnack, H G; Kemner, S M; Hillegers, M H J; Sarkisyan, G; van der Schot, A C; Vonk, R; Hulshoff Pol, H E; Nolen, W A; Kahn, R S; van Haren, N E M

    2016-08-01

    This is the first longitudinal twin study examining genetic and environmental contributions to the association between liability to bipolar disorder (BD) and changes over time in global brain volumes, and global and regional measures of cortical surface area, cortical thickness and cortical volume. A total of 50 twins from pairs discordant or concordant for BD (monozygotic: 8 discordant and 3 concordant pairs, and 1 patient and 3 co-twins from incomplete pairs; dizygotic: 6 discordant and 2 concordant pairs, and 1 patient and 7 co-twins from incomplete pairs) underwent magnetic resonance imaging twice. In addition, 57 twins from healthy twin pairs (15 monozygotic and 10 dizygotic pairs, and 4 monozygotic and 3 dizygotic subjects from incomplete pairs) were also scanned twice. Mean follow-up duration for all twins was 7.5 years (standard deviation: 1.5 years). Data were analyzed using structural equation modeling software OpenMx. The liability to BD was not associated with global or regional structural brain changes over time. Although we observed a subtle increase in cerebral white matter in BD patients, this effect disappeared after correction for multiple comparisons. Heritability of brain changes over time was generally low to moderate. Structural brain changes appear to follow similar trajectories in BD patients and healthy controls. Existing brain abnormalities in BD do not appear to progressively change over time, but this requires additional confirmation. Further study with large cohorts is recommended to assess genetic and environmental influences on structural brain abnormalities in BD, while taking into account the influence of lithium on the brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Is there change in intelligence quotient in chronically ill schizophrenia patients? A longitudinal study in twins discordant for schizophrenia.

    PubMed

    Hedman, A M; van Haren, N E M; van Baal, G C M; Brans, R G H; Hijman, R; Kahn, R S; Hulshoff Pol, H E

    2012-12-01

    Intellectual deficits are commonly found in schizophrenia patients. These intellectual deficits have been found to be heritable. However, whether the intellectual deficits change over time and, if so, whether the change is related with an increased genetic risk for the disease are not known. We investigated change of intelligence quotient (IQ) in a twin sample of chronically ill schizophrenia patients, the discordant co-twins and healthy controls during a follow-up period of 5 years. A total of 52 twins completed two IQ assessments: nine patients [three monozygotic (MZ) and six dizygotic (DZ)], 10 unaffected co-twins (three MZ and seven DZ) and 33 healthy control twins (21 MZ and 12 DZ). A significant interaction effect over time was found between IQ measurement and illness (F=4.22, df=1, p<0.05), indicating that change in IQ over time is significantly different between the groups. A stable course in IQ over time was found in the patients with schizophrenia (mean IQ from 109.78 at baseline to 108.44 at follow-up) relative to both the healthy control twins who showed a small increase (from 114.61 at baseline to 119.18 at follow-up) (t=2.06, p<0.05) and the unaffected co-twins (from 111.60 to 117.60, t=-2.32, p<0.05). IQ change in the unaffected co-twins of schizophrenia patients was comparable with that in healthy control twins (t=-0.49, p=0.63). Patients with schizophrenia in the chronic phase of the disease, but not the discordant co-twins, show a lack of increase in IQ, which is probably due to environmental (non-genetic) factors related to the disease.

  1. Changes in weight and cardiovascular disease risk factors in monozygotic twins: the healthy twin study.

    PubMed

    Song, Yun-Mi; Lee, Kayoung; Sung, Joohon

    2015-04-01

    We aimed to assess the non-genetic contribution to the associations between the change in weight and changes in cardiovascular disease (CVD) risk factors. This analysis included 194 Korean monozygotic (MZ) twin pairs (116 men, 272 women; mean age, 38.5 ± 6.8 years) who were first examined for weight and CVD risk factors (blood pressure (BP), glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL)) between December 2005 and December 2008, and returned for a repeat examination after 2.7 ± 0.9 years. The within-pair correlations were 0.21 for the change in weight and 0.05-0.42 for the changes in CVD risk factors. Bivariate analyses showed significant environmental correlations shared between the change in weight and the changes in CVD risk factors (p < .05), except for glucose, while there were no significant genetic effects shared between the phenotypes. After adjusting for baseline values of weight, smoking, and alcohol consumption, diastolic blood pressure (DBP), TG, TC, and LDL significantly increased by 1.6 mmHg, 0.09 mmol/L, 0.10 mmol/L, and 0.09 mmol/L, respectively, per 1 kg increase in within-pair differences in weight change. In Korean MZ twins, similarity between twins for changes in weight and CVD risk factors were small to moderate, and non-genetic factors were responsible for the associations between the change in weight and changes in DBP, TG, TC, and LDL.

  2. Verbal recall and recognition in twins discordant for schizophrenia

    PubMed Central

    van Erp, Theo G.M.; Therman, Sebastian; Pirkola, Tiia; Tuulio-Henriksson, Annamari; Glahn, David C.; Bachman, Peter; Huttunen, Matti O.; Lönnqvist, Jouko; Hietanen, Marja; Kaprio, Jaakko; Koskenvuo, Markku; Cannon, Tyrone D.

    2008-01-01

    The nature, neural underpinnings, and etiology of deficits in verbal declarative memory in patients with schizophrenia remain unclear. To examine the contributions of genes and environment to verbal recall and recognition performance in this disorder, the California Verbal Learning Test was administered to a large population-based Finnish twin sample, which included schizophrenic and schizoaffective patients, their non-ill monozygotic (MZ) and dizygotic (DZ) co-twins, and healthy control twins. Compared with controls, patients and their co-twins showed relatively greater performance deficits on free recall compared with recognition. Intra-pair differences between patients and their non-ill co-twins in hippocampal volume and memory performance were highly positively correlated. These findings are consistent with the view that genetic influences are associated with reduced verbal recall in schizophrenia, but that non-genetic influences further compromise these abnormalities in patients who manifest the full-blown schizophrenia phenotype, with this additional degree of disease-related declarative memory deficit mediated in part by hippocampal pathology. PMID:18442861

  3. Comparisons of dermatoglyphic patterns in monochorionic and dichorionic monozygotic twins.

    PubMed Central

    Reed, T; Uchida, I A; Norton, J A; Christian, J C

    1978-01-01

    The data presented here indicate that different influences affect dermatoglyphic pattern development in MC-MZ and DC-MZ twins. Only five of 84 variables had significant mean differences but their clustering suggested a real difference in mean placement of the atd angle. Nineteen of 84 variables had significantly different within-pair mean squares for the two twin types. Larger numbers of twins will be required to obtain accurate estimates of the magnitude of the dermatoglyphic differences between MC-MZ and DC-MZ twins. Studies of dermatoglyphics in MC-MZ and DC-MZ twins are important to the understanding of factors which influence early embryonic development and when better documented may provide a mechanism for retrospectively diagnosing placental type of MZ twins. PMID:568879

  4. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor

    PubMed Central

    Smith, Michelle I.; Yatsunenko, Tanya; Manary, Mark J.; Trehan, Indi; Mkakosya, Rajhab; Cheng, Jiye; Kau, Andrew L.; Rich, Stephen S.; Concannon, Patrick; Mychaleckyj, Josyf C.; Liu, Jie; Houpt, Eric; Li, Jia V.; Holmes, Elaine; Nicholson, Jeremy; Knights, Dan; Ursell, Luke K.; Knight, Rob; Gordon, Jeffrey I.

    2013-01-01

    Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well-nourished, while 43% became discordant and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor microbiomes that regressed when RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor. PMID:23363771

  5. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor.

    PubMed

    Smith, Michelle I; Yatsunenko, Tanya; Manary, Mark J; Trehan, Indi; Mkakosya, Rajhab; Cheng, Jiye; Kau, Andrew L; Rich, Stephen S; Concannon, Patrick; Mychaleckyj, Josyf C; Liu, Jie; Houpt, Eric; Li, Jia V; Holmes, Elaine; Nicholson, Jeremy; Knights, Dan; Ursell, Luke K; Knight, Rob; Gordon, Jeffrey I

    2013-02-01

    Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.

  6. Ectopic neuroblastoma in monozygotic twins with different ages of onset: possible twin-to-twin metastasis in utero with distinct genetic alterations after birth.

    PubMed

    Taketani, Takeshi; Takita, Junko; Ueyama, Junichi; Kanai, Rie; Kumori, Koji; Maruyama, Riruke; Hayashi, Kazuhiko; Ogawa, Seishi; Fukuda, Seiji; Yamaguchi, Seiji

    2014-03-01

    We describe neuroblastoma (NB) in monozygotic twins whose ages at the onset of the disease had a 3-year interval. The primary tumor site of twin 1 was the adrenal gland, whereas that of twin 2 was the jejunum/mesentery. MYCN amplification, DNA index, ALK mutation, and copy number alterations of DNA were different between each primary tumor. NB in ectopic sites may have resulted from twin-to-twin metastasis through vascular anastamoses in the placenta. The pathogenesis of this NB involved a premalignant stage of NB during the fetal development and subsequent molecular alterations after birth, resulting in NBs that were phenotypically similar but genetically different.

  7. Neonatal morbidity in growth-discordant monochorionic twins: comparison between the larger and the smaller twin.

    PubMed

    Lopriore, Enrico; Sluimers, Carolien; Pasman, Suzanne A; Middeldorp, Johanna M; Oepkes, Dick; Walther, Frans J

    2012-08-01

    Fetal growth restriction in singletons has been shown to enhance fetal lung maturation and reduce the risk of respiratory distress syndrome due to increased endogenous steroid production. However, data on lung maturation in growth-discordant monochorionic (thus, identical) twins are lacking. Our objective was to compare the risk of severe neonatal morbidity between the larger and the smaller twin in monochorionic twins with birth weight discordance (BWD). We included in the study all consecutive monochorionic diamniotic pregnancies with severe BWD (≥25%) and two live-born twins delivered at our center (n=47 twin pairs). We compared the incidence of neonatal morbidity, particularly respiratory distress syndrome (RDS), and cerebral lesions between the larger and the smaller co-twin. The incidence of severe neonatal morbidity in the larger and smaller twin was 38% (18/47) and 19% (9/47), respectively (odds ratio (OR) 2.66, 95% confidence interval (CI) 0.94-7.44) and was due primarily to the higher incidence of RDS, 32% (15/47) and 6% (3/47), respectively (OR 6.88, 95% CI 1.66-32.83). In conclusion, this study shows that the larger twin in monochorionic twin pairs with BWD is at increased risk of severe neonatal morbidity, particularly RDS, compared to the smaller twin.

  8. Objective assessment of facial skin aging and the associated environmental factors in Japanese monozygotic twins

    PubMed Central

    Ichibori, Ryoko; Fujiwara, Takashi; Tanigawa, Tomoko; Kanazawa, Shigeyuki; Shingaki, Kenta; Torii, Kosuke; Tomita, Koichi; Yano, Kenji; Sakai, Yasuo; Hosokawa, Ko

    2014-01-01

    Twin studies, especially those involving monozygotic (MZ) twins, facilitate the analysis of factors affecting skin aging while controlling for age, gender, and genetic susceptibility. The purpose of this study was to objectively assess various features of facial skin and analyze the effects of environmental factors on these features in MZ twins. At the Osaka Twin Research Center, 67 pairs of MZ twins underwent medical interviews and photographic assessments, using the VISIA® Complexion Analysis System. First, the average scores of the right and left cheek skin spots, wrinkles, pores, texture, and erythema were calculated; the differences between the scores were then compared in each pair of twins. Next, using the results of medical interviews and VISIA data, we investigated the effects of environmental factors on skin aging. The data were analyzed using Pearson's correlation coefficient test and the Wilcoxon signed-rank test. The intrapair differences in facial texture scores significantly increased as the age of the twins increased (P = 0.03). Among the twin pairs who provided answers to the questions regarding history differences in medical interviews, the twins who smoked or did not use skin protection showed significantly higher facial texture or wrinkle scores compared with the twins not exposed to cigarettes or protectants (P = 0.04 and 0.03, respectively). The study demonstrated that skin aging among Japanese MZ twins, especially in terms of facial texture, was significantly influenced by environmental factors. In addition, smoking and skin protectant use were important environmental factors influencing skin aging. PMID:24910280

  9. Brain activation during cognitive planning in twins discordant or concordant for obsessive–compulsive symptoms

    PubMed Central

    van ’t Ent, Dennis; Cath, Danielle C.; Wagner, Judith; Boomsma, Dorret I.; de Geus, Eco J. C.

    2010-01-01

    Neuroimaging studies have indicated abnormalities in cortico-striatal-thalamo-cortical circuits in patients with obsessive–compulsive disorder compared with controls. However, there are inconsistencies between studies regarding the exact set of brain structures involved and the direction of anatomical and functional changes. These inconsistencies may reflect the differential impact of environmental and genetic risk factors for obsessive–compulsive disorder on different parts of the brain. To distinguish between functional brain changes underlying environmentally and genetically mediated obsessive–compulsive disorder, we compared task performance and brain activation during a Tower of London planning paradigm in monozygotic twins discordant (n = 38) or concordant (n = 100) for obsessive–compulsive symptoms. Twins who score high on obsessive–compulsive symptoms can be considered at high risk for obsessive–compulsive disorder. We found that subjects at high risk for obsessive–compulsive disorder did not differ from the low-risk subjects behaviourally, but we obtained evidence that the high-risk subjects differed from the low-risk subjects in the patterns of brain activation accompanying task execution. These regions can be separated into those that were affected by mainly environmental risk (dorsolateral prefrontal cortex and lingual cortex), genetic risk (frontopolar cortex, inferior frontal cortex, globus pallidus and caudate nucleus) and regions affected by both environmental and genetic risk factors (cingulate cortex, premotor cortex and parts of the parietal cortex). Our results suggest that neurobiological changes related to obsessive–compulsive symptoms induced by environmental factors involve primarily the dorsolateral prefrontal cortex, whereas neurobiological changes induced by genetic factors involve orbitofrontal–basal ganglia structures. Regions showing similar changes in high-risk twins from discordant and concordant pairs may

  10. Brain activation during cognitive planning in twins discordant or concordant for obsessive-compulsive symptoms.

    PubMed

    den Braber, Anouk; van 't Ent, Dennis; Cath, Danielle C; Wagner, Judith; Boomsma, Dorret I; de Geus, Eco J C

    2010-10-01

    Neuroimaging studies have indicated abnormalities in cortico-striatal-thalamo-cortical circuits in patients with obsessive-compulsive disorder compared with controls. However, there are inconsistencies between studies regarding the exact set of brain structures involved and the direction of anatomical and functional changes. These inconsistencies may reflect the differential impact of environmental and genetic risk factors for obsessive-compulsive disorder on different parts of the brain. To distinguish between functional brain changes underlying environmentally and genetically mediated obsessive-compulsive disorder, we compared task performance and brain activation during a Tower of London planning paradigm in monozygotic twins discordant (n=38) or concordant (n=100) for obsessive-compulsive symptoms. Twins who score high on obsessive-compulsive symptoms can be considered at high risk for obsessive-compulsive disorder. We found that subjects at high risk for obsessive-compulsive disorder did not differ from the low-risk subjects behaviourally, but we obtained evidence that the high-risk subjects differed from the low-risk subjects in the patterns of brain activation accompanying task execution. These regions can be separated into those that were affected by mainly environmental risk (dorsolateral prefrontal cortex and lingual cortex), genetic risk (frontopolar cortex, inferior frontal cortex, globus pallidus and caudate nucleus) and regions affected by both environmental and genetic risk factors (cingulate cortex, premotor cortex and parts of the parietal cortex). Our results suggest that neurobiological changes related to obsessive-compulsive symptoms induced by environmental factors involve primarily the dorsolateral prefrontal cortex, whereas neurobiological changes induced by genetic factors involve orbitofrontal-basal ganglia structures. Regions showing similar changes in high-risk twins from discordant and concordant pairs may be part of compensatory

  11. Proinsulin immunoreactivity in identical twins discordant for noninsulin-dependent diabetes mellitus.

    PubMed

    Røder, M E; Vaag, A; Hartling, S G; Dinesen, B; Lanng, S; Beck-Nielsen, H; Binder, C

    1995-08-01

    Disproportionate elevation [increased proinsulin/insulin (PI/INS) ratio] of PI immunoreactivity is associated with noninsulin-dependent diabetes mellitus (NIDDM). The nature of this abnormality is not known. To address the question of whether genetic factors contribute to hyperproinsulinemia, we measured fasting levels of PI immunoreactivity, intact INS, and C peptide (CP) in 12 pairs of monozygotic twins discordant for NIDDM for a mean (+/- SEM) period of 9 +/- 3 yr. Thirteen age- and body mass index-matched healthy subjects without any family history of NIDDM acted as controls. The nondiabetic twins had levels of fasting INS, CP, PI, PI/CP, and PI/INS similar to those of control subjects. Fasting levels of PI, and PI/CP and PI/INS ratios were significantly 2- to 3-fold elevated in NIDDM twins compared to those in both nondiabetic twins and control subjects. To investigate whether hyperproinsulinemia in these NIDDM patients was due to a differential elevation of intact PI or conversion intermediates, we analyzed PI profiles in NIDDM twins and normal subjects by high pressure liquid chromatography. PI was heterogeneous and consisted mainly of des(31,32)-PI and intact PI in both NIDDM patients and normal subjects, with no major difference in composition between the groups. Small amounts of des(64,65)-PI (0-11%) were measured in some patients and normal subjects. The results suggest that hyperproinsulinemia is not a genetically determined trait per se in NIDDM. Disproportionately elevated PI levels seem to be related to the actual disease process. Further conversion of intact PI and des(31,32)-PI may be equally impaired in NIDDM.

  12. LINE-1 DNA methylation: A potential forensic marker for discriminating monozygotic twins.

    PubMed

    Xu, Jie; Fu, Guangping; Yan, Lina; Craig, Jeffery M; Zhang, Xiaojing; Fu, Lihong; Ma, Chunling; Li, Shujin; Cong, Bin

    2015-11-01

    Discriminating individuals within a pair of monozygotic (MZ) twins using genetic markers remains unresolved. This inability causes problems in criminal or paternity cases involving MZ twins as suspects or alleged fathers. Our previous study showed DNA methylation differences in interspersed repeat sequences such as Alu and LINE-1 within pairs of newborn MZ twins. To further evaluate the possible value of LINE-1 DNA methylation for discriminating MZ twins, this study investigated the LINE-1 DNA methylation of a large number of twins. We collected blood samples and buccal cell samples from 119 pairs of MZ and 57 pairs of dizygotic (DZ) twins. Genomic DNA was extracted and LINE-1 methylation level was detected using bisulfite pyrosequencing. The mean methylation level of the three CpG sites in the blood sample among the 176 unrelated individuals was 76.60% and 70.08% in buccal samples. This difference was significant, indicating the tissue specificity of LINE-1 DNA methylation. Among 119 pairs of MZ twins, 15 pairs could be discriminated according to the difference of CpG methylation level between them, which accounted for 12.61% of total number of MZ pairs. As for DZ twins, 10 pairs had significant differences between two individuals, which accounted for 17.54% of the total 57 DZ pairs. In conclusion, there are global DNA methylation differences within some healthy concordant monozygotic (MZ) twin pairs. LINE-1 DNA methylation might be a potential marker for helping to discriminate individuals within MZ twin pairs, and the tissue specificity must be considered in practice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. [Variation of growth in monozygotic twins analyzed by longitudinal method].

    PubMed

    Tzatcheva, L S; Kadanoff, D D; Paskova, D G

    1981-01-01

    On the base of a "genetic model" of MZ twins a longitudinal investigation was carried out during a period of 12 years. A global dimension - body height - and two basic body proportions - the frontal anterior length of the trunk and the length of the lower limb - were traced by the method of percentage deviation between the twin partners. During the whole period of growth, the global dimension are nearly equal, while the parts of the body, vary up to some limits.

  14. Co-existence of lichen sclerosus and localized scleroderma in female monozygotic twins.

    PubMed

    Lis-Święty, Anna; Mierzwińska, Katarzyna; Wodok-Wieczorek, Karolina; Widuchowska, Małgorzata; Brzezińska-Wcisło, Ligia

    2014-12-01

    Etiology of lichen sclerosus (LiS) and localized scleroderma (LoS) is uncertain and probably multifactorial. We describe a case of female monozygotic twins who presented co-existence of LiS and LoS. Skin lesions typical for LoS occurred in both patients, at the age of 10. One sister was diagnosed with linear LoS of the lower limb affecting deeper situated subcutaneous tissue and muscles. The other sister was diagnosed with guttate LoS of the trunk, with slow progression of the skin lesions. In both sisters vulvar LiS developed at the age of 19. Co-existence of LiS and LoS in monozygotic twins indicates the possible genetic contribution to the pathogenesis of these diseases and the close relationship between them. Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  15. Recurrent digital infections and osteomyelitis in monozygotic twins with congenital analgesia and compulsive onychophagia.

    PubMed

    Iorio, Matthew L; Barbour, John R

    2014-07-01

    Congenital insensitivity to pain is a rare sensory neuropathy that manifests with multiple and recurrent injuries secondary to a lack of negative pain stimuli. When present with compulsive onychophagia, prompt recognition and behavioral management to prevent chronic digital infection or amputation is imperative. We present the case of two 7 year-old monozygotic twins that presented with congenital insensitivity to pain and compulsive onychophagia without directed parental counseling or behavioral modification strategies. The presenting child was noted to have an acute digital felon and osteomyelitis of several distal phalanges, and the sister had a similar history with distal phalangeal amputations. The occurrence of these overlapping disorders in monozygotic twins has not been previously reported, however, patient and parental education with behavioral modifications of injurious and compulsive behavior is the cornerstone of management. In addition, we have provided a review of the diagnosis for clinical differentiation. © The Author(s) 2013.

  16. Suicidal Behaviors in Surviving Monozygotic and Dizygotic Co-Twins: Is the Nature of the Co-Twin's Cause of Death a Factor?

    ERIC Educational Resources Information Center

    Segal, Nancy L.

    2009-01-01

    Genetically informative samples can address hereditary and experiential influences on suicide-related behaviors. The frequency of suicide-related behaviors was compared in twins from two survivor groups: (1) those whose co-twins' deaths were suicides (monozygotic [MZ]: n = 47; dizygotic [DZ]: n = 31), and (2) those whose co-twins' deaths were…

  17. Suicidal Behaviors in Surviving Monozygotic and Dizygotic Co-Twins: Is the Nature of the Co-Twin's Cause of Death a Factor?

    ERIC Educational Resources Information Center

    Segal, Nancy L.

    2009-01-01

    Genetically informative samples can address hereditary and experiential influences on suicide-related behaviors. The frequency of suicide-related behaviors was compared in twins from two survivor groups: (1) those whose co-twins' deaths were suicides (monozygotic [MZ]: n = 47; dizygotic [DZ]: n = 31), and (2) those whose co-twins' deaths were…

  18. Monozygotic twins with fetal akinesia: the importance of clinicopathological work-up in predicting risks of recurrence.

    PubMed

    Ho, N C

    2000-10-01

    Fetal Akinesia Deformation Sequence (FADS) or Pena-Shokeir Sequence is a heterogeneous group of disorders in which prolonged decrease or absence of fetal movements results in a series of deformational anomalies: multiple contractures, pulmonary hypoplasia, craniofacial anomalies, polyhydramnios, intrauterine growth retardation, and short umbilical cord. Three sets of monozygotic twins, and their affected sibs, are presented. Detailed pathological work-up established that the two pairs of twins concordant for FADS were of myogenic etiology while the set discordant was due to anoxic-ischemic damage. In the myogenic cases, the rate of recurrence was high, in agreement with the findings from the study on arthrogryposis multiplex congenita of myogenic origin. In light of these findings, in sporadic cases of myogenic FADS, counselling, a recurrence risk of 25% seems prudent. In neurogenic cases associated with primary cerebral malformations, there are cases cited in the literature that are clearly recessive as indicated by affected sibs, but many reported are isolated occurrences. Therefore, in this scenario, giving a recurrent risk of 10-15% appears appropriate. In light of autosomal recessive spinal muscular atrophy and reports of familial FADS due to primary anterior horn cell loss, counselling a 25% risk seems prudent. In cases due to anoxic-ischemic damage, offering a low recurrent risk of 1% appears justified.

  19. Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity

    PubMed Central

    Moller, Frederik Trier; Knudsen, Lina; Harbord, Marcus; Satsangi, Jack; Gordon, Hannah; Christiansen, Lene; Christensen, Kaare; Jess, Tine; Andersen, Vibeke

    2016-01-01

    AIM: To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers. METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80 °C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria. RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 μg/g in 2 participants, and above 50 μg/g in a further 5 participants. CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins. PMID:27275097

  20. Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity.

    PubMed

    Moller, Frederik Trier; Knudsen, Lina; Harbord, Marcus; Satsangi, Jack; Gordon, Hannah; Christiansen, Lene; Christensen, Kaare; Jess, Tine; Andersen, Vibeke

    2016-06-07

    To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers. We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80 °C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria. We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 μg/g in 2 participants, and above 50 μg/g in a further 5 participants. The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins.

  1. Agenesis of the Gallbladder in Monozygotic Twin Sisters

    PubMed Central

    Hoshi, Koki; Irisawa, Atsushi; Shibukawa, Goro; Yamabe, Akane; Fujisawa, Mariko; Igarashi, Ryo; Sato, Ai; Maki, Takumi

    2016-01-01

    Agenesis of the gallbladder, a rare anomaly, is generally regarded as an organogenic failure. Several reports suggest that this congenital defect is inherited but that supposition remains controversial. We described agenesis of the gallbladder in identical twins. A 21-year-old female presented with a history of acute pain in the epigastrium and right hypochondrium. Various imaging modalities showed “gallbladder agenesis.” Moreover, her older identical twin sister had also no visualized gallbladder in imaging modalities. This case report strongly suggested that agenesis of the gallbladder would be caused by a genetic abnormality. PMID:26925274

  2. Agenesis of the Gallbladder in Monozygotic Twin Sisters.

    PubMed

    Hoshi, Koki; Irisawa, Atsushi; Shibukawa, Goro; Yamabe, Akane; Fujisawa, Mariko; Igarashi, Ryo; Sato, Ai; Maki, Takumi

    2016-01-01

    Agenesis of the gallbladder, a rare anomaly, is generally regarded as an organogenic failure. Several reports suggest that this congenital defect is inherited but that supposition remains controversial. We described agenesis of the gallbladder in identical twins. A 21-year-old female presented with a history of acute pain in the epigastrium and right hypochondrium. Various imaging modalities showed "gallbladder agenesis." Moreover, her older identical twin sister had also no visualized gallbladder in imaging modalities. This case report strongly suggested that agenesis of the gallbladder would be caused by a genetic abnormality.

  3. Shared Psychotic Manic Syndrome in Monozygotic Twins: A Case Report

    PubMed Central

    Ghasemzadeh, Mohammad Reza; Ghadiri Vasfi, Mohammad; Nohesara, Shabnam; Shabani, Amir

    2012-01-01

    Objective: A rare phenomenon of Shared Psychosis Disorder occurring in the context of Bipolar I Disorder, in identical twins is reported. Case Presentation: Two identical twins with shared Psychotic Manic Syndrome were admitted and received antipsychotic and lithium as their treatment. Psychotic symptoms of primary case did not improve and her diagnosis changed into Schizophrenia. They had hypothyroidism at the same time. Conclusion: Completely shared manic syndrome along with the psychotic features shows a need for the criteria of shared syndromes to develop, including both psychotic and mood symptoms. PMID:24644474

  4. Brain Activation during Memory Encoding in Type 2 Diabetes Mellitus: A Discordant Twin Pair Study

    PubMed Central

    Wood, Amanda G.; Chen, Jian; Moran, Christopher; Phan, Thanh; Beare, Richard; Cooper, Kimberley; Litras, Stacey; Srikanth, Velandai

    2016-01-01

    Type 2 diabetes mellitus increases the risk of dementia and neuronal dysfunction may occur years before perceptible cognitive decline. We aimed to study the impact of type 2 diabetes on brain activation during memory encoding in middle-aged people, controlling for age, sex, genes, and early-shared environment. Twenty-two twin pairs discordant for type 2 diabetes mellitus (mean age 60.9 years) without neurological disease were recruited from the Australian Twin Registry (ATR) and underwent functional magnetic resonance imaging (fMRI) during a memory encoding task, cognitive tests, and structural MRI. Type 2 diabetes was associated with significantly reduced activation in left hemisphere temporoparietal regions including angular gyrus, supramarginal gyrus, and middle temporal gyrus and significantly increased activation in bilateral posteriorly distributed regions. These findings were present in the absence of within-pair differences in standard cognitive test scores, brain volumes, or vascular lesion load. Differences in activation were more pronounced among monozygotic (MZ) pairs, with MZ individuals with diabetes also displaying greater frontal activation. These results provide evidence for preclinical memory-related neuronal dysfunction in type 2 diabetes. They support the search for modifiable later-life environmental factors or epigenetic mechanisms linking type 2 diabetes and cognitive decline. PMID:27314047

  5. Brain Activation during Memory Encoding in Type 2 Diabetes Mellitus: A Discordant Twin Pair Study.

    PubMed

    Wood, Amanda G; Chen, Jian; Moran, Christopher; Phan, Thanh; Beare, Richard; Cooper, Kimberley; Litras, Stacey; Srikanth, Velandai

    2016-01-01

    Type 2 diabetes mellitus increases the risk of dementia and neuronal dysfunction may occur years before perceptible cognitive decline. We aimed to study the impact of type 2 diabetes on brain activation during memory encoding in middle-aged people, controlling for age, sex, genes, and early-shared environment. Twenty-two twin pairs discordant for type 2 diabetes mellitus (mean age 60.9 years) without neurological disease were recruited from the Australian Twin Registry (ATR) and underwent functional magnetic resonance imaging (fMRI) during a memory encoding task, cognitive tests, and structural MRI. Type 2 diabetes was associated with significantly reduced activation in left hemisphere temporoparietal regions including angular gyrus, supramarginal gyrus, and middle temporal gyrus and significantly increased activation in bilateral posteriorly distributed regions. These findings were present in the absence of within-pair differences in standard cognitive test scores, brain volumes, or vascular lesion load. Differences in activation were more pronounced among monozygotic (MZ) pairs, with MZ individuals with diabetes also displaying greater frontal activation. These results provide evidence for preclinical memory-related neuronal dysfunction in type 2 diabetes. They support the search for modifiable later-life environmental factors or epigenetic mechanisms linking type 2 diabetes and cognitive decline.

  6. Proteomic analysis of hair shafts from monozygotic twins: Expression profiles and genetically variant peptides.

    PubMed

    Wu, Pei-Wen; Mason, Katelyn E; Durbin-Johnson, Blythe P; Salemi, Michelle; Phinney, Brett S; Rocke, David M; Parker, Glendon J; Rice, Robert H

    2017-07-01

    Forensic association of hair shaft evidence with individuals is currently assessed by comparing mitochondrial DNA haplotypes of reference and casework samples, primarily for exclusionary purposes. Present work tests and validates more recent proteomic approaches to extract quantitative transcriptional and genetic information from hair samples of monozygotic twin pairs, which would be predicted to partition away from unrelated individuals if the datasets contain identifying information. Protein expression profiles and polymorphic, genetically variant hair peptides were generated from ten pairs of monozygotic twins. Profiling using the protein tryptic digests revealed that samples from identical twins had typically an order of magnitude fewer protein expression differences than unrelated individuals. The data did not indicate that the degree of difference within twin pairs increased with age. In parallel, data from the digests were used to detect genetically variant peptides that result from common nonsynonymous single nucleotide polymorphisms in genes expressed in the hair follicle. Compilation of the variants permitted sorting of the samples by hierarchical clustering, permitting accurate matching of twin pairs. The results demonstrate that genetic differences are detectable by proteomic methods and provide a framework for developing quantitative statistical estimates of personal identification that increase the value of hair shaft evidence. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Double trisomy (48,XXY,+21) in monozygotic twins: case report and review of the literature.

    PubMed

    Iliopoulos, Dimitrios; Poultsides, George; Peristeri, Vasiliki; Kouri, Georgia; Andreou, Alexandros; Voyiatzis, Nikolaos

    2004-01-01

    The occurrence of double aneuploidy in the same individual is a relatively rare phenomenon. We describe twin newborns with typical clinical features of Down's syndrome, of which one revealed 48,XXY,+21 GTG-band karyotype. The second newborn died 2 days after its birth, and was clinically diagnosed having Down syndrome. Due to the same clinical features of the twins, the common placenta and amniotic sac, we speculate that they were monozygotics and as a result the second newborn should also be a Klinefelter. The purpose of this report is to present a rare case of possible coincidence of double aneuploidy in newborn twins. A review of the literature showed that double trisomy (48,XXY,+21) in a twin newborn infant has never occurred.

  8. [Concordant deuteranomaly in monozygotic twin sisters (author's transl)].

    PubMed

    Franceschetti, A T; Klein, D; Dieterle, P

    1976-12-01

    Colorblind twin sisters were born from the marriage of a hemizygote with a carrier for colorblindness. The proof of monozygosity is given by the blood-group typing and the dermatoglyphs. The deuteranomaly is of the same degree in each but is more marked in one of the sisters. The mother has none of the microsymptoms sometimes found in carriers.

  9. The Impact of the in utero and Early Postnatal Environments on Grey and White Matter Volume: A Study with Adolescent Monozygotic Twins.

    PubMed

    Levesque, Melissa L; Fahim, Cherine; Ismaylova, Elmira; Verner, Marie-Pier; Casey, Kevin F; Vitaro, Frank; Brendgen, Mara; Dionne, Ginette; Boivin, Michel; Tremblay, Richard E; Booij, Linda

    2015-01-01

    Prenatal and early postnatal adversities have been shown to be associated with brain development. However, we do not know how much of this association is confounded by genetics, nor whether the postnatal environment can moderate the impact of in utero adversity. This study used a monozygotic (MZ) twin design to assess (1) the association between birth weight (BW) and brain volume in adolescence, (2) the association between within-twin-pair BW discordance and brain volume discordance in adolescence, and (3) whether the association between BW and brain volume in adolescence is mediated or moderated by early negative maternal parenting behaviours. These associations were assessed in a sample of 108 MZ twins followed longitudinally since birth and scanned at age 15. The total grey matter (GM) and white matter (WM) volumes were obtained using the Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) toolbox in the Statistical Parametric Mapping version 8 (SPM8). We found that the BW was significantly associated with the total GM and WM volumes, particularly in the superior frontal gyrus and thalamus. Within-twin-pair discordance in BW was also significantly associated with within-pair discordance in both the GM and the WM volumes, supporting the hypothesis that the specific in utero environment is associated with brain development independently of genetics. Early maternal hostile parenting behaviours and depressive symptoms were associated with total GM volume but not WM volume. Finally, greater early maternal hostility may moderate the association between the BW and GM volume in adolescence, since the positive association between the BW and total GM volume appeared stronger at higher levels of maternal hostility (trend). Together, these findings support the importance of the in utero and early environments for brain development.

  10. Brazilian Twin Registry: A Bright Future for Twin Studies/Twin Research: Twin Study of Alcohol Consumption and Mortality; Oxygen Uptake in Adolescent Twins/In the News: Superfecundated Twins In Vietnam; Adolescent Twin Relations; Twin and Triplet Co-Workers; A Special Twin Ultrasound; Monozygotic Twins With Different Skin Color; Identical Twin Returns from Space.

    PubMed

    Segal, Nancy L

    2016-06-01

    The establishment of the Brazilian Twin Registry for the study of genetic, social, and cultural influences on behavior is one of eleven newly funded projects in the Department of Psychology at the University of São Paulo. These 11 interrelated projects form the core of the university's Center for Applied Research on Well-Being and Human Behavior. An overview of the planned twin research and activities to date is presented. Next, two recent twin studies are reviewed, one on the relationship between alcohol consumption and mortality, and the other on factors affecting maximal oxygen uptake. Twins cited in the media include the first identified superfecundated twins in Vietnam, adolescent twin relations, twins and triplets who work together, monozygotic twins with different skin tones and a co-twin control study that addresses the effects of space travel.

  11. Differentiating between monozygotic twins through next-generation mitochondrial genome sequencing.

    PubMed

    Wang, Zheng; Zhu, Ruxin; Zhang, Suhua; Bian, Yinnan; Lu, Daru; Li, Chengtao

    2015-12-01

    Monozygotic (MZ) twins, considered to be genetically identical, cannot be distinguished from one another by standard forensic DNA testing. A recent study employed whole genome sequencing to identify extremely rare mutations and reported that mutation analysis could be used to differentiate between MZ twins. Compared with nuclear DNA, mitochondrial DNA (mtDNA) has higher mutation rates; therefore, minor differences theoretically exist in MZ twins' mitochondrial genome (mtGenome). However, conventional Sanger-type sequencing (STS) is neither amenable to, nor feasible for, the detection of low-level sequence variants. The recent introduction of massively parallel sequencing (MPS) has the capability to sequence many targeted regions of multiple samples simultaneously with desirable depth of coverage. Thus, the aim of this study was to assess whether full mtGenome sequencing analysis can be used to differentiate between MZ twins. Ten sets of MZ twins provided blood samples that underwent extraction, quantification, mtDNA enrichment, library preparation, and ultra-deep sequencing. Point heteroplasmies were observed in eight sets of MZ twins, and a single nucleotide variant (nt15301) was detected in five sets of MZ twins. Thus, this study demonstrates that ultra-deep mtGenome sequencing could be used to differentiate between MZ twins.

  12. PRRT2 mutation causes paroxysmal kinesigenic dyskinesia and hemiplegic migraine in monozygotic twins.

    PubMed

    Castiglioni, Claudia; López, Isabel; Riant, Florence; Bertini, Enrico; Terracciano, Alessandra

    2013-05-01

    PRRT2 gene mutations have recently been identified as a causative gene of Paroxysmal kinesigenic dyskinesia (PKD), a rare movement disorder characterised by the occurrence of chorea, dystonia or athetosis triggered by sudden action. Some patients have additional intermittent neurologic disorders like infantile convulsions. The association with migraine has been rarely reported in this condition. Here we report the coexistence of PKD and hemiplegic migraine in twins harbouring a heterozygous mutation in PRRT2. Two monozygotic twins manifesting PKD together with repeated episodes of migraine with some severe attacks of hemiplegic migraine have been followed and treated for more than 10 years. Molecular genetic analysis disclosed the c.649_650insC, p.R217Pfs*8 heterozygous mutation in both twins. This mutation was segregating from the mother who likewise harboured the same mutation c.649dupC although she had never manifested PKD but complained of rare common migraine attacks in her past history. The association of PKD and hemiplegic migraine has been previously reported in one large family, associated to febrile convulsions and afebrile seizures in some individuals, but our report relates this association of symptoms to a mutation in PRRT2. The co-occurrence of both hemiplegic migraine and PKD in monozygotic twins expands the phenotypic spectrum of intermittent manifestations related to PRRT2 and perhaps suggests an additional causing gene for hemiplegic migraine.

  13. Growth and Development of Dentofacial Complex influenced by Genetic and Environmental Factors using Monozygotic Twins.

    PubMed

    Manjusha, K K; Jyothindrakumar, K; Nishad, A; Manoj, K Madhav

    2017-09-01

    The purpose of this study was to determine the possible effects of genetic and environmental factors on dentofacial complex using monozygotic twins. The study sample was made of 21 pairs of monozygotic twins (14 female pairs and seven male pairs) between 10 and 25 years. Pretreatment lateral cephalo-grams were used which were traced and digitized, and various landmarks to determine the anteroposterior and vertical proportions were marked. Samples were divided into two groups. The correlation between groups was found by calculating Pearson's product moment correlation coefficients. The range of the correlation coefficient was from 0.705 to 0.952. Gonial angle showed the highest correlation coefficient (0.952), while saddle angle showed the lowest correlation coefficient (0.705). The growth and development of craniofacial complex is under mutifactorial control. However, genetic influences do tend to play a dominant role. By studying identical twins, we can study about the interaction of the environment with the genes and how it affects the growth and development of the body in general and dentofacial complex in particular. By utilizing twin studies, we can identify whether a particular trait, disease, or disorder is influenced more strongly by genetics or by the environment. Success of orthodontic treatment depends on a proper diagnosis of the problem including its etiological factors. Genetic studies let the orthodontists to understand the effects of genetic and environmental factors in the growth and development of dentofacial complex better and allows to prevent or treat malocclusions and skeletal anomalies in better ways.

  14. IQ similarity in monozygotic and dizygotic twin children: effects of the same versus different examiners: a research note.

    PubMed

    Segal, N L; Russell, J

    1991-05-01

    The Wechsler Intelligence Scale for Children--Revised was administered to two independently identified samples of monozygotic (MZ) and dizygotic (DZ) twin children. Co-twins in the first sample were tested by the same examiner, while co-twins in the second sample were tested by different examiners. IQ intraclass correlations were similar for the two MZ twin samples (.84 and .88), and identical for the two DZ twin samples (.54). The implications of this analysis are discussed with reference to twin study methodology, research on IQ similarity and replication of child development research.

  15. Vocal Fold Bowing in Elderly Male Monozygotic Twins: A Case Study

    PubMed Central

    Tanner, Kristine; Sauder, Cara; Thibeault, Susan L.; Dromey, Christopher; Smith, Marshall E.

    2009-01-01

    Objectives This study examined case histories, diagnostic features, and treatment response in two 79-year-old male monozygotic (identical) twins with vocal fold bowing, exploring both genetic and environmental factors. Study Design Case study. Methods DNA concordance was examined via cheek swab. Case histories, videostroboscopy, auditory- and visual-perceptual assessment, electromyography, acoustic measures, and Voice Handicap ratings were undertaken. Both twins underwent surgical intervention and subsequent voice therapy. Results Monozygosity was confirmed for DNA polymorphisms, with 10 of 10 concordance for STR DNA markers. For both twins, auditory and visual-perceptual assessments indicated severe bowing, hoarseness and breathiness, although Twin 1 was judged to be extremely severe. Differences in RMS amplitudes were observed for TA and LCA muscles, with smaller relative amplitudes observed for the Twin 1 versus Twin 2. No consistent voice improvement was observed following surgical intervention(s), despite improved mid-membranous vocal fold closure. Marked reductions in Voice Handicap Index total scores were observed following behavioral voice therapy, coinciding with increased mid-membranous and posterior laryngeal (interarytenoid) glottal closure. No substantive differences in acoustic measures were observed. Conclusions Vocal fold bowing was more severe for Twin 1 versus Twin 2 despite identical heritability factors. Overall voice improvement with treatment was greater for Twin 2 than Twin 1. Environmental factors might partially account for the differences observed between the twins, including variability in their responsiveness to behavioral voice therapy. Voice therapy was useful in improving mid-membranous and posterior laryngeal closure, although dysphonia remained severe in both cases. PMID:19664899

  16. Objective assessment of facial skin aging and the associated environmental factors in Japanese monozygotic twins.

    PubMed

    Ichibori, Ryoko; Fujiwara, Takashi; Tanigawa, Tomoko; Kanazawa, Shigeyuki; Shingaki, Kenta; Torii, Kosuke; Tomita, Koichi; Yano, Kenji; Sakai, Yasuo; Hosokawa, Ko

    2014-06-01

    Twin studies, especially those involving monozygotic (MZ) twins, facilitate the analysis of factors affecting skin aging while controlling for age, gender, and genetic susceptibility. The purpose of this study was to objectively assess various features of facial skin and analyze the effects of environmental factors on these features in MZ twins. At the Osaka Twin Research Center, 67 pairs of MZ twins underwent medical interviews and photographic assessments, using the VISIA(®) Complexion Analysis System. First, the average scores of the right and left cheek skin spots, wrinkles, pores, texture, and erythema were calculated; the differences between the scores were then compared in each pair of twins. Next, using the results of medical interviews and VISIA data, we investigated the effects of environmental factors on skin aging. The data were analyzed using Pearson's correlation coefficient test and the Wilcoxon signed-rank test. The intrapair differences in facial texture scores significantly increased as the age of the twins increased (P = 0.03). Among the twin pairs who provided answers to the questions regarding history differences in medical interviews, the twins who smoked or did not use skin protection showed significantly higher facial texture or wrinkle scores compared with the twins not exposed to cigarettes or protectants (P = 0.04 and 0.03, respectively). The study demonstrated that skin aging among Japanese MZ twins, especially in terms of facial texture, was significantly influenced by environmental factors. In addition, smoking and skin protectant use were important environmental factors influencing skin aging.

  17. [Birth weight discordance in dichorionic twins: diagnosis, obstetrical and neonatal prognosis].

    PubMed

    Mottet, N; Guillaume, M; Martin, A; Ramanah, R; Riethmuller, D

    2014-09-01

    To describe neonatal and obstetrical prognosis in dichorionic (DC) twins with a birth weight discordance under 20% and evaluate the influence of intrauterine growth restriction on the management. We studied retrospectively 67 DC twins birth between July 2002 and July 2012 at our university labour ward. Birth weight discordance was considered slight between 20-25%, moderate between 25-30%, and severe over 30%. Prevalence of birth weight discordance in DC twins is estimated at 11.4% in our study. Eighty percent of severe discordance was diagnosed before delivery, 41% for moderate discordance and 20% for slight discordance. We note 30% of pre eclampsia in our population with 44% in the severe discordance group. Mean gestational age was 35.1 weeks for slight and moderate discordances, and 33 weeks for severe discordance. Caesarean section rate was 48% for severe discordance and only 36% for slight discordance. Vaginal delivery rate is 56.7%. More than half of patient with a severe discordance gave birth vaginally. Intrauterine growth restriction rate under the 10th percentile was 18.7%. Prevalence of IUGR was 24% in sever discordance group, 23.5% in the moderate discordance group and 10% in the slight group. Neonatal morbidity rate was 20.8% mainly in children with IUGR. Neonatal mortality and morbidity rate are mainly increased in severe discordant twins. These pregnancies are at high risk of maternal morbidity. Vaginal delivery must be preferred for slight and moderate discordances. In case of severe discordance, vaginal delivery should be considered depending on the degree of intrauterine growth retardation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Differentiating between monozygotic twins through DNA methylation-specific high-resolution melt curve analysis.

    PubMed

    Stewart, Leander; Evans, Neil; Bexon, Kimberley J; van der Meer, Dieudonne J; Williams, Graham A

    2015-05-01

    Although short tandem repeat profiling is extremely powerful in identifying individuals from crime scene stains, it is unable to differentiate between monozygotic (MZ) twins. Efforts to address this include mutation analysis through whole genome sequencing and through DNA methylation studies. Methylation of DNA is affected by environmental factors; thus, as MZ twins age, their DNA methylation patterns change. This can be characterized by bisulfite treatment followed by pyrosequencing. However, this can be time-consuming and expensive; thus, it is unlikely to be widely used by investigators. If the sequences are different, then in theory the melting temperature should be different. Thus, the aim of this study was to assess whether high-resolution melt curve analysis can be used to differentiate between MZ twins. Five sets of MZ twins provided buccal swabs that underwent extraction, quantification, bisulfite treatment, polymerase chain reaction amplification and high-resolution melting curve analysis targeting two markers, Alu-E2F3 and Alu-SP. Significant differences were observed between all MZ twins targeting Alu-E2F3 and in four of five MZ twins targeting Alu-SP (P<0.05). Thus, it has been demonstrated that bisulfite treatment followed by high-resolution melting curve analysis could be used to differentiate between MZ twins.

  19. The Discordant MZ-Twin Method: One Step Closer to the Holy Grail of Causality

    ERIC Educational Resources Information Center

    Vitaro, Frank; Brendgen, Mara; Arseneault, Louise

    2009-01-01

    Twin studies are well known for their value in quantifying the contribution of genes to population variation in behaviors and personality traits. Twin studies also provide a unique opportunity to untangle the contribution of environmental experiences to emotional and behavioral development. This is particularly true when examining monozygotic (MZ)…

  20. The Discordant MZ-Twin Method: One Step Closer to the Holy Grail of Causality

    ERIC Educational Resources Information Center

    Vitaro, Frank; Brendgen, Mara; Arseneault, Louise

    2009-01-01

    Twin studies are well known for their value in quantifying the contribution of genes to population variation in behaviors and personality traits. Twin studies also provide a unique opportunity to untangle the contribution of environmental experiences to emotional and behavioral development. This is particularly true when examining monozygotic (MZ)…

  1. Double jeopardy: multi-modality imaging of monozygotic "twin cap" atherosclerosis.

    PubMed

    Murray, Scott W; Cooper, Robert M; Appleby, Clare; McCann, Caroline; Binukrishnan, Sukumaran; Radu, Maria D; Stables, Rodney H

    2014-11-01

    The investigation of asymptomatic but potentially vulnerable atherosclerosis is not yet a major focus for clinical Cardiologists. We have illustrated the contemporary investigation and treatment of such disease using a clinical case that involved monozygotic twins. One twin (T1) had unfortunately suffered a cardiac arrest whilst jogging and survived only due to bystander CPR and prompt defibrillation. His identical twin brother (T2), on subsequent investigation, harbours a compositionally identical lesion in a proximal coronary vessel that has not yet ruptured or provoked a clinical event. Following the presentation of both non-invasive and invasive images, we discuss the need for active suspicion and intensive treatment for those people with a 'genetic' risk of future myocardial infarction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Nonshared environmental effects on adulthood psychopathic personality traits: results from a monozygotic twin difference scores analysis.

    PubMed

    Beaver, Kevin M; Vaughn, Michael G; Delisi, Matt

    2013-09-01

    An emerging body of empirical research has revealed that nonshared environmental factors are associated with explaining variance in measures of psychopathy and psychopathic personality traits. The current study adds to this existing knowledge base by analyzing a measure of psychopathy derived, in part, from the five factor model in a sample of monozygotic (MZ) twin pairs drawn from the National Longitudinal Study of Adolescent Health. The results of the MZ twin difference scores analysis revealed that nonshared environmental factors found within the family were unrelated to between-twin differences in psychopathic personality traits. Only one nonshared factor--levels of self-control--consistently predicted psychopathy. We conclude by discussing the implications of our findings and the limitations of our study.

  3. Case of early childhood-onset narcolepsy with cataplexy: comparison with a monozygotic co-twin.

    PubMed

    Ito, Hiromichi; Mori, Kenji; Mori, Tatsuo; Goji, Aya; Kagami, Shoji

    2014-10-01

    We describe here a rare case of early childhood-onset (5 years of age) narcolepsy. This case was interesting because of the ability to compare the patient's symptoms to the condition of her healthy monozygotic co-twin sister. The only environmental difference between the co-twins was head injury, which may be associated with the presence of narcolepsy. The co-twin was extroverted, sociable, reliable, and dexterous. In contrast, the patient could be described as introverted, gentle, honest and persevering, but was weak at conversation, assessment of a situation, memory, planning, activity (she was inactive), a sense of time, understanding of an analog clock, operating efficiency, and physical education (due to obesity). The sisters showed the same degree of appetite and dexterity with their fingers. Narcolepsy is often under-recognized or underdiagnosed, especially when the onset occurs in childhood. When we observe preschoolers with excessive daytime sleepiness, we should consider the possibility of narcolepsy with cataplexy.

  4. Monozygotic twin differences in non-shared environmental factors associated with chronotype.

    PubMed

    Barclay, Nicola L; Eley, Thalia C; Parsons, Michael J; Willis, Thomas A; Gregory, Alice M

    2013-02-01

    Twin studies have highlighted that a large proportion of variability in chronotype is accounted for by individual-specific environmental factors (non-shared environmental influences). However, little research has aimed to identify specific non-shared environmental influences on chronotype. Although epidemiological studies have shed light on possible environmental influences on chronotype, a substantial amount of research has highlighted the importance of genetic influences on exposure toward specific environments, a process termed gene-environment correlation. It is possible that associations between the environment and chronotype are in part determined by genetics, rather than being purely environmental in origin. One way of exploring the contribution of purely non-shared environmental components on associations between chronotype and the environment is to use the monozygotic twin differences design. This design allows us to tease apart the influences of genetics and the environment to identify purely environmental components. One hundred eighty-nine monozygotic twin pairs (mean age 19.81 years, SD = 1.26, range = 18-22 years, 66.1% female) completed the Horne and Östberg Morningness-Eveningness Questionnaire as a measure of chronotype and questionnaires assessing the following candidate non-shared environmental influences: dependent and independent negative life events, educational attainment, employment status, relationship status, deviant peers, affiliation with deviant peers, general health, smoking, drug use, and alcohol use. Linear regression analyses indicated the presence of gene-environment correlation for the majority of associations between chronotype and candidate environmental influences. When controlling for genetic and shared environmental effects, within monozygotic twin-pair differences in chronotype were associated with within monozygotic twin-pair differences in dependent negative life events (β = -0.27, p < 0.001), educational attainment (

  5. Mirror-image solitary bone cyst of the humerus in a pair of mirror-image monozygotic twins.

    PubMed

    Goto, Takahiro; Nemoto, Tetsuo; Okuma, Tomotake; Kobayashi, Hiroshi; Funata, Nobuaki

    2008-12-01

    Mirror-image solitary bone cysts (SBCs) of the humerus in a pair of mirror-image monozygotic twins are presented. One twin was right-handed and had SBC at the left humerus. The other twin was left-handed and had SBC at the right humerus. The directions of the whirl of hair on their heads were opposite with each other. These findings strongly suggest cytogenetic factors in the aetiology or pathogenesis of SBC.

  6. Hyperthyroidism is associated with work disability and loss of labour market income. A Danish register-based study in singletons and disease-discordant twin pairs.

    PubMed

    Brandt, Frans; Thvilum, Marianne; Hegedüs, Laszlo; Brix, Thomas Heiberg

    2015-11-01

    To examine the risk of disability pension and changes in labour market income in patients with hyperthyroidism. From a 5% random sample of the Danish population and twins from the Danish Twin Registry we identified 1942 hyperthyroid singletons and 7768 non-hyperthyroid (matched 1:4) controls as well as 584 same-sex twin pairs discordant for hyperthyroidism. Singletons and twins were followed for a mean of 9 years (range 1-20). Cox regression analysis was used to examine the risk of disability pension and a difference-in-differences model was used to evaluate changes in labour market income. Hyperthyroid individuals had an increased risk of receiving disability pension: hazard ratio (HR) was 1.88, (95% CI: 1.57-2.24). Subdividing as to the cause of hyperthyroidism did not change this finding: Graves' disease (GD) HR was 1.51 (95% CI: 0.87-2.63) and toxic nodular goitre (TNG) HR was 2.10 (95% CI: 1.02-4.36). With respect to labour market income, the income of hyperthyroid individuals increased on average 1189 € less than their controls (P<0.001). This difference in income was more pronounced in GD (2539 €) than in TNG (132 €). Essentially similar results, with respect to disability pension and labour market income, were seen within monozygotic twin pairs discordant for hyperthyroidism. Hyperthyroidism is associated with severe work disability as reflected by an 88% increased risk of receiving disability pension and a significant loss of labour market income. Similar results in monozygotic twins discordant for hyperthyroidism suggest that genetic confounding is unlikely. © 2015 European Society of Endocrinology.

  7. Prevalence and Heritability of Early Childhood Caries Among Monozygotic and Dizygotic Twins.

    PubMed

    Kuppan, Anuradha; Rodrigues, Steven; Samuel, Victor; Ramakrishnan, Mahesh; Halawany, Hassan S; Abraham, Nimmi B; Jacob, Vimal; Anil, Sukumaran

    2017-02-01

    Deciphering the relative importance of genetic and environmental factors, which play a major role in the prevalence of early childhood caries (ECC), can help clinicians with planning a long-term preventive treatment. The objective of the study was to determine the prevalence and heritability of ECC among monozygotic (MZ) and dizygotic (DZ) twins in Chennai, India, in the year 2013. A cross-sectional study was designed to estimate the prevalence of ECC among twins. Zygosity classification for the survey framework was adapted from a highly accurate parental report questionnaire pertaining to the physical similarity between twins. The associated heritability index was estimated. The Decayed, Missing, Filled Surface (DMFS) Index was used as the diagnostic criterion for dental caries. The prevalence of ECC was estimated at 18.7%. The correlation coefficient between the twin pair showed significant correlation. The heritability index for ECC was estimated at 15% higher prevalence of ECC found among children in the age group 25-36 months. The heritability estimate indicated a relatively low genetic influence for early childhood caries among twins. There was no significant difference detected in the concordance rate for the MZ and DZ twins. Further research could be directed toward the prevalence of ECC among higher age group children to explore the role of genetic and environmental factors.

  8. A spare or an individual? Cloning and the implications of monozygotic twinning.

    PubMed

    Bryan, E M

    1998-01-01

    The creation of Dolly, the cloned sheep, raises the scenario of cloning in humans. Neither the case for, nor against, the ethics of cloning in humans is discussed in this paper. Instead, it considers the neglected issue of the likely happiness or otherwise of the resulting children if they are born as monozygotic twins or triplets. The advantages and disadvantages of twinship are discussed in detail, and it is concluded that recognized medical risks, and incompletely understood psychological effects, should be given serious consideration.

  9. Production of monozygotic twin calves using the blastomere separation technique and Well of the Well culture system.

    PubMed

    Tagawa, M; Matoba, S; Narita, M; Saito, N; Nagai, T; Imai, K

    2008-03-15

    The present study was conducted to establish a simple and efficient method of producing monozygotic twin calves using the blastomere separation technique. To produce monozygotic twin embryos from zona-free two- and eight-cell embryos, blastomeres were separated mechanically by pipetting to form two demi-embryos; each single blastomere from the two-cell embryo and tetra-blastomeres from the eight-cell embryo were cultured in vitro using the Well of the Well culture system (WOW). This culture system supported the successful arrangement of blastomeres, resulting in their subsequent aggregation to form a demi-embryo developing to the blastocyst stage without a zona pellucida. There was no significant difference in the development to the blastocyst stage between blastomeres separated from eight-cell (72.0%) and two-cell (62.0%) embryos. The production rates of the monozygotic pair blastocysts and transferable paired blastocysts for demi-embryos obtained from eight-cell embryos (64.0 and 45.0%, respectively) were higher than those for demi-embryos obtained from two-cell embryos (49.0 and 31.0%, P<0.05). The separated demi-embryos obtained from eight-cell embryos produced by IVM/IVF of oocytes collected by ovum pick-up (OPU) from elite cows and cultured in wells tended to have a higher pregnancy rate (78.9% vs. 57.1%) and similar monozygotic twinning rate (40.0% vs. 33.3%) compared with monozygotic twin blastocysts obtained by the conventional bisection of in vivo derived blastocysts. In conclusion, producing twins by separation of blastomeres in OPU-IVF embryos, followed by the WOW culture system, yielded viable monozygotic demi-embryos, resulting in high rates of pregnancy and twinning rates after embryo transfer.

  10. Sleep EEG composition in the first three months of life in monozygotic and dizygotic twins.

    PubMed

    Vucinovic, Mirjana; Kardum, Goran; Bonkovic, Mirjana; Resic, Biserka; Ursic, Anita; Vukovics, Jonatan

    2014-07-01

    We investigated genetic influence on sleep electroencephalogram (EEG) composition by a classical twin study of monozygotic (MZ) and dizygotic (DZ) twins in the first 3 months of life. Polysomnographic (PSG) recordings were obtained in 10 MZ and 20 DZ twin pairs in the 37th, 46th, and 52nd week of postmenstrual age (PMA). The EEG power spectra were generated on the basis of fast Fourier transformation (FFT). Genetic influence on active sleep/rapid eye movement (AS/REM)] and quiet sleep/non rapid eye movement (QS/NREM) sleep composition was estimated by calculating within pair concordance and the intraclass correlation coefficients (ICCs) for delta (0.5-3.5 Hz), theta (4-7.5 Hz), alpha (8-11.5 Hz), sigma (12-14 Hz), and beta (14.5-20 Hz) at central derivation. MZ twins show higher ICCs than DZ twins for alpha, sigma, and beta spectral powers during QS/NREM sleep in the 37th, 46th, and 52nd week PMA. However, there was no significant difference (P > .05) between the 2 types of twins in absolute differences of EEG spectral power of the alpha, beta, and sigma frequency ranges in the 37th, 46th, and 52nd week PMA. The greatest mean absolute difference within MZ and DZ twin pairs and also between MZ and DZ twin groups was identified in the delta frequency range. Our findings gave an indication of genetic influence on alpha, sigma, and beta frequency ranges in the QS/NREM sleep stage.

  11. Impact of Early Environment on Children's Mental Health: Lessons From DNA Methylation Studies With Monozygotic Twins.

    PubMed

    Chiarella, Julian; Tremblay, Richard E; Szyf, Moshe; Provençal, Nadine; Booij, Linda

    2015-12-01

    Over the past decade, epigenetic analyses have made important contributions to our understanding of healthy development and a wide variety of adverse conditions such as cancer and psychopathology. There is increasing evidence that DNA methylation is a mechanism by which environmental factors influence gene transcription and, ultimately, phenotype. However, differentiating the effects of the environment from those of genetics on DNA methylation profiles remains a significant challenge. Monozygotic (MZ) twin study designs are unique in their ability to control for genetic differences because each pair of MZ twins shares essentially the same genetic sequence with the exception of a small number of de novo mutations and copy number variations. Thus, differences within twin pairs in gene expression and phenotype, including behavior, can be attributed in the majority of cases to environmental effects rather than genetic influence. In this article, we review the literature showing how MZ twin designs can be used to study basic epigenetic principles, contributing to understanding the role of early in utero and postnatal environmental factors on the development of psychopathology. We also highlight the importance of initiating longitudinal and experimental studies with MZ twins during pregnancy. This approach is especially important to identify: (1) critical time periods during which the early environment can impact brain and mental health development, and (2) the specific mechanisms through which early environmental effects may be mediated. These studies may inform the optimum timing and design for early preventive interventions aimed at reducing risk for psychopathology.

  12. Blood DNA methylation age is not associated with cognitive functioning in middle-aged monozygotic twins.

    PubMed

    Starnawska, A; Tan, Q; Lenart, A; McGue, M; Mors, O; Børglum, A D; Christensen, K; Nyegaard, M; Christiansen, L

    2017-02-01

    The epigenetic clock, also known as DNA methylation age (DNAmAge), represents age-related changes of DNA methylation at multiple sites of the genome and is suggested to be a biomarker for biological age. Elevated blood DNAmAge is associated with all-cause mortality, with the strongest effects reported in a recent intrapair twin study where epigenetically older twins had increased mortality risk in comparison to their co-twins. In the study presented here, we hypothesize that DNAmAge in blood is associated with cross-sectional and longitudinal cognitive abilities in middle-aged individuals. In 486 monozygotic twins, we investigated the association of DNAmAge, difference between DNAmAge and chronological age and age acceleration with cognition. Despite using a powerful paired twin design, we found no evidence for association of blood DNAmAge with cognitive abilities. This observation was confirmed in unpaired analyses, where DNAmAge initially correlated with cognitive abilities, until adjusting for chronological age. Overall, our study shows that for middle-aged individuals DNAmAge calculated in blood does not correlate with cognitive abilities. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Results of in vitro contracture tests for the diagnosis of malignant hyperthermia susceptibility in monozygote twins.

    PubMed

    Islander, G; Ranklev Twetman, E

    1997-06-01

    Malignant hyperthermia susceptibility is a pharmacogenetic disorder in which susceptible individuals may develop a potentially life-threatening hypermetabolism when exposed to certain anaesthetic agents. The most common diagnostic method is the in vitro contracture test (IVCT) of skeletal muscle biopsies. There is a wide variation in the size of contractures between susceptible individuals and the reproducibility of the test in humans has not been evaluated. We have performed the IVCT in 4 monozygote pairs of twins, which gave us on opportunity to study the reproducibility. The clinical diagnoses were consistent in all twin pairs, although slight differences in contractures and thresholds were seen. In this material the reproducibility of the IVCT was found to be satisfactory.

  14. Ocular motor behaviour of monozygotic twins with tyrosinase negative oculocutaneous albinism.

    PubMed Central

    Abadi, R V; Pascal, E

    1994-01-01

    The involuntary nystagmus movements of 16-year-old monozygotic twins with tyrosinase negative oculocutaneous albinism were examined. On primary gaze both girls exhibited bilateral conjugate horizontal nystagmus, a jerk with extended foveation waveform, and similar frequencies (2.0 Hz:1.9 Hz), although the fast phases were in opposite directions. The mean amplitudes differed markedly (6.8 degrees:3.7 degrees), as did the position of the null zones (+20 degrees to +30 degrees:-25 degrees to -35 degrees) and the widths of the neutral zones (-25 degrees to +20 degrees:-25 degrees to -35 degrees). Since the twins have identical genotypes these differences must have arisen from other sources. Images PMID:8025067

  15. Discordant Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome in identical twins - a case report and implications for reproduction in MRKH women.

    PubMed

    Milsom, Stella Ruth; Ogilvie, Cara Megan; Jefferies, Craig; Cree, Lynsey

    2015-01-01

    Infertility has previously been considered as an inevitable consequence of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. With modern assisted reproductive technology (ART) techniques becoming increasingly accessible, MRKH women have the opportunity for their own genetic offspring. The availability of such technology, however, increases the importance of understanding the aetiology of this complex condition. The literature debating the relevance of genetic versus post-zygotic events in the aetiology of MRKH syndrome is reviewed in the context of this report of monozygotic twins discordant for MRKH syndrome.

  16. Physical growth and cognitive abilities in concordant versus discordant birth weight twins at three years old.

    PubMed

    Ross, Gail S; Krauss, Alfred N; Perlman, Jeffrey M

    2012-09-01

    Discordant birth weight twins have been shown to have high rates of adverse perinatal outcomes, but little is known about their growth and development. To determine whether smaller and larger birth weight premature twins in concordant and discordant birth weight groups differ on measures of physical growth and intelligence at 3 years. Prospective cohort study. Eight-four children, 52 concordant and 32 discordant birth weight twin pairs, were measured for height, weight, and head circumference and on intelligence at 3 years. Perinatal and demographic variables, including birth weight, head circumference, small for gestational age, zygosity, in vitro fertilization, gender and social class were recorded. Smaller and larger birth weight twins did not differ significantly from each other on any growth parameters in either concordant or discordant birth weight groups at 3 years of age. Smaller birth weight twins in the discordant birth weight group performed significantly less well on Verbal, Performance, and Full Scale IQ scores (Verbal IQ for smaller twins was 8.6 points lower, p<0.005; Performance IQ, 11.9 points lower, p<0.03; Full Scale IQ, 12.4 points lower, p<0.004), but there were no significant intra-twin differences between larger and smaller birth weight concordant twins. Smaller discordant birth weight twins performed significantly less well on intelligence, although they did not differ significantly from their larger twins on growth parameters at 3 years old. We conclude that smaller discordant birth weight twins had less optimal intra-uterine environments than their larger birth weight twin, which affected both their birth weights and brain development. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Simultaneous atelectasis in human bocavirus infected monozygotic twins: was it plastic bronchitis?

    PubMed Central

    2013-01-01

    Background Plastic bronchitis is an extremely rare disease characterized by the formation of tracheobronchial airway casts, which are composed of a fibrinous exudate with rubber-like consistency and cause respiratory distress as a result of severe airflow obstruction. Bronchial casts may be associated with congenital and acquired cardiopathies, bronchopulmonary diseases leading to mucus hypersecretion, and pulmonary lymphatic abnormalities. In recent years, however, there is growing evidence that plastic bronchitis can also be triggered by common respiratory tract infections and thereby cause atelectasis even in otherwise healthy children. Case presentation We report on 22-month-old monozygotic twins presenting with atelectasis triggered by a simple respiratory tract infection. The clinical, laboratory, and radiographic findings given, bronchial cast formation was suspected in both infants but could only be confirmed after bronchoscopy in the first case. Real-time polymerase chain reaction of the removed cast as well as nasal lavage fluid of both infants demonstrated strong positivity for human bocavirus. Conclusion Our case report is the first to describe two simultaneously affected monozygotic twins and substantiates the hypothesis of a contributing genetic factor in the pathophysiology of this disease. In this second report related to human bocavirus, we show additional evidence that this condition can be triggered by a simple respiratory tract infection in previously healthy infants. PMID:24344641

  18. Simultaneous atelectasis in human bocavirus infected monozygotic twins: was it plastic bronchitis?

    PubMed

    Rüegger, Christoph M; Bär, Walter; Iseli, Peter

    2013-12-18

    Plastic bronchitis is an extremely rare disease characterized by the formation of tracheobronchial airway casts, which are composed of a fibrinous exudate with rubber-like consistency and cause respiratory distress as a result of severe airflow obstruction. Bronchial casts may be associated with congenital and acquired cardiopathies, bronchopulmonary diseases leading to mucus hypersecretion, and pulmonary lymphatic abnormalities. In recent years, however, there is growing evidence that plastic bronchitis can also be triggered by common respiratory tract infections and thereby cause atelectasis even in otherwise healthy children. We report on 22-month-old monozygotic twins presenting with atelectasis triggered by a simple respiratory tract infection. The clinical, laboratory, and radiographic findings given, bronchial cast formation was suspected in both infants but could only be confirmed after bronchoscopy in the first case. Real-time polymerase chain reaction of the removed cast as well as nasal lavage fluid of both infants demonstrated strong positivity for human bocavirus. Our case report is the first to describe two simultaneously affected monozygotic twins and substantiates the hypothesis of a contributing genetic factor in the pathophysiology of this disease. In this second report related to human bocavirus, we show additional evidence that this condition can be triggered by a simple respiratory tract infection in previously healthy infants.

  19. Placental sharing, birthweight discordance, and vascular anastomoses in monochorionic diamniotic twin placentas.

    PubMed

    Lewi, Liesbeth; Cannie, Mieke; Blickstein, Isaac; Jani, Jacques; Huber, Agnes; Hecher, Kurt; Dymarkowski, Steven; Gratacós, Eduard; Lewi, Paul; Deprest, Jan

    2007-12-01

    The purpose of this study was to examine the relationship between placental territory and birthweight discordance and vascular anastomoses in monochorionic diamniotic twin placentas from pregnancies that were not complicated by twin-to-twin transfusion syndrome with 2 liveborn twins. Placentas originated from a prospective follow-up study of monochorionic diamniotic twins included in the first trimester. After injection with dyed barium sulphate, a digital x-ray angiography and high-resolution digital photograph were taken. The 2 venous territories were delineated on the angiogram. The diameter of each arterioarterial anastomosis and of each vein that participated in an arteriovenous anastomosis was measured on the digital photograph. Net transfusion over the arteriovenous anastomoses was calculated as the difference between the total venous diameters of the 2 placental parts. One hundred placentas were analyzed. Birthweight discordance increased with placental territory discordance (P < .0001). Arterioarterial diameter (P < .01), net arteriovenous transfusion (P < .001), and total anastomotic diameter (P < .01) increased with placental territory discordance. On the other hand, birthweight discordance for a given placental territory discordance decreased with increasing arterioarterial diameter (P < .01), net arteriovenous transfusion (P < .001), and total anastomotic diameter (P < .01). In unequally shared placentas, the 2 fetal circulations are more tightly linked than in equally shared placentas, which may reduce the birthweight discordance for a given placental territory discordance.

  20. Monozygotic twinning after assisted reproductive technologies: a case report of asymmetric development and incidence during 19 years in an international group of in vitro fertilization clinics.

    PubMed

    Tocino, Antonia; Blasco, Víctor; Prados, Nicolás; Vargas, Manuel J; Requena, Antonio; Pellicer, Antonio; Fernández-Sánchez, Manuel

    2015-05-01

    To describe a case of monozygotic twinning with asymmetric development following a single fresh embryo transfer as part of an intracytoplasmic sperm injection (ICSI) treatment. Secondarily, to report the incidence of monozygotic twinning at the IVI (Instituto Valenciano de Infertilidad) clinics. Case report. Private fertility centers. A 33-year-old woman with a 2-year history of primary infertility. Controlled ovarian hyperstimulation and ICSI treatment with single-embryo transfer. Incidence of monozygotic twinning at the IVI clinics. We report a twin pregnancy after a single-embryo transfer. Twins were dichorionic and diamniotic. One fetus had a 6-day delay in its growth compared with the other when observed by ultrasound. Two female infants were delivered, and despite presenting congenital diseases, they were successfully treated and evolved correctly. A subsequent DNA analysis confirmed that the infants were monozygotic. Furthermore, we estimated a monozygotic twinning rate of 1.17% at the IVI clinics, taking into account those cases in which two or more embryos with heart beats were observed by ultrasound scanning after single-embryo transfers. Ultrasound scans performed during pregnancy suggested a possible dizygotic origin of the twins, but DNA analysis performed after birth established that they were monozygotic. Genetic analysis is the only valid tool to confirm if like-sex dichorionic twins are monozygotic or dizygotic. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  1. Health-Related Findings Among Twin Pairs Discordant for Leisure-Time Physical Activity for 32 Years: The TWINACTIVE Study Synopsis.

    PubMed

    Leskinen, Tuija; Kujala, Urho M

    2015-06-01

    We are lacking very long-term and controlled intervention studies investigating the effects of habitual physical activity on health-related factors. To address this gap, we performed a natural experiment by identifying same-sex twin pairs in which the co-twins of each pair differed with respect to leisure-time physical-activity habits throughout their adult life. Our criterion for the discordance was that the same co-twin had a higher leisure time-activity volume than that of the other member of the pair at the majority -- if not all -- of the follow-up time points according to reported/interviewed physical-activity data. Overall, we identified and conducted multidimensional health-related measurements (including fitness, body composition, cardiometabolic risk factor levels, bone and arterial status, and exercise motivation) of 16 twin pairs (seven monozygotic (MZ) and nine dizygotic (DZ) pairs, mean age 60 years) who had persistent discordance in leisure-time physical-activity habits over three decades (TWINACTIVE study). In our discordant-pair study design, after adjusting for sequence-level genes, both systemic-level metabolic, and site-specific structural findings differed significantly in the pairwise analysis in MZ pairs only. These findings included intrapair differences in accumulated fat depots and structure of heart, arteries, and bones. In addition, our study revealed intrapair differences in metabolic and regulatory pathways, which may partly explain the mechanistic links between long-term physical activity, phenotypic changes, and decreased risk of cardiometabolic diseases.

  2. Metabolism of sex steroids is influenced by acquired adiposity-A study of young adult male monozygotic twin pairs.

    PubMed

    Vihma, Veera; Naukkarinen, Jussi; Turpeinen, Ursula; Hämäläinen, Esa; Kaprio, Jaakko; Rissanen, Aila; Heinonen, Sini; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Mikkola, Tomi S; Tikkanen, Matti J; Pietiläinen, Kirsi H

    2017-09-01

    Obesity and ageing are associated with lower serum testosterone levels in men. How fat distribution or adipose tissue metabolism, independent of genetic factors and age, are related to sex steroid metabolism is less clear. We studied the associations between adiposity and serum sex hormone concentrations, and mRNA expression of genes regulating sex hormone metabolism in adipose tissue in young adult male monozygotic (MZ) twin pairs. The subjects [n=18 pairs; mean age, 32 years; individual body mass indexes (BMIs) 22-36kg/m(2)] included 9 male MZ twin pairs discordant for BMI [intra-pair difference (Δ) in BMI ≥3kg/m(2)]. Sex steroid concentrations were determined by liquid chromatography-tandem mass spectrometry, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and mRNA expressions from subcutaneous adipose tissue by Affymetrix. In BMI-discordant pairs (mean ΔBMI=5.9kg/m(2)), serum dihydrotestosterone (DHT) was lower [mean 1.9 (SD 0.7) vs. 2.4 (1.0) nmol/l, P=0.040] and mRNA expressions of DHT-inactivating AKR1C2 (P=0.021) and cortisol-producing HSD11B1 (P=0.008) higher in the heavier compared to the leaner co-twins. Serum free 17β-estradiol (E2) was higher [2.3 (0.5) vs. 1.9 (0.5) pmol/l, P=0.028], and in all twin pairs, serum E2 and estrone concentrations were higher in the heavier than in the leaner co-twins [107 (28) vs. 90 (22) pmol/l, P=0.006; and 123 (43) vs. 105 (27) pmol/l, P=0.025]. Within all twin pairs, i.e. independent of genetic effects and age, 1) the amount of subcutaneous fat inversely correlated with serum total and free testosterone, DHT, and sex hormone-binding globulin (SHBG) concentrations (P<0.01 for all), 2) intra-abdominal fat with total testosterone and SHBG (P<0.05), and 3) liver fat with SHBG (P=0.006). Also, 4) general and intra-abdominal adiposity correlated positively with mRNA expressions of AKR1C2, HSD11B1, and aromatase in adipose tissue (P<0.05). In conclusion, acquired adiposity was

  3. Different Complicated Brain Pathologies in Monozygotic Twins With Gerstmann-Sträussler-Scheinker Disease.

    PubMed

    Honda, Hiroyuki; Sasaki, Kensuke; Takashima, Hiroshi; Mori, Daisuke; Koyama, Sachiko; Suzuki, Satoshi O; Iwaki, Toru

    2017-10-01

    Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal, dominantly inherited prion disease. In this study, we present different complicated brain pathologies determined postmortem of monozygotic GSS twin sisters. Case 1 showed cerebellar ataxia at the age of 58 years, and died at 66 years. Case 2 became symptomatic at the age of 75 years, and died at 79 years. There was a 17-year difference in the age of onset between the twins. Postmortem examination revealed numerous prion protein (PrP) plaques in the brains of both cases. The spongiform change and brain atrophy in case 1 were more severe compared with those in case 2. Western-blot analysis identified proteinase-resistant PrP (PrPres) at the molecular weight of 21-30 kDa and 8 kDa in the twins. Gel filtration revealed that PrPres was mainly composed of PrP oligomer. PrPres signal patterns were similar between the twins. Additionally, case 1 showed α-synucleinopathy and case 2 showed Alzheimer disease pathology. These different proteinopathies were involved in the amyloid plaque formations of both cases. The degree of GSS pathology was mainly related to disease duration. The amyloid plaque formations could be decorated by concomitant neuropathological changes such as α-synucleinopathy and tauopathy. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  4. Association Between Promoter Methylation of Serotonin Transporter Gene and Depressive Symptoms: A Monozygotic Twin Study

    PubMed Central

    Zhao, Jinying; Goldberg, Jack; Bremner, James D.; Vaccarino, Viola

    2013-01-01

    Objective Epigenetic mechanisms have been implicated in the pathogenesis of psychiatric disorders. The serotonin transporter gene (SLC6A4) is a key candidate gene for depression. We examined the association between SLC6A4 promoter methylation variation and depressive symptoms using 84 monozygotic twin pairs. Methods DNA methylation level in the SLC6A4 promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The number of current depressive symptoms was assessed using the Beck Depressive Inventory II (BDI-II). The association between methylation variation and depressive symptoms was examined using matched twin-pair analyses, adjusting for body mass index, smoking, physical activity, and alcohol consumption. Multiple testing was controlled by adjusted false discovery rate (q value). Results Intrapair difference in DNA methylation variation at 10 of the 20 studied CpG sites is significantly correlated with intrapair difference in BDI scores. Linear regression using intrapair differences demonstrates that intrapair difference in BDI score was significantly associated with intrapair differences in DNA methylation variation after adjusting for potential confounders and correction for multiple testing. On average, a 10% increase in the difference in mean DNA methylation level was associated with 4.4 increase in the difference in BDI score (95% confidence interval = 0.9–7.9, p = .01). Conclusions This study provides evidence that variation in methylation level within the promoter region of the serotonin transporter gene is associated with variation in depressive symptoms in a large sample of monozygotic twin pairs. This relationship is not confounded by genetic and shared environment. The 5-HTTLPR genotype also does not modulate this association. PMID:23766378

  5. Association between promoter methylation of serotonin transporter gene and depressive symptoms: a monozygotic twin study.

    PubMed

    Zhao, Jinying; Goldberg, Jack; Bremner, James D; Vaccarino, Viola

    2013-01-01

    Epigenetic mechanisms have been implicated in the pathogenesis of psychiatric disorders. The serotonin transporter gene (SLC6A4) is a key candidate gene for depression. We examined the association between SLC6A4 promoter methylation variation and depressive symptoms using 84 monozygotic twin pairs. DNA methylation level in the SLC6A4 promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The number of current depressive symptoms was assessed using the Beck Depressive Inventory II (BDI-II). The association between methylation variation and depressive symptoms was examined using matched twin-pair analyses, adjusting for body mass index, smoking, physical activity, and alcohol consumption. Multiple testing was controlled by adjusted false discovery rate (q value). Intrapair difference in DNA methylation variation at 10 of the 20 studied CpG sites is significantly correlated with intrapair difference in BDI scores. Linear regression using intrapair differences demonstrates that intrapair difference in BDI score was significantly associated with intrapair differences in DNA methylation variation after adjusting for potential confounders and correction for multiple testing. On average, a 10% increase in the difference in mean DNA methylation level was associated with 4.4 increase in the difference in BDI score (95% confidence interval = 0.9-7.9, p = .01). This study provides evidence that variation in methylation level within the promoter region of the serotonin transporter gene is associated with variation in depressive symptoms in a large sample of monozygotic twin pairs. This relationship is not confounded by genetic and shared environment. The 5-HTTLPR genotype also does not modulate this association.

  6. First Language Attrition in the Speech of Dutch-English Bilinguals: The Case of Monozygotic Twin Sisters

    ERIC Educational Resources Information Center

    Mayr, Robert; Price, Sacha; Mennen, Ineke

    2012-01-01

    Recent years have seen a proliferation of research on attrition in L1 speech (de Leeuw, Mennen & Scobbie, in press; de Leeuw, Schmid & Mennen, 2010; Dmitrieva, Jongman & Sereno, 2010; Mennen, 2004). Adding to this line of inquiry, the present study investigates the speech of a 62-year-old bilingual monozygotic twin who emigrated to an L2-speaking…

  7. First Language Attrition in the Speech of Dutch-English Bilinguals: The Case of Monozygotic Twin Sisters

    ERIC Educational Resources Information Center

    Mayr, Robert; Price, Sacha; Mennen, Ineke

    2012-01-01

    Recent years have seen a proliferation of research on attrition in L1 speech (de Leeuw, Mennen & Scobbie, in press; de Leeuw, Schmid & Mennen, 2010; Dmitrieva, Jongman & Sereno, 2010; Mennen, 2004). Adding to this line of inquiry, the present study investigates the speech of a 62-year-old bilingual monozygotic twin who emigrated to an L2-speaking…

  8. Nonshared Environmental Influences on Teacher-Reported Behaviour Problems: Monozygotic Twin Differences in Perceptions of the Classroom

    ERIC Educational Resources Information Center

    Oliver, Bonamy R.; Pike, Alison; Plomin, Robert

    2008-01-01

    Background: The identification of specific nonshared environments responsible for the variance in behaviour problems is a key challenge. Methods: Nonshared environmental influences on teacher-reported behaviour problems were explored independently of genetics using the monozygotic (MZ) twin differences design. Six aspects of classroom environment…

  9. Anxiety-related experience-dependent white matter structural differences in adolescence: A monozygotic twin difference approach.

    PubMed

    Adluru, Nagesh; Luo, Zhan; Van Hulle, Carol A; Schoen, Andrew J; Davidson, Richard J; Alexander, Andrew L; Goldsmith, H Hill

    2017-08-18

    Anxiety is linked to deficits in structural and functional connectivity between limbic structures and pre-frontal cortices. We employed a monozygotic (MZ) twin difference design to examine the relationship between structural characteristics of the uncinate fasciculus (UF) measured by Diffusion Tensor Imaging (DTI) and anxiety symptoms in a sample of N = 100 monozygotic (genetically identical), adolescent twins. The MZ difference design allowed us focus on environmental factors that vary within twin pairs while controlling for genetic and environmental factors shared by twin pairs. Twins aged 13-18 years reported on symptoms of generalized anxiety and social phobia prior to participating in a neuroimaging visit. Regions of interest from the JHU ICBM atlas, including uncinate fasciculus and sagittal stratum as a control tract, were registered to the study template. We incorporated multiple diffusion tensor measures to characterize the white matter differences. Within twin pairs, the more anxious twin exhibited decreased fractional anisotropy (t = -2.22, p = 0.032) and axial diffusivity (t = -2.38, p = 0.022) in the left UF compared to the less anxious twin, controlling for age and gender. This study demonstrated the feasibility and advantages of adopting the MZ twin design for DTI measures in neuroimaging research.

  10. Configural Cue Performance in Identical Twins Discordant for Posttraumatic Stress Disorder: Theoretical Implications for the Role of Hippocampal Function

    PubMed Central

    Gilbertson, Mark W.; Williston, Stephanie K.; Paulus, Lynn A.; Lasko, Natasha B.; Gurvits, Tamara V.; Shenton, Martha E.; Pitman, Roger K.; Orr, Scott P.

    2009-01-01

    Background A significant subgroup of individuals with posttraumatic stress disorder (PTSD) exhibits chronic, unremitting symptomatology that has also been associated with smaller hippocampal volume. The hippocampus plays a significant role in configural processing of contextual cues that facilitates context-appropriate extinction of conditioned fear. We test the hypothesis that hippocampus-based configural processing deficits are a pre-existing vulnerability factor for unremitting forms of PTSD. Methods Participants included male monozygotic twin pairs who were discordant for combat trauma. In 18 twin pairs the combat-exposed brother developed unremitting PTSD, whereas in 23 pairs the combat-exposed brother never developed PTSD. Participants were compared in the capacity to solve allocentric spatial processing tasks, and this performance was examined for its relationship to the severity of PTSD symptomatology and hippocampal volume. Results Although not completely differentiated from overall IQ, PTSD combat veterans demonstrated significantly impaired performance in configural processing relative to non-PTSD combat veterans. Despite having neither combat-exposure nor PTSD, the unexposed co-twins of combat veterans with PTSD displayed the same decrements as their brothers. Deficits were significantly related to PTSD severity and hippocampal volume. Conclusions The current study provides the first evidence that the relevance of the hippocampus in PTSD might be related to pre-existing configural cue processing deficits that predispose individuals to develop unremitting forms of the disorder. PMID:17509537

  11. Epigenetic Variation in Monozygotic Twins: A Genome-Wide Analysis of DNA Methylation in Buccal Cells

    PubMed Central

    van Dongen, Jenny; Ehli, Erik A.; Slieker, Roderick C.; Bartels, Meike; Weber, Zachary M.; Davies, Gareth E.; Slagboom, P. Eline; Heijmans, Bastiaan T.; Boomsma, Dorret I.

    2014-01-01

    DNA methylation is one of the most extensively studied epigenetic marks in humans. Yet, it is largely unknown what causes variation in DNA methylation between individuals. The comparison of DNA methylation profiles of monozygotic (MZ) twins offers a unique experimental design to examine the extent to which such variation is related to individual-specific environmental influences and stochastic events or to familial factors (DNA sequence and shared environment). We measured genome-wide DNA methylation in buccal samples from ten MZ pairs (age 8–19) using the Illumina 450k array and examined twin correlations for methylation level at 420,921 CpGs after QC. After selecting CpGs showing the most variation in the methylation level between subjects, the mean genome-wide correlation (rho) was 0.54. The correlation was higher, on average, for CpGs within CpG islands (CGIs), compared to CGI shores, shelves and non-CGI regions, particularly at hypomethylated CpGs. This finding suggests that individual-specific environmental and stochastic influences account for more variation in DNA methylation in CpG-poor regions. Our findings also indicate that it is worthwhile to examine heritable and shared environmental influences on buccal DNA methylation in larger studies that also include dizygotic twins. PMID:24802513

  12. Risk Factors and Relationship of Cutaneous and Uveal Melanocytic Lesions in Monozygotic and Dizygotic Twin Pairs

    PubMed Central

    Varga, Anita; Szabó, Hajnalka; Orvos, Hajnalka; Kemény, Lajos; Oláh, Judit

    2016-01-01

    Background The similar genetic background of a pair of twins, and the similar environmental impacts to which they are exposed allow an exact and objective investigation of various constitutional and environmental factors in naevus development. As far as we are aware, this is the first published survey that simultaneously examines cutaneous and ocular pigmented lesions in an appreciable sample of identical and non-identical twins. Methods 172 pairs of twins of Caucasian origin were included in this study. A whole-body skin examination and a detailed ophthalmological examination were performed to determine the density of melanocytic lesions. A standardized questionnaire was used to assess the data relating to constitutional, sun exposure and other variables. Results A notably high proportion of the subjects (36.78%) manifested one or more clinically atypical melanocytic naevi (CAMNs), and approximately one-third (31.4%) of them at least one benign uveal pigmented lesion (BUPL). The incidence of iris freckles (IFs), iris naevi (INs) and choroidal naevi (CHNs) proved to be 25.35%, 5.98% and 3.52%, respectively. The interclass correlation coefficients for common melanocytic naevi (CMNs), CAMNs, and INs were 0.77, 0.76 and 0.86 in monozygotic twins, as compared with 0.5, 0.27 and 0.25 in dizygotic twin pairs, respectively. A statistically significant correlation was found between the prevalence of CAMNs and that of INs. Conclusions This significant correlation suggests the existence of a subgroup of Caucasian people with an increased susceptibility to both cutaneous and ocular naevus formation. There is accumulating evidence that, besides the presence of cutaneous atypical naevi, INs can serve as a marker of a predisposed phenotype at risk of uveal melanoma. The correlation between cutaneous and ocular pigmented lesions underlines the need for the adequate ophthalmological screening of subjects with CAMNs and INs. PMID:27486750

  13. Nongenetic factors influence severity of episodic ataxia type 1 in monozygotic twins(Video)

    PubMed Central

    Graves, T.D.; Rajakulendran, S.; Zuberi, S.M.; Morris, H.R.; Schorge, S.; Hanna, M.G.; Kullmann, D.M.

    2010-01-01

    Objective: Episodic ataxia type 1 (EA1) is a monogenic channelopathy caused by mutations of the potassium channel gene KCNA1. Affected individuals carrying the same mutation can exhibit considerable variability in the severity of ataxia, neuromyotonia, and other associated features. We investigated the phenotypic heterogeneity of EA1 in 2 sets of identical twins to determine the contribution of environmental factors to disease severity. One of the mutations was also found in a distantly related family, providing evidence of the influence of genetic background on the EA1 phenotype. Methods: We evaluated 3 families with an EA1 phenotype, 2 of which included monozygotic twins. We sequenced the KCNA1 gene and studied the biophysical consequences of the mutations in HEK cells. Results: We identified a new KCNA1 mutation in each pair of twins. Both pairs reported striking differences in the clinical severity of symptoms. The F414S mutation identified in one set of twins also occurred in a distantly related family in which seizures complicated the EA1 phenotype. The other twins had an R307C mutation, the first EA1 mutation to affect an arginine residue in the voltage-sensor domain. Both mutants when expressed exerted a dominant-negative effect on wild-type channels. Conclusion: These results broaden the range of KCNA1 mutations and reveal an unexpectedly large contribution of nongenetic factors to phenotypic variability in EA1. The occurrence of epilepsy in 1 of 2 families with the F414S mutation suggests an interplay of KCNA1 with other genetic factors. GLOSSARY EA1 = episodic ataxia type 1. PMID:20660867

  14. Determinants of paraspinal muscle cross-sectional area in male monozygotic twins.

    PubMed

    Gibbons, L E; Videman, T; Battié, M C; Kaprio, J

    1998-06-01

    The purpose of this study was to investigate the general magnitude and relative contributions of anthropometric, lifestyle, and medical history factors and familial aggregation (combined effects of genes and early environment) as determinants of paraspinal muscle cross-sectional area (CSA). The subjects were 65 pair of male monozygotic twins aged 35 to 65 years (mean = 49, SD = 8). Study methods included magnetic resonance imaging, percentage body fat determination, and a detailed interview. Most of the anthropometric factors were associated with the CSAs. Familial aggregation was the strongest determinant, however, explaining 66% to 73% of the variance in the outcomes beyond what age alone predicted. Levels of occupational, sport, and leisure-time physical activities reported by the subjects had negligible effects. The CSAs of the paraspinal muscles were influenced more by some combination of genes and early environmental factors than by anthropometric factors and lifestyle choices in adulthood.

  15. Mechanisms of twinning. I. Effect of environmental diversity on genetic expression in monozygotic multifetal pregnancies.

    PubMed

    Steinman, G

    2001-05-01

    To examine, using fingerprint homology, the interaction of genetic and environmental factors in arriving at the final phenotypic expression in uniovular triplets, quadruplets and quintuplets. The fingerprints of several multifetal sets were collected and matched. A total of 250 fingers were printed. A comparison based on the classic dactylographic patterns was made. Zygosity of each set was known from placental chorionicity studies, as well as blood typing and physical similarities. As the monozygotic set size increased, the ipsilateral print concordance diminished. At one extreme, with twins there is 88% homology; at the other end, with quintuplets the correspondence is 71%. The overall trend of these results paralleled increasing intrauterine environmental diversity and tended to support the volar pad pressure hypothesis of prenatal fingerprint development.

  16. Presumed monozygotic twins develop following transfer of an in vitro-produced equine embryo

    PubMed Central

    ROBERTS, Melissa Ann; LONDON, Kelly; CAMPOS-CHILLÓN, Lino Fernando; ALTERMATT, Joy Lynn

    2015-01-01

    ABSTRACT An equine embryo produced by intracytoplasmic sperm injection (ICSI) was trans-cervically transferred to a recipient mare and pregnancy was confirmed via ultrasound examination on days 11, 12 and 15. On days 20 and 22, a single embryonic proper with a heartbeat was observed. On day 29, two embryos proper appeared during ultrasound examination, each possessing a heartbeat. Subsequent examinations on days 35 and 39 revealed continued viability and development of both embryos proper. On day 49, demise of both fetuses was present. Although no DNA analysis or post-partum examinations were performed, it is presumed that the fetuses were monozygotic twins based on membrane classification by ultrasound imaging as well as development occurring after the transfer of a single in vitro-produced embryo. PMID:26435682

  17. [An attempt to determine the variability of thermal phenotypes in monozygotic twins].

    PubMed

    Kempińska, Agnieszka

    2006-01-01

    All solid bodies emit electromagnetic radiation at temperatures above absolute zero. The radiation spectrum depends, among other factors, on temperature. Thermovision is a method in which an infrared camera is used to record infrared radiation (IR) emitted by human skin. It is widely used in medicine, for instance to diagnose inflammation of the skin, some types of neoplasms, collagenosis, and peripheral vascular disease. The literature, however, lacks reports on the variability in thermal emission by the skin of healthy individuals or twins. Interpretation of the results is based on simply analysing the subject individually or comparing symmetrical body sides. Hence, there is a need to study thermal emission using monozygotic twins as a model. An attempt was made in the present study to determine the variability of thermal phenotypes of faces, backs, and hands in monozygotic twins (MZ), compare thermal emission in MZ and dizygotic twins (DZ), and establish the thermal norm. Using the ThermaCAM SC500 camera, 44 pairs of MZ and 15 pairs of DZ were studied. Descriptive statistics are given as means, standard deviation, and max. and min. values. The following tests were used for statistical analysis: Shapiro-Wilk's, Snedecor's, Brown-Forsythe's, Mann-Whitney's U, and Kruskal-Wallis. Data from the digital image analyser were tested using the cluster analysis methods, especially the k-means method. The following conclusions were drawn: 1. Full genetic identity does not produce a thermal consistency within the range of isotherms tested, whether in relation to their values or distribution. 2. Differences in the thermal image may have their source in ontogenetic development during intra-uterine and postnatal stages and may be related to individual differences in adaptation to the environment. 3. These results are potentially useful to compare physiological states between individuals and to differentiate pathological changes. 4. The results of this study do not allow for

  18. Growth hormone deficiency in monozygotic twins with autosomal dominant pseudohypoparathyroidism type Ib.

    PubMed

    Sano, Shinichiro; Iwata, Hiromi; Matsubara, Keiko; Fukami, Maki; Kagami, Masayo; Ogata, Tsutomu

    2015-01-01

    Pseudohypoparathyroidism (PHP) is associated with compromised signal transductions via PTH receptor (PTH-R) and other G-protein-coupled receptors including GHRH-R. To date, while GH deficiency (GHD) has been reported in multiple patients with PHP-Ia caused by mutations on the maternally expressed GNAS coding regions and in two patients with sporadic form of PHP-Ib accompanied by broad methylation defects of maternally derived GNAS differentially methylated regions (DMRs), it has not been identified in a patient with an autosomal dominant form of PHP-Ib (AD-PHP-Ib) accompanied by an STX16 microdeletion and an isolated loss of methylation (LOM) at exon A/B-DMR. We studied 5 4/12-year-old monozygotic twins with short stature (both -3.4 SD) and GHD (peak GH values, <6.0 μg/L after arginine and clonidine stimulations). Molecular studies revealed maternally derived STX16 microdeletions and isolated LOMs at exon A/B-DMR in the twins, confirming the diagnosis of AD-PHP-Ib. GNAS mutation was not identified, and neither mutation nor copy number variation was detected in GH1, POU1F1, PROP1, GHRHR, LHX3, LHX4, and HESX1 in the twins. The results, in conjunction with the previous finding that GNAS shows maternal expression in the pituitary, suggest that GHD of the twins is primarily ascribed to compromised GHRH-R signaling caused by AD-PTH-Ib. Thus, resistance to multiple hormones including GHRH should be considered in AD-PHP-Ib.

  19. Promoter methylation of serotonin transporter gene is associated with obesity measures: a monozygotic twin study.

    PubMed

    Zhao, J; Goldberg, J; Vaccarino, V

    2013-01-01

    Epigenetic mechanisms are increasingly being recognized as an important factor for obesity. The serotonin transporter gene (SLC6A4) has a critical role in regulating food intake, body weight and energy balance. This study examines the potential association between SLC6A4 promoter methylation and obesity measures in a monozygotic (MZ) twin sample. We studied 84 MZ twin pairs drawn from the Vietnam Era Twin Registry. Obesity measures include body mass index (BMI), body weight, waist circumference (WC) and waist-hip ratio (WHR). The SLC6A4 promoter methylation profile in peripheral blood leukocytes was quantified by bisulfite pyrosequencing. The association between methylation variation and obesity parameters was examined by mixed-model regression and matched pair analysis, adjusting for age, smoking, alcohol consumption, physical activity and total daily energy intake. Multiple testing was controlled using the adjusted false discovery rate (q-value). Mean methylation level was positively correlated with BMI (r=0.29; P=0.0002), body weight (r=0.31; P<0.0001) and WC (r=0.20; P=0.009), but not WHR. Intra-pair differences in mean methylation were significantly correlated with intra-pair differences in BMI, body weight and WC, but not WHR. On average, a 1% increase in mean methylation was associated with 0.33 kg m(-2) increase in BMI (95% CI: 0.02-0.65; P=0.03), 1.16 kg increase in body weight (95% CI, 0.16-2.16; P=0.02) and 0.78 cm increase in WC (95% CI, 0.05-1.50; P=0.03) after controlling for potential confounders. SLC6A4 promoter hypermethylation is significantly associated with an increased prevalence of obesity within a MZ twin study.

  20. Monozygotic Twin Pregnancy Associated with In Vitro Fertilization: Report and Revision of Three Cases Presented in a Clinic at 10,925 Feet Above Sea Level.

    PubMed

    Tominaga, Luis Vargas; Cáceres, Ricardo Pella; Lechuga, Alberto Vargas; Durán, Livia Bartolo; Vargas, Mariela Serrano

    2015-08-01

    3 cases of monozygotic twin pregnancies associated with IVF presented at Centro de Fertilidad y Ginecología del Sur. In this study, we describe the cases and review the literature, noting possible related factors.

  1. Leptin is differentially expressed and epigenetically regulated across monochorionic twin placenta with discordant fetal growth.

    PubMed

    Schrey, S; Kingdom, J; Baczyk, D; Fitzgerald, B; Keating, S; Ryan, G; Drewlo, S

    2013-11-01

    Severely growth-discordant monochorionic (MC) twins offer a unique opportunity to study fetal and placental growth based on a similar genetic background and maternal host environment where the healthy twin serves as an ideal control. Differences in development of MC twins may therefore be due to differential epigenetic regulation of genes involved in placental development and function. Growth-discordant twins are known for abnormal angio-architecture in the placenta of the smaller twin. Since the reasons for this phenotype are mostly unknown this study was aimed to investigate the expression and regulation of genes known to be involved in angiogenesis. We studied 10 severely growth-discordant MC twin placentas (birthweight difference ≥20%) without twin-twin-transfusion syndrome and 5 growth-concordant MC twin placentas. Growth-discordant twin placentas were phenotyped by histology. Placental mRNA expression of 88 angiogenesis-related genes was measured by PCR array. ELISA assay and immunohistochemistry were used to confirm PCR results. EpiTYPTER for DNA methylation was used to determine if methylation ratios were responsible for differential gene expression. The PCR array analysis showed significant mRNA up-regulation in the placental share of the smaller twin for several genes. These included leptin (24.6-fold, P = 0.017), fms-like tyrosine kinase 1 (Flt1, 2.4-fold, P = 0.016) and Endoglin (Eng, 1.86-fold, P = 0.078). None of the other 84 angiogenesis-related genes showed significant differences. ELISA confirmed significantly increased leptin protein expression (49.22 versus 11.03 pg/ml, P = 0.049) in the smaller twin of the discordant growth cohort. Leptin expression in smaller twins' placentas was associated with elevated DNA methylation of the leptin promotor region suggesting the inhibition of binding of a transcriptional activator/inhibitor in that region. We attempted to overcome the limitation of sample size by careful patient selection. We minimized any

  2. The variability of ovum pick-up response and in vitro embryo production from monozygotic twin cows.

    PubMed

    Machado, Sergio Abreu; Reichenbach, Horst-Dieter; Weppert, Myriam; Wolf, Eckhard; Gonçalves, Paulo Bayard Dias

    2006-02-01

    Oocytes were recovered by ovum pick up (OPU) from nine pairs of monozygotic twin German Simmental cows. The hypothesis was that there is less variability between identical twins versus among non-related individuals in the variation in the recovery of oocytes by OPU and in the efficiency of in vitro embryo production. Estrous cycles were synchronized with two doses of cloprostenol, 11 days apart. Beginning 3-4 days after synchronized estrus, OPU was done twice weekly (every 3 or 4 days; total of 11 sessions). The influence of repeated OPU on estrous cyclicity was established by estrus detection, plasma progesterone concentrations, and ovarian ultrasonography. There were no differences among days of collection for the number and quality of cumulus oocyte-complexes (COCs), and rates of cleavage and blastocyst formation. A total of 1,661 COCs, including 657 (39.6%) good-quality COCs, were recovered. From 1,457 (87.7%) cultured COCs, 827 zygotes cleaved and 314 blastocysts were produced on Day 7. The total number of COCs and the blastocyst rates varied among pairs of monozygotic twins; within pairs, only slight differences were observed. In conclusion, recovery of COCs and production of embryos had substantially less variation within pairs of monozygotic twins than among non-related cattle.

  3. Magnetic resonance imaging of cerebral central sulci: a study of monozygotic twins.

    PubMed

    Bonan, I; Argenti, A M; Duyme, M; Hasboun, D; Dorion, A; Marsault, C; Zouaoui, A

    1998-01-01

    The cerebral central sulci, seat of the sensorimotor cortex, vary anatomically in form, length and depth among individuals and present a left/right asymmetry. The purpose of this work was to measure central sulcus's lengths, at the surface and in-depth, in each hemisphere of monozygotic twins in order to evaluate the influence of environmental factors on the morphometry and asymmetry of this structure. A measurement technique on MR images of the brains using 3 D software was developed. Two operators applied this technique to measure central sulcus lengths at the surface of the brain and in-depth in each hemisphere. Besides the fact that the technique developed gave high Intraclass Correlation Coefficients (ICC) for the surface lengths (mean value 0.94), and slightly less high for the in-depth length (mean value 0.87), we found a weak (from 0.57 to 0.73 for raw data) but significant ICC between homologous sulci in pairs of twins. In addition, the ICC for asymmetry indices were not significant. Hence, if central sulcus morphometry is in part genetically influenced, these results show that nongenetic factors are nonetheless important in their development.

  4. Heritability of bone density: regional and gender differences in monozygotic twins.

    PubMed

    Tse, Kevin Y; Macias, Brandon R; Meyer, R Scott; Hargens, Alan R

    2009-02-01

    Bone mineral density (BMD) is a measure of a person's skeletal mineral content, and assessing BMD by dual x-ray absorptiometry (DEXA) can help to diagnose diseases of low bone density. In this study, we determine the heritability of BMD in male and female monozygotic twin subjects using DEXA in 13 specific anatomical regions. In an attempt to quantify the genetic contribution of gender and skeletal region to BMD heritability, we scanned 14 pairs of identical twins using DEXA and calculated the broad-sense heritability coefficient (H(2)) in each of the 13 different body regions. The region of the body that was most heritable for both genders was the head (H(2) >or= 95%). When males were compared to females, H(2) values for male hip (H(2) = 87%) and lower extremities (H(2) = 90%) were higher than those in females (H(2) = 49% and 56%, respectively). Conversely, H(2) value for the female pelvis (H(2) = 68%) was higher than that for males (H(2) = 26%). These data show that different regions of the skeleton exhibit different degrees of heritability, and that the variation depends on gender.

  5. Cedar pollen aggravates atopic dermatitis in childhood monozygotic twin patients with allergic rhino conjunctivitis.

    PubMed

    Murakami, Yukako; Matsui, Saki; Kijima, Akiko; Kitaba, Shun; Murota, Hiroyuki; Katayama, Ichiro

    2011-09-01

    We report a case of 7-year-old monozygotic twin patients with atopic dermatitis. The HLA haplotypes were HLA A2, A11, B27, B61, DR1, and DR4. Both serum IgE levels and cedar pollen radioallergosorbent test (RAST) scores were high in the twins (elder/younger sister: IgE: 5170/3980 IU/ml and Japansese cedar pollen: >100/64.0) in contrast to low mite and food RAST scores (Dermatophagoides Pterygonium; 0.59/0.4 and egg white 9.24/4.6). The patients showed positive immediate (20 min in both sisters) and delayed (24 hours in elder sister, 24, 48, 72 hours in younger sister) reactions to a scratch test with Japanese cedar pollen. Skin lesions on the face were aggravated and extended to the trunk and extremities during the Japanese cedar pollen season and gradually subsided in summer. Oral provocation with egg white or cow milk showed no exacerbations, and topical corticosteroid did not improve the eczema. In contrast, successful protection from severe scratching behaviors was achieved by use of topical anti-allergic eye drops and wearing nightgowns made by the mother.

  6. Stability of Gut Enterotypes in Korean Monozygotic Twins and Their Association with Biomarkers and Diet

    PubMed Central

    Lim, Mi Young; Rho, Mina; Song, Yun-Mi; Lee, Kayoung; Sung, Joohon; Ko, GwangPyo

    2014-01-01

    Studies on the human gut microbiota have suggested that human individuals could be categorized into enterotypes based on the compositions of their gut microbial communities. Here, we report that the gut microbiota of healthy Koreans are clustered into two enterotypes, dominated by either Bacteroides (enterotype 1) or Prevotella (enterotype 2). More than 72% of the paired fecal samples from monozygotic twin pairs were assigned to the same enterotype. Our longitudinal analysis of these twins indicated that more than 80% of the individuals belonged to the same enterotype after about a 2-year interval. Microbial functions based on KEGG pathways were also divided into two clusters. For enterotype 2, 100% of the samples belonged to the same functional cluster, while for enterotype 1, approximately half of the samples belonged to each functional cluster. Enterotype 2 was significantly associated with long-term dietary habits that were high in dietary fiber, various vitamins, and minerals. Among anthropometrical and biochemical traits, the level of serum uric acid was associated with enterotype. These results suggest that host genetics as well as host properties such as long-term dietary patterns and a particular clinical biomarker could be important contributors to the enterotype of an individual. PMID:25482875

  7. Monozygotic twins with infantile neuroaxonal dystrophy: A case report and literature review

    PubMed Central

    Li, Haifeng; Zou, Yan; Bao, Xinhua; Wang, Hui; Wang, Jiangping; Jin, Huiying; Che, Yuping; Tang, Xiaoyan

    2016-01-01

    Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disease with early onset. PLA2G6 gene mutations have been identified in the majority individuals with INAD. In future, molecular diagnosis of INAD will replace the invasive biopsies used previously. In the present report, monozygotic male twins with INAD were referred The Children's Hospital (Zhejiang University School of Medicine, Zhejiang, China) at fifteen months old for delayed development. The older brother was found to have developmental stagnation when he was 6 months old. The patient could not stand securely without support, and had poor eye tracking and listening ability. Magnetic resonance imaging (MRI) of the patient's brain revealed cerebellar atrophy and electromyography identified signs of peripheral neuropathy. The younger brother displayed similar clinical features and findings. Two different phospholipase A2 group VI (PLA2G6; 22q13.1) gene mutations were detected in the twins by DNA sequencing. The results of the present study indicate that neurogenetic disease should be considered when child patients present with idiopathic developmental stagnation, particularly when similar cases have appeared in the same family. In addition, INAD should be considered as a possible diagnosis when the patient has developmental delay of the central and peripheral nerves. In the future, molecular genetic testing will be the primary method of INAD diagnosis, enabling better prevention of this genetic disease. PMID:27882168

  8. Monozygotic twins with infantile neuroaxonal dystrophy: A case report and literature review.

    PubMed

    Li, Haifeng; Zou, Yan; Bao, Xinhua; Wang, Hui; Wang, Jiangping; Jin, Huiying; Che, Yuping; Tang, Xiaoyan

    2016-11-01

    Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disease with early onset. PLA2G6 gene mutations have been identified in the majority individuals with INAD. In future, molecular diagnosis of INAD will replace the invasive biopsies used previously. In the present report, monozygotic male twins with INAD were referred The Children's Hospital (Zhejiang University School of Medicine, Zhejiang, China) at fifteen months old for delayed development. The older brother was found to have developmental stagnation when he was 6 months old. The patient could not stand securely without support, and had poor eye tracking and listening ability. Magnetic resonance imaging (MRI) of the patient's brain revealed cerebellar atrophy and electromyography identified signs of peripheral neuropathy. The younger brother displayed similar clinical features and findings. Two different phospholipase A2 group VI (PLA2G6; 22q13.1) gene mutations were detected in the twins by DNA sequencing. The results of the present study indicate that neurogenetic disease should be considered when child patients present with idiopathic developmental stagnation, particularly when similar cases have appeared in the same family. In addition, INAD should be considered as a possible diagnosis when the patient has developmental delay of the central and peripheral nerves. In the future, molecular genetic testing will be the primary method of INAD diagnosis, enabling better prevention of this genetic disease.

  9. [Neonatal expression of beta-thalassemia trait associated with hereditary spherocytosis in two monozygotic twins].

    PubMed

    Ben Hamouda, H; Mahjoub, B; Soua, H; Laradi, S; Miled, A; Sfar, M T

    2017-02-01

    The beta-thalassemia trait is a heterozygous beta-thalassemia characterized by a partial deficiency of the synthesis of beta-globin chains of hemoglobin. It is usually asymptomatic and the diagnosis is often made on the occasion of the completion of a systematic blood count or a family survey. Clinical expression during the neonatal period is impossible and its association with hereditary spherocytosis is common. We report two monozygotic twins who, on the 3rd day of life, presented intense jaundice, unconjugated bilirubin associated with anemia, without hepatosplenomegaly. Laboratory tests found nonimmune hemolytic anemia with microcytosis and hypochromia justifying iterative blood transfusions. The etiological investigation found heterozygous beta-thalassemia associated with hereditary spherocytosis. The family investigation and molecular analysis objectified the beta-thalassemic mutation IVS1nt110 (G→A) in the heterozygous state in the twins, the father, the mother, and in one of the two brothers. With any nonimmune hemolytic anemia in newborns, the etiological investigation should be systematic for early diagnosis and to plan appropriate treatment.

  10. Korean Monozygotic Twins with Lethal Acantholytic Epidermolysis Bullosa Caused by Two Novel DSP Mutations.

    PubMed

    Kim, Se Jin; Ko, Jung Min; Shin, Seung Han; Kim, Ee-Kyung; Kim, Han-Suk; Lee, Kyung-A

    2017-03-01

    Desmoplakin is an essential cytoplasmic plaque protein in desmosomes, and it is the major linker between intercellular junctions in the skin and heart. The role of desmoplakin is anchoring transmembrane cadherins to cytoplasmic intermediate filaments. The desmoplakin gene (DSP) is located on chromosome 6, and six common allelic disorders are associated with this gene, including autosomal-dominant or -recessive disorders that affect the skin, heart, hair, and nails. In particular, lethal acantholytic epidermolysis bullosa (LAEB) is an autosomal recessively inherited and extremely rare genetic skin disorder, and only three molecularly confirmed families with LAEB have been reported previously. Generalized oozing erosion of the entire skin is the main clinical feature, which leads to excessive transcutaneous fluid loss and neonatal death. Histopathologically, this disorder is classified as a suprabasal subtype of epidermolysis bullosa simplex. In this study, we report for the first time in Korea on monozygotic twins with LAEB caused by two novel nonsense mutations in the DSP gene. Both of the twins exhibited severe and rapid progressive whole body skin erosion, and they died shortly after birth because of multiorgan failure followed by excessive fluid loss. © 2017 by the Association of Clinical Scientists, Inc.

  11. Adolescent Drinking and Motivated Decision-Making: A Cotwin-Control Investigation with Monozygotic Twins

    PubMed Central

    Malone, Stephen M.; Luciana, Monica; Wilson, Sylia; Sparks, Jordan C.; Hunt, Ruskin H.; Thomas, Kathleen M.; Iacono, William G.

    2014-01-01

    The present study used a monozygotic (MZ) cotwin-control (CTC) design to investigate associations between alcohol use and performance on the Iowa Gambling Task (IGT) in a sample of 96 adolescents (half female). The MZ CTC design is well suited to shed light on whether poor decision-making, as reflected on IGT performance, predisposes individuals to abuse substances or is a consequence of use. Participants completed structural MRI scans as well, from which we derived gray matter volumes for cortical and subcortical regions involved in IGT performance and reduced in adolescents with problematic alcohol use. Drinking was associated with poorer task performance and with reduced volume of the left lateral orbital-frontal cortex. CTC analyses indicated that the former was due to differences between members of twin pairs in alcohol use (suggesting a causal effect of alcohol), whereas the latter was due to factors shared by twins (consistent with a pre-existing vulnerability for use). Although these preliminary findings warrant replication, they suggest that normative levels of alcohol use may diminish the quality of adolescent decision-making and thus have potentially important public health implications. PMID:24676464

  12. MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample.

    PubMed

    Zhao, Jinying; Forsberg, Christopher W; Goldberg, Jack; Smith, Nicholas L; Vaccarino, Viola

    2012-11-02

    Atherosclerosis is a complex process involving both genetic and epigenetic factors. The monoamine oxidase A (MAOA) gene regulates the metabolism of key neurotransmitters and has been associated with cardiovascular risk factors. This study investigates whether MAOA promoter methylation is associated with atherosclerosis, and whether this association is confounded by familial factors in a monozygotic (MZ) twin sample. We studied 84 monozygotic (MZ) twin pairs drawn from the Vietnam Era Twin Registry. Carotid intima-media thickness (IMT) was measured by ultrasound. DNA methylation in the MAOA promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The association between DNA methylation and IMT was first examined by generalized estimating equation, followed by matched pair analyses to determine whether the association was confounded by familial factors. When twins were analyzed as individuals, increased methylation level was associated with decreased IMT at four of the seven studied CpG sites. However, this association substantially reduced in the matched pair analyses. Further adjustment for MAOA genotype also considerably attenuated this association. The association between MAOA promoter methylation and carotid IMT is largely explained by familial factors shared by the twins. Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment. Clarification of familial factors associated with DNA methylation and early atherosclerosis will provide important information to uncover clinical correlates of disease.

  13. MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample

    PubMed Central

    2012-01-01

    Background Atherosclerosis is a complex process involving both genetic and epigenetic factors. The monoamine oxidase A (MAOA) gene regulates the metabolism of key neurotransmitters and has been associated with cardiovascular risk factors. This study investigates whether MAOA promoter methylation is associated with atherosclerosis, and whether this association is confounded by familial factors in a monozygotic (MZ) twin sample. Methods We studied 84 monozygotic (MZ) twin pairs drawn from the Vietnam Era Twin Registry. Carotid intima-media thickness (IMT) was measured by ultrasound. DNA methylation in the MAOA promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The association between DNA methylation and IMT was first examined by generalized estimating equation, followed by matched pair analyses to determine whether the association was confounded by familial factors. Results When twins were analyzed as individuals, increased methylation level was associated with decreased IMT at four of the seven studied CpG sites. However, this association substantially reduced in the matched pair analyses. Further adjustment for MAOA genotype also considerably attenuated this association. Conclusions The association between MAOA promoter methylation and carotid IMT is largely explained by familial factors shared by the twins. Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment. Clarification of familial factors associated with DNA methylation and early atherosclerosis will provide important information to uncover clinical correlates of disease. PMID:23116433

  14. Discordance in Pena-Shokeir phenotype/fetal akinesia deformation sequence in a monoamniotic twin.

    PubMed

    Mayumi, Miyuki; Obata-Yasuoka, Mana; Ogura, Tsuyoshi; Hamada, Hiromi; Miyazono, Yayoi; Yoshikawa, Hiroyuki

    2013-01-01

    We here report the first case of discordant Pena-Shokeir phenotype observed in monoamniotic twins. A 34-year-old woman, pregnant with twins, was referred at 10 weeks' gestation because one of the twins had increased nuchal translucency. Serial ultrasonographic examinations suggested that twin A may have had several other abnormalities, including pleural effusion at 21 weeks' gestation, decreased movement and contracted limbs at 24 weeks, and fetal growth restriction at 26 weeks. No abnormalities were observed in twin B. At 34 weeks of gestation, the twins were delivered by cesarean section. There were cord entanglements, and although the resuscitation of twin A was attempted, it proved difficult due to lockjaw. Twin A died during the second hour of life, and autopsy findings were consistent with the diagnosis of Pena-Shokeir phenotype. We suggest that cord entanglement during early gestation is a possible cause for the occurrence of Pena-Shokeir phenotype through an anoxic-ischemic mechanism.

  15. Genome-wide methylation study on depression: differential methylation and variable methylation in monozygotic twins

    PubMed Central

    Córdova-Palomera, A; Fatjó-Vilas, M; Gastó, C; Navarro, V; Krebs, M-O; Fañanás, L

    2015-01-01

    Depressive disorders have been shown to be highly influenced by environmental pathogenic factors, some of which are believed to exert stress on human brain functioning via epigenetic modifications. Previous genome-wide methylomic studies on depression have suggested that, along with differential DNA methylation, affected co-twins of monozygotic (MZ) pairs have increased DNA methylation variability, probably in line with theories of epigenetic stochasticity. Nevertheless, the potential biological roots of this variability remain largely unexplored. The current study aimed to evaluate whether DNA methylation differences within MZ twin pairs were related to differences in their psychopathological status. Data from the Illumina Infinium HumanMethylation450 Beadchip was used to evaluate peripheral blood DNA methylation of 34 twins (17 MZ pairs). Two analytical strategies were used to identify (a) differentially methylated probes (DMPs) and (b) variably methylated probes (VMPs). Most DMPs were located in genes previously related to neuropsychiatric phenotypes. Remarkably, one of these DMPs (cg01122889) was located in the WDR26 gene, the DNA sequence of which has been implicated in major depressive disorder from genome-wide association studies. Expression of WDR26 has also been proposed as a biomarker of depression in human blood. Complementarily, VMPs were located in genes such as CACNA1C, IGF2 and the p38 MAP kinase MAPK11, showing enrichment for biological processes such as glucocorticoid signaling. These results expand on previous research to indicate that both differential methylation and differential variability have a role in the etiology and clinical manifestation of depression, and provide clues on specific genomic loci of potential interest in the epigenetics of depression. PMID:25918994

  16. Differential parenting and risk for psychopathology: a monozygotic twin difference approach.

    PubMed

    Long, E C; Aggen, S H; Gardner, C; Kendler, K S

    2015-10-01

    Consistent and non-specific associations have been found between parenting style and major depression, anxiety disorders, and externalizing behavior. Although often considered part of twins' shared environment, parenting can also be conceptualized as non-shared environment. Non-shared environmental influences have important effects on development but are difficult to test and sort out because of the possible confounding effects of gene-environment interactions and evocative gene-environment correlations. The monozygotic (MZ) differences approach is one way to analytically investigate non-shared environment. The aim of the present study is to use the MZ differences approach to investigate the relationship between differential parenting among 1303 twin pairs (mean age 36.69 ± 8.56) and differences in total symptom counts of major depression (MD), generalized anxiety disorder (GAD), conduct disorder (CD), and anti-social behavior (ASB) during adulthood. Although effect sizes tended to be small, a number of results were significantly different from zero. Perceived differences in parental coldness was positively associated with internalizing disorders. Differences in protectiveness were negatively associated with MD, GAD, and ASB. Differences in authoritarianism were positively associated with MD and CD, but negatively associated with ASB. Perceived differences in parenting style are associated with differences in MD, GAD, CD, and ASB outcomes in a sample of MZ twins. Despite the lack of a basis for making causal inferences about parenting style and psychopathology, these results are suggestive of such a relationship and show that non-shared environmental influence of parenting does in some cases significantly predict adult psychopathology.

  17. Promoter methylation of glucocorticoid receptor gene is associated with subclinical atherosclerosis: A monozygotic twin study.

    PubMed

    Zhao, Jinying; An, Qiang; Goldberg, Jack; Quyyumi, Arshed A; Vaccarino, Viola

    2015-09-01

    Endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is a marker of early atherosclerosis. Glucocorticoid receptor gene (NR3C1) regulates many biological processes, including stress response, behavioral, cardiometabolic and immunologic functions. Genetic variants in NR3C1 have been associated with atherosclerosis and related risk factors. This study investigated the association of NR3C1 promoter methylation with FMD, independent of genetic and family-level environmental factors. We studied 84 middle-aged, male-male monozygotic twin pairs recruited from the Vietnam Era Twin Registry. Brachial artery FMD was measured by ultrasound. DNA methylation levels at 22 CpG residues in the NR3C1 exon 1F promoter region were quantified by bisulfite pyrosequencing in genomic DNA isolated from peripheral blood leukocytes. Co-twin control analyses were conducted to examine the association of methylation variation with FMD, adjusting for smoking, physical activity, body mass index, lipids, blood pressure, fasting glucose, and depressive symptoms. Multiple testing was corrected using the false discovery rate. Mean methylation level across the 22 studied CpG sites was 2.02%. Methylation alterations at 12 out of the 22 CpG residues were significantly associated with FMD. On average, a 1% increase in the intra-pair difference in mean DNA methylation was associated with 2.83% increase in the intra-pair difference in FMD (95% CI: 1.46-4.20; P < 0.0001) after adjusting for risk factors and multiple testing. Methylation variation in NR3C1 exon 1F promoter significantly influences subclinical atherosclerosis, independent of genetic, early family environmental and other risk factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Population based study of prevalence of islet cell autoantibodies in monozygotic and dizygotic Danish twin pairs with insulin dependent diabetes mellitus.

    PubMed Central

    Petersen, J. S.; Kyvik, K. O.; Bingley, P. J.; Gale, E. A.; Green, A.; Dyrberg, T.; Beck-Nielsen, H.

    1997-01-01

    OBJECTIVE: To study the comparative importance of environment and genes in the development of islet cell autoimmunity associated with insulin dependent diabetes mellitus. DESIGN: Population based study of diabetic twins. SETTING: Danish population. SUBJECTS: 18 monozygotic and 36 dizygotic twin pairs with one or both partners having insulin dependent diabetes. MAIN OUTCOME MEASURES: Presence of islet cell antibodies, insulin autoantibodies, and autoantibodies to glutamic acid decarboxylase (GAD65) in serum samples from twin pairs 10 years (range 0-30 years) and 9.5 years (2-30 years) after onset of disease. RESULTS: In those with diabetes the prevalence of islet cell antibodies, insulin autoantibodies, and autoantibodies to glutamic acid decarboxylase in the 26 monozygotic twins was 38%, 85%, and 92%, respectively, and in the dizygotic twins was 57%, 70%, and 57%, respectively. In those without diabetes the proportions were 20%, 50%, and 40% in the 10 monozygotic twins and 26%, 49%, and 40% in the 35 dizygotic twins. CONCLUSION: There is no difference between the prevalence of islet cell autoantibodies in dizygotic and monozygotic twins without diabetes, suggesting that islet cell autoimmunity is environmentally rather than genetically determined. Furthermore, the prevalence of islet cell antibodies was higher in the non-diabetic twins than in other first degree relatives of patients with insulin dependent diabetes. This implies that the prenatal or early postnatal period during which twins are exposed to the same environment, in contrast with that experienced by first degree relatives, is of aetiological importance. PMID:9169400

  19. A study of pathophysiological factors associated with gastro-esophageal reflux disease in twins discordant for gastro-esophageal reflux symptoms.

    PubMed

    Iovino, P; Mohammed, I; Anggiansah, A; Anggiansah, R; Cherkas, L F; Spector, T D; Trudgill, N J

    2013-08-01

    Differences in lower esophageal sphincter (LES) and peristaltic function and in transient LES relaxations (TLESR) have been described in patients with gastro-esophageal reflux disease (GERD). However, some of these differences may be the result of chronic GERD rather than being an underlying contributory factor. Twins discordant for GERD symptoms, i.e., only one twin had GERD symptoms, underwent standard LES and esophageal body manometry, and then using a sleeve sensor prolonged LES and pH monitoring, 30 min before and 60 min after a 250 mL 1200 kcal lipid meal. Eight monozygotic and 24 dizygotic female twins were studied. Although there was no difference in preprandial LES pressure (symptomatic 13.2 ± 7.1 mmHg vs asymptomatic 15.1 ± 6.2 mmHg, P = 0.4), LES pressure fell further postprandially in symptomatic twins (LES pressure area under the curve 465 ± 126 vs 331 ± 141 mmHg h, P < 0.01). 12/37 (32%) of acid reflux episodes in symptomatic twins occurred due to low LES pressure or deep inspiration/strain and 0/17 in asymptomatic twins (P = 0.01). There was no difference between symptomatic and asymptomatic twins in: peristaltic amplitude, ineffective esophageal body motility, hiatus hernia prevalence, or LES length. There was also no difference in TLESR frequency preprandially (symptomatic median 1(range 0-2) vs asymptomatic 0(0-2), P = 0.08) or postprandially (2.5(1-8) vs 3(1-6), P = 0.81). Twins with GERD symptoms had lower postprandial LES pressure and given the close genetic link between the twins, it is possible that such differences are caused by GERD. Acid reflux episodes associated with a hypotensive LES were seen in symptomatic, but not in asymptomatic twins. © 2013 John Wiley & Sons Ltd.

  20. EBV-positive primary central nervous system lymphomas in monozygote twins with common variable immunodeficiency and suspected multiple sclerosis.

    PubMed

    Jensen, M K; Koch-Henriksen, N; Johansen, P; Varming, K; Christiansen, C B; Knudsen, F

    1997-12-01

    Common variable immunodeficiency represents the most frequently occurring primary immunodeficiency disorder and is usually detected sporadically in patients with no family history of immunodeficiency. We present the case stories of two monozygote twins, who following a period of decreasing serum immunoglobulins developed primary central nervous system lymphomas. One twin had clinical and paraclinical features mimicking multiple sclerosis. Immunohistochemical investigations on biopsy tissue showed expression of the bcl-2 and p53 gene products, and Epstein-Barr virus (EBV) encoded small RNA's (EBER) indicating latent infection were detected in lymphoma cells using in situ hybridisation techniques. The pathogenetic role of EBV in oncogenesis is discussed.

  1. Is growth-discordance in twins a substantial risk factor in adverse neonatal outcomes?

    PubMed

    Frezza, Simonetta; Gallini, Francesca; Puopolo, Maria; De Carolis, Maria P; D'Andrea, Vito; Guidone, Paola I; Luciano, Rita; Zuppa, Antonio A; Romagnoli, Costantino

    2011-10-01

    To evaluate whether growth discordance is an independent risk factor in the neonatal outcome of the smaller twin, all medical records of twin pregnancies delivered between 26 and 41 weeks during a 5-year period (January 2004-December 2008) were reviewed. Among the 49 selected twins, weight discordance was 15-20% in 7 infants, 21-30% in 16 infants, 31-40% in 16 infants and > 40% in 10 infants. No significant differences between the four groups were found with regards to obstetric complications and neonatal disease. Occurrence of birthweight below the 10th percentile and rate of admission to the neonatal intensive care unit significantly increased as intra-pair birthweight difference increased (p = .03). The > 40% discordant group had a significantly lower gestational age (p = .03), lower birthweight (p = .007) and a significantly higher mortality rate (4/10 versus 3/39 p = .04) in comparison with the other discordant groups. Multiple logistic regression analysis showed that birthweight was the single independent and consistent factor associated with elevated risks of mortality. For every 250 g increase in birthweight, the risk for mortality decreased by about 84% [RR 0.16(CI 0.00-0.70)]. Gestational age was the most reliable predictor for major neonatal complications. For every 1-week increase in gestational age a significant decreased risk for all outcomes was found. Discordance alone should not be considered as a predictor for adverse neonatal outcome. Neonatal outcome in discordant twins appears to be related to gestational age and birthweight rather than to the degree of discordance.

  2. A longitudinal investigation of the associations among parenting, deviant peer affiliation, and externalizing behaviors: a monozygotic twin differences design.

    PubMed

    Hou, Jinqin; Chen, Zhiyan; Natsuaki, Misaki N; Li, Xinying; Yang, Xiaodong; Zhang, Jie; Zhang, Jianxin

    2013-06-01

    Non-shared parenting and deviant peer affiliation are linked to differences in externalizing behaviors between twins. However, few studies have examined these two non-shared environments simultaneously. The present study examined the transactional roles of differential parenting (i.e., warmth and hostility) and deviant peer affiliation on monozygotic (MZ) twin differences in externalizing behaviors using a two-wave longitudinal study of twins and their parents. The sample consisted of 520 pairs of MZ twins (46.5% males, 53.5% females), with a mean age of 13.86 years (SD = 2.10) at the T1 assessment, residing in Beijing, China. The association between non-shared hostility in parenting and adolescent externalizing behaviors was mainly explained by a child-driven effect whereby the twin with a higher level of externalizing behaviors than his or her co-twin was more likely to receive more hostility from the parents. Similarly, the relationship between deviant peer affiliation and adolescent externalizing behaviors supported the selection effect whereby the twin with a higher level of externalizing behaviors than his or her co-twin was more likely to affiliate with deviant peers. The theoretical and practical implications of these findings are discussed.

  3. Associations of Mother's and Father's Parenting Practices with Children's Observed Social Reticence in a Competitive Situation: A Monozygotic Twin Difference Study

    ERIC Educational Resources Information Center

    Guimond, Fanny-Alexandra; Brendgen, Mara; Forget-Dubois, Nadine; Dionne, Ginette; Vitaro, Frank; Tremblay, Richard E.; Boivin, Michel

    2012-01-01

    This study used the monozygotic (MZ) twin difference method to examine whether the unique environmental effects of maternal and paternal overprotection and hostility at the age of 30 months predict twins' observed social reticence in a competitive situation in kindergarten, while controlling for the effect of family-wide influences, including…

  4. Associations of Mother's and Father's Parenting Practices with Children's Observed Social Reticence in a Competitive Situation: A Monozygotic Twin Difference Study

    ERIC Educational Resources Information Center

    Guimond, Fanny-Alexandra; Brendgen, Mara; Forget-Dubois, Nadine; Dionne, Ginette; Vitaro, Frank; Tremblay, Richard E.; Boivin, Michel

    2012-01-01

    This study used the monozygotic (MZ) twin difference method to examine whether the unique environmental effects of maternal and paternal overprotection and hostility at the age of 30 months predict twins' observed social reticence in a competitive situation in kindergarten, while controlling for the effect of family-wide influences, including…

  5. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor

    USDA-ARS?s Scientific Manuscript database

    Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin ...

  6. Clinical outcome and placental characteristics of monochorionic diamniotic twin pairs with early- and late-onset discordant growth.

    PubMed

    Lewi, Liesbeth; Gucciardo, Leonardo; Huber, Agnes; Jani, Jacques; Van Mieghem, Tim; Doné, Elisa; Cannie, Mieke; Gratacós, Eduardo; Diemert, Anke; Hecher, Kurt; Lewi, Paul; Deprest, Jan

    2008-11-01

    The purpose of this study was to examine the clinical and placental characteristics of monochorionic diamniotic twin pregnancies with early-onset discordant growth diagnosed at 20 weeks, late-onset discordant growth diagnosed at 26 weeks or later, and concordant growth. We studied a prospective cohort that underwent an ultrasound scan in the first trimester, at 16, 20, and 26 weeks. We excluded pregnancies complicated by twin-to-twin transfusion syndrome, miscarriage, fetal death less than 16 weeks, or severe congenital anomalies. Placental sharing and angioarchitecture were assessed by injection of each cord vessel with dyed barium sulphate. The 2 territories were delineated on an X-ray angiogram. The diameter of each intertwin anastomosis was measured on a digital photograph. We included 178 twin pairs. Early onset discordant growth, late-onset discordant growth, and concordant growth occurred in 15, 13, and 150 pregnancies, respectively. Twin pairs with early-onset discordant growth had lower survival rates and were delivered at an earlier gestational age than pairs with late-onset discordant and concordant growth. The degree of birthweight discordance was similar in early- and late-onset discordant growth. Severe intertwin hemoglobin differences at the time of birth occurred in 0%, 38%, and 3% of pairs with early-onset discordant growth, late-onset discordant growth, and concordant growth, respectively. The placentas of pairs with early-onset discordant growth were more unequally shared and had larger arterioarterial anastomoses and a larger total anastomotic diameter as compared with placentas of pairs with late onset-discordant or concordant growth. Unequal placental sharing appears to be involved in the etiology of early-onset discordant growth, whereas a late intertwin transfusion imbalance may be involved in some cases with late-onset discordant growth.

  7. Congenital Kyphoscoliosis in Monozygotic Twins: Ten-Year Follow-up Treated by Posterior Vertebral Column Resection (PVCR)

    PubMed Central

    Chang, Dong-Gune; Yang, Jae Hyuk; Lee, Jung-Hee; Kim, Young-Hoon; Kim, Jin-Hyok; Suh, Seung-Woo; Ha, Kee-Yong; Suk, Se-Il

    2016-01-01

    Abstract The etiology of congenital scoliosis and its development remains unclear and has not yet been fully identified, even there are theories that congenital scoliosis could be derived from the failure of formation or failure of segmentation, which are etiologically heterogeneous with genetic, epigenetic, and environmental factors contributing to their occurrence. We reported a case of long-term follow-up after posterior vertebral column resection (PVCR) in both identical twins with similar congenital kyphoscoliosis at thoracolumbar levels. Twin I had been noticed by his parents to have asymmetry of his back at age 5 years, but no treatment was given. Twin II was first noticed to have a spinal problem at 11 years of age by his parents. Overtime, spine of both twins became further deviated to the left with kyphosis and was referred to our hospital. Both monozygotic twins were treated by PVCR and satisfactory results were demonstrated at 10-year follow-up. This case is the first report on the surgical treatment with PVCR, almost simultaneously, in both identical twins who had similar congenital vertebral anomalies causing kyphoscoliosis. Both identical twins with congenital kyphoscoliosis had undergone surgical correction by PVCR, anterior support with a mesh cage and posterior fusion using pedicle screws at the age of 14 years and achieved a satisfactory correction and a stable spine without curve progression with 10-year follow-up. PMID:27124052

  8. Successful management of discordant alobar holoprosencephaly in monochorionic diamniotic twins with normal karyotype: a case report.

    PubMed

    Zhang, J; Yang, T; Wang, X; Yu, H

    2015-01-01

    Holoprosencephaly (HPE), a complex brain malformation resulting from incomplete cleavage of the prosencephalon into distinct cerebral hemispheres, is rare in newborns. Two preterm male neonates were born at 34 weeks' and five days' gestation in the monochorionic diamniotic twin pregnancy complicated with pre-eclampsia and intrahepatic cholestasis of pregnancy, and one of them was prenatally diagnosed with alobar HPE by ultrasonography with frontal bossing, hydrocephaly, hypotelorism of eyes, flat nasal bridge, macroglossia, and cheilo/palatoschisis at birth. Karyotyping by G-banding of amniocentesis specimens in normal twin and fetal umbilical blood in both fetuses showed 46, XY. This report expands discordant alobar holoprosencephaly in monochorionic diamniotic twins.

  9. De novo deletion of chromosome 11q12.3 in monozygotic twins affected by Poland Syndrome.

    PubMed

    Vaccari, Carlotta Maria; Romanini, Maria Victoria; Musante, Ilaria; Tassano, Elisa; Gimelli, Stefania; Divizia, Maria Teresa; Torre, Michele; Morovic, Carmen Gloria; Lerone, Margherita; Ravazzolo, Roberto; Puliti, Aldamaria

    2014-05-30

    Poland Syndrome (PS) is a rare disorder characterized by hypoplasia/aplasia of the pectoralis major muscle, variably associated with thoracic and upper limb anomalies. Familial recurrence has been reported indicating that PS could have a genetic basis, though the genetic mechanisms underlying PS development are still unknown. Here we describe a couple of monozygotic (MZ) twin girls, both presenting with Poland Syndrome. They carry a de novo heterozygous 126 Kbp deletion at chromosome 11q12.3 involving 5 genes, four of which, namely HRASLS5, RARRES3, HRASLS2, and PLA2G16, encode proteins that regulate cellular growth, differentiation, and apoptosis, mainly through Ras-mediated signaling pathways. Phenotype concordance between the monozygotic twin probands provides evidence supporting the genetic control of PS. As genes controlling cell growth and differentiation may be related to morphological defects originating during development, we postulate that the observed chromosome deletion could be causative of the phenotype observed in the twin girls and the deleted genes could play a role in PS development.

  10. MOTOR DEVELOPMENT AND PHYSICAL ACTIVITY: A LONGITUDINAL DISCORDANT TWIN-PAIR STUDY

    PubMed Central

    Aaltonen, Sari; Latvala, Antti; Rose, Richard J.; Pulkkinen, Lea; Kujala, Urho M.; Kaprio, Jaakko; Silventoinen, Karri

    2015-01-01

    Introduction Previous longitudinal research suggests that motor proficiency in early life predicts physical activity in adulthood. Familial effects including genetic and environmental factors could explain the association, but no long-term follow-up studies have taken into account potential confounding by genetic and social family background. The present twin study investigated whether childhood motor skill development is associated with leisure-time physical activity levels in adulthood independent of family background. Methods Altogether, 1 550 twin pairs from the FinnTwin12 study and 1 752 twin pairs from the FinnTwin16 study were included in the analysis. Childhood motor development was assessed by the parents’ report of whether one of the co-twins had been ahead of the other in different indicators of motor skill development in childhood. Leisure-time physical activity (MET hours/day) was self-reported by the twins in young adulthood and adulthood. Statistical analyses included conditional and ordinary linear regression models within twin pairs. Results Using all activity-discordant twin pairs, the within-pair difference in a sum score of motor development in childhood predicted the within-pair difference in the leisure-time physical activity level in young adulthood (p<0.001). Within specific motor development indicators, learning to stand unaided earlier in infancy predicted higher leisure-time MET values in young adulthood statistically significantly in both samples (FinnTwin12 p=0.02, FinnTwin16 p=0.001) and also in the pooled dataset of the FinnTwin12 and FinnTwin16 studies (p<0.001). Having been more agile than the co-twin as a child predicted higher leisure-time MET values up to adulthood (p=0.03). Conclusions More advanced childhood motor development is associated with higher leisure-time MET values in young adulthood at least partly independent of family background, in both men and women. PMID:26378945

  11. Motor Development and Physical Activity: A Longitudinal Discordant Twin-Pair Study.

    PubMed

    Aaltonen, Sari; Latvala, Antti; Rose, Richard J; Pulkkinen, Lea; Kujala, Urho M; Kaprio, Jaakko; Silventoinen, Karri

    2015-10-01

    Previous longitudinal research suggests that motor proficiency in early life predicts physical activity in adulthood. Familial effects including genetic and environmental factors could explain the association, but no long-term follow-up studies have taken into account potential confounding by genetic and social family background. The present twin study investigated whether childhood motor skill development is associated with leisure-time physical activity levels in adulthood independent of family background. Altogether, 1550 twin pairs from the FinnTwin12 study and 1752 twin pairs from the FinnTwin16 study were included in the analysis. Childhood motor development was assessed by the parents' report of whether one of the co-twins had been ahead of the other in different indicators of motor skill development in childhood. Leisure-time physical activity (MET·h·d) was self-reported by the twins in young adulthood and adulthood. Statistical analyses included conditional and ordinary linear regression models within twin pairs. Using all activity-discordant twin pairs, the within-pair difference in a sum score of motor development in childhood predicted the within-pair difference in the leisure-time physical activity level in young adulthood (P < 0.001). Within specific motor development indicators, learning to stand unaided earlier in infancy predicted higher leisure-time MET values in young adulthood statistically significantly in both samples (FinnTwin12, P = 0.02; and FinnTwin16, P = 0.001) and also in the pooled data set of the FinnTwin12 and FinnTwin16 studies (P < 0.001). Having been more agile than the co-twin as a child predicted higher leisure-time MET values up to adulthood (P = 0.03). More advanced childhood motor development is associated with higher leisure-time MET values in young adulthood at least partly independent of family background in both men and women.

  12. Differentially Methylated Genomic Regions in Birth-Weight Discordant Twin Pairs.

    PubMed

    Chen, Mubo; Baumbach, Jan; Vandin, Fabio; Röttger, Richard; Barbosa, Eudes; Dong, Mingchui; Frost, Morten; Christiansen, Lene; Tan, Qihua

    2016-03-01

    Poor nutrition during critical growth phases may alter the structural and physiologic development of vital organs thus "programming" the susceptibility to adult-onset diseases and disease-related health conditions. Epigenome-wide association studies have been performed in birth-weight discordant twin pairs to find evidence for such "programming" effects, but no significant results emerged. We further investigated this issue using a new computational approach: Instead of probing single genomic sites for significant alterations in epigenetic marks, we scan for differentially methylated genomic regions. Whole genome DNA methylation levels were measured in whole blood from 150 pairs of adult identical twins discordant for birth-weight. Intrapair differential DNA methylation was associated with qualitative (large or small) and quantitative (percentage) birth-weight discordance at each genomic site using regression models adjusting for age and sex. Based on the regression results, genomic regions with consistent alteration patterns of DNA methylation were located and tested for significant robustness using computational permutation tests. This yielded an interesting genomic region on chromosome 1, which is significantly differentially methylated for quantitative birth-weight discordance. The region covers two genes (TYW3 and CRYZ) both reportedly associated with metabolism. We conclude that prenatal conditions for birth-weight discordance may result in persistent epigenetic modifications potentially affecting even adult health.

  13. Causes of delivery and outcomes of very preterm twins stratified to zygosity.

    PubMed

    Spiegler, Juliane; Härtel, Christoph; Schulz, Lena; von Wurmb-Schwark, Nicole; Hoehn, Thomas; Kribs, Angela; Küster, Helmut; Siegel, Jens; Wieg, Christian; Weichert, Jan; Herting, Egbert; Göpel, Wolfgang

    2012-08-01

    The increasing rates of preterm birth among twins implicate that solid data on associated risks and outcomes are required. Assessment of zygosity is often based on clinical criteria (evaluation of placenta; same gender, birth weight discordance as surrogate criteria for monochorionic/monozygotic twins). The aim of this study was to compare clinical versus genetic assessment of zygosity and to compare causes of preterm delivery as well as outcome data of very-low-birth-weight (VLBW; birth weight <1,500 g) twins stratified to zygosity. In a multicenter study, we selected n=176 sets of same gender twins and determined zygosity genetically. In a subgroup of 123 sets of twins, the attending physicians at the study centers were asked to document the parameter 'zygosity' (monozygotic/dizygotic) on the basis of their clinical judgment. Concordance between genetic and clinical assessment was 62.7% for monozygotic twins and 88.9% for dizygotic twins, respectively. Outcome parameters (death, BPD, ROP, NEC, IVH) were comparable in both groups. Genetically dizygotic twins were significantly more often born due to intrauterine infection (33% vs. 20% in monozygotic twins, p<.01) and antenatal antibiotics were more frequently given to mothers of dizygotic twins (62% vs. 47% in monozygotic twins, p<.01). Obstetric complications such as twin-twin-transfusion-syndrome were only seen in monozygotic twins as expected. The unexpected increase of antenatal antibiotic treatment and birth due to intrauterine infection in dizygotic twins should be confirmed in additional VLBW twin-cohorts.

  14. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition

    PubMed Central

    Reyes, Alejandro; Blanton, Laura V.; Cao, Song; Zhao, Guoyan; Manary, Mark; Trehan, Indi; Smith, Michelle I.; Wang, David; Virgin, Herbert W.; Rohwer, Forest; Gordon, Jeffrey I.

    2015-01-01

    The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota’s viral component in populations at risk for malnutrition. PMID:26351661

  15. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition.

    PubMed

    Reyes, Alejandro; Blanton, Laura V; Cao, Song; Zhao, Guoyan; Manary, Mark; Trehan, Indi; Smith, Michelle I; Wang, David; Virgin, Herbert W; Rohwer, Forest; Gordon, Jeffrey I

    2015-09-22

    The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota's viral component in populations at risk for malnutrition.

  16. Monochorionic and dichorionic twin pregnancies discordant for fetal anencephaly: a systematic review of prenatal management options.

    PubMed

    Lust, Annelies; De Catte, Luc; Lewi, Liesbeth; Deprest, Jan; Loquet, Philippe; Devlieger, Roland

    2008-04-01

    The aim of this study was to evaluate the effect of selective feticide (SF) compared to expectant management (EM) on perinatal outcome in dichorionic and monochorionic twins discordant for anencephaly. For this purpose, we conducted a systematic review of literature and added ten unpublished cases. As a result, we found that in dichorionic twins, mean gestational age (GA) at birth in the SF group was 38.0 weeks versus 34.9 weeks (P = 0.0002). Mean birth weight was 2922 g in the SF group versus 2474 g (P = 0.03). In monochorionic twins, mean GA at birth was 35.2 weeks versus 32.7 weeks (P = 0.1). Mean birth weight was 2711 g versus 1667 g (P = 0.0001). We conclude that while SF does not reduce perinatal mortality, it does result in significantly longer gestations and higher birth weight, and appears to be the management of choice in dichorionic twins discordant for anencephaly. In monochorionic twins, SF also increases birth weight, but in view of the complexity of this group, no clear recommendations can be made.

  17. DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker

    PubMed Central

    Esteller, Manel

    2013-01-01

    Using whole blood from 15 twin pairs discordant for breast cancer and high-resolution (450K) DNA methylation analysis, we identified 403 differentially methylated CpG sites including known and novel potential breast cancer genes. Confirming the results in an independent validation cohort of 21 twin pairs determined the docking protein DOK7 as a candidate for blood-based cancer diagnosis. DNA hypermethylation of the promoter region was also seen in primary breast cancer tissues and cancer cell lines. Hypermethylation of DOK7 occurs years before tumor diagnosis, suggesting a role as a powerful epigenetic blood-based biomarker as well as providing insights into breast cancer pathogenesis. PMID:23054610

  18. A monozygotic twin pair with β-thalassemia carrier status in a Dudh Kharia tribal family of Orissa

    PubMed Central

    Balgir, R. S.

    2007-01-01

    -thalassemia (trait) genotypes with identical clinical manifestations and hematological profile of the twin sons under similar environmental conditions, hence they were labeled as identical monozygotic twins. CONCLUSIONS: It is a rare occasion when a single pregnancy carries either one or two abnormal genotypes at a time in a womb in human beings. Monozygotic twins are genetically alike and provide appraisal of the expression of identical genotype under the different environmental conditions. PMID:21957337

  19. A Discordant Monozygotic Twin Design Shows Blunted Cortisol Reactivity among Bullied Children

    ERIC Educational Resources Information Center

    Ouellet-Morin, Isabelle; Danese, Andrea; Bowes, Lucy; Shakoor, Sania; Ambler, Antony; Pariante, Carmine M.; Papadopoulos, Andrew S.; Caspi, Avshalom; Moffitt, Terrie E.; Arseneault, Louise

    2011-01-01

    Objective: Childhood adverse experiences are known to engender persistent changes in stress-related systems and brain structures involved in mood, cognition, and behavior in animal models. Uncertainty remains about the causal effect of early stressful experiences on physiological response to stress in human beings, as the impact of these…

  20. Genes and Memory: The Neuroanatomical Correlates of Emotional Memory in Monozygotic Twin Discordant for Schizophrenia

    ERIC Educational Resources Information Center

    Fahim, Cherine; Stip, Emmanuel; Mancini-Marie, Adham; Beauregard, Mario

    2004-01-01

    Background: Brain morphology and physiological measures in schizophrenia have yielded inconsistent results. This may be due in part to difficulties in ascertaining precisely to what degree each measure deviates from its genetically and environmentally determined potential level. We attempted to surmount this problem in a paradigm involving…

  1. Phenotypic discordance in a family with monozygotic twins and non-syndromic cleft lip and palate

    SciTech Connect

    Wyszynski, D.F. |; Lewanda, A.F. |; Beaty, T.H.

    1996-12-30

    Despite considerable research, the cause of non-syndromic cleft lip with or without cleft palate (NSCLP) is still an enigma. Case-control and cohort studies have searched for environmental factors that might influence the development of this common malformation, such as maternal cigarette smoking, periconceptional supplementation of folic acid and multivitamins, agricultural chemical use, and place of residence, among others. However, these studies are subject to numerous biases, and their results have often been contradictory and inconclusive. 41 refs., 1 fig.

  2. A Discordant Monozygotic Twin Design Shows Blunted Cortisol Reactivity among Bullied Children

    ERIC Educational Resources Information Center

    Ouellet-Morin, Isabelle; Danese, Andrea; Bowes, Lucy; Shakoor, Sania; Ambler, Antony; Pariante, Carmine M.; Papadopoulos, Andrew S.; Caspi, Avshalom; Moffitt, Terrie E.; Arseneault, Louise

    2011-01-01

    Objective: Childhood adverse experiences are known to engender persistent changes in stress-related systems and brain structures involved in mood, cognition, and behavior in animal models. Uncertainty remains about the causal effect of early stressful experiences on physiological response to stress in human beings, as the impact of these…

  3. Childhood adversity and psychosis: examining whether the association is due to genetic confounding using a monozygotic twin differences approach.

    PubMed

    Alemany, S; Goldberg, X; van Winkel, R; Gastó, C; Peralta, V; Fañanás, L

    2013-05-01

    To test whether the association between childhood adversity and positive and negative psychotic experiences is due to genetic confounding. Childhood adversity and psychotic experiences were assessed in an ongoing sample of 226 twins from the general population. A monozygotic (MZ) twin differences approach was used to assess possible genetic confounding. In the whole sample, childhood adversity was significantly associated with positive (β=45; SE=0.16; P=0.008) and negative psychotic experiences (β=0.77; SE=0.18; P<0.01). Within-pair MZ twin differences in exposure to childhood adversity were significantly associated with differences in positive (β=71; SE=0.29; P=0.016) and negative psychotic experiences (β=98; SE=0.38; P=0.014) in a subsample of 85 MZ twin pairs. Individuals exposed to childhood adversity are more likely to report psychotic experiences. Furthermore, our findings indicate that this association is not due to genetic confounding. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. Genome-wide analysis of DNA methylation associated with HIV infection based on a pair of monozygotic twins

    PubMed Central

    Zhang, Yinfeng; Li, Sai-Kam; Tsui, Stephen Kwok-Wing

    2015-01-01

    Alteration of DNA methylation in mammalian cells could be elicited by many factors, including viral infections [1]. HIV has shown the ability to interact with host cellular factors to change the methylation status of some genes [2], [3], [4]. However, the change of the DNA methylation associated with HIV infection based on the whole genome has not been well illustrated. In this study, a unique pair of monozygotic twins was recruited: one of the twins was infected with HIV without further anti-retroviral therapy while the other one was healthy, which could be considered as a relatively ideal model for profiling the alterations of DNA methylation associated with HIV infection. Therefore, using methylated DNA immunoprecipitation–microarray method (MeDIP–microarray), we found the increased DNA methylation level in peripheral blood mononuclear cells from HIV infected twin compared to her normal sibling. Moreover, several distinguished differential methylation regions (DMRs) in HIV infected twin worth further study. The raw data has been deposited in Gene Expression Omnibus (GEO) datasets with reference number GSE68028. PMID:26697319

  5. Premorbid school performance in twins concordant and discordant for bipolar disorder.

    PubMed

    Vonk, R; van der Schot, A C; van Baal, G C M; van Oel, C J; Nolen, W A; Kahn, R S

    2012-02-01

    Although the genetic risk to develop bipolar disorder is present from conception, the first frank symptoms of the illness generally become evident in late adolescence or early adulthood. However, except for pediatric bipolar disorder (PBD), it is still unclear when the first signs of the illness in adults become apparent and whether these are related to the genetic risk to develop bipolar disorder. This study examined whether underperformance at school precedes the onset of the illness and is a genetically related risk marker for developing bipolar disorder. Information on school performance was obtained using objective archival data from 53 bipolar twin pairs (24 monozygotic (MZ), 29 dizygotic (DZ)) and 42 healthy matched control twin pairs (23 MZ, 19 DZ). Affected twin pairs completed significantly fewer years of education than did control twin pairs with no difference between bipolar patients and their non-bipolar cotwins. The underperformance at school in the affected twin pairs occurred in early adolescence at a significantly younger age than the control twin pairs and preceded the onset of the first frank episode of bipolar disorder by thirteen years. Median age at onset of underperformance was not different in the patients and their non-bipolar cotwins. The association between liability of bipolar disease and age of first underperformance was significant and could be explained by genetic factors. The sample is not a population based twin sample. Underperformance at school during early adolescence may be a genetic marker for the vulnerability to develop bipolar disorder. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Recurrence risk for offspring of twins discordant for oral cleft: a population-based cohort study of the Danish 1936-2004 cleft twin cohort.

    PubMed

    Grosen, Dorthe; Bille, Camilla; Pedersen, Jacob Krabbe; Skytthe, Axel; Murray, Jeffrey C; Christensen, Kaare

    2010-10-01

    Our objective in this Danish population-based cohort study was to estimate the recurrence risk of isolated oral cleft (OC) for offspring of the unaffected co-twins of OC discordant twin pairs and to compare this risk to the recurrence risk in the offspring of the affected co-twin as well as to the risk in the background population. During 1936-2004, 207 twin pairs were ascertained, among whom at least one twin had an OC. The index persons were twins discordant for OC who had children (N=117), and their offspring (N=239). The participants were ascertained by linkage between The Danish Facial Cleft Database, The Danish Twin Registry and The Danish Civil Registration System. In the study OC recurrence risk for offspring of the affected and unaffected twin and relative risk were compared to the background prevalence. We found that among 110 children of the 54 OC affected twins, two (1.8%) children had OC corresponding to a significantly increased relative risk (RR=10; 95% CI 1.2-35) when compared to the frequency in the background population. Among the 129 children of the 63 unaffected twins, three (2.3%) children were affected, corresponding to a significantly increased relative risk (RR=13; 95% CI 2.6-36) when compared the background prevalence. We concluded that in OC discordant twin pairs similar increased recurrence risks were found among offspring of both OC affected and OC unaffected twins. This provides further evidence for a genetic component in cleft etiology and is useful information for genetic counseling of twin pairs discordant for clefting. Copyright © 2010 Wiley-Liss, Inc.

  7. Recurrence Risk for Offspring of Twins Discordant for Oral Cleft - A Population-based Cohort Study of the Danish 1936–2004 Cleft Twin Cohort

    PubMed Central

    Grosen, Dorthe; Bille, Camilla; Pedersen, Jacob Krabbe; Skytthe, Axel; Murray, Jeffrey C; Christensen, Kaare

    2010-01-01

    Our objective in this Danish population-based cohort study was to estimate the recurrence risk of isolated oral cleft (OC) for offspring of the unaffected co-twins of OC discordant twin pairs and to compare this risk to the recurrence risk in the offspring of the affected co-twin as well as to the risk in the background population. During 1936–2004, 207 twin pairs were ascertained, among whom at least one twin had an OC. The index persons were twins discordant for OC who had children (N=117), and their offspring (N=239). The participants were ascertained by linkage between The Danish Facial Cleft Database, The Danish Twin Registry and The Danish Civil Registration System. In the study OC recurrence risk for offspring of the affected and unaffected twin and relative risk were compared to the background prevalence. We found that among 110 children of the 54 OC affected twins, two (1.8%) children had OC corresponding to a significantly increased relative risk (RR = 10; 95% CI 1.2 to 35) when compared to the frequency in the background population. Among the 129 children of the 63 unaffected twins, three (2.3%) children were affected, corresponding to a significantly increased relative risk (RR = 13; 95% CI 2.6 to 36) when compared the background prevalence. We concluded that in OC discordant twin pairs similar increased recurrence risks were found among offspring of both OC affected and OC unaffected twins. This provides further evidence for a genetic component in cleft etiology and is useful information for genetic counseling of twin pairs discordant for clefting. PMID:20799319

  8. Gut microbiota from twins discordant for obesity modulate metabolism in mice.

    PubMed

    Ridaura, Vanessa K; Faith, Jeremiah J; Rey, Federico E; Cheng, Jiye; Duncan, Alexis E; Kau, Andrew L; Griffin, Nicholas W; Lombard, Vincent; Henrissat, Bernard; Bain, James R; Muehlbauer, Michael J; Ilkayeva, Olga; Semenkovich, Clay F; Funai, Katsuhiko; Hayashi, David K; Lyle, Barbara J; Martini, Margaret C; Ursell, Luke K; Clemente, Jose C; Van Treuren, William; Walters, William A; Knight, Rob; Newgard, Christopher B; Heath, Andrew C; Gordon, Jeffrey I

    2013-09-06

    The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.

  9. Enhanced neurocognitive functioning and positive temperament in twins discordant for bipolar disorder.

    PubMed

    Higier, Rachel G; Jimenez, Amy M; Hultman, Christina M; Borg, Jacqueline; Roman, Cristina; Kizling, Isabelle; Larsson, Henrik; Cannon, Tyrone D

    2014-11-01

    Based on evidence linking creativity and bipolar disorder, a model has been proposed whereby factors influencing liability to bipolar disorder confer certain traits with positive effects on reproductive fitness. The authors tested this model by examining key traits known to be associated with evolutionary fitness, namely, temperament and neurocognition, in individuals carrying liability for bipolar disorder. Schizophrenia probands and their co-twins were included as psychiatric controls. Twin pairs discordant for bipolar disorder and schizophrenia and control pairs were identified through the Swedish Twin Registry. The authors administered a neuropsychological test battery and temperament questionnaires to samples of bipolar probands, bipolar co-twins, schizophrenia probands, schizophrenia co-twins, and controls. Multivariate mixed-model analyses of variance were conducted to compare groups on temperament and neurocognitive scores. Bipolar co-twins showed elevated scores on a "positivity" temperament scale compared with controls and bipolar probands, while bipolar probands scored higher on a "negativity" scale compared with their co-twins and controls, who did not differ. Additionally, bipolar co-twins showed superior performance compared with controls on tests of verbal learning and fluency, while bipolar probands showed performance decrements across all neurocognitive domains. In contrast, schizophrenia co-twins showed attenuated impairments in positivity and overall neurocognitive functioning relative to their ill proband counterparts. These findings suggest that supra-normal levels of sociability and verbal functioning may be associated with liability for bipolar disorder. These effects were specific to liability for bipolar disorder and did not apply to schizophrenia. Such benefits may provide a partial explanation for the persistence of bipolar illness in the population.

  10. Genetic and Environmental Influences on Regional Brain Uptake of 18F-FDG: A PET Study on Monozygotic and Dizygotic Twins.

    PubMed

    Watanabe, Shinichiro; Kato, Hiroki; Shimosegawa, Eku; Hatazawa, Jun

    2016-03-01

    Genetic or environmental influences on cerebral glucose metabolism are unknown. We attempted to reveal these influences in elderly twins by means of (18)F-FDG PET. (18)F-FDG uptake was studied in 40 monozygotic and 18 dizygotic volunteer twin pairs aged 30 y or over. We also created 18 control pairs by pairing age- and sex-matched genetically unrelated subjects from dizygotic and monozygotic pairs. SUV images of the brain were reconstructed and analyzed by voxel-based statistical analysis with automated region-of-interest setting. The (18)F-FDG uptake in each cerebral lobe was semiquantified by taking a ratio of SUVmean in each region of interest to whole-brain SUVaverage. We calculated an intraclass correlation coefficient of SUV ratio in each region of interest for monozygotic and dizygotic pairs. By comparing differences in coefficients between monozygotic and dizygotic pairs, genetic and environmental contributions were estimated. The intraclass correlation coefficient in monozygotic pairs was significantly higher than that in dizygotic pairs in the parietal lobes bilaterally (P < 0.001) and in the left temporal lobe (P < 0.05) but was not significantly different in other lobes. The present study indicated that in the right and left parietal lobes and left temporal lobe, cerebral glucose metabolism is influenced more by genetics than by environment, whereas in other brain regions the influence of environment is dominant. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  11. Serial MR imaging and 1H-MR spectroscopy in monozygotic twins with Tay-Sachs disease.

    PubMed

    Imamura, A; Miyajima, H; Ito, R; Orii, K O

    2008-10-01

    Four-year-old monozygotic female twins with early onset Tay-Sachs disease are described. The sisters showed similar slowly progressive clinical symptoms and deterioration, however the younger sister also demonstrated intractable myoclonus in the right leg. The serial MR images and (1)H-MR spectroscopy of the brain were obtained in both twins. MR images showed high intensity on T (2)-weighted image in the bilateral white matter, however there were no signal changes in the basal ganglia and thalamus during any of the phases. The ratio of N-acetylaspartate (NAA)/creatine (Cr) was decreased in the both white matter lesions and the corpus striatum, and that of myoinositol (mI)/Cr was increased in the damaged white matter on MR spectroscopy. The elevation of the lactate peak was clearly demonstrated in the left basal ganglia of the younger sister; however it was not shown in cerebral lesions of the elder sister. Changes in metabolites on MR spectroscopy were closely linked to the respective clinical features of each twin. Follow-up examination by (1)H-MR spectroscopy is useful for the evaluation of neuronal changes in children with Tay-Sachs disease.

  12. The Rate of Nonallelic Homologous Recombination in Males Is Highly Variable, Correlated between Monozygotic Twins and Independent of Age

    PubMed Central

    MacArthur, Jacqueline A. L.; Spector, Timothy D.; Lindsay, Sarah J.; Mangino, Massimo; Gill, Raj; Small, Kerrin S.; Hurles, Matthew E.

    2014-01-01

    Nonallelic homologous recombination (NAHR) between highly similar duplicated sequences generates chromosomal deletions, duplications and inversions, which can cause diverse genetic disorders. Little is known about interindividual variation in NAHR rates and the factors that influence this. We estimated the rate of deletion at the CMT1A-REP NAHR hotspot in sperm DNA from 34 male donors, including 16 monozygotic (MZ) co-twins (8 twin pairs) aged 24 to 67 years old. The average NAHR rate was 3.5×10−5 with a seven-fold variation across individuals. Despite good statistical power to detect even a subtle correlation, we observed no relationship between age of unrelated individuals and the rate of NAHR in their sperm, likely reflecting the meiotic-specific origin of these events. We then estimated the heritability of deletion rate by calculating the intraclass correlation (ICC) within MZ co-twins, revealing a significant correlation between MZ co-twins (ICC = 0.784, p = 0.0039), with MZ co-twins being significantly more correlated than unrelated pairs. We showed that this heritability cannot be explained by variation in PRDM9, a known regulator of NAHR, or variation within the NAHR hotspot itself. We also did not detect any correlation between Body Mass Index (BMI), smoking status or alcohol intake and rate of NAHR. Our results suggest that other, as yet unidentified, genetic or environmental factors play a significant role in the regulation of NAHR and are responsible for the extensive variation in the population for the probability of fathering a child with a genomic disorder resulting from a pathogenic deletion. PMID:24603440

  13. Outcome following selective fetal reduction in monochorionic and dichorionic twin pregnancies discordant for structural, chromosomal and genetic disorders.

    PubMed

    Nobili, Elena; Paramasivam, Gowrishankar; Kumar, Sailesh

    2013-04-01

    To investigate the indications for offering selective fetal reduction in monochorionic (MC) and dichorionic (DC) twins and to correlate obstetric outcome with the antenatal procedure. All cases of MC and DC twins discordant for structural anomalies and for chromosomal/genetic abnormalities were included. Selective reductions performed for twin-to-twin transfusion syndrome or growth restriction were excluded. For DC twins, feticide was achieved using intracardiac injection of potassium chloride (KCl). For MC twins, bipolar cord occlusion (BCO), interstitial laser or radiofrequency ablation (RFA) was used. There were 121 twin pregnancies discordant for structural and chromosomal abnormalities. Only 88 (56 were MC twins and 32 were DC twins) had selective reduction. For both MC and DC twins, the leading indication for selective reduction was structural anomalies with CNS malformations the most common. For all MC fetal reduction techniques, the overall pregnancy loss rate (<24 weeks) was 8.9% with RFA having the lowest procedure loss rate (7.7%). The preterm delivery rate was lowest with reduction in DC pregnancies. The live birth rates for MC twins were >87% and 100% for DC twins. Selective reduction in MC pregnancies carries an increased procedure-related and preterm delivery rate compared with DC pregnancies. The main indication for selective reduction was structural malformations, with a predominance of CNS anomalies. © 2013 The Authors ANZJOG © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  14. Quantifying familial influences on brain activation during the monetary incentive delay task: an adolescent monozygotic twin study.

    PubMed

    Silverman, Merav H; Krueger, Robert F; Iacono, William G; Malone, Stephen M; Hunt, Ruskin H; Thomas, Kathleen M

    2014-12-01

    Although altered brain activation during reward tasks has been found in a number of heritable psychiatric disorders and health outcomes, the familial nature of reward-related brain activation remains unexplored. In this study, we investigated the degree to which the magnitude of mesocorticolimbic reward system signal intensities in anticipation of reward during the monetary incentive delay (MID) task was similar within 46 pairs of adolescent, monozygotic twins. Significant within-pair correlations in brain activation during anticipation of gain were found in one third of the 18 reward-related regions investigated. These regions were the right nucleus accumbens, left and right posterior caudate, right anterior caudate, left insula, and anterior cingulate cortex. This serves as evidence for a shared familial contribution to individual differences in reward related brain activity in certain key reward processing regions. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition

    PubMed Central

    Giloteaux, Ludovic; Hanson, Maureen R.; Keller, Betsy A.

    2016-01-01

    Patient: Male, 34 Final Diagnosis: ME/CFS Symptoms: Exertion intolerance • loss of functional capacity • pain • severe fatigue Medication: — Clinical Procedure: Cardiopulmonary exercise test Specialty: Sports Medicine Objective: Unknown ethiology Background: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with profound fatigue, flu-like symptoms, pain, cognitive impairment, orthostatic intolerance, post-exertional malaise (PEM), and exacerbation of some or all of the baseline symptoms. Case Report: We report on a pair of 34-year-old monozygotic twins discordant for ME/CFS, with WELL, the non-affected twin, and ILL, the affected twin. Both twins performed a two-day cardiopulmonary exercise test (CPET), preand post-exercise blood samples were drawn, and both provided stool samples for biochemical and molecular analyses. At peak exertion for both CPETs, ILL presented lower VO2peak and peak workload compared to WELL. WELL demonstrated normal reproducibility of VO2@ventilatory/anaerobic threshold (VAT) during CPET2, whereas ILL experienced an abnormal reduction of 13% in VAT during CPET2. A normal rise in lactate dehydrogenase (LDH), creatine kinase (CK), adrenocorticotropic hormone (ACTH), cortisol, creatinine, and ferritin content was observed following exercise for both WELL and ILL at each CPET. ILL showed higher increases of resistin, soluble CD40 ligand (sCD40L), and soluble Fas ligand (sFasL) after exercise compared to WELL. The gut bacterial microbiome and virome were examined and revealed a lower microbial diversity in ILL compared to WELL, with fewer beneficial bacteria such as Faecalibacterium and Bifidobacterium, and an expansion of bacteriophages belonging to the tailed dsDNA Caudovirales order. Conclusions: Results suggest dysfunctional immune activation in ILL following exercise and that prokaryotic viruses may contribute to mucosal inflammation and bacterial dysbiosis. Therefore, a two-day CPET and molecular

  16. Discordance in fetal biometry and Doppler are independent predictors of the risk of perinatal loss in twin pregnancies.

    PubMed

    Khalil, Asma A; Khan, Naila; Bowe, Sophie; Familiari, Alessandra; Papageorghiou, Aris; Bhide, Amar; Thilaganathan, Basky

    2015-08-01

    Impaired fetal growth might be better evaluated in twin pregnancies by assessing the intertwin discordance rather than the individual fetal size. The aim of this study was to investigate the prediction of perinatal loss in twin pregnancy using discordance in fetal biometry and Doppler. This was a retrospective cohort study in a tertiary referral center. The estimated fetal weight (EFW), umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebroplacental ratio (CPR), and their discordance recorded at the last ultrasound assessment before delivery or demise of one or both fetuses were converted into centiles or multiples of the median (MoM). The discordance was calculated as the larger value-smaller value/larger value. A logistic regression analysis was performed to identify, and adjust for, potential confounders. The predictive accuracy was assessed using receiver-operating characteristic curve analysis. The analysis included 620 (464 dichorionic diamniotic and 156 monochorionic diamniotic) twin pregnancies (1240 fetuses). Perinatal loss of one or both fetuses complicated 16 pregnancies (2.6%). The combination of EFW discordance and CPR discordance had the best predictive performance (area under the curve, 0.96; 95% confidence interval, 0.92-1.00) for perinatal mortality. The detection rate, false-positive rate, positive likelihood ratio, and negative likelihood ratio were 87.5%, 6.7%, 13.08, and 0.13, respectively. The EFW centile, EFW below the 10th centile (small for gestational age), UA PI discordance, MCA PI discordance, and MCA PI MoM were significantly associated with the risk of perinatal loss on univariate analysis, but these associations became nonsignificant after adjusting for other confounders (P = .097, P = .090, P = .687, P = .360, and P = .074, respectively). The UA PI MoM, CPR MoM, EFW discordance, and CPR discordance were all independent predictors of the risk of perinatal loss, even after adjusting for potential

  17. Leptin and adiponectin levels in discordant dichorionic twins at 72 hours of age-associations with anthropometric parameters and insulin resistance.

    PubMed

    Milenković, Svetlana J; Mirković, Ljiljana B; Jovandarić, Miljana Z; Milenković, Dušan M; Banković, Violeta V; Janković, Borisav Z

    2017-04-01

    Insulin resistance (IR) in adults has been associated with intrauterine growth restriction (IUGR). Leptin and adiponectin correlations with anthropometric parameters and IR at 72 h in discordant twins were tested. We included 24 discordant (birth weight discordance ≥20% in relation to the heavier cotwin) and 30 concordant (birth weight discordance ≤10%) twins. A correlation between leptin (but not adiponectin) level and birth weight (BW), birth length and head circumference in IUGR twins was recorded (p<0.05). Insulin sensitivity (IS) and homeostatic model assessment (HOMA)-IR in IUGR twins were similar to appropriate-for-gestational-age cotwins and unrelated to adipokines. In IUGR twins, adiponectin and insulin associated positively. In larger concordant twins' leptin level correlated with HOMA-IR and insulin. Leptin, but not adiponectin, levels correlate positively with anthropometric parameters in IUGR twins. IR in IUGR twins is unrelated to adipokines in the first few days of life.

  18. Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood pressure in borderline hypertensive monozygotic twins.

    PubMed

    Perrinjaquet-Moccetti, Tania; Busjahn, Andreas; Schmidlin, Caesar; Schmidt, Annette; Bradl, Barbara; Aydogan, Cem

    2008-09-01

    Hypertension is a harmful disease factor that develops unnoticed over time. The treatment of hypertension is aimed at an early diagnosis followed by adequate lifestyle changes rather than pharmacological treatment. The olive leaf extract EFLA943, having antihypertensive actions in rats, was tested as a food supplement in an open study including 40 borderline hypertensive monozygotic twins. Twins of each pair were assigned to different groups receiving 500 or 1000 mg/day EFLA943 for 8 weeks, or advice on a favourable lifestyle. Body weight, heart rate, blood pressure, glucose and lipids were measured fortnightly. Blood pressure changed significantly within pairs, depending on the dose, with mean systolic differences of < or =6 mmHg (500 mg vs control) and < or =13 mmHg (1000 vs 500 mg), and diastolic differences of < or =5 mmHg. After 8 weeks, mean blood pressure remained unchanged from baseline in controls (systolic/diastolic: 133 +/- 5/77 +/- 6 vs 135 +/- 11/80 +/- 7 mmHg) and the low-dose group (136 +/- 7/77 +/- 7 vs 133 +/- 10/76 +/- 7), but had significantly decreased for the high dose group (137 +/- 10/80 +/- 10 vs 126 +/- 9/76 +/- 6). Cholesterol levels decreased for all treatments with significant dose-dependent within-pair differences for LDL-cholesterol. None of the other parameters showed significant changes or consistent trends. Concluding, the study confirmed the antihypertensive and cholesterol-lowering action of EFLA943 in humans.

  19. Parkinsonism in a pair of monozygotic CADASIL twins sharing the R1006C mutation: a transcranial sonography study.

    PubMed

    Ragno, Michele; Sanguigni, Sandro; Manca, Antonio; Pianese, Luigi; Paci, Cristina; Berbellini, Alfonso; Cozzolino, Valeria; Gobbato, Roberto; Peluso, Silvio; De Michele, Giuseppe

    2016-06-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common hereditary cerebral small vessel disease, is caused by mutations in the NOTCH3 gene on chromosome 19. Clinical manifestations of CADASIL include recurrent transient ischemic attacks, strokes, cognitive defects, epilepsy, migraine and psychiatric symptoms. Parkinsonian features have variably been reported in CADASIL patients, but only a few patients showed a clear parkinsonian syndrome. We studied two patients, a pair of monozygotic twins, carrying the R1006C mutation of the NOTCH3 gene and affected by a parkinsonian syndrome. For the first time in CADASIL patients, we used transcranial sonography (TCS) to assess basal ganglia abnormalities. TCS showed a bilateral hyperechogenic pattern of substantia nigra in one twin, and a right hyperechogenic pattern in the other. In both patients, lenticular nuclei showed a bilateral hyperechogenic pattern, and the width of the third ventricle was slightly increased. The TCS pattern found in our CADASIL patients is characteristic neither for Parkinson's disease, nor for vascular parkinsonism and seems to be specific and related to the disease-specific pathological features.

  20. Does the Environment Have an Enduring Effect on ADHD? A Longitudinal Study of Monozygotic Twin Differences in Children.

    PubMed

    Livingstone, Luisa T; Coventry, William L; Corley, Robin P; Willcutt, Erik G; Samuelsson, Stefan; Olson, Richard K; Byrne, Brian

    2016-11-01

    Environmental factors play a key role in the development of Attention-Deficit/Hyperactivity Disorder (ADHD), but the long-term effects of these factors are still unclear. This study analyses data from 1024 monozygotic (identical) twins in Australia, the United States, and Scandinavia who were assessed for ADHD in Preschool, Kindergarten, Grade 1, and Grade 2. Differences within each twin pair were used as a direct measure of non-shared environmental effects. The Trait-State-Occasion (TSO) model developed by Cole et al. (Psychological Methods, 10, 3-20, 2005) was used to separate the non-shared environmental effects into stable factors, and transient factors that excluded measurement error. Stable factors explained, on average, 44 % and 39 % of the environmental variance in hyperactive-impulsive and inattentive symptoms, respectively. Transient effects explained the remaining 56 % and 60 % of variance. The proportion of stable variance was higher than expected based on previous research, suggesting promise for targeted interventions if future research identifies these stable risk factors.

  1. Nonshared environmental influences on teacher-reported behaviour problems: monozygotic twin differences in perceptions of the classroom.

    PubMed

    Oliver, Bonamy R; Pike, Alison; Plomin, Robert

    2008-06-01

    The identification of specific nonshared environments responsible for the variance in behaviour problems is a key challenge. Nonshared environmental influences on teacher-reported behaviour problems were explored independently of genetics using the monozygotic (MZ) twin differences design. Six aspects of classroom environment were rated by a representative sample of 570 nine-year-old MZ twins in the UK in different classrooms and were related to their different teachers' reports of prosocial behaviour, hyperactivity, conduct problems, peer problems and emotional symptoms. Within-pair differences in perceptions of the classroom were significantly correlated with teacher-reported behaviour problems, indicating that children with less favourable perceptions of their classroom environment were reported by their teachers as less prosocial, more hyperactive, and to have more conduct and peer problems. Socioeconomic status did not significantly moderate any of these relationships. However, parent-reported household chaos was a significant moderator. The classroom environment is related to behaviour problems even when genetic factors are held constant. Classroom environment is more strongly associated with behaviour problems when the home environment is more chaotic.

  2. Monozygotic twins, folie à deux and heritability: a case report and critical review.

    PubMed

    Shiwach, R S; Sobin, P B

    1998-05-01

    A case report of shared delusional disorder, with a primary diagnosis of delusional disorder, is described in identical twins of proven zygosity. A review of literature shows that the primary diagnosis in identical twin pairs, suffering from folie à deux, is delusional disorder. This is in contrast to the reported excess of schizophrenia, as a primary diagnosis, in non-twin cases of folie à deux. Moreover, schizophrenia is poorly related to delusional disorders on the basis of demographic and familial studies. In the light of this paradox, nosological status of this disorder and the sociogenic and genetic factors are critically discussed.

  3. Accessory pathway reciprocating tachycardia involving twin AV nodes in a patient with atrioventricular discordance and mitral atresia.

    PubMed

    Miyazaki, Aya; Sakaguchi, Heima; Uchiyama, Takamichi; Kurita, Takashi; Ohuchi, Hideo; Yamada, Osamu

    2010-05-01

    The atrioventricular (AV) conduction system in AV discordance remains unclear, especially in cases with complex cardiac anomaly. We report a case of accessory pathway reciprocating tachycardia in atrioventricular discordance (AVD) and mitral atresia with twin AV nodes. In this case, the anterior AV node was located along the atretic mitral valve. The anterior AV node was involved in tachycardia and the posterior AV node acted as a bystander during tachycardia. The anterior AV node in AVD can be located along the atretic mitral valve, and one of twin AV nodes might act as a bystander during AV reciprocating tachycardia.

  4. Two de novo mutations in the AR gene cause the complete androgen insensitivity syndrome in a pair of monozygotic twins.

    PubMed

    Mongan, Nigel P; Jääskeläinen, Jarmo; Green, Katherine; Schwabe, John W; Shimura, Naoto; Dattani, Mehul; Hughes, Ieuan A

    2002-03-01

    The androgen insensitivity syndrome (AIS) is the most common cause of male undermasculinization and is typically caused by mutations in the AR gene. Affected individuals may exhibit either complete external feminization (complete AIS) or a partial phenotype (partial AIS). Here we describe monozygotic twins diagnosed with complete AIS who each possess two substitutions (C-->G at position 2930 and T-->C at position 2955, both in exon 7), leading to Phe(856)Leu and Ser(865)Pro mutations, respectively. Neither parent was found to be a carrier for these mutations, indicating that the double mutation arose de novo. Both mutations were recreated by site-directed mutagenesis and compared functionally with the wild-type receptor. The Phe(856)Leu mutation did not affect androgen binding when expressed in COS-1 cells, nor did this mutation decrease androgen-dependent trans-activation in transfected HeLa cells. However, the Ser(865)Pro mutation completely ablated androgen binding and trans-activation. In this study we demonstrate that the replacement of serine by proline at position 865 is sufficient in itself to cause complete AIS in these twins. Analyses of nuclear receptor structures suggest that this mutation is likely to perturb the conformation of helix 10/11, which plays a role in ligand binding, dimerization, and receptor activation. To our knowledge this is the first confirmed instance of AIS (complete or partial) due to an AR mutation occurring in twins. Furthermore, the phenotype was associated with two mutations that were both novel in nature.

  5. Are stressful life events causally related to the severity of obsessive-compulsive symptoms? A monozygotic twin difference study

    PubMed Central

    Vidal-Ribas, P.; Stringaris, A.; Rück, C.; Serlachius, E.; Lichtenstein, P.; Mataix-Cols, D.

    2015-01-01

    Traumatic or stressful life events have long been hypothesized to play a role in causing or precipitating obsessive-compulsive symptoms but the impact of these environmental factors has rarely been investigated using genetically informative designs. We tested whether a wide range of retrospectively-reported stressful life events (SLEs) influence the lifetime presence and severity of obsessive-compulsive symptoms (OCS) in a large Swedish population-based cohort of 22,084 twins. Multiple regression models examined whether differences in SLEs within twin pairs were significantly associated with differences in OCS. In the entire sample (i.e., both monozygotic [MZ] and dizygotic twin pairs), two SLEs factors, “abuse and family disruption” and “sexual abuse”, were significantly associated with the severity of OCS even after controlling for depressive symptoms. Other SLEs factors were either not associated with OCS (“loss”, “non-sexual assault”) or were no longer associated with OCS after controlling for depression (“illness/injury”). Within MZ pair analyses, which effectively control for genetic and shared environmental effects, showed that only the “abuse and family disruption” factor remained independently related to within-pair differences in OCS severity, even after controlling for depressive symptoms. Despite being statistically significant, the magnitude of the associations was small; “abuse and family disruption” explained approximately 3% of the variance in OCS severity. We conclude that OCS are selectively associated with certain types of stressful life events. In particular, a history of interpersonal abuse, neglect and family disruption may make a modest but significant contribution to the severity of OCS. Further replication in longitudinal cohorts is essential before causality can be firmly established. PMID:25511316

  6. Are stressful life events causally related to the severity of obsessive-compulsive symptoms? A monozygotic twin difference study.

    PubMed

    Vidal-Ribas, P; Stringaris, A; Rück, C; Serlachius, E; Lichtenstein, P; Mataix-Cols, D

    2015-02-01

    Traumatic or stressful life events have long been hypothesized to play a role in causing or precipitating obsessive-compulsive symptoms but the impact of these environmental factors has rarely been investigated using genetically informative designs. We tested whether a wide range of retrospectively-reported stressful life events (SLEs) influence the lifetime presence and severity of obsessive-compulsive symptoms (OCS) in a large Swedish population-based cohort of 22,084 twins. Multiple regression models examined whether differences in SLEs within twin pairs were significantly associated with differences in OCS. In the entire sample (i.e., both monozygotic [MZ] and dizygotic twin pairs), two SLEs factors, "abuse and family disruption" and "sexual abuse", were significantly associated with the severity of OCS even after controlling for depressive symptoms. Other SLEs factors were either not associated with OCS ("loss", "non-sexual assault") or were no longer associated with OCS after controlling for depression ("illness/injury"). Within MZ pair analyses, which effectively control for genetic and shared environmental effects, showed that only the "abuse and family disruption" factor remained independently related to within-pair differences in OCS severity, even after controlling for depressive symptoms. Despite being statistically significant, the magnitude of the associations was small; "abuse and family disruption" explained approximately 3% of the variance in OCS severity. We conclude that OCS are selectively associated with certain types of stressful life events. In particular, a history of interpersonal abuse, neglect and family disruption may make a modest but significant contribution to the severity of OCS. Further replication in longitudinal cohorts is essential before causality can be firmly established. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. Discordance

    NASA Astrophysics Data System (ADS)

    Villa, I. M.; Hanchar, J. M.

    2013-12-01

    Half a century ago, discordant U-Pb ages of metamorphic zircon were viewed as Pb loss by diffusion. Various diffusionist schools of thought debated vigorously whether diffusion was episodic or continuous [1], but nobody questioned the reality of diffusive Pb loss. Only imaging by cathodoluminescence (CL) [2] and back-scattered electrons (BSE) [3] brought a paradigm change in U-Pb geochronology. In situ dating shows routinely accretion of young zircon rims onto older cores that never display Pb diffusion gradients across the interface. Other minerals (monazite, xenotime, etc.) show the same pattern: irregular patches of uniform age separated by sharp age gradients coinciding with petrologic boundaries. As U-Pb discordance is caused by diachronous, heterochemical mineral generations, zircon and monazite closure temperatures, and strict diffusionism, are irrelevant [4]. Knowing what to pay attention to, analytical protocols for U-Pb dating include both of the following: (i) CL/BSE characterization of phase mixtures; (ii) mass spectrometric analysis including U/Th ratios (and ideally trace element fingerprinting on the same fraction [5]). It is clear that the petrologic context is just as essential as mass spectrometry for accurate geochronology. The K-Ar community rarely uses imaging, and the tight context between microstructures, mineral chemistry, petrology and geochronology is missed. Yet the data would be clear if one looked for it. CL and/or BSE imaging and X-ray mapping of K-feldspar and micas is finding ubiquitous evidence of discrete patches of juxtaposed mineral generations. The Ca/Cl/K ratios in 39Ar-40Ar dating fulfill the same role as U/Th ratios in U-Pb dating for fingerprinting successive heterochemical mineral generations. Any linear correlation in a common-denominator three-isotope correlation diagram is certain evidence of binary mixing between heterochemical end-members. A correlation in a Ca/K vs Ar/K diagram requires two minerals having different

  8. Crown-rump length discordance and adverse perinatal outcome in twin pregnancies: systematic review and meta-analysis.

    PubMed

    D'Antonio, F; Khalil, A; Pagani, G; Papageorghiou, A T; Bhide, A; Thilaganathan, B

    2014-08-01

    The aim of this systematic review was to explore the relationship between crown-rump length (CRL) discordance detected at 11-14 weeks of gestation and adverse outcome in twin pregnancy and to assess its predictive accuracy. A protocol designed a priori following MOOSE guidelines and recommended for systematic review and meta-analysis was used. The outcomes observed were: total fetal and perinatal loss, fetal loss at <24 weeks, fetal loss at ≥ 24 weeks, birth-weight (BW) discordance, preterm delivery (PTD) at < 34 weeks and fetal anomalies. The analysis was performed for all twins and for dichorionic (DC) and monochorionic (MC) twins separately. A total of 2008 articles were identified and 17 studies were included in the systematic review. Twin pregnancies with CRL discordance ≥ 10% were at significantly higher risk of perinatal loss (RR, 2.80; 95% CI, 1.25-6.27; P = 0.012), fetal loss at ≥ 24 weeks (RR, 4.07; 95% CI, 1.47-11.23; P = 0.006), BW discordance (RR, 2.24; 95% CI, 1.89-2.64; P < 0.001) and PTD at < 34 weeks (RR, 1.49; 95% CI, 1.23-1.80; P < 0.001) but not of fetal loss at < 24 weeks (P = 0.130). A meta-analysis of fetal anomalies was not possible because fewer than two studies explored this outcome. However, when used alone to screen for adverse pregnancy outcome, the predictive accuracy of CRL discordance was low for each of the outcomes explored. CRL discordance is associated with an increased risk of adverse pregnancy outcome. However, the accuracy of CRL discordance in predicting adverse outcome is poor and thus limits its routine use in clinical practice. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

  9. Pyrosequencing of Plaque Microflora In Twin Children with Discordant Caries Phenotypes

    PubMed Central

    Zhang, Meng; Chen, Yongxing; Xie, Lingzhi; Li, Yuhong; Jiang, Han; Du, Minquan

    2015-01-01

    Despite recent successes in the control of dental caries, the mechanism of caries development remains unclear. To investigate the causes of dental decay, especially in early childhood caries, the supragingival microflora composition of 20 twins with discordant caries phenotypes were analyzed using high-throughput pyrosequencing. In addition, the parents completed a lifestyle questionnaire. A total of 228,789 sequencing reads revealed 10 phyla, 84 genera, and 155 species of microflora, the relative abundances of these strains varied dramatically among the children, Comparative analysis between groups revealed that Veillonella, Corynebacterium and Actinomyces were presumed to be caries-related genera, Fusobacterium, Kingella and Leptotrichia were presumed to be healthy-related genus, yet this six genera were not statistically significant (P>0.05). Moreover, a cluster analysis revealed that the microbial composition of samples in the same group was often dissimilar but that the microbial composition observed in twins was usually similar. Although the genetic and environmental factors that strongly influence the microbial composition of dental caries remains unknown, we speculate that genetic factors primarily influence the individual's susceptibility to dental caries and that environmental factors primarily regulate the microbial composition of the dental plaque and the progression to caries. By using improved twins models and increased sample sizes, our study can be extended to analyze the specific genetic and environmental factors that affect the development of caries. PMID:26524687

  10. Pyrosequencing of Plaque Microflora In Twin Children with Discordant Caries Phenotypes.

    PubMed

    Zhang, Meng; Chen, Yongxing; Xie, Lingzhi; Li, Yuhong; Jiang, Han; Du, Minquan

    2015-01-01

    Despite recent successes in the control of dental caries, the mechanism of caries development remains unclear. To investigate the causes of dental decay, especially in early childhood caries, the supragingival microflora composition of 20 twins with discordant caries phenotypes were analyzed using high-throughput pyrosequencing. In addition, the parents completed a lifestyle questionnaire. A total of 228,789 sequencing reads revealed 10 phyla, 84 genera, and 155 species of microflora, the relative abundances of these strains varied dramatically among the children, Comparative analysis between groups revealed that Veillonella, Corynebacterium and Actinomyces were presumed to be caries-related genera, Fusobacterium, Kingella and Leptotrichia were presumed to be healthy-related genus, yet this six genera were not statistically significant (P>0.05). Moreover, a cluster analysis revealed that the microbial composition of samples in the same group was often dissimilar but that the microbial composition observed in twins was usually similar. Although the genetic and environmental factors that strongly influence the microbial composition of dental caries remains unknown, we speculate that genetic factors primarily influence the individual's susceptibility to dental caries and that environmental factors primarily regulate the microbial composition of the dental plaque and the progression to caries. By using improved twins models and increased sample sizes, our study can be extended to analyze the specific genetic and environmental factors that affect the development of caries.

  11. Fryns syndrome: a lethal mesoectodermal birth defect with variable expression in a pair of monozygotic twins.

    PubMed

    Pratap, A; Agrawal, A; Raja, S; Khaniya, S; Tiwari, A; Kumar, A

    2007-04-01

    We report a pair of twins with variable expressions of Fryns syndrome, both of whom died in the neonatal period. The syndrome is characterised by craniofacial dysmorphism, diaphragmatic hernia and distal limb hypoplasia. With this report, there are a total of 83 cases reported in the literature and this further serves to illustrate the clinical variability of this disorder.

  12. Monochorionic twins with the same blood karyotype of 46,XY/47,XYY but different phenotypes.

    PubMed

    Wuttikonsammakit, Piyawadee; Tanawattanacharoen, Somchai; Uerpairojkit, Boonchai

    2010-02-01

    We report the case of a 13-year-old woman who was pregnant with phenotypically discordant monochorionic twins: one with cystic hygroma and hydrops, the other one normal. Fetal blood sampling was performed by intrahepatic blood collection for karyotyping of both fetuses, revealing the same genotype of 46,XY/47,XYY in 2:1 proportion. Phenotypic discordance in monozygotic twins can have various causes, such as placental vascular anatomy, differences in allocation of the number of blastomeres or genetic postzygotic events.

  13. Monochorionic-diamniotic discordant growth in a twin pregnancy with one fetus affected by Ebstein's anomaly of tricuspid leaflets.

    PubMed

    Fukami, Tatsuya; Goto, Maki; Matsuoka, Sakiko; Sorano, Sumire; Tohyama, Atsushi; Yamamoto, Hiroko; Nakamura, Sumie; Matsuoka, Ryoei; Tsujioka, Hiroshi; Eguchi, Fuyuki

    2016-07-01

    Our patient was diagnosed as having discordant twin growth with Ebstein's anomaly in the larger fetus. Cardiac function was deteriorated in accordance with progression of gestational age. Our observation indicated cardiac failure of the larger fetus. The most important issue in this situation is management of the timing of delivery.

  14. Experience-Driven Differences in Childhood Cortisol Predict Affect-Relevant Brain Function and Coping in Adolescent Monozygotic Twins

    PubMed Central

    Burghy, Cory A.; Fox, Michelle E.; Cornejo, M. Daniela; Stodola, Diane E.; Sommerfeldt, Sasha L.; Westbrook, Cecilia A.; Van Hulle, Carol; Schmidt, Nicole L.; Goldsmith, H. Hill; Davidson, Richard J.; Birn, Rasmus M.

    2016-01-01

    Stress and emotion involve diverse developmental and individual differences. Partially attributed to the development of the prefrontal cortex (PFC), the amygdala, and hypothalamic-pituitary-adrenal axis, the precise genetic and experiential contributions remain unknown. In previous work, childhood basal cortisol function predicted adolescent resting-state functional connectivity (rs-FC) and psychopathology. To parse experience-driven (non-genetic) contributions, we investigated these relations with a monozygotic (MZ) twin design. Specifically, we examined whether intrapair differences in childhood afternoon cortisol levels predicted cotwin differences in adolescent brain function and coping. As expected, intrapair differences in childhood cortisol forecast amygdala-perigenual PFC rs-FC (R2 = 0.84, FWE-corrected p = 0.01), and amygdala recovery following unpleasant images (R2 = 0.40, FWE-corrected p < 0.05), such that the cotwin with higher childhood cortisol evinced relatively lower rs-FC and poorer amygdala recovery in adolescence. Cotwin differences in amygdala recovery also predicted coping styles. These data highlight experience-dependent change in childhood and adolescence. PMID:27872489

  15. Cognitive deficits and magnetic resonance spectroscopy in adult monozygotic twins with lead poisoning.

    PubMed Central

    Weisskopf, Marc G; Hu, Howard; Mulkern, Robert V; White, Roberta; Aro, Antonio; Oliveira, Steve; Wright, Robert O

    2004-01-01

    Seventy-one-year-old identical twin brothers with chronic lead poisoning were identified from an occupational medicine clinic roster. Both were retired painters, but one brother (J.G.) primarily removed paint and had a history of higher chronic lead exposure. Patella and tibia bone lead concentrations measured by K-X-ray fluorescence in each brother were 5-10 times those of the general population and about 2.5 times higher in J.G. than in his brother (E.G.). Magnetic resonance spectroscopy (MRS) studies examined N-acetylaspartate:creatine ratios, a marker of neuronal density. Ratios were lower in J.G. than in his brother. Scores on neurocognitive tests that assess working memory/executive function were below expectation in both twins. Short-term memory function was dramatically worse in J.G. than in his brother. These results demonstrate some of the more subtle long-term neurologic effects of chronic lead poisoning in adults. In particular, they suggest the presence of frontal lobe dysfunction in both twins, but more dramatic hippocampal dysfunction in the brother with higher lead exposure. The MRS findings are consistent with the hypothesis that chronic lead exposure caused neuronal loss, which may contribute to the impairment in cognitive function. Although a causal relation cannot be inferred, the brothers were genetically identical, with similar life experiences. Although these results are promising, further study is necessary to determine whether MRS findings correlate both with markers of lead exposure and tests of cognitive function. Nevertheless, the results point to the potential utility of MRS in determining mechanisms of neurotoxicity not only for lead but also for other neurotoxicants as well. PMID:15064171

  16. Dermatoglyphics in relation to brain volumes in twins concordant and discordant for bipolar disorder.

    PubMed

    Vonk, R; van der Schot, A C; van Baal, G C M; van Oel, C J; Nolen, W A; Kahn, R S

    2014-12-01

    Palmar and finger dermatoglyphics are formed between the 10th and the 17th weeks of gestation and their morphology can be influenced by genetic or environmental factors, interfering with normal intrauterine development. As both the skin and the brain develop from the same embryonal ectoderm, dermatoglyphic alterations may be informative for early abnormal neurodevelopmental processes in the brain. We investigated whether dermatoglyphic alterations are related to structural brain abnormalities in bipolar disorder and to what extent they are of a genetic and of an environmental origin. Dermatoglyphics and volumetric data from structural MRI were obtained in 53 twin pairs concordant or discordant for bipolar disorder and 51 healthy matched control twin pairs. Structural equation modeling was used. Bipolar disorder was significantly positively associated with palmar a-b ridge count (ABRC), indicating higher ABRC in bipolar patients (rph=.17 (CI .04-.30)). Common genes appear to be involved because the genetic correlation with ABRC was significant (rph-A=.21 (CI .05-.36). Irrespective of disease, ABRC showed a genetically mediated association with brain volume, indicated by a significant genetic correlation rph-A of respectively -.36 (CI -.52 to -.22) for total brain, -.34 (CI -.51 to -.16) total cortical volume, -.27 (CI -.43 to -.08) cortical gray matter and -.23 (CI -.41 to -.04) cortical white matter. In conclusion, a genetically determined abnormal development of the foetal ectoderm between the 10th and 15th week of gestation appears related to smaller brain volumes in (subjects at risk for) bipolar disorder.

  17. Fragile X syndrome and the (CGG)[sub n] mutation: Two families with discordant MZ twins

    SciTech Connect

    Kruyer, H.; Estivill, X.; Mila, M.; Ballesta, F.; Glover, G.; Carbonell, P. )

    1994-03-01

    The fragile X phenotype has been found, in the majority of cases, to be due to the expansion of a CGG repeat in the 5'UTR region of the FMR-1 gene, accompanied by methylation of the adjacent CpG island and inactivation of the FMR-1 gene. Although several important aspects of genetics of fragile X have been resolved, it remains to be elucidated at which stage in development the transition from the premutation to the full mutation occurs. The authors present two families in which discordance between two sets of MZ twins illustrates two important genetic points. In one family, two affected MZ brothers differed in the number of CGG repeats, demonstrating in vivo mitotic instability of this CGG repeat and suggesting that the transition to the full mutation occurred postzygotically. In the second family, two MZ sisters had the same number of repeats, but only one was mentally retarded. When the methylation status of the FMR-1 CpG island was studied, the authors found that the majority of normal chromosomes had been inactivated in the affected twin, thus leading to the expression of the fragile X phenotype. 29 refs., 3 figs., 1 tab.

  18. Differential Parenting and Risk for Psychopathology: A Monozygotic Twin Difference Approach

    PubMed Central

    Long, E.C.; Aggen, S. H.; Gardner, C.; Kendler, K. S.

    2015-01-01

    Purpose Consistent and non-specific associations have been found between parenting style and major depression, anxiety disorders, and externalizing behavior. Although often considered part of twins’ shared environment, parenting can also be conceptualized as non-shared environment. Non-shared environmental influences have important effects on development but are difficult to test and sort out because of the possible confounding effects of gene-environment interactions and evocative gene-environment correlations. The MZ differences approach is one way to analytically investigate non-shared environment. Methods The aim of the present study is to use the MZ differences approach to investigate the relationship between differential parenting among 1,303 twin pairs (mean age 36.69 +/− 8.56) and differences in total symptom counts of major depression (MD), generalized anxiety disorder (GAD), conduct disorder (CD), and anti-social behavior (ASB) during adulthood. Results Although effect sizes tended to be small, a number of results were significantly different from zero. Perceived differences in parental coldness was positively associated with internalizing disorders. Differences in protectiveness were negatively associated with MD, GAD, and ASB. Differences in authoritarianism were positively associated with MD and CD, but negatively associated with ASB. Conclusions Perceived differences in parenting style are associated with differences in MD, GAD, CD, and ASB outcomes in a sample of MZ twins. Despite the lack of a basis for making causal inferences about parenting style and psychopathology, these results are suggestive of such a relationship and show that non-shared environmental influence of parenting does in some cases significantly predict adult psychopathology. PMID:25940788

  19. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins.

    PubMed

    McNulty, Nathan P; Yatsunenko, Tanya; Hsiao, Ansel; Faith, Jeremiah J; Muegge, Brian D; Goodman, Andrew L; Henrissat, Bernard; Oozeer, Raish; Cools-Portier, Stéphanie; Gobert, Guillaume; Chervaux, Christian; Knights, Dan; Lozupone, Catherine A; Knight, Rob; Duncan, Alexis E; Bain, James R; Muehlbauer, Michael J; Newgard, Christopher B; Heath, Andrew C; Gordon, Jeffrey I

    2011-10-26

    Understanding how the human gut microbiota and host are affected by probiotic bacterial strains requires carefully controlled studies in humans and in mouse models of the gut ecosystem where potentially confounding variables that are difficult to control in humans can be constrained. Therefore, we characterized the fecal microbiomes and metatranscriptomes of adult female monozygotic twin pairs through repeated sampling 4 weeks before, 7 weeks during, and 4 weeks after consumption of a commercially available fermented milk product (FMP) containing a consortium of Bifidobacterium animalis subsp. lactis, two strains of Lactobacillus delbrueckii subsp. bulgaricus, Lactococcus lactis subsp. cremoris, and Streptococcus thermophilus. In addition, gnotobiotic mice harboring a 15-species model human gut microbiota whose genomes contain 58,399 known or predicted protein-coding genes were studied before and after gavage with all five sequenced FMP strains. No significant changes in bacterial species composition or in the proportional representation of genes encoding known enzymes were observed in the feces of humans consuming the FMP. Only minimal changes in microbiota configuration were noted in mice after single or repeated gavage with the FMP consortium. However, RNA-Seq analysis of fecal samples and follow-up mass spectrometry of urinary metabolites disclosed that introducing the FMP strains into mice results in significant changes in expression of microbiome-encoded enzymes involved in numerous metabolic pathways, most prominently those related to carbohydrate metabolism. B. animalis subsp. lactis, the dominant persistent member of the FMP consortium in gnotobiotic mice, up-regulates a locus in vivo that is involved in the catabolism of xylooligosaccharides, a class of glycans widely distributed in fruits, vegetables, and other foods, underscoring the importance of these sugars to this bacterial species. The human fecal metatranscriptome exhibited significant changes

  20. A twin study on age-related macular degeneration.

    PubMed Central

    Meyers, S M

    1994-01-01

    A prospective twin study on age-related macular degeneration (AMD) recruited 83 monozygotic pairs, 28 dizygotic pairs, and one triplet set from 1986 through 1993. Zygosity was determined by genetic testing of red cell markers, HLA antigens, or specific DNA loci. There were no twin pairs in which I collected data on only one twin. To decrease ascertainment bias, after 1991 the recruitment notice did not mention AMD, and I did not ask about a history of eye disease before the eye examination. Because of this, twin pairs recruited from 1986 through 1991 were statistically analyzed separately from those after January 1, 1992. From 1986 through 1991, 23 twin pairs were recruited; 11 monozygotic and 2 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 9 monozygotic pairs with AMD were all concordant, and 1 dizygotic pair was discordant for basal laminar drusen. The concordance rate of AMD did not differ significantly between monozygotic and dizygotic twin pairs (P = .10) for 1986 through 1991. In 1992 and 1993, 88 twin pairs and one triplet set were recruited; 49 monozygotic and 19 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 14 monozygotic pairs with AMD were all concordant, and 2 of 7 dizygotic pairs were concordant for AMD. The nonidentical triplets (1 with and 2 without AMD) were categorized as one of the discordant dizygotic pairs in the statistical evaluation. In nontwin age-matched (within 2 or 5 years of age) or age- and sex-matched sibling pairs the concordance rate of AMD ranged from 16% to 25%. The concordance rate of AMD was significantly higher in monozygotic than in dizygotic twins (P = .001) for 1992 and 1993. The concordance rate was higher for monozygotic twin pairs recruited in 1992 and 1993 than in any of the four subsets of nontwin age-method or age- and sex-matched sibling pairs (P < .0001). Overall, from 1986 through 1993, 23 of 23 monozygotic and 2 of 8 dizygotic twin pairs were concordant for AMD

  1. Discordant twins with the smaller baby appropriate for gestational age – unusual manifestation of superfoetation: A case report

    PubMed Central

    Baijal, Noopur; Sahni, Mohit; Verma, Neeraj; Kumar, Amit; Parkhe, Nittin; Puliyel, Jacob M

    2007-01-01

    Background Documentation of superfoetation is extremely rare in humans., The younger foetus has invariably been small for gestational age (estimated from the date of the last menstrual bleed) in all the cases reported in the literature. We report a case where the younger twin was of appropriate size for gestation. Case Presentation The first of twins was of 32 weeks gestation and the baby was of appropriate size and development for the gestational age. The second twin was of 36 weeks gestation. Gestational age was estimated with the New Ballard score, x-ray of the lower limbs, dental age on x-ray, and ophthalmic examination. Conclusion Bleeding on implantation of the first foetus probably helped demarcate the two pregnancies. Dental age and the New Ballard score can be used to diagnose superfoetation in discordant twins, when detailed first trimester ultra-sound data is not available. PMID:17239246

  2. Monoamniotic twins discordant for anencephaly managed conservatively with good outcomes: two case reports and a review of the literature.

    PubMed

    Lim, K I; Dy, C; Pugash, D; Williams, K P

    2005-08-01

    Monoamniotic twin pregnancy discordant for anencephaly (MATDA) is a rare occurrence with only seven prior reported cases. Selective termination has been advocated in managing discordant monoamniotic twins. We report two cases managed expectantly with good outcomes and review other previously reported cases. The first case was a primigravid woman diagnosed with MATDA at 18 weeks. She was managed expectantly until 32 + 5 weeks when a Cesarean section was performed for preterm labor. The surviving female infant weighed 1610 g. The second case was a multigravid woman who was diagnosed with MATDA at 17 + 5 weeks and was managed as an outpatient. An emergency Cesarean section was performed at 31 weeks for non-reassuring monitoring and the surviving male infant weighed 1790 g. In both cases, the survivors were discharged home in good condition. A review of these two cases and those in the literature suggests that expectant management should be considered among management options for this rare condition.

  3. Fetal fraction estimate in twin pregnancies using directed cell-free DNA analysis.

    PubMed

    Struble, Craig A; Syngelaki, Argyro; Oliphant, Arnold; Song, Ken; Nicolaides, Kypros H

    2014-01-01

    To estimate fetal fraction (FF) in monozygotic and dizygotic twin pregnancies. Maternal plasma samples were obtained from 35 monochorionic twin pregnancies with male fetuses (monozygotic) and 35 dichorionic pregnancies discordant for fetal sex (dizygotic) at 11-13 weeks' gestation. Cell-free DNA was extracted and chromosome-selective sequencing with digital analysis of selected regions (DANSR™) was carried out. The fetal-fraction optimized risk of trisomy evaluation (FORTE™) algorithm was used to estimate FF using polymorphic alleles. In dizygotic twins the FORTE algorithm was modified to estimate the smallest FF contribution of the 2 fetuses. In both types of twins, FF was also determined by analysis of Y-chromosome sequences. In monozygotic twins, the median total FF was 14.0% (range 8.2-27.0%) and in dizygotic twins the median smallest FF was 7.9% (4.9-14.0%). There were significant associations in FF between the methods using polymorphic alleles and Y-chromosome sequences for both monozygotic (r=0.951, p<0.0001) and dizygotic (r=0.743, p<0.0001) twins. The study demonstrates the feasibility of an approach for cfDNA testing in twin pregnancies. This involves estimation of total FF in monozygotic twins and estimation of the lower FF of the 2 fetuses in dizygotic twins. © 2013 S. Karger AG, Basel.

  4. Placenta share discordance and umbilical artery Doppler change after antenatal betamethasone administration in monochorionic twins with selective intrauterine growth restriction: is there a link?

    PubMed

    Chang, Yao-Lung; Chang, Shuenn-Dyh; Chao, An-Shine; Hsieh, Peter C C; Wang, Chao-Nin; Wang, Tzu-Hao

    2012-10-01

    This study was designed to evaluate the degree of placenta share discordance in relation to the betamethasone-induced return of positive end-diastolic flow in monochorionic twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery Doppler. Monochorionic twins with sIUGR was defined as one twin having an estimated fetal weight below the 10th percentile combined with an estimated fetal weight discordance >25%. The umbilical artery Doppler directly prior to (D0) and 24 hours (D1) and 48 hours (D2) after the first dose of betamethasone administration was recorded. The estimated individual placental weight in monochorionic twins was obtained by cutting the placenta along the vascular equator into two territories; the placenta share discordance was calculated as [(estimated individual placental weight of appropriated for gestational age twin- estimated individual placental weight of growth restricted twin)/estimated individual placental weight of appropriated for gestational age twin] × 100%. Six (23.1%) of the 26 included cases achieved betamethasone-induced return of positive umbilical artery end-diastolic flow. The difference of placenta share discordance and birth weight discordance were not significantly different between twins with and without betamethasone-induced return of positive umbilical artery end-diastolic flow. Thus, according to our study results, it was proposed that although the placenta share discordance correlated with the abnormal umbilical artery Doppler in the IUGR fetus in monochorionic twin, the betamethasone-induced return of positive umbilical artery end-diastolic flow, however, did not reveal the similar relationship with the severity of placenta share discordance.

  5. A review of the mechanisms and evidence for typical and atypical twinning.

    PubMed

    McNamara, Helen C; Kane, Stefan C; Craig, Jeffrey M; Short, Roger V; Umstad, Mark P

    2016-02-01

    The mechanisms responsible for twinning and disorders of twin gestations have been the subject of considerable interest by physicians and scientists, and cases of atypical twinning have called for a reexamination of the fundamental theories invoked to explain twin gestations. This article presents a review of the literature focusing on twinning and atypical twinning with an emphasis on the phenomena of chimeric twins, phenotypically discordant monozygotic twins, mirror-image twins, polar body twins, complete hydatidiform mole with a coexistent twin, vanishing twins, fetus papyraceus, fetus in fetu, superfetation, and superfecundation. The traditional models attributing monozygotic twinning to a fission event, and more recent models describing monozygotic twinning as a fusion event, are critically reviewed. Ethical restrictions on scientific experimentation with human embryos and the rarity of cases of atypical twinning have limited opportunities to elucidate the exact mechanisms by which these phenomena occur. Refinements in the modeling of early embryonic development in twin pregnancies may have significant clinical implications. The article includes a series of figures to illustrate the phenomena described.

  6. Associations of mother's and father's parenting practices with children's observed social reticence in a competitive situation: a monozygotic twin difference study.

    PubMed

    Guimond, Fanny-Alexandra; Brendgen, Mara; Forget-Dubois, Nadine; Dionne, Ginette; Vitaro, Frank; Tremblay, Richard E; Boivin, Michel

    2012-04-01

    This study used the monozygotic (MZ) twin difference method to examine whether the unique environmental effects of maternal and paternal overprotection and hostility at the age of 30 months predict twins' observed social reticence in a competitive situation in kindergarten, while controlling for the effect of family-wide influences, including genetic and shared environmental factors, family socio-economical status and twin's birth weight. It was also examined whether these associations are moderated by parental depressive symptoms. Participants were 137 MZ twin pairs who were part of an ongoing longitudinal study. Hierarchical linear regressions revealed that differences in maternal and paternal overprotection predicted differences in twins' social reticence, albeit only in boys. Differences in paternal hostile parenting predicted differences in girls' reticent behavior, but only when fathers showed high levels of depressive symptoms. Hence, overprotected boys, as well as girls confronted with father's hostility and depressive symptoms, may tend to withdraw rather than face the challenge when experiencing difficult social situations such as competition. The results from the present study suggest that targeting maladaptive maternal as well as paternal child-rearing practices and psychopathology early on may be useful for reducing later internalizing behavior in the offspring.

  7. Frequent Extreme Cold Exposure and Brown Fat and Cold-Induced Thermogenesis: A Study in a Monozygotic Twin

    PubMed Central

    Vosselman, Maarten J.; Vijgen, Guy H. E. J.; Kingma, Boris R. M.; Brans, Boudewijn; van Marken Lichtenbelt, Wouter D.

    2014-01-01

    Introduction Mild cold acclimation is known to increase brown adipose tissue (BAT) activity and cold-induced thermogenesis (CIT) in humans. We here tested the effect of a lifestyle with frequent exposure to extreme cold on BAT and CIT in a Dutch man known as ‘the Iceman’, who has multiple world records in withstanding extreme cold challenges. Furthermore, his monozygotic twin brother who has a ‘normal’ sedentary lifestyle without extreme cold exposures was measured. Methods The Iceman (subject A) and his brother (subject B) were studied during mild cold (13°C) and thermoneutral conditions (31°C). Measurements included BAT activity and respiratory muscle activity by [18F]FDG-PET/CT imaging and energy expenditure through indirect calorimetry. In addition, body temperatures, cardiovascular parameters, skin perfusion, and thermal sensation and comfort were measured. Finally, we determined polymorphisms for uncoupling protein-1 and β3-adrenergic receptor. Results Subjects had comparable BAT activity (A: 1144 SUVtotal and B: 1325 SUVtotal), within the range previously observed in young adult men. They were genotyped with the polymorphism for uncoupling protein-1 (G/G). CIT was relatively high (A: 40.1% and B: 41.9%), but unlike during our previous cold exposure tests in young adult men, here both subjects practiced a g-Tummo like breathing technique, which involves vigorous respiratory muscle activity. This was confirmed by high [18F]FDG-uptake in respiratory muscle. Conclusion No significant differences were found between the two subjects, indicating that a lifestyle with frequent exposures to extreme cold does not seem to affect BAT activity and CIT. In both subjects, BAT was not higher compared to earlier observations, whereas CIT was very high, suggesting that g-Tummo like breathing during cold exposure may cause additional heat production by vigorous isometric respiratory muscle contraction. The results must be interpreted with caution given the low

  8. Multimodal brain imaging in autism spectrum disorder and the promise of twin research.

    PubMed

    Mevel, Katell; Fransson, Peter; Bölte, Sven

    2015-07-01

    Current evidence suggests the phenotype of autism spectrum disorder to be driven by a complex interaction of genetic and environmental factors impacting onto brain maturation, synaptic function, and cortical networks. However, findings are heterogeneous, and the exact neurobiological pathways of autism spectrum disorder still remain poorly understood. The co-twin control or twin-difference design is a potentially powerful tool to disentangle causal genetic and environmental contributions on neurodevelopment in autism spectrum disorder. To this end, monozygotic twins discordant for this condition provide unique means for the maximum control of potentially confounding factors. Unfortunately, only few studies of a rather narrow scope, and limited sample size, have been conducted. In an attempt to highlight the great potential of combining the brain connectome approach with monozygotic twin design, we first give an overview of the existing neurobiological evidence for autism spectrum disorder and its cognitive correlates. Then, a special focus is made onto the brain imaging findings reported within populations of monozygotic twins phenotypically discordant for autism spectrum disorder. Finally, we introduce the brain connectome model and describe an ongoing project using this approach among the largest cohort of monozygotic twins discordant for autism spectrum disorder ever recruited. © The Author(s) 2014.

  9. Evidence that BMI and type 2 diabetes share only a minor fraction of genetic variance: a follow-up study of 23,585 monozygotic and dizygotic twins from the Finnish Twin Cohort Study.

    PubMed

    Lehtovirta, M; Pietiläinen, K H; Levälahti, E; Heikkilä, K; Groop, L; Silventoinen, K; Koskenvuo, M; Kaprio, J

    2010-07-01

    We investigated whether BMI predicts type 2 diabetes in twins and to what extent that is explained by common genetic factors. This was a population-based twin cohort study. Monozygotic (n = 4,076) and dizygotic (n = 9,109) non-diabetic twin pairs born before 1958 answered a questionnaire in 1975, from which BMI was obtained. Information on incident cases of diabetes was obtained by linkage to nationwide registers until 2005. Altogether, 1,332 twins (6.3% of men, 5.1% of women) developed type 2 diabetes. The HR for type 2 diabetes increased monotonically with a mean of 1.22 (95% CI 1.20-1.24) per BMI unit and of 1.97 (95% CI 1.87-2.08) per SD of BMI. The HRs for lean, overweight, obese and morbidly obese participants were 0.59, 2.96, 6.80 and 13.64 as compared with normal weight participants. Model heritability estimates for bivariate variance due to an additive genetic component and non-shared environmental component were 75% (men) and 71% (women) for BMI, and 73% and 64%, respectively for type 2 diabetes. The correlations between genetic variance components (r (g)) indicated that one fifth of the covariance of BMI and type 2 diabetes was due to shared genetic influences. Although the mean monozygotic concordance for type 2 diabetes was approximately twice the dizygotic one, age of onset of diabetes within twin pair members varied greatly, irrespective of zygosity. A 28-year follow-up of adult Finnish twins showed that despite high trait heritability estimates, only a fraction of covariation in BMI and incident type 2 diabetes was of genetic origin.

  10. Nonshared environmental mediation of the association between deviant peer affiliation and adolescent externalizing behaviors over time: results from a cross-lagged monozygotic twin differences design.

    PubMed

    Burt, S Alexandra; McGue, Matt; Iacono, William G

    2009-11-01

    It has been argued that peers are the most important agent of adolescent socialization and, more specifically, that this socialization process occurs at the child-specific (or nonshared environmental) level (J. R. Harris, 1998; R. Plomin & Asbury, 2005). The authors sought to empirically evaluate this nonshared environmental peer influence hypothesis by examining the association between externalizing behaviors and deviant peer affiliation in a sample of 454 pairs of monozygotic (genetically identical) twins, assessed at ages 14 and 17, within a cross-lagged twin differences design. Results argued against a causal nonshared environmental influence of peer affiliation on the development of externalizing behaviors and in favor of nonshared environmental "selection." In particular, the twin with more externalizing behaviors at age 14 reported increased deviant peer affiliation relative to his or her co-twin 3 years later, regardless of his or her genetic predispositions toward externalizing behavior. Such findings suggest that adolescents with higher levels of externalizing behaviors select or shape (either intentionally or inadvertently) subsequent environmental experiences to involve increased affiliation with deviant peers. Implications are discussed.

  11. Tests of a Direct Effect of Childhood Abuse on Adult Borderline Personality Disorder Traits: A Longitudinal Discordant Twin Design

    PubMed Central

    Bornovalova, Marina A.; Huibregtse, Brooke M.; Hicks, Brian M.; Keyes, Margaret; McGue, Matt; Iacono, William

    2012-01-01

    We used a longitudinal twin design to examine the causal association between sexual, emotional, and physical abuse in childhood (before age 18) and borderline personality disorder (BPD) traits at age 24 using a discordant twin design and biometric modeling. Additionally, we examined the mediating and moderating effects of symptoms of childhood externalizing and internalizing disorders on the link between childhood abuse and BPD traits. Although childhood abuse, BPD traits, and internalizing and externalizing symptoms were all correlated, the discordant twin analyses and biometric modeling showed little to no evidence that consistent with a causal effect of childhood abuse on BPD traits. Instead, our results indicate that the association between childhood abuse and BPD traits stems from common genetic influences that, in some cases, also overlap with internalizing and externalizing disorders. These findings are inconsistent with the widely held assumption that childhood abuse causes BPD, and suggests that BPD traits in adulthood are better accounted for by heritable vulnerabilities to internalizing and externalizing disorders. PMID:22686871

  12. Bioinformatics analysis of abnormal DNA methylation in muscle samples from monozygotic twins discordant for type 2 diabetes.

    PubMed

    Liu, Fei; Sun, Qianqian; Wang, Lingxiao; Nie, Shuangshuang; Li, Jun

    2015-07-01

    The present study aimed to examine the changes in DNA methylation of gene promoters associated with type 2 diabetes (T2D). The DNA methylation profile dataset GSE38291 was downloaded from the Gene Expression Omnibus database. A paired t-test was used to analyze differences in the DNA methylation of gene promoters between T2D and normal muscle samples. Gene Ontology (GO) enrichment analysis was performed using online tool, The Database for Annotation, Visualization and Integrated Discovery. Whole-Genome rVISTA was used to analyze the enriched transcription factor (TF) binding sites upstream of the transcription start site in the differentially methylated genes. A total of 38 genes, including Sirtuin 1, N-acetyltransferase 6, phospholipase A2 group XIIB and nuclear factor of activated T cells calcineurin-dependent 1, were identified to be differentially methylated between these two groups. One GO term, DNA geometric change (GO:0032392), was significantly enriched (P<0.05) by the hyper-methylated genes. In addition, the binding sites of one gene, zinc finger E-box binding homeobox 1, and three TFs, methyl CpG binding protein 2, TFEB and TFAP4, were significantly enriched in the hyper- and hypo-methylated genes, respectively. The resulting T2D‑associated genes and potential TFs provided a novel insight into the molecular mechanisms underlying the pathology of T2D. These genes may become promising target genes for the development of treatments for T2D.

  13. Haemoglobin discordances in twins: due to differences in timing of cord clamping?

    PubMed

    Verbeek, Lianne; Zhao, Depeng P; Middeldorp, Johanna M; Oepkes, Dick; Hooper, Stuart B; Te Pas, Arjan B; Lopriore, Enrico

    2017-07-01

    Our objective was to study the differences in haemoglobin (Hb) at birth in dichorionic (DC) versus monochorionic (MC) twins in relation to birth order and mode of delivery. All consecutive DC twin pregnancies and uncomplicated MC twin pregnancies with two live-born twins delivered at our centre were included in this retrospective cohort study. Hb levels at birth and on day 2 were evaluated in association with birth order and mode of delivery. The occurrence of polycythaemia (venous haematocrit >65%) was also recorded. A total of 300 DC and 290 MC twin pairs were included. In DC and MC twins delivered vaginally, second-born twins had a higher Hb level at birth compared with their co-twin (mean Hb level 16.7 vs 15.9 g/dL (p<0.01) in DC twins and 17.8 vs 16.1 g/dL (p<0.01) in MC twins). In twins delivered through caesarean section, no intertwin differences in Hb levels were detected. Polycythaemia occurred significantly more often in second-born twins compared with first-born twins delivered vaginally: 10 (5%) vs 2 (1%) (p=0.02) in DC twins and 20 (12%) vs 2 (1%) (p<0.01) in MC twins. Second-born DC and MC twins delivered vaginally have higher Hb levels at birth compared with first-born twins. Intertwin Hb differences in MC twins may partly be related to blood transfusion through the vascular anastomoses. Since DC twins do not have anastomoses, other factors may lead to Hb differences, including differences in timing of umbilical cord clamping. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. Methylation matters? Decreased methylation status of genomic DNA in the blood of schizophrenic twins.

    PubMed

    Bönsch, Dominikus; Wunschel, Michael; Lenz, Bernd; Janssen, Gesa; Weisbrod, Matthias; Sauer, Heinrich

    2012-08-15

    Studies of schizophrenia inheritance in identical twins show a concordance of about 50%, which supports an epigenetic model. In our present study we investigated methylation of genomic DNA and promoter methylation of Reelin and SOX10 genes in peripheral blood of twins suffering from schizophrenia. Global DNA methylation was reduced (52.3%) in schizophrenic twins if compared with healthy control twins (65.7%). The reduced methylation was significant in males only. We also found a similar hypomethylation in the non-affected twins of discordant pairs and a mixed group of psychiatric controls. In discordant twins there was a relative hypermethylation of the SOX10 promoter. Within-pair-difference of methylation of Reelin promoter was significantly lower in monozygotic twins than in dizygotic twins.

  15. Clones in the Classroom: A Daily Diary Study of the Nonshared Environmental Relationship Between Monozygotic Twin Differences in School Experience and Achievement

    PubMed Central

    Asbury, Kathryn; Almeida, David; Hibel, Jacob; Harlaar, Nicole; Plomin, Robert

    2010-01-01

    Do genetically identical children experience the same classroom differently? Are nonshared classroom experiences associated with differences in achievement? We designed a telephone diary measure which we administered every school day for 2 weeks to 122 10-year-olds in 61 monozygotic (MZ) twin pairs. Each pair shared genes, a classroom, peers and a teacher. We found that MZ twins did experience their classrooms differently (rMZ < 0.65 for all measures of classroom experience). Furthermore, MZ differences in peer problems were significantly associated with MZ differences in Mathematics achievement (ES = 8%); differences in positivity about school were significantly associated with differences in Mathematics (ES = 15%) and Science (ES = 8%) achievement; and differences in ‘flow’ in Science lessons were associated with differences in Science achievement (ES = 12%). In a multiple regression analysis, MZ differences in positivity about school significantly predicted MZ differences in Mathematics achievement (R2 = 0.16, p < .01) and MZ differences in ‘flow’ in Science significantly predicted MZ differences in Science achievement (R2 = 0.10, p < .05). These results indicate that MZ twins experience the classroom differently and that differences in their experience are associated with differences in their achievement. PMID:19016614

  16. Nature and nurture: a case of transcending haematological pre-malignancies in a pair of monozygotic twins adding possible clues on the pathogenesis of B-cell proliferations.

    PubMed

    Hansen, Marcus C; Nyvold, Charlotte G; Roug, Anne S; Kjeldsen, Eigil; Villesen, Palle; Nederby, Line; Hokland, Peter

    2015-05-01

    We describe a comprehensive molecular analysis of a pair of monozygotic twins, who came to our attention when one experienced amaurosis fugax and was diagnosed with JAK2+ polycythaemia vera. He (Twin A) was also found to have an asymptomatic B-cell chronic lymphocytic leukaemia (B-CLL). Although JAK2-, Twin B was subsequently shown to have a benign monoclonal B-cell lymphocytosis (MBL). Flow cytometric and molecular analyses of the B-cell compartments revealed different immunoglobulin light and heavy chain usage in each twin. We hypothesized that whole exome sequencing could help delineating the pattern of germline B-cell disorder susceptibility and reveal somatic mutations potentially contributing to the differential patterns of pre-malignancy. Comparing bone marrow cells and T cells and employing in-house engineered integrative analysis, we found aberrations in Twin A consistent with a myeloid neoplasm, i.e. in TET2, RUNX1, PLCB1 and ELF4. Employing the method for detecting high-ranking variants by extensive annotation and relevance scoring, we also identified shared germline variants in genes of proteins interacting with B-cell receptor signalling mediators and the WNT-pathway, including IRF8, PTPRO, BCL9L, SIT1 and SIRPB1, all with possible implications in B-cell proliferation. Similar patterns of IGHV-gene usage to those demonstrated here have been observed in inherited acute lymphoblastic leukaemia. Collectively, these findings may help in facilitating identification of putative master gene(s) involved in B-cell proliferations in general and MBL and B-CLL in particular.

  17. Motives for and barriers to physical activity in twin pairs discordant for leisure time physical activity for 30 years.

    PubMed

    Aaltonen, S; Leskinen, T; Morris, T; Alen, M; Kaprio, J; Liukkonen, J; Kujala, U

    2012-02-01

    Long-term persistent physical activity is important in the prevention of chronic diseases, but a large number of people do not participate in physical activity to obtain health benefits. The purpose of this study was to examine the motives and perceived barriers to long-term engagement in leisure time physical activity. Same-sex twin pairs (N=16, mean age 60) discordant for physical activity over 30 years were identified from the Finnish Twin Cohort. We evaluated participants' physical activity motivation with the 73-item Recreational Exercise Motivation Measure and assessed barriers to physical activity with a 25-item questionnaire. The characteristics of physical activity motivation and perceived barriers between the active and inactive co-twins were analysed using paired tests. Motives related to the sub-dimensions of enjoyment and physical fitness and psychological state were the most important reasons for participation in physical activity among all the twin individuals analysed. The sub-dimensions mastery (p=0.018, Cohen's d=0.76), physical fitness (p=0.029, Cohen's d=0.69), and psychological state (p=0.039, Cohen's d=0.65) differed significantly between active and inactive co-twins. More than half of the participants reported no reasons for not being physically active. If reasons existed, participation in physical activity was deterred mostly by pain and various health problems. This study found no differences in perceived barriers between active and inactive co-twins. We conclude from our results that the main factors promoting persistent leisure time physical activity were participants' wish to improve or maintain their physical skills or techniques, a feeling that exercise would improve their mental and physical health and that they found the activity enjoyable. This study helps us understand the importance of the role of motives and the minor role of perceived barriers for engagement in persistent physical activity.

  18. P300 amplitude in nonalcoholic adolescent twin pairs who become discordant for alcoholism as adults.

    PubMed

    Carlson, Scott R; Iacono, William G; McGue, Matt

    2004-11-01

    Past reports suggest that reduced P300 amplitude is associated with risk for alcoholism. We examined whether visual P300 amplitude could identify familial risk for alcohol disorders in individuals not known to be at risk at the time P300 was recorded. These individuals were twins from pairs where neither twin had an alcohol disorder at age 17 but familial risk was established at age 20 when one twin developed an alcohol disorder whereas the other did not. Of special interest was the P300 of the unaffected twin recorded at age 17 when both twins were alcoholism free. We found reduced P300 in the unaffected twin compared to pairs where both members were continuously disorder free. Hence, P300 was reduced in alcohol disorder-free individuals whose twin siblings subsequently developed alcoholism, further supporting reduced P300 amplitude as an endophenotype indexing familial risk for alcoholism.

  19. Gene Expression Profiles from Disease Discordant Twins Suggest Shared Antiviral Pathways and Viral Exposures among Multiple Systemic Autoimmune Diseases.

    PubMed

    Gan, Lu; O'Hanlon, Terrance P; Lai, Zhennan; Fannin, Rick; Weller, Melodie L; Rider, Lisa G; Chiorini, John A; Miller, Frederick W

    2015-01-01

    Viral agents are of interest as possible autoimmune triggers due to prior reported associations and widely studied molecular mechanisms of antiviral immune responses in autoimmunity. Here we examined new viral candidates for the initiation and/or promotion of systemic autoimmune diseases (SAID), as well as possible related signaling pathways shared in the pathogenesis of those disorders. RNA isolated from peripheral blood samples from 33 twins discordant for SAID and 33 matched, unrelated healthy controls was analyzed using a custom viral-human gene microarray. Paired comparisons were made among three study groups-probands with SAID, their unaffected twins, and matched, unrelated healthy controls-using statistical and molecular pathway analyses. Probands and unaffected twins differed significantly in the expression of 537 human genes, and 107 of those were associated with viral infections. These 537 differentially expressed human genes participate in overlapping networks of several canonical, biologic pathways relating to antiviral responses and inflammation. Moreover, certain viral genes were expressed at higher levels in probands compared to either unaffected twins or unrelated, healthy controls. Interestingly, viral gene expression levels in unaffected twins appeared intermediate between those of probands and the matched, unrelated healthy controls. Of the viruses with overexpressed viral genes, herpes simplex virus-2 (HSV-2) was the only human viral pathogen identified using four distinct oligonucleotide probes corresponding to three HSV-2 genes associated with different stages of viral infection. Although the effects from immunosuppressive therapy on viral gene expression remain unclear, this exploratory study suggests a new approach to evaluate shared viral agents and antiviral immune responses that may be involved in the development of SAID.

  20. Gene Expression Profiles from Disease Discordant Twins Suggest Shared Antiviral Pathways and Viral Exposures among Multiple Systemic Autoimmune Diseases

    PubMed Central

    Gan, Lu; O’Hanlon, Terrance P.; Lai, Zhennan; Fannin, Rick; Weller, Melodie L.; Rider, Lisa G.; Chiorini, John A.; Miller, Frederick W.

    2015-01-01

    Viral agents are of interest as possible autoimmune triggers due to prior reported associations and widely studied molecular mechanisms of antiviral immune responses in autoimmunity. Here we examined new viral candidates for the initiation and/or promotion of systemic autoimmune diseases (SAID), as well as possible related signaling pathways shared in the pathogenesis of those disorders. RNA isolated from peripheral blood samples from 33 twins discordant for SAID and 33 matched, unrelated healthy controls was analyzed using a custom viral-human gene microarray. Paired comparisons were made among three study groups—probands with SAID, their unaffected twins, and matched, unrelated healthy controls—using statistical and molecular pathway analyses. Probands and unaffected twins differed significantly in the expression of 537 human genes, and 107 of those were associated with viral infections. These 537 differentially expressed human genes participate in overlapping networks of several canonical, biologic pathways relating to antiviral responses and inflammation. Moreover, certain viral genes were expressed at higher levels in probands compared to either unaffected twins or unrelated, healthy controls. Interestingly, viral gene expression levels in unaffected twins appeared intermediate between those of probands and the matched, unrelated healthy controls. Of the viruses with overexpressed viral genes, herpes simplex virus-2 (HSV-2) was the only human viral pathogen identified using four distinct oligonucleotide probes corresponding to three HSV-2 genes associated with different stages of viral infection. Although the effects from immunosuppressive therapy on viral gene expression remain unclear, this exploratory study suggests a new approach to evaluate shared viral agents and antiviral immune responses that may be involved in the development of SAID. PMID:26556803

  1. Communicative Development in Twins with Discordant Histories of Recurrent Otitis Media.

    ERIC Educational Resources Information Center

    Hemmer, Virginia Hoey; Ratner, Nan Bernstein

    1994-01-01

    The communicative abilities of six sets of same-sex, preschool dizygotic twins were examined. In each dyad, one sibling had a strong history of recurrent otitis media (ROM) but the other twin did not. History of ROM was associated with lowered receptive vocabulary, with no consistent effects detected in expressive speech and language tasks.…

  2. Communicative Development in Twins with Discordant Histories of Recurrent Otitis Media.

    ERIC Educational Resources Information Center

    Hemmer, Virginia Hoey; Ratner, Nan Bernstein

    1994-01-01

    The communicative abilities of six sets of same-sex, preschool dizygotic twins were examined. In each dyad, one sibling had a strong history of recurrent otitis media (ROM) but the other twin did not. History of ROM was associated with lowered receptive vocabulary, with no consistent effects detected in expressive speech and language tasks.…

  3. The nasal septum and the development of the midface. A longitudinal study of a pair of monozygotic twins.

    PubMed

    Grymer, L F; Bosch, C

    1997-03-01

    The development of the nose and the growth of the midface has been followed in a pair of identical twins. One of them (twin A) had nasal septum destruction after septal haematoma and abscess at the age of 7 years, and was treated by immediate implantation of homologous septal cartilage from a tissue bank. From 7-17 years of age the growth and development of the nose and face were followed. Lateral cephalograms, photographs, acoustic rhinometry and rhinoscopy were performed. Twin B presented a normal nasal and facial growth and served as control. Twin A developed a saddle nose, an upward displacement of the anterior part of the maxilla, diminished vertical development of the nasal cavity, and a retrognathically positioned maxilla due to decreased anteroposterior maxillary growth. This case report seems to indicate that the cartilaginous nasal septum is an important factor influencing vertical and sagittal growth of the maxilla.

  4. Dizygotic twins discordant for early-onset Citrobacter koseri and group B streptococcal sepsis.

    PubMed

    Lin, Wei-Jen; Wang, Chih-Chien; Lo, Wen-Tsung; Chu, Mong-Ling; Lee, Chuen-Ming

    2005-05-01

    Early-onset neonatal sepsis is usually a multisystem fulminant illness with prominent respiratory symptoms, and typically the infant has acquired the organism from the maternal genital tract during the intrapartum period. In this article, we report a rare case of dizygotic twins where each individual suffered early-onset sepsis caused by a different pathogen. Group B streptococcal (GBS) sepsis was diagnosed in twin A 1 day after birth; sepsis and meningitis caused by Citrobacter koseri was diagnosed in twin B at the age of the 4 days. The mother developed pre-eclampsia and fever and the twins were delivered via cesarean section at 35 week's gestation. Twin A received ampicillin treatment for 14 days and recovered fully. Twin B was treated with ceftriaxone for 4 weeks and follow-up brain ultrasound revealed persistent enlargement of the bilateral-lateral ventricles. When empiric antibiotic is considered for the symptomatic twin of a sibling with early-onset GBS infection, samples of blood and cerebrospinal fluid (CSF) should be obtained for culture study before treatment. Adjustment of antibiotic treatment based on the results of cultures and CSF Gram stain and antibiotic susceptibility test is essential.

  5. Behavioral versus genetic determination of lipoproteins andidentical twins discordant for exercise

    SciTech Connect

    Williams, Paul T.; Blanche, Patricia J.; Krauss, Ronald M.

    2004-06-01

    Lipoprotein and weight differences between vigorously active and sedentary MZ twins are used to: (1) estimate the effects of training while controlling for genotype; (2) estimate genetic concordance in the presence of divergent lifestyles.

  6. Low Birth Weight in MZ Twins Discordant for Birth Weight is Associated with Shorter Telomere Length and lower IQ, but not Anxiety/Depression in Later Life.

    PubMed

    Strohmaier, Jana; van Dongen, Jenny; Willemsen, Gonneke; Nyholt, Dale R; Zhu, Gu; Codd, Veryan; Novakovic, Boris; Hansell, Narelle; Wright, Margaret J; Rietschel, Liz; Streit, Fabian; Henders, Anjali K; Montgomery, Grant W; Samani, Nilesh J; Gillespie, Nathan A; Hickie, Ian B; Craig, Jeffrey M; Saffery, Richard; Boomsma, Dorret I; Rietschel, Marcella; Martin, Nicholas G

    2015-04-01

    Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.

  7. Use of monozygotic twins to investigate the relationship between 5HTTLPR genotype, depression and stressful life events: an application of Item Response Theory.

    PubMed

    Wray, Naomi R; Coventry, William L; James, Michael R; Montgomery, Grant W; Eaves, Lindon J; Martin, Nicholas G

    2008-01-01

    We examine the interaction between stressful life events (SLE) and genotypes for the length polymorphism of the serotonin receptor gene (5HTTLPR) on risk of depression. We hypothesize that if the interaction is real, monozygotic twin pairs (MZT) homozygous for the short allele (SS) will have a greater within pair variance in depression measures than MZT homozygous for the long allele (LL), as a reflection of their increased sensitivity to unknown environmental risk factors. Telephone interviews were used to assess symptoms of depression and suicidality on 824 MZT. Rather than using the interview items to calculate sum scores or allocate diagnostic classes we use Item Response Theory to model the contribution of each item to each individual's underlying liability to depression. SLE were also measured on the MZT assessed by mailed questionnaire on average 3.8 years previously, and these were used in follow-up analyses. We find no evidence for significant differences in within pair variance between 5HTTLPR genotypic classes and so can provide no support for interaction between these genotypes and the environment. The use of MZT provides a novel framework for examining genotype x environment interaction in the absence of measures on SLE.

  8. Observed Rate of Down Syndrome in Twin Pregnancies.

    PubMed

    Sparks, Teresa N; Norton, Mary E; Flessel, Monica; Goldman, Sara; Currier, Robert J

    2016-11-01

    To evaluate the observed incidence of Down syndrome in twins compared with that expected based on maternal age-matched singletons, which is the current clinical approach. This was a retrospective review of California Prenatal Screening Program participants with expected delivery dates between July 1995 and December 2012. Cases confirmed prenatally or postnatally with a genetic imbalance leading to phenotypic Down syndrome (trisomy 21, mosaic trisomy 21, or translocations) were included. Pregnancies conceived with ovum donation and women older than 45 years were excluded. We compared the observed Down syndrome incidence per pregnancy for twins with expected incidence by extrapolating from singleton data and expected zygosity as is the current clinical approach. This extrapolation assumes that monozygotic pregnancies have equivalent Down syndrome risk per pregnancy relative to maternal age-matched singletons and dizygotic pregnancies have twice the risk of at least one affected fetus. Zygosity for affected cases was presumed to be monozygotic with Down syndrome concordance and dizygotic with Down syndrome discordance. Counts were compared using cumulative Poisson distributions. Of 77,279 twin pregnancies, 182 (0.2%) had at least one fetus with Down syndrome confirmed by karyotype. The ratio of observed-to-expected Down syndrome incidence per pregnancy was 33.6%, 75.2%, and 70.0% for monozygotic, dizygotic, and all twins, respectively (P<.001 for all comparisons). Considering maternal age subgroups and twin zygosity, a significantly lower-than-expected Down syndrome incidence was seen for women aged 25 to 45 years with monozygotic pregnancies and overall for women aged 25 to 45 years with dizygotic pregnancies. The observed incidence of Down syndrome in twin pregnancies is lower than expected, most notably for monozygotic pregnancies and with increasing maternal age. Risk-based counseling can strongly affect women's choices regarding testing and management during

  9. A twin approach to unraveling epigenetics.

    PubMed

    Bell, Jordana T; Spector, Tim D

    2011-03-01

    The regulation of gene expression plays a pivotal role in complex phenotypes, and epigenetic mechanisms such as DNA methylation are essential to this process. The availability of next-generation sequencing technologies allows us to study epigenetic variation at an unprecedented level of resolution. Even so, our understanding of the underlying sources of epigenetic variability remains limited. Twin studies have played an essential role in estimating phenotypic heritability, and these now offer an opportunity to study epigenetic variation as a dynamic quantitative trait. High monozygotic twin discordance rates for common diseases suggest that unexplained environmental or epigenetic factors could be involved. Recent genome-wide epigenetic studies in disease-discordant monozygotic twins emphasize the power of this design to successfully identify epigenetic changes associated with complex traits. We describe how large-scale epigenetic studies of twins can improve our understanding of how genetic, environmental and stochastic factors impact upon epigenetics, and how such studies can provide a comprehensive understanding of how epigenetic variation affects complex traits.

  10. A twin approach to unraveling epigenetics

    PubMed Central

    Bell, Jordana T.; Spector, Tim D.

    2011-01-01

    The regulation of gene expression plays a pivotal role in complex phenotypes, and epigenetic mechanisms such as DNA methylation are essential to this process. The availability of next-generation sequencing technologies allows us to study epigenetic variation at an unprecedented level of resolution. Even so, our understanding of the underlying sources of epigenetic variability remains limited. Twin studies have played an essential role in estimating phenotypic heritability, and these now offer an opportunity to study epigenetic variation as a dynamic quantitative trait. High monozygotic twin discordance rates for common diseases suggest that unexplained environmental or epigenetic factors could be involved. Recent genome-wide epigenetic studies in disease-discordant monozygotic twins emphasize the power of this design to successfully identify epigenetic changes associated with complex traits. We describe how large-scale epigenetic studies of twins can improve our understanding of how genetic, environmental and stochastic factors impact upon epigenetics, and how such studies can provide a comprehensive understanding of how epigenetic variation affects complex traits. PMID:21257220

  11. Monozygotic twin model reveals novel embryo-induced transcriptome changes of bovine endometrium in the preattachment period.

    PubMed

    Klein, Claudia; Bauersachs, Stefan; Ulbrich, Susanne E; Einspanier, Ralf; Meyer, Heinrich H D; Schmidt, Susanne E M; Reichenbach, Horst-Dieter; Vermehren, Margarete; Sinowatz, Fred; Blum, Helmut; Wolf, Eckhard

    2006-02-01

    Initiation and maintenance of pregnancy are critically dependent on an intact embryo-maternal communication in the preimplantation period. To get new insights into molecular mechanisms underlying this complex dialog, a holistic transcriptome study of endometrium samples from Day 18 pregnant vs. nonpregnant twin cows was performed. This genetically defined model system facilitated the identification of specific conceptus-induced changes of the endometrium transcriptome. Using a combination of subtracted cDNA libraries and cDNA array hybridization, 87 different genes were identified as upregulated in pregnant animals. Almost one half of these genes are known to be stimulated by type I interferons. For the ISG15ylation system, which is assumed to play an important role in interferon tau (IFNT) signaling, mRNAs of four potential components (IFITM1, IFITM3, HSXIAPAF1, and DTX3L) were found at increased levels in addition to ISG15 and UBE1L. These results were further substantiated by colocalization of these mRNAs in the endometrium of pregnant animals shown by in situ hybridization. A functional classification of the identified genes revealed several different biological processes involved in the preparation of the endometrium for the attachment and implantation of the embryo. Specifically, elevated transcript levels were found for genes involved in modulation of the maternal immune system, genes relevant for cell adhesion, and for remodeling of the endometrium. This first systematic study of maternal transcriptome changes in response to the presence of an embryo on Day 18 of pregnancy in cattle is an important step toward deciphering the embryo-maternal dialog using a systems biology approach.

  12. Progression and determinants of quantitative magnetic resonance imaging measures of lumbar disc degeneration: a five-year follow-up of adult male monozygotic twins.

    PubMed

    Videman, Tapio; Battié, Michele C; Parent, Eric; Gibbons, Laura E; Vainio, Pauli; Kaprio, Jaakko

    2008-06-01

    A longitudinal study. Our goal was to explore the role of digital magnetic resonance imaging (MRI) data, by extending our earlier 5-year follow-up study of progression of lumbar spine degeneration with quantitative measures of disc degeneration. A longitudinal study is optimal for investigating disc degeneration but only a few studies (with small sample sizes) or short follow-up studies include repeated MRI data. Subjects consisted of 134 male monozygotic twins (age 35-69 years). Quantitative MRI measures included changes in disc bulging and height. Inter-rater reliability coefficients were between 0.77 and 0.96. At baseline and follow-up, an extensive interview about exposures to suspected determinants was conducted. Reduction in disc height and increases in bulges (worsening) were seen in 2/3 of subjects. The mean reduction in disc height was 2.2% to 3.6%. A mean increase in bulging of 7% to 10% was found in the L1-L4 discs and 4% in L4-S1 discs. Although the mean changes were small, few reverse changes were observed. Familial aggregation, a proxy for genetic influences, explained 17% of changes in disc height, and 11% and 0% of changes in the sizes of anterior and posterior bulges in the regression models. Higher maximal occupational lifting (AR2 = 4.9%) and smoking (AR2 = 3.5%) during follow-up predicted more disc height reduction. Greater increases in bulging (AR2 = 7.4%-10.2%) were predicted by smaller bulges at baseline. The mean annual changes in disc heights (<1%) and bulges (<2%) were small, and included both decreases and increases, with only a few subjects showing more major changes in either direction. The role of genetics was largest except in posterior bulges, but lifting and smoking were also associated with disc height reduction but none of the other studied risk factors were associated with anterior or posterior disc bulging. Different degenerative findings have different determinants of progression.

  13. Test of a Potential Causal Influence of Earlier Age of Gambling Initiation on Gambling Involvement and Disorder: A Multi-level Discordant Twin Design

    PubMed Central

    Slutske, Wendy S.; Deutsch, Arielle R.; Richmond-Rakerd, Leah S.; Chernyavskiy, Pavel; Statham, Dixie J.; Martin, Nicholas G.

    2014-01-01

    The premise that an association between an earlier age of gambling initiation and the later development of disordered gambling is causal has not yet been empirically examined. The current study used a multi-level discordant twin design to examine the nature of this association. Participants were 3,546 same-sex twins (mean age = 37.7 years) from the Australian Twin Registry who completed a telephone interview that included an extensive assessment of gambling and related behaviors. Multilevel models were employed to estimate individual (within-twin-pair comparison) and family-level (between-twin-pair comparison) effects, as well as the cross-level interaction between these effects. Family-level effects (genetic or environmental factors shared by family members) of age of gambling initiation robustly predicted later adult gambling frequency and disorder; the evidence for individual-level effects (unique factors not shared by family members, including a potentially causal effect of earlier age of gambling onset) was less robust. The results of this study suggest that the relation between earlier age of gambling initiation and later gambling involvement and disorder is primarily non-causal; efforts to delay the onset of gambling among young people may not necessarily reduce the number who later go on to develop gambling-related problems. PMID:24635489

  14. Gender identity disorder in twins: a review of the case report literature.

    PubMed

    Heylens, Gunter; De Cuypere, Griet; Zucker, Kenneth J; Schelfaut, Cleo; Elaut, Els; Vanden Bossche, Heidi; De Baere, Elfride; T'Sjoen, Guy

    2012-03-01

    The etiology of gender identity disorder (GID) remains largely unknown. In recent literature, increased attention has been attributed to possible biological factors in addition to psychological variables. To review the current literature on case studies of twins concordant or discordant for GID. A systematic, comprehensive literature review. Of 23 monozygotic female and male twins, nine (39.1%) were concordant for GID; in contrast, none of the 21 same-sex dizygotic female and male twins were concordant for GID, a statistically significant difference (P=0.005). Of the seven opposite-sex twins, all were discordant for GID. These findings suggest a role for genetic factors in the development of GID. © 2011 International Society for Sexual Medicine.

  15. Personality and birth order in monozygotic twins adopted apart: a test of Sulloway's theory; Research Reviews: twin births and cancer risk in mothers, male sexual dysfunction, twin study of ultimatum game behavior; Human Interest: 'The Land of Twins', twin-like reunion-I, twin-like reunion-II.

    PubMed

    Segal, Nancy L

    2008-02-01

    A brief overview of Sulloway's (1996) theory of birth order and personality is presented. A reared apart twin approach for testing his personality findings regarding openness to experience and conscientiousness in first borns and later borns is described. This is followed by summaries of three recent twin studies. The topics include cancer risk in mother of twins, sexual dysfunction in males and responder behavior during ultimatum games. This article concludes with a discussion of twinning rates and rituals among the Yoruba of western Nigeria, and descriptions of two unusual reunions between siblings and twins.

  16. Heritability of myopic refractive errors in identical and fraternal twins.

    PubMed

    Angi, M R; Clementi, M; Sardei, C; Piattelli, E; Bisantis, C

    1993-10-01

    The existence of a visual feedback control of eye growth in humans is controversial, as the contributions of genetic and environmental factors are still unknown. To evaluate the heritability of refractive defects, we measured ocular refraction in 19 monozygote and 20 dizygote twin pairs (mean age 5 years). Monozygosity was ascertained by a common chorion, similarity of somatic traits, and identical dermatogliphes and was confirmed in myopes by blood marker diagnosis. Ocular refractive defects and axial length were evaluated by cycloplegic autorefractometry and biometry. By comparing identical and fraternal twins heritability of refractive defects was estimated to be 0.08-0.14; this low value indicates that the observed variability in refractive errors is nongenetic in origin. Three monozygote pairs were anisomyopic; differences between eyes in identical twins were related to the increased axial length of myopic eyes. In one eye, myopia was attributed to visual deprivation induced by a congenital cataract, while in five eyes it was correlated directly to the degree of astigmatic defects. The discordant axial length observed in monozygote twins is nongenetic. In agreement with previous findings reported in the literature, it is proposed that visual impoverishment of retinal images may play an early regulatory role in postnatal eye growth.

  17. Managing Monoamniotic Twin Pregnancies.

    PubMed

    Post, Annalisa; Heyborne, Kent

    2015-09-01

    Monoamniotic twins comprise a rare but important subset of twins at risk of unique and serious complications, placing them at the highest risk of perinatal mortality of all twin gestations. In addition to risks faced by all twins (prematurity, selective growth restriction), all monochorionic twins (twin-twin transfusion syndrome), and all monozygotic twins (congenital anomalies), monoamniotic twins face the unique risk of cord entanglement. Accordingly, early diagnosis, screening for fetal anomalies, surveillance for twin-twin transfusion syndrome, decisions related to monitoring after viability, and timing and route of delivery are all critical. Herein, we present recommendations for optimal management.

  18. Physical activity, fitness, glucose homeostasis, and brain morphology in twins.

    PubMed

    Rottensteiner, Mirva; Leskinen, Tuija; Niskanen, Eini; Aaltonen, Sari; Mutikainen, Sara; Wikgren, Jan; Heikkilä, Kauko; Kovanen, Vuokko; Kainulainen, Heikki; Kaprio, Jaakko; Tarkka, Ina M; Kujala, Urho M

    2015-03-01

    The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity. From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses. According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P < 0.001. Among healthy adult male twins in their mid-30s, a greater level of physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

  19. Nephrolithiasis in identical twins: the impact of nature vs nurture.

    PubMed

    Haleblian, George E; Cantor, David A; Sur, Roger L; Assimos, Dean G; Preminger, Glenn M

    2007-09-01

    To assess possible underlying metabolic abnormalities in three sets of monozygotic twins, to evaluate the interplay among the factors of kidney stone formation, a complex multifactorial process influenced by environmental, genetic and anatomical factors. Three sets of identical twins with either cystine or calcium oxalate stones were identified. Demographic data, medical histories and the results of 24-h urine testing, with samples collected on self-selected diets, were reviewed and analysed. The cystinuric twins had very similar cystine excretion rates, while stone activity was significantly more pronounced in one. Metabolic abnormalities were concordant in one set of twins with calcium oxalate stones, both being hypercalciuric and hyperuricosuric. However, metabolic abnormalities were discordant in the other pair, one twin with hypercalciuria and the other with hypocitraturia. Two of the three pairs had low urinary volume. These results support previous observations that environmental, genetic and potentially, anatomical factors play roles in kidney-stone formation. Additional controlled studies of monozygotic stone-forming twins might help to define the interplay between environmental and genetic factors, and allow the identification of susceptibility genes involved in stone generation.

  20. Familial risk and ADHD-specific neural activity revealed by case-control, discordant twin pair design.

    PubMed

    Godinez, Detre A; Willcutt, Erik G; Burgess, Gregory C; Depue, Brendan E; Andrews-Hanna, Jessica R; Banich, Marie T

    2015-09-30

    Individuals with ADHD, as well as their family members who do not meet clinical criteria, have shown deficits in executive function. However, it remains unclear whether underlying neural alterations are familial or ADHD-specific. To investigate this issue, neural activation underlying executive function was assessed using functional magnetic resonance imaging during performance of a Stroop task in three groups of individuals: 20 young adults who were diagnosed with ADHD in childhood, their 20 dizygotic co-twins without ADHD in childhood, and 20 unrelated controls selected from dizygotic twin pairs in which neither twin had ADHD in childhood (total n=60). Implicating the frontoparietal network as a location of effects specific to ADHD, activation in the superior frontal (Brodmann's Area - BA 6) and parietal regions (BA 40) was significantly reduced in twins with childhood ADHD compared to both their control co-twins and unrelated control twins. Consistent with familial influences, activity in the anterior cingulate and insula was significantly reduced in both the twins with ADHD and their co-twins compared to the unrelated controls. These results show that both ADHD-specific and familial influences related to an ADHD diagnosis impact neural systems underlying executive function.

  1. Monozygotic transplantation: Concerns and Opportunities

    PubMed Central

    N, Krishnan; PM, Buchanan; N, Dzebisashvili; H, Xiao; MA, Schnitzler; DC, Brennan

    2008-01-01

    We describe the case of a 24 year-old female with end stage renal disease from focal segmental glomerulosclerosis (FSGS) diagnosed at age 16, who underwent monozygotic triplet transplantation at age 21 from her sister. Monozygosity was established by buccal smear DNA PCR amplification using short tandem repeat (1) profiling for 16 genetic alleles. All immunosuppression was discontinued by one-month post-transplant. To evaluate the use of immunosuppression in HLA identical monozygotic transplantation, we interrogated the OPTN (Organ Procurement Transplant Network) database for all transplants conducted from 1987–2006. We identified 194 probable identical twin transplantations based on age, gender, race, ethnic category, blood type and HLA match. We evaluated the use of various immunosuppressive agents at discharge, 6-months and 1, 2, and 3 years after transplantation. Seventy one percent of these patients at discharge and 34% at the end of one-year were on immunosuppression. At discharge 61% received steroids and 30% received calcineurin-inhibitors and 66% of these remained on calcineurin-inhibitors at one-year. Renal function was superior among those not maintained on immunosuppression. Thus, monozygotic transplantation confers an immunologic advantage that allows immunosuppression elimination despite a risk of recurrent glomerular disease such as FSGS with appropriate evaluation and management. PMID:18808409

  2. Differences in muscle and adipose tissue gene expression and cardio-metabolic risk factors in the members of physical activity discordant twin pairs.

    PubMed

    Leskinen, Tuija; Rinnankoski-Tuikka, Rita; Rintala, Mirva; Seppänen-Laakso, Tuulikki; Pöllänen, Eija; Alen, Markku; Sipilä, Sarianna; Kaprio, Jaakko; Kovanen, Vuokko; Rahkila, Paavo; Oresic, Matej; Kainulainen, Heikki; Kujala, Urho M

    2010-09-16

    High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50-74 years) who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing active vs. inactive co-twin gene expression ratios. Our findings showed that among the physically active members of twin pairs, as compared to their inactive co-twins, gene expression in the muscle tissue samples was chronically up-regulated for the central pathways related to energy metabolism, including oxidative phosphorylation, lipid metabolism and supportive metabolic pathways. Up-regulation of these pathways was associated in particular with aerobic fitness and high HDL cholesterol levels. In fat tissue we found physical activity-associated increases in the expression of polyunsaturated fatty acid metabolism and branched-chain amino acid degradation gene sets both of which associated with decreased 'high-risk' ectopic body fat and plasma glucose levels. Consistent with other findings, plasma lipidomics analysis showed up-regulation of the triacylglycerols containing the polyunsaturated fatty acids. Our findings identified skeletal muscle and fat tissue pathways which are associated with the long-term physical activity and reduced cardio-metabolic disease risk, including increased aerobic fitness. In particular, improved skeletal muscle oxidative energy and lipid metabolism as well as changes in adipocyte function and redistribution of body fat are associated with reduced

  3. Mixed-Handedness in Identical Twins Discordant for Combat Exposure in Vietnam: Relationship to Posttraumatic Stress Disorder.

    PubMed

    Goetz, Jared M; Pitman, Seth R; Tanev, Kaloyan S; Pitman, Roger K; Chemtob, Claude M

    2016-01-01

    This study evaluated the degree of mixed-handedness in predominantly right-handed Vietnam combat veteran twins and their identical, combat-unexposed cotwins. The "high-risk" cotwins of combat veterans with combat-related posttraumatic stress disorder (PTSD) had more mixed-handedness (i.e., less right-handedness) than the "low-risk" cotwins of combat veterans without PTSD. Self-reported combat exposure in combat-exposed twins was a mediator of the association between handedness in their unexposed cotwins and PTSD in the twins themselves. We conclude that mixed-handedness is a familial risk factor for combat-related PTSD. This risk may be mediated in part by a proclivity for mixed-handed soldiers and Marines to experience heavier combat.

  4. Co-twin study of the effect of environment and dietary elements on acquisition of Helicobacter pylori infection.

    PubMed

    Malaty, H M; Graham, D Y; Isaksson, I; Engstrand, L; Pedersen, N L

    1998-10-15

    The rate of Helicobacter pylori infection is inversely related to socioeconomic status, and childhood is thought to be the major acquisition period. The authors investigated the importance of childhood environment in the acquisition of H. pylori infection. A cross-sectional study was conducted of monozygotic and dizygotic twins who were reared apart or reared together. Three hundred twins from a subregistry of the Swedish Twin Registry were studied. H. pylori status was evaluated by using an enzyme-linked immunosorbent assay for anti-H. pylori immunoglobulin G. Socioeconomic status during childhood was assessed on the basis of the density of the living conditions and the economic situation of the family that reared the twins. Current socioeconomic status was estimated by using a scale that combined income and education. Dietary elements that were studied included fat and fiber intake and ascorbic acid consumption. The density of the childhood home was consistently found to be significantly associated with the acquisition of H. pylori infection (p = 0.04). Among monozygotic twins reared apart and discordant for H. pylori status, affected twins were raised in homes under poorer socioeconomic conditions than those of their unaffected co-twins (p = 0.02). Additionally, infected twins consumed more ascorbic acid than their unaffected co-twins (p = 0.04). The finding of an effect of socioeconomic status during childhood on the acquisition of H. pylori among monozygotic twins who were reared apart and had an identical genetic makeup but not a common environment confirms the hypothesis that childhood acquisition of H. pylori infection is linked to hygiene practices.

  5. Ontogenetic de novo copy number variations (CNVs) as a source of genetic individuality: studies on two families with MZD twins for schizophrenia.

    PubMed

    Maiti, Sujit; Kumar, Kiran Halagur Bhoge Gowda; Castellani, Christina A; O'Reilly, Richard; Singh, Shiva M

    2011-03-02

    Genetic individuality is the foundation of personalized medicine, yet its determinants are currently poorly understood. One issue is the difference between monozygotic twins that are assumed identical and have been extensively used in genetic studies for decades. Here, we report genome-wide alterations in two nuclear families each with a pair of monozygotic twins discordant for schizophrenia evaluated by the Affymetrix 6.0 human SNP array. The data analysis includes characterization of copy number variations (CNVs) and single nucleotide polymorphism (SNPs). The results have identified genomic differences between twin pairs and a set of new provisional schizophrenia genes. Samples were found to have between 35 and 65 CNVs per individual. The majority of CNVs (~80%) represented gains. In addition, ~10% of the CNVs were de novo (not present in parents), of these, 30% arose during parental meiosis and 70% arose during developmental mitosis. We also observed SNPs in the twins that were absent from both parents. These constituted 0.12% of all SNPs seen in the twins. In 65% of cases these SNPs arose during meiosis compared to 35% during mitosis. The developmental mitotic origin of most CNVs that may lead to MZ twin discordance may also cause tissue differences within individuals during a single pregnancy and generate a high frequency of mosaics in the population. The results argue for enduring genome-wide changes during cellular transmission, often ignored in most genetic analyses.

  6. DNA stability and schizophrenia in twins.

    PubMed

    Nguyen, Giang H; Bouchard, Joseph; Boselli, Monica G; Tolstoi, Linda G; Keith, Louis; Baldwin, Clinton; Nguyen, Nam C; Schultz, Mark; Herrera, Victoria L M; Smith, Cassandra L

    2003-07-01

    The goal of these experiments was to understand DNA changes relevant to schizophrenia. This work compared DNA of monozygotic (MZ) twins surrounding (CAG)(n) repeating sequences, and characterized the relationship between fragile sites and schizophrenia. Twelve twin-pairs, previously classified as MZ and 18 unrelated sib-pairs, from seven families were studied. Eight twin-pairs were affected by schizophrenia, four concordantly and four discordantly. DNA comparisons were made using profiles of electrophoretic size fractionations of PCR amplified (CAG)(n) containing genomic fragments. These profiles were generated by a new method, developed by us, called targeted genomic differential display (TGDD). Surprisingly, the number of peak profile differences in MZ twin-pairs discordant for schizophrenia was greater than the concordantly ill twins and the well twins and, in some cases, overlapped the range of sib-pairs. These results might mean that some twins were not MZ but it was not possible to definitively test these samples for zygosity. Alternatively, the results might be explained as an increased mutation rate (or genomic instability) around (CAG)(n) sites in individuals afflicted with schizophrenia. Also, we uncovered an association of schizophrenia (i.e., a linkage of chromosomal abnormalities and gene localizations) with fragile sites spread throughout the genome (chi(2), P = 0.001). Furthermore, it appears that an increasing number of genes linked to schizophrenia are associated with (CAG)(n) sequences. Fragile sites and (CAG)(n) repeat sequences are known to be unstable. We speculate the association of genomic instability with schizophrenia accounts for seemingly disparate biological and environmental factors that influence disease occurrence. Copyright 2003 Wiley-Liss, Inc.

  7. Monozygotic twins with a de novo 0.32 Mb 16q24.3 deletion, including TUBB3 presenting with developmental delay and mild facial dysmorphism but without overt brain malformation.

    PubMed

    Grønborg, Sabine; Kjaergaard, Susanne; Hove, Hanne; Larsen, Vibeke André; Kirchhoff, Maria

    2015-11-01

    Nervous system development is highly dependent on the function of microtubules, which are assembled from tubulin heterodimers containing several α- and β-tubulin isotypes encoded by separate genes. A spectrum of neurological disorders with malformations of the central nervous system has recently been associated with missense mutations in this group of genes. Here, we report two patients, monozygotic twins, carrying a de novo 0.32 Mb deletion of chromosome 16q24.3 including the TUBB3 gene. The patients presented with global developmental delay, mild facial dysmorphism, secondary microcephaly, and mild spastic diplegia. Cerebral magnetic resonance imaging of the patients did not reveal cortical malformations, malformations of the corticospinal tracts, basal ganglia, corpus callosum, or optic nerves. This observation is in contrast to the group of neurological disorders that are associated with heterozygous missense mutations in genes encoding different neuronal α- and β-tubulin isotypes, termed tubulinopathies. On the background of current knowledge regarding the function and genotype-phenotype correlations of mutations in the neuronal tubulin isotypes, the clinical and diagnostic findings in these patients are discussed. To our knowledge, this is the first report of patients with a de novo deletion of the TUBB3 gene. The lack of cortical or other cerebral malformations supports the current hypothesis that TUBB3-related tubulinopathies are caused by altered protein function. © 2015 Wiley Periodicals, Inc.

  8. Twins as a tool for evaluating the influence of genetic susceptibility in thyroid autoimmunity.

    PubMed

    Brix, T H; Hegedüs, L

    2011-04-01

    By means of large twin cohorts, it has been possible to provide relatively valid and unbiased data regarding the influence of genetic and to some extent epigenetic factors in the aetiology of thyroid autoimmunity. The comparison of concordance rates between monozygotic and dizygotic twins provides irrefutable evidence of a genetic component in the aetiology of both Graves' disease and Hashimoto's thyroiditis, as well as for harbouring thyroid autoantibodies. Biometric modelling shows that approximately 75% of the total phenotypic variance in autoimmune thyroid disease is due to genetic effects. Despite the well known gender difference in the prevalence of autoimmune thyroid disease, the analyzes suggest that it is the same set of genes that operate in males and females. The lack of complete phenotypic concordance in monozygotic twin pairs indicates that also environmental and/or epigenetic factors are of importance. The impact of specific environmental and epigenetic exposures can be evaluated by investigating disease discordant twin pairs. Our studies show that skewed X chromosome inactivation is associated with clinically overt AITD but not with the presence of TPOAb in euthyroid individuals. It is now recognized that twin studies offer several features that uniquely enhance our ability to localize genes and understand their function. Future twin studies will incorporate information on genetic and epigenetic variation making it possible to quantify the precise effect of specific susceptibility genes and/or epigenetic variation on estimates of heritability. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  9. A possible genetic influence in parenchyma and small airway changes in COPD: a pilot study of twins using HRCT.

    PubMed

    Tarnoki, D L; Tarnoki, A D; Lazar, Zs; Korom, Cs; Berczi, V; Horvath, I; Karlinger, K

    2014-06-01

    Genetic effects that contribute to the risk of developing chronic obstructive pulmonary disease (COPD) have been reported. Our purpose was to estimate the possible genetic influence on CT features related to COPD in twins. Two COPD-discordant and one COPD-concordant monozygotic (MZ) twin pair, in addition to 2 control dizygotic (DZ) twin pairs underwent a low-dose high resolution computer tomography (HRCT) in inspiration and expiration (Philips Brilliance 16). Monozygotic twins were more similar in lung volume expiration and in air trapping score compared to dizygotics (382 cm(3) vs. 2303 cm(3) and 17.6% vs. 26.6%, respectively). In general, MZ twin pairs showed almost identical HRCT features independently of smoking attitude and COPD status. The dizygotic twin pairs showed larger differences in HRCT features compared to MZ twins. Lung parenchymal and small airway changes (lung density, presence of bronchial wall thickening, bronchiectasis and/or mucus plug formation, air trapping and emphysema score) seem to be genetically associated traits, independently of smoking/COPD history. A future study with a larger sample size should confirm our findings.

  10. Oblique discord

    NASA Astrophysics Data System (ADS)

    Xu, Jianwei

    2017-01-01

    Discord and entanglement characterize two kinds of quantum correlations, and discord captures more correlation than entanglement in the sense that even separable states may have nonzero discord. In this paper, we propose a new kind of quantum correlation that we call as oblique discord. A zero-discord state corresponds to an orthonormal basis, while a zero-oblique-discord state corresponds to a basis which is not necessarily orthogonal. Under this definition, the set of zero-discord states is properly contained inside the set of zero-oblique-discord states, and the set of zero-oblique-discord states is properly contained inside the set of separable states. We give a characterization of zero-oblique-discord states via quantum mapping, provide a geometric measure for oblique discord, and raise a conjecture, which if it holds, then we can define an information-theoretic measure for oblique discord. Also, we point out that the definition of oblique discord can be properly extended to some different versions just as the case of quantum discord.

  11. Role of genetic and environmental factors in British twins with inflammatory bowel disease.

    PubMed

    Ng, Siew C; Woodrow, Susannah; Patel, Nisha; Subhani, Javaid; Harbord, Marcus

    2012-04-01

    Twin studies provide insight into the complex interaction between genetic and environmental factors in the development of inflammatory bowel disease (IBD). We assessed associations between childhood environmental factors and development of Crohn's disease (CD) and ulcerative colitis (UC) in twins. Questionnaires on clinical demographics and exposure to environmental factors were sent to twins with IBD, their healthy co-twins, and their doctors. Kappa statistics were used to examine agreement between twin pairs and odds ratios were calculated by conditional logistic regression. In all, 250 IBD twin pairs (122 CD; 125 UC; 3 CD/UC; 28 concordant pairs) were analyzed. Concordant monozygotic twins with CD showed good agreement for disease location (κ 0.88; 95% confidence interval [CI]: 0.45-1.00), disease behavior (κ 1.00; 95% CI: 0.43-1.00), and moderate agreement for age at diagnosis and need for medical and surgical therapy. Concordant monozygotic twins with UC showed good agreement for disease extent (κ 0.60; CI 0.13-1.00) and use of thiopurines (κ 0.73; CI 0.10-1.00). In discordant twins, symptomatic childhood mumps infection (odds ratio [OR], 3.8; 95% CI, 1.2-11.3) and oral contraceptives (OR, 4.0; 1.1-14.2) were associated with CD. Smoking was associated with CD (OR, 4.3; 95% CI, 1.9-9.8) but inversely associated with UC (OR, 0.3; 95% CI, 0.1-0.9). Both CD and UC twins had suffered more "gastroenteritis" and spent more time with animals than their co-twins. Disease phenotype in CD and disease extent in UC appeared to be genetically influenced. Smoking is a risk factor for CD but is protective for UC. Early exposure to "infections" during childhood may be associated with the development of IBD. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  12. Acardiac twin: an unusual case report.

    PubMed

    Kariappa, T M; Chidananda, H T; Mamatha, R

    2007-10-01

    Acardiac twinning is a rare anomaly .75% of cases occurring in monzygotic triplet pregnancies and the rest in monozygotic twins. We report an antenatally undiagnosed case of acardius amorphous. The condition results from abnormal placental vascular anastomoses termed as twin reversed arterial perfusion (TRAP) theory. Early sonographic prenatal diagnosis improves the survival of the normal twin called the pump twin.

  13. One Year Developmental Stability and Covariance among Oddball, Novelty, Go/Nogo, and Flanker Event-Related Potentials in Adolescence: a Monozygotic Twin Study

    PubMed Central

    Burwell, Scott J.; Malone, Stephen M.; Iacono, William G.

    2016-01-01

    Event-related potential (ERP) measures may index genetic risk for psychopathology before disorder-onset in adolescence, but little is known about their developmental rank-order stability during this period of significant brain maturation. We studied ERP stability in 48 pairs of identical twins (age 14 – 16 years) tested one year apart. Trial-averaged voltage waveforms were extracted from electroencephalographic recordings from Oddball/Novelty, Go/Nogo, and Flanker tasks, and 16 amplitude measures were examined. Members of twin pairs were highly similar, whether based on ERP amplitude measures (intraclass correlation [ICC] median = .64, range = .44 – .86) or 3 factor scores (all ICCs ≥ .69) derived from them. Stability was high overall, with 69% of the 16 individual measures generating stability coefficients exceeding .70 and all factor scores showing stability above .75. Measures from 10 difference waveforms calculated from paired conditions within tasks were also examined, and were associated with lower twin similarity (ICC median = .52, .38 – .64) and developmental stability (only 30% exceeding .70). In a supplemental analysis, we found significant developmental stability for error-related negativity (range = .45 – .55) and positivity (.56 – .70) measures when average waveforms were based on 1 or more trials, and that these values were equivalent to those derived from averages using the current field recommendation which requires 6 or more trials. Overall, we conclude that the studied brain measures are largely stable over one year of mid- to late-adolescence, likely reflecting familial etiologic influences on brain functions pertaining to cognitive control and salience recognition. PMID:26997525

  14. One-year developmental stability and covariance among oddball, novelty, go/no-go, and flanker event-related potentials in adolescence: A monozygotic twin study.

    PubMed

    Burwell, Scott J; Malone, Stephen M; Iacono, William G

    2016-07-01

    ERP measures may index genetic risk for psychopathology before disorder onset in adolescence, but little is known about their developmental rank-order stability during this period of significant brain maturation. We studied ERP stability in 48 pairs of identical twins (age 14-16 years) tested 1 year apart. Trial-averaged voltage waveforms were extracted from electroencephalographic recordings from oddball/novelty, go/no-go, and flanker tasks, and 16 amplitude measures were examined. Members of twin pairs were highly similar, whether based on ERP amplitude measures (intraclass correlation [ICC] median = .64, range = .44-.86) or three factor scores (all ICCs ≥ .69) derived from them. Stability was high overall, with 69% of the 16 individual measures generating stability coefficients exceeding .70 and all factor scores showing stability above .75. Measures from 10 difference waveforms calculated from paired conditions within tasks were also examined, and were associated with lower twin similarity (ICC median = .52, .38-.64) and developmental stability (only 30% exceeding .70). In a supplemental analysis, we found significant developmental stability for error-related negativity (range = .45-.55) and positivity (.56-.70) measures when average waveforms were based on one or more trials, and that these values were equivalent to those derived from averages using the current field recommendation, which requires six or more trials. Overall, we conclude that the studied brain measures are largely stable over 1 year of mid- to late adolescence, likely reflecting familial etiologic influences on brain functions pertaining to cognitive control and salience recognition. © 2016 Society for Psychophysiological Research.

  15. British motor neuron disease twin study.

    PubMed Central

    Graham, A J; Macdonald, A M; Hawkes, C H

    1997-01-01

    OBJECTIVES: To investigate the cause of sporadic motor neuron disease (MND) by twin study, so allowing (1) estimation of the genetic contribution, and (2) collection of matched pairs for a case-control study of possible environmental factors. METHODS: 10872 death certificates bearing the diagnosis MND were collected from 1979 to 1989 inclusive. Inspection of individual birth entries allowed identification of potential twins. The status of each co-twin was determined and contact made through the National Health Service Central Register (NHS-CR) and their general practitioner (GP). The diagnosis of MND was verified via the co-twin and relatives, and medical records where available. Zygosity was assessed using a recognised questionnaire. Details concerning environmental exposures and health were gathered by interview of cotwin and relatives using a semistructured questionnaire. Heritability (h2) of MND was estimated, and the environmental information was analysed by conditional logistic regression modelling. RESULTS: Seventy seven probands were identified, of whom 26 were monozygotic and 51 dizygotic. Four monozygotic probands were concordant, but two probands came from a family known to have familial MND. The estimated heritability was between 0.38 and 0.85. Most environmental risk factors were not significant. Regular vehicle maintenance (odds ratio (OR) = 7.0; 95% confidence interval (95% CI) 1.3-89.9) and occupational paint usage (OR = 3.75; 95% CI 1.0-17.1), however, occurred significantly more often in the affected cases. CONCLUSIONS: This "death discordant" method for twin collection has proved to be viable, and has allowed the ascertainment of a large population sample in a rare disease. The genetic role in sporadic MND is substantial, and higher than expected. Exposure to industrial chemicals, particularly constituents of petrochemicals and paints, may contribute to the aetiology of MND. PMID:9219739

  16. Chorionicity and Heritability Estimates from Twin Studies: The Prenatal Environment of Twins and Their Resemblance Across a Large Number of Traits.

    PubMed

    van Beijsterveldt, C E M; Overbeek, L I H; Rozendaal, L; McMaster, M T B; Glasner, T J; Bartels, M; Vink, J M; Martin, N G; Dolan, C V; Boomsma, D I

    2016-05-01

    There are three types of monozygotic (MZ) twins. MZ twins can either share one chorion and one amnion, each twin can have its own amnion, or MZ twins can-like dizygotic twins-each have their own chorion and amnion. Sharing the same chorion may create a more similar/dissimilar prenatal environment and bias heritability estimates, but most twin studies do not distinguish between these three types of MZ twin pairs. The aim of this paper is to investigate the effect of chorion sharing on the similarity within MZ twin pairs for a large number of traits. Information on chorion status was obtained for the Netherlands twin register (NTR) by linkage to the records from the database of the dutch pathological anatomy national automated archive (PALGA). Record linkage was successful for over 9000 pairs. Effect of chorion type was tested by comparing the within-pair similarity between monochorionic (MC) and dichorionic (DC) MZ twins on 66 traits including weight, height, motor milestones, child problem behaviors, cognitive function, wellbeing and personality. For only 10 traits, within-pair similarity differed between MCMZ and DCMZ pairs. For traits influenced by birth weight (e.g. weight and height in young children) we expected that MC twins would be more discordant. This was found for 5 out of 13 measures. When looking at traits where blood supply is important, we saw MCMZ twins to be more concordant than DCMZ's for 3 traits. We conclude that the influence on the MZ twin correlation of the intra-uterine prenatal environment, as measured by sharing a chorion type, is small and limited to a few phenotypes. This implies that the assumption of equal prenatal environment of mono- and DC MZ twins, which characterizes the classical twin design, is largely tenable.

  17. Gene expression profiles in Finnish twins with multiple sclerosis

    PubMed Central

    Särkijärvi, Silja; Kuusisto, Hanna; Paalavuo, Raija; Levula, Mari; Airla, Nina; Lehtimäki, Terho; Kaprio, Jaakko; Koskenvuo, Markku; Elovaara, Irina

    2006-01-01

    Background Since genetic alterations influencing susceptibility to multiple sclerosis (MS), the most common autoimmune demyelinating disease of the central nervous system (CNS), are as yet poorly understood, the purpose of this study was to identify genes responsible for MS by studying monozygotic (MZ) twin pairs discordant for MS. Methods In order to identify genes involved in MS development, the gene expression profiles in blood mononuclear cells obtained from eight MZ twin pairs discordant for MS were analyzed by cDNA microarray technology detecting the expression of 8 300 genes. The twins were collected from the Finnish Twin Cohort Study and both affected subjects and their healthy siblings underwent neurological evaluation and cerebral and spinal magnetic resonance imaging. Gene expressions were confirmed by relative quantitative reverse transcription PCR. Results It appeared that 25 genes were at least two-fold up-regulated and 15 genes down-regulated in 25% (2/8) of twins with MS when compared to their healthy siblings. Moreover, 6/25 genes were up-regulated in 40% of MS twins and one gene, interferon alpha-inducible protein (clone IFI-6-16) (G1P3), in 50% of them. The six most constantly expressed genes are (1) G1P3, (2) POU domain, class 3, transcription factor 1, (3) myxovirus resistance 2, (4) lysosomal-associated multispanning membrane protein-5, (5) hemoglobin alpha 2 and (6) hemoglobin beta. Conclusion Over two-fold up-regulation of these six genes in almost half of MZ twins with MS suggests their role in MS pathogenesis. Studies using MZ MS twins obtained from genetically homogeneous population offer a unique opportunity to explore the genetic nature of MS. PMID:16504146

  18. Autism spectrum disorders and coexisting disorders in a nationwide Swedish twin study.

    PubMed

    Lundström, Sebastian; Reichenberg, Abraham; Melke, Jonas; Råstam, Maria; Kerekes, Nóra; Lichtenstein, Paul; Gillberg, Christopher; Anckarsäter, Henrik

    2015-06-01

    Evidence from twin and molecular genetic studies is accumulating that Autism Spectrum Disorder (ASD) shares substantial etiological factors with other disorders. This is mirrored in clinical practice where ASD without coexisting disorders is rare. The present study aims to examine the range of coexisting disorders in ASD in a genetically informative cohort. Parents of all Swedish 9-year-old twins born between 1992 and 2001 (n = 19,130) underwent a telephone interview designed to screen for child psychiatric disorders, including ASD. To ensure full coverage of child psychiatric disorders, data were also retrieved from population-based health registers. We investigated the coexistence of eight psychiatric disorders known to coexist with ASDs in probands and their co-twins. Half of the individuals with ASDs (50.3%) had four or more coexisting disorders and only 4% did not have any concomitant disorder. The 'healthy co-twin' in ASD discordant monozygotic twin pairs was very often (79% of boys and 50% of girls) affected by at least one non-ASD disorder. The corresponding figures for ASD discordant dizygotic twin pairs were significantly lower (46% of males and 30% of females). Detailed phenotypic descriptions including symptoms of problems associated with a wide range of child psychiatric disorders may aid in unraveling the genetic architecture of ASD and should guide the development of intervention strategies addressing each problem type specifically. © 2014 Association for Child and Adolescent Mental Health.

  19. Sleep quality and body mass index: a co-twin study.

    PubMed

    Madrid-Valero, Juan J; Martínez-Selva, José M; Ordoñana, Juan R

    2017-01-19

    There is a consistent relationship between body mass index and sleep quality. However, the directionality and possible confounding factors of this relationship are unclear. Our aim is to confirm the association between sleep quality and body mass index, independent of possible genetic confounding, as well as to provide some indirect inferences about the directionality of this association. The co-twin study design was used to analyse the body mass index-sleep relationship in a sample of 2150 twins. We selected two parallel sub-samples of twins discordant for body mass index (n = 430 pairs), or discordant for sleep quality (n = 316 pairs). Sleep quality and body mass index showed an inverse relationship (b = 0.056, P = 0.032) in the global sample. When twins discordant for body mass index were selected, this association maintained a similar effect size and statistical significance, at all levels of the case-control analysis (all discordant pairs b = 0.173, P < 0.001; dizygotic twins b = 0.174, P = 0.002; monozygotic twins b = 0.173, P = 0.050). Nevertheless, when twin pairs were selected on the basis of their discordance for sleep quality, the association between body mass index and sleep quality appeared weaker and lost significance (b = 0.021, P = 0.508). The analyses including only dizygotic (b = 0.028, P = 0.526) or monozygotic (b = 0.001, P = 0.984) pairs produced similar non-significant results. Our results confirm the relationship between sleep quality and body mass index, even after applying high levels of control, including genetic factors. Moreover, this study suggests a possible directionality of this relationship, such that sleep quality would strongly affect body mass index, while the opposite would be less robust and consistent in non-clinical samples.

  20. [Possible role of the cytoplasm in the course of morphogenesis, namely, in the case of twinning].

    PubMed

    Giroud, A

    1975-01-01

    A number of facts that cannot be interpreted in terms of nuclear genes would seem to be interpretable in terms of cytoplasmic heredity. The hereditary role of the mitochondria has already been demonstrated in molds. The role of the cytoplasm (matrilineal heredity) has also been shown in some phanerogams, and analogous facts have been noted in insects and molluscs. In amphibians, the influence of an alteration of the egg cortical cytoplasm has been shown to reappear in the following generations. This cortical cytoplasm includes the morphological plan of the organism with its bilateral symmetry. In Tatusia novemcincta the twins may be morphologically or chemically different, which may only be explained by an unequal subdivision of a heterogenic cytoplasm. Similar facts are observed in human twinning. Monozygotic twins are usually discordant with respect to congenital malformations (especially symmelia and anencephaly), which may only be interpreted in terms of unequal distribution of cytoplasmic properties.

  1. Association of body mass index with arterial stiffness and blood pressure components: a twin study.

    PubMed

    Tarnoki, Adam Domonkos; Tarnoki, David Laszlo; Bogl, Leonie H; Medda, Emanuela; Fagnani, Corrado; Nisticò, Lorenza; Stazi, Maria Antonietta; Brescianini, Sonia; Lucatelli, Pierleone; Boatta, Emanuele; Zini, Chiara; Fanelli, Fabrizio; Baracchini, Claudio; Meneghetti, Giorgio; Osztovits, Janos; Jermendy, Gyorgy; Kiss, Robert Gabor; Preda, Istvan; Karlinger, Kinga; Lannert, Agnes; Molnar, Andrea Agnes; Littvay, Levente; Garami, Zsolt; Berczi, Viktor; Pucci, Giacomo; Baffy, Gyorgy; Schillaci, Giuseppe; Pietiläinen, Kirsi H

    2013-08-01

    Obesity, blood pressure and arterial stiffness are heritable traits interconnected to each other but their possible common genetic and environmental etiologies are unknown. We studied 228 monozygotic and 150 dizygotic twin pairs aged 18-82 years from Italy, Hungary and the United States, of which 45 monozygotic and 38 dizygotic pairs were discordant for body mass index (BMI; intrapair difference (Δ) in BMI ≥ 3 kg/m(2)). Blood pressure components and arterial stiffness were measured by TensioMed Arteriograph. Hypertension was more prevalent among obese than non-obese individuals (55% vs. 29%, p < 0.001). Age-, sex- and country-adjusted heritability estimates were high for hemodynamic measures (45%-58%) and BMI (78%). According to bivariate Cholesky decomposition, phenotypic correlations between BMI and blood pressure components (r = -0.15 to 0.24, p < 0.05) were largely explained by additive genetic factors (65%-77%) with the remaining explained by the unique environment. When controlling for genetic factors within all monozygotic pairs, ΔBMI was significantly correlated with Δbrachial systolic blood pressure (SBP) and diastolic blood pressure (DBP), Δmean arterial pressure, and Δaortic SBP (r = 0.15-0.17, p < 0.05). For the same measures, heavier co-twins of BMI-discordant monozygotic pairs had significantly higher values than their leaner counterparts (p < 0.05). Blood pressure components are moderately correlated with BMI, largely because of shared genetic factors. However, for the association of BMI with brachial SBP and DBP, aortic SBP and mean arterial pressure, acquired, modifiable factors were also found to be important. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Early menarche is associated with increased risk of asthma: Prospective population-based study of twins.

    PubMed

    Lieberoth, Sofie; Gade, Elisabeth; Kyvik, Kirsten Ohm; Backer, Vibeke; Thomsen, Simon Francis

    2015-05-01

    To examine the association between early menarche and risk of post-menarcheal asthma. Using data from two multidisciplinary questionnaire surveys, conducted eight years apart, we prospectively studied 10,648 female twins, 12-41 years of age, from the nationwide Danish Twin Registry. Early menarche was defined as menarche before 12 years of age. We performed a cohort analysis and a co-twin control analysis including twin pairs discordant for incident asthma. Early menarche was observed in 9.3% of the individuals. The eight-year cumulative incidence of asthma was higher in girls with early menarche compared to girls without early menarche (7.4 vs. 4.5%), OR = 1.71 (1.31-2.22), p < 0.001; also after adjustment for BMI, current age, physical activity, education, and smoking, OR = 1.53 (1.15-2.04), p = 0.003. The unadjusted risk of asthma was increased by 8% (1-15%), p = 0.041 per year earlier menarche occurred. Among 167 twin pairs discordant for incident asthma, there was a non-significant tendency towards early menarche being more common in the asthmatic than the non-asthmatic co-twin (12.0 vs. 9.6%), OR = 1.57 (0.61-4.05), p = 0.350. The risk of asthma was not uniform in discordant monozygotic and dizygotic twins. Early menarche is associated with increased risk of asthma among Danish female twins independently of BMI, age, physical activity, educational level and smoking. Results indicate a complex relationship possibly mediated through innate and non-genetic effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Analysis of the T-cell receptor V beta usage in monozygotic and dizygotic twins living in a Plasmodium falciparum endemic area in west Africa.

    PubMed

    Troye-Blomberg, M; Fogdell, A; el-Ghazali, G; Larsson, A; King, M H; Sisay-Joof, F; Olerup, O; Grunewald, J; Jepson, A

    1997-05-01

    To investigate the influence of genetic and/or environmental factors in the development and shaping of the human peripheral T cell repertoire the authors studied the T-cell receptor (TCR) V beta usage in 10 adult monozygous (Mz) and nine dizygous (Dz) twin pairs living in a Plasmodium falciparum endemic area in West Africa. The TCR repertoire was determined using a small panel of anti-V beta specific monoclonal antibodies (MoAbs) using conventional immunofluorescence assays. The results revealed that the V beta repertoire was similar to that recently described for a Caucasian population using a similar panel of antibodies. The frequencies of particular V beta genes tested were influenced neither by anti-malarial antibody titres nor by parasite densities, indicating that the P. falciparum parasite is not a dominating factor in determining the peripheral T cell repertoire. All donors were human leucocyte antigen (HLA) class I and II typed; no association was found between the expression of any V beta genes and MHC haplotype. The V beta usage was more concordant within the Mz than within the Dz pairs. For a group comprising four HLA class II identical individuals, the average within-pair difference was significantly greater than for the whole Mz group, but similar to that seen for the total Dz group. Thus, the data suggest that genetic, rather than environmental, factors have a profound effect on the shaping of the human circulating T cell repertoire and that the major genetic factors are encoded by non-HLA class II genes.

  4. Antenatal Diagnosis of Dizygotic, Monochorionic Twins Following IVF/ICSI.

    PubMed

    Korsun, P; Bals-Pratsch, M; Ortmann, O; Markus, S; Germer, U

    2016-06-01

    Monochorionic twins are usually monozygotic and thus usually have the same sex. A case of monochorionic diamniotic twins following IVF/ICSI and laser treatment of the zona pellucida ("assisted hatching") is presented in which partial embryo amalgamation appears to have occurred. Discordant sex between the twins was suspected on detailed antenatal ultrasound at 13 + 3 weeks gestation and was confirmed on subsequent examinations. The sexual phenotype at birth was female for one twin and male for the other. Placental histology confirmed the monochorionic, diamniotic situation. Cytogenetic analysis of both twins was carried out postpartum on various tissues. On karyotyping of blood lymphocytes the male and female twins each had one mosaic of male and female cells. Oral mucosal cells showed normal male and female karyotypes respectively. Analysis of urothelium showed a normal result for the male infant, and a weak gonosomal mosaic with an XX and XY constellation for the female infant. At least for blood lymphocytes, a diagnosis of chimerism was proven.

  5. Antenatal Diagnosis of Dizygotic, Monochorionic Twins Following IVF/ICSI

    PubMed Central

    Korsun, P.; Bals-Pratsch, M.; Ortmann, O.; Markus, S.; Germer, U.

    2016-01-01

    Monochorionic twins are usually monozygotic and thus usually have the same sex. A case of monochorionic diamniotic twins following IVF/ICSI and laser treatment of the zona pellucida (“assisted hatching”) is presented in which partial embryo amalgamation appears to have occurred. Discordant sex between the twins was suspected on detailed antenatal ultrasound at 13 + 3 weeks gestation and was confirmed on subsequent examinations. The sexual phenotype at birth was female for one twin and male for the other. Placental histology confirmed the monochorionic, diamniotic situation. Cytogenetic analysis of both twins was carried out postpartum on various tissues. On karyotyping of blood lymphocytes the male and female twins each had one mosaic of male and female cells. Oral mucosal cells showed normal male and female karyotypes respectively. Analysis of urothelium showed a normal result for the male infant, and a weak gonosomal mosaic with an XX and XY constellation for the female infant. At least for blood lymphocytes, a diagnosis of chimerism was proven. PMID:27365544

  6. The Peri/postnatal Epigenetic Twins Study (PETS).

    PubMed

    Loke, Yuk Jing; Novakovic, Boris; Ollikainen, Miina; Wallace, Euan M; Umstad, Mark P; Permezel, Michael; Morley, Ruth; Ponsonby, Anne-Louise; Gordon, Lavinia; Galati, John C; Saffery, Richard; Craig, Jeffrey M

    2013-02-01

    The Peri/postnatal Epigenetic Twins Study (PETS) is a longitudinal cohort of 250 pairs of Australian twins and their mothers, who were recruited mid-way through pregnancy from January 2007 to September 2009. The study is centered on the developmental origins of health and disease paradigm (DOHaD) in which an adverse intrauterine environment predisposes the individual to complex disease in later life by reducing growth in utero and adversely altering developmental plasticity. Data concerning diet and lifestyle were collected from mothers during pregnancy, and samples of plasma and serum taken at 28 weeks' gestation. We attended 75% of all births, at which time we collected multiple biological samples including placenta, cord blood, and neonatal cheek cells, the latter from 91% of pairs. Chorionicity was recorded and zygosity was determined by DNA testing where necessary. Approximately 40% of the twins are monozygotic, two-thirds of which are dichorionic. Twins were seen again at 18 months of age and repeat blood and cheek swabs taken where possible. Studies of gene expression and the epigenetic marks of DNA methylation have so far revealed that twins exhibit a wide range of epigenetic discordance at birth, that one-third of the epigenome changes significantly between birth and 18 months; shared (maternal) environment, genetic factors, and non-shared intrauterine environment contribute to an increasing proportion of epigenetic variation at birth, respectively, and affect tissues differently, and that within-pair birth weight discordance correlates with epigenetic discordance in genes associated with lipid metabolism, supporting an epigenetic mechanism for DOHaD.

  7. Abdominal obesity and circulating metabolites: A twin study approach.

    PubMed

    Bogl, Leonie H; Kaye, Sanna M; Rämö, Joel T; Kangas, Antti J; Soininen, Pasi; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Ortega-Alonso, Alfredo; Rissanen, Aila; Ala-Korpela, Mika; Kaprio, Jaakko; Pietiläinen, Kirsi H

    2016-03-01

    To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors. Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (rg) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference ≥3 kg/m(2)). Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (rg=0.40), glycoprotein (rg=0.37), serum triglycerides (rg=0.36), BCAAs (rg=0.30-0.40), HDL particle diameter (rg=-0.33) and HDL cholesterol (rg=-0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins. A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Marital Status and Twins’ Health and Behavior: An Analysis of Middle-Aged Danish Twins

    PubMed Central

    Osler, Merete; McGue, Matt; Lund, Rikke; Christensen, Kaare

    2013-01-01

    Objective To disentangle the influences on health of selection processes related to genetic and rearing environmental factors from factors related to marriage benefits. We compared health status among same-sex male and female twin pairs who lived together during childhood and were discordant or concordant on adult marital status. Methods A cross-sectional survey of a random sample of middle-aged Danish twins was conducted in 1998 to 1999. This study included 1175 same-sex twin pairs (52.5% monozygotic (MZ) and 47.5% dizygotic (DZ)). Data were obtained on adult marital status and on height, body mass index (BMI), depression symptoms, self-rated health, cognitive function, physical activity, smoking, and alcohol intake. Results Among all 2350 individual twins, men who were divorced/widowed or never married had higher depression scores, lower cognitive test scores, lower physical activity scores, and were also less often moderate drinkers and nonsmokers compared with married men. Divorced/widowed women had higher depression scores and those divorced/widowed or never married were more often smokers than married women. Within twin pairs discordant on marital status, the divorced/widowed twin had higher average depression scores and was more likely to be a smoker. Never married twins had lower physical activity scores and never married male twins had higher BMI and higher depression scores than their married co-twin. Conclusion This study suggests that the relationships of adult divorce with depression and smoking in Danish twins are due to the stressful effects of marital dissolution, but that marital differences in other health and behavioral outcomes are most consistent with selection effects related to genetic or rearing environmental factors. PMID:18480194

  9. Twin studies as a model for exploring the aetiology of autoimmune thyroid disease.

    PubMed

    Brix, Thomas Heiberg; Hegedüs, Laszlo

    2012-04-01

    Twins are an important resource for evaluating the relative contribution of genetic and environmental factors in determining a phenotype. During the last decades, a number of twin studies have investigated the aetiology of several phenotypes related to thyroid autoimmunity. Taken together, these studies have provided valid and unbiased information regarding the influence of genetic and environmental factors in the aetiology of autoimmune thyroid disease (AITD). The comparison of concordance rates between monozygotic (MZ) and dizygotic twins provides irrefutable evidence of a genetic component, and biometric twin modelling shows that approximately 75% of the total phenotypic variance in AITD is because of genetic effects. On the other hand, the lack of complete concordance in MZ twin pairs is proof of environmental and/or epigenetic factors also playing an important role. The impact of environmental triggers such as cigarette smoking, birth characteristics, infection with Yersinia enterocolitica, microchimerism and degree of X chromosome inactivation (XCI) has been evaluated by investigating AITD discordant twin pairs. These studies indicate that smoking, Y. enterocolitica infection and skewed XCI may be causally associated with clinically overt AITD, but not with the presence of thyroid autoantibodies in euthyroid subjects. Microchimerism, but not birth weight, might play a role in AITD. Twin studies offer several features that uniquely enhance our ability to localize genes and understand their function. Future twin studies should incorporate information on genetic, epigenetic and environmental variation thereby enhancing our ability to quantify the precise effect of specific risk factors.

  10. Genetic influences on Chronic Obstructive Pulmonary Disease - a twin study.

    PubMed

    Ingebrigtsen, Truls; Thomsen, Simon F; Vestbo, Jørgen; van der Sluis, Sophie; Kyvik, Kirsten O; Silverman, Edwin K; Svartengren, Magnus; Backer, Vibeke

    2010-12-01

    Genes that contribute to the risk of developing Chronic Obstructive Pulmonary Disease (COPD) have been identified, but an attempt to accurately quantify the total genetic contribution to COPD has to our knowledge never been conducted. Hospital discharge diagnoses data on COPD were analysed in 22,422 Danish twin pairs, 20-71 years of age. The analyses were replicated in a population of 27,668 Swedish twin pairs, 45-108 years of age. A Cox-regression model was applied to the discordant time from the age at first hospital admission for COPD in the co-twin of an affected twin. Latent factor models were used to estimate genetic and environmental effects. The probandwise concordance rate for COPD was higher in monozygotic (MZ) than in dizygotic (DZ) twins, 0.19 vs. 0.07 (p = 0.08) in the Danish population, and 0.20 vs. 0.08 (p = 0.006) in the Swedish population. After adjusting for sex, smoking and age at first hospital admission the risk of developing COPD in the co-twin of an affected twin was higher in MZ than in DZ twins, with hazards ratio 4.3 (95% confidence interval 1.2-15.8, p = 0.03) in Danish twins and 3.4 (1.5-7.7, p = 0.004) in Swedish twins. According to the most parsimonious model, additive genetic factors explained 63% (46-77%) of the individual COPD-susceptibility in the Danish population and 61% (48-72%) in the Swedish population. The susceptibility to develop severe COPD, as defined by hospitalizations, is strongly influenced by genetic factors. Approximately 60% of the individual susceptibility can be explained by genetic factors. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Abnormal N400 Semantic Priming Effect May Reflect Psychopathological Processes in Schizophrenia: A Twin Study

    PubMed Central

    Sauer, Heinrich; Hill, Holger; Kaufmann, Claudia; Bender, Stephan; Weisbrod, Matthias

    2017-01-01

    Objective Activation of semantic networks is indexed by the N400 effect. We used a twin study design to investigate whether N400 effect abnormalities reflect genetic/trait liability or are related to psychopathological processes in schizophrenia. Methods We employed robust linear regression to compare N400 and behavioral priming effects across 36 monozygotic twin pairs (6 pairs concordant for schizophrenia/schizoaffective disorder, 11 discordant pairs, and 19 healthy control pairs) performing a lexical decision task. Moreover, we examined the correlation between Brief Psychiatric Rating Scale (BPRS) score and the N400 effect and the influence of medication status on this effect. Results Regression yielded a significant main effect of group on the N400 effect only in the direct priming condition (p = 0.003). Indirect condition and behavioral priming effect showed no significant effect of group. Planned contrasts with the control group as a reference group revealed that affected concordant twins had significantly reduced N400 effect compared to controls, and discordant affected twins had a statistical trend for reduced N400 effect compared to controls. The unaffected twins did not differ significantly from the controls. There was a trend for correlation between reduced N400 effect and higher BPRS scores, and the N400 effect did not differ significantly between medicated and unmedicated patients. Conclusions Reduced N400 effect may reflect disease-specific processes in schizophrenia implicating frontotemporal brain network in schizophrenia pathology. PMID:28932600