bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discordant MZ Twins With Cleft Lip and Palate: A Model for Identifying Genes in Complex Traits
Authors: Mansilla Maria Adela , Kimani Jane , Mitchell Laura E. , Christensen Kaare , Boomsma Dorret I. , Daack-Hirsch Sandy , Nepomucena Buena , Wyszynski Diego F. , Felix Temis M. , Martin Nicholas G. , Murray Jeffrey C. 
Published: May 2007

AbstractMonozygotic (MZ) twins may be discordant for complex traits due to differential environmental exposure in utero, epigenetic variability in imprinting, X chromosome inactivation, or stochastic effects. Occasionally MZ twins may be discordant for chromosomal and single gene disorders due to somatic mosaicism. For complex traits, which are due to the interactive effects of multiple genes and environmental factors, the affected twin of a discordant MZ pair offers the possibility for identifying somatic mutations in candidate genes. DNA sequencing of candidate genes in discordant MZ twins can identify those rare etiologic mutational events responsible for the different phenotypes since the confounding effects of common single nucleotide polymorphisms are eliminated, as DNA sequences should be identical in MZ pairs. In this report we describe the extensive DNA sequencing of 18 candidate genes in a sample of MZ and dizygotic (DZ) twins with nonsyndromic cleft lip with or without cleft palate. We were unable to identify any somatic differences in approximately 34 Kb of DNA sequenced in 13 MZ pairs, for a total of approximately 900 Kb of sequence comparisons, supporting the hypothesis that nonetiologic posttwinning mutations are rare. While no etiologic variants were identified in this study, sequence comparisons of discordant MZ twins can serve as a tool for identifying etiologic mutations in clefting and other complex traits.
Changes in Twinning Rates in South Korea: 1981–2002
Authors: Hur Yoon-Mi , Kwon Jun Soo 
Published: May 2007

AbstractThe present study investigates the twinning rate trends in South Korea for the years 1981 to 2002 utilizing the birth record data from the South Korea National Statistical Office. The twinning rates between 1981 and 1991 remained nearly constant and were slightly less than 10 twin individuals, that is, approximately five pairs per thousand births. Since the early 1990s, however, the twinning rate has increased sharply and reached 19.30 twin individuals, that is, around 10 pairs per thousand births in the year 2002. Application of the Weinberg method to birth data for the years 2000 to 2002 revealed that the dizygotic twin rate in South Korea increased almost threefold between 1981 to 1991 and 2002. In the 1980s the effect of maternal age on twinning rates appeared to be minimal. In the 1990s, however, increases in twinning rates occurred more markedly among older mothers than among younger mothers. We speculate that the rapid rise in twinning rates in South Korea in the 1990s is probably attributable to the spread of Assisted Reproductive Technologies among older mothers who seek treatments for infertility. The present study also examined whether residing in industrial areas is associated with multiple births in the South Korean population. The results did not support the recent finding of higher twinning incidence in industrialized regions.
Auditory Systems of Opposite-Sex Twins; Twin Study Summaries; In the News; Tribute to Inna Vladimirovna Ravich-Scherbo
Authors: Segal Nancy L. 
Published: May 2007

AbstractResearch comparing the auditory systems of opposite-sex co-twins, homosexual females and bisexual females is reviewed. Suggestions for how the findings may apply to other populations are provided. Next, recent twin studies of disputed memories and male sexual behaviors are summarized, as are recent events of scientific interest to twin researchers. Finally, a tribute to the late Russian twin researcher Dr. Inna Vladimirovna Ravich-Scherbo is presented.
Paternal Alcoholism and Offspring Conduct Disorder: Evidence for the ‘Common Genes’ Hypothesis
Authors: Haber Jon R. , Jacob Theodore , Heath Andrew C. 
Published: May 2007

AbstractNot only are alcoholism and externalizing disorders frequently comorbid, they often co-occur in families across generations; for example, paternal alcoholism predicts offspring conduct disorder just as it does offspring alcoholism. To clarify this relationship, the current study examined the ‘common genes’ hypothesis utilizing a children-of-twins research design. Participants were male monozygotic (MZ) and dizygotic (DZ) twins from the Vietnam Era Twin Registry who were concordant or discordant for alcohol dependence together with their offspring and the mothers of those offspring. All participants were conducted through a structured psychiatric interview. Offspring risk of conduct disorder was examined as a function of alcoholism genetic risk (due to paternal and co-twin alcohol dependence) and alcoholism environmental risk (due to being reared by a father with an alcohol dependence diagnosis). After controlling for potentially confounding variables, the offspring of alcohol- dependent fathers were significantly more likely to exhibit conduct disorder diagnoses than were off- spring of nonalcohol-dependent fathers, thus indicating diagnostic crossover in generational family transmission. Comparing offspring at high genetic and high environmental risk with offspring at high genetic and low environmental risk indicated that genetic factors were most likely responsible for the alcoholism–conduct disorder association. The observed diagnostic crossover (from paternal alcoholism to offspring conduct disorder) across generations in the context of both high and low environmental risk (while genetic risk remained high) supported the common genes hypothesis.
Human Cytokine Response toex vivoAmyloid-β Stimulation is Mediated by Genetic Factors
Authors: Posthuma Danielle , Meulenbelt Ingrid , de Craen Anton J. M. , de Geus Eco J. C. , Slagboom P. Eline , Boomsma Dorret I. , Westendorp Rudi G. J. 
Published: May 2007

AbstractThrough its ability to induce the enhanced release and production of cytokines, amyloid-β is responsible for the chronic inflammatory response that contributes to Alzheimer's disease (AD). Determining whether the response of monocytes to amyloid-β stimulation is under genetic control may help understand the basis of why some people are more prone to develop neuronal degeneration than others. In the current study we investigated the heritability of the cytokine (IL-10, IL-6, IL-1β, IL-1ra, TNF-[.alpha]) production capacity upon ex vivo stimulation with amyloid-β in whole blood samples of 222 twins and 85 singleton siblings from 139 extended twin families. It was found that individual differences in amyloid-β-induced cytokine production capacity are to a large extent of genetic origin, with heritability estimates ranging from 55% (IL-1β) to 68% (IL-6). We conclude that genes influencing amyloid-β-induced cytokine response may provide clues to the progression of AD pathology.
Birthweight and Adult Health in a Population-Based Sample of Norwegian Twins
Authors: Grjibovski Andrej M. , Harris Jennifer R. , Magnus Per 
Published: May 2007

AbstractPopulation-based twin data were used to test (a) whether lower birthweight confers a greater risk of adult health disorders, and (b) whether within-pair birthweight differences in twins explain discordance for health outcomes. The sample consisted of 1201 monozygotic (MZ) male twins, 1048 dizygotic (DZ) male twins, 1679 MZ female twins, 1489 DZ female twins, and 2423 opposite-sex DZ twins, born in Norway between 1967 and 1979. The relationship between birthweight and self-reported health outcomes were studied using multivariable logistic regression. In the full sample (n= 7840), birthweight was negatively associated with risk for nearsightedness (odds ratio OR = 0.76, 95% CI: 0.65 – 0.92) and minimal brain disorder (OR = 0.27, 95% CI: 0.16–0.44) when adjusted for gestational age, sex, zygosity, age, education and body mass index after correction for intraclass correlations and multiple comparisons. Within-pair analysis of 159 MZ and 224 DZ pairs revealed that myopic twins were on average 2 g (p= .966) and 64 g (p= .040) lighter than nonmyopic twins in MZ and DZ pairs respectively, suggesting that genetic factors may play an important role in the associations between birthweight and nearsightedness. Within-pair analysis of twins discordant for a minimal brain disorder indicated that affected twins were 80 g (p= .655) and 85 g (p= .655) lighter than their healthy co-twins in MZ and DZ pairs respectively, although there were only 2 MZ and 2 DZ discordant pairs.
The Effects of Twins, Parity and Age at First Birth on Cancer Risk in Swedish Women
Authors: Neale Rachel E. , Darlington Steven , Murphy Michael F. G. , Silcocks Paul B. S. , Purdie David M. , Talbäck Mats 
Published: May 2007

AbstractThe effect of reproductive history on the risk of cervical, colorectal and thyroid cancers and melanoma has been explored but the results to date are inconsistent. We aimed to examine in a record- linkage cohort study the risk of developing these cancers, as well as breast, ovarian and endometrial cancers, among mothers who had given birth to twins compared with those who had only singleton pregnancies. Women who delivered a baby in Sweden between 1961 and 1996 and who were 15 years or younger in 1961 were selected from the Swedish civil birth register and linked with the Swedish cancer registry. We used Poisson regression to assess associations between reproductive factors and cancer. Twinning was associated with reduced risks of breast, colorectal, ovarian and uterine cancers, although no relative risks were statistically significant. The delivery of twins did not increase the risk of any cancers studied. Increasing numbers of maternities were associated with significantly reduced risks of all tumors except thyroid cancer. We found positive associations between a later age at first birth and breast cancer and melanoma, while there were inverse associations with cervix, ovarian, uterine and colorectal cancers. These findings lend weight to the hypothesis that hormonal factors influence the etiology of colorectal cancer in women, but argue against any strong effect of hormones on the development of melanoma or tumors of the thyroid.
Allele Frequencies and ther2Measure of Linkage Disequilibrium: Impact on Design and Interpretation of Association Studies
Authors: Wray Naomi R. 
Published: May 2007

AbstractThe design and interpretation of genetic association studies depends on the relationship between the genotyped variants and the underlying functional variant, often parameterized as the squared correlation orr2measure of linkage disequilibrium between two loci. While it has long been recognized that placing a constraint on ther2between two loci also places a constraint on the difference in frequencies between the coupled alleles, this constraint has not been quantified. Here, quantification of this severe constraint is presented. For example, forr2≥ .8, the maximum difference in allele frequency is ± .06 which occurs when one locus has allele frequency .5. Forr2≥ .8 and allele frequency at one locus of .1, the maximum difference in allele frequency at the second locus is only ± .02. The impact on the design and interpretation of association studies is discussed.
New Concepts for Distinguishing the Hidden Patterns of Linkage Disequilibrium Which Underlie Association Between Genotypes and Complex Phenotypes
Authors: Wicks Jacqueline , Treloar Susan A. , Martin Nicholas G. , Duffy David L. 
Published: May 2007

AbstractAdisappointing feature of conventional methods for detecting association between DNA variation and a phenotype of interest is that they tell us little about the hidden pattern of linkage disequilibrium (LD) with the functional variant that is actually responsible for the association. This limitation applies to case-control studies and also to the transmission/disequilibrium test (TDT) and other family-based association methods. Here we present a fresh perspective on genetic association based on two novel concepts called ‘LD squares’ and ‘equi- risk alleles’. These describe and characterize the different patterns of gametic LD which underlie genetic association. These concepts lead to a general principle – the Equi-Risk Allele Segregation Principle – which captures the way in which underlying LD patterns affect the transmission patterns of genetic variants associated with a phenotype. This provides a basis for distinguishing the hidden LD patterns and might help to locate the functional variants responsible for the association.
Estimating the Extent of Parameter Bias in the Classical Twin Design: A Comparison of Parameter Estimates From Extended Twin-Family and Classical Twin Designs
Authors: Coventry William L. , Keller Matthew C. 
Published: May 2007

AbstractTheclassical twin design(CTD) circumvents parameter indeterminacy by assuming (1) negligible higher-order epistasis; and (2) either nonadditive genetic or common environmental effects are nonexistent, creating two potential sources of bias (Eaves et al., 1978; Grayson, 1989). Because the extended twin-family design (ETFD) uses many more unique covariance observations to estimate parameters, common environmental and nonadditive genetic parameters can be simultaneously estimated. The ETFD thereby corrects for what is likely to be the largest of the two sources of bias in CTD parameter estimates (Keller & Coventry, 2005). In the current paper, we assess the extent of this and other potential sources of bias in the CTD by comparing all published ETFD parameter estimates to CTD parameter estimates derived from the same data. CTD estimates of the common environment were lower than ETFD estimates of the common environment for some phenotypes, but for other phenotypes (e.g., stature in females and certain social attitudes), what appeared as the common environment was resolved to be assortative mating in the ETFD. On average, CTD estimates of nonadditive genetic factors were 43% lower, and additive genetic factors 63% higher, than ETFD estimates. However, broad-sense heritability estimates from the CTD were only 18% higher than ETFD estimates, highlighting that the CTD is useful for estimating broad-sense but not narrow-sense heritability. These results suggest that CTD estimates can be misleading when interpreted literally, but useful, albeit coarse, when interpreted properly.
Midupper Arm Circumference (MUAC) Changes in Late Pregnancy Predict Fetal Growth in Twins
Authors: Hediger Mary L. , Luke Barbara , van de Ven Cosmas , Nugent Clark 
Published: May 2007

AbstractThe objective of the study was to test the hypothesis that changes in arm anthropometry can be used to determine the risk of faltering growth in twin gestations. Serial data on midupper arm circumference (MUAC) and maternal weight gain were collected from a sample of 156 mothers. Changes in MUAC were monitored from 20 to 34 weeks. Women with a large loss of MUAC (greater than 1.5 cm), particularly when it occurred within two to four weeks of delivery, were significantly heavier, had higher pregravid Body Mass Indexes (BMIs), but gained less weight than mothers with no change in MUAC. In analysis of covariance models adjusting for length of gestation, black ethnicity, males per twin pair, monochorionicity, and baseline MUAC at 20 weeks, a large loss of MUAC was associated with significantly lower birthweight (2263 g vs. 2499 g) and birthweight z-score (–0.92 SDU vs. –0.39 SDU). Changes in MUAC from 20 to 34 weeks, and especially near delivery, are significantly associated with fetal growth in twin pregnancies. A positive change may indicate that the mother has adequate dietary intake or nutrient stores to continue to accrue lean body mass and support fetal growth, while a loss of MUAC indicates that dietary intake or nutrient stores may be inadequate. This simple, relatively precise, measure of change in maternal body composition during pregnancy may be useful in identifying twin pregnancies at risk for faltering intrauterine growth, particularly among overweight or obese women.
Hematopoietic Progenitor Cell Mobilization Results in Hypoxia with Increased Hypoxia-Inducible Transcription Factor-1α and Vascular Endothelial Growth Factor A in Bone Marrow
Authors: Lévesque Jean-Pierre , Winkler Ingrid G. , Hendy Jean , Williams Brenda , Helwani Falak , Barbier Valérie , Nowlan Bianca , Nilsson Susan K. 
Published: May 2007

AbstractDespite the fact that many hypoxia-inducible genes are important in hematopoiesis, the spatial distribution of oxygen in the bone marrow (BM) has not previously been explored in vivo. Using the hypoxia bioprobe pimonidazole, we showed by confocal laser scanning microscopy that the endosteum at the bone-BM interface is hypoxic, with constitutive expression of hypoxia-inducible transcription factor-1α (HIF-1α) protein in steady-state mice. Interestingly, at the peak of hematopoietic stem and progenitor cell (HSPC) mobilization induced by either granulocyte colony-stimulating factor or cyclophosphamide, hypoxic areas expand through the central BM. Furthermore, we found that HSPC mobilization leads to increased levels of HIF-1α protein and increased expression of vascular endothelial growth factor A (VEGF-A) mRNA throughout the BM, with an accumulation of VEGF-A protein in BM endothelial sinuses. VEGF-A is a cytokine known to induce stem cell mobilization, vasodilatation, and vascular permeability in vivo. We therefore propose that the expansion in myeloid progenitors that occurs during mobilization depletes the BM hematopoietic microenvironment of O2, leading to local hypoxia, stabilization of HIF-1α transcription factor in BM cells, increased transcription of VEGF-A, and accumulation of VEGF-A protein on BM sinuses that increases vascular permeability.Disclosure of potential conflicts of interest is found at the end of this article.
Bcl-2 Engineered MSCs Inhibited Apoptosis and Improved Heart Function
Authors: Li Wenzhong , Ma Nan , Ong Lee-Lee , Nesselmann Catharina , Klopsch Christian , Ladilov Yury , Furlani Dario , Piechaczek Christoph , Moebius Jeannette M. , Lützow Karola , Lendlein Andreas , Stamm Christof , Li Ren-Ke , Steinhoff Gustav 
Published: May 2007

AbstractEngraftment of mesenchymal stem cells (MSCs) derived from adult bone marrow has been proposed as a potential therapeutic approach for postinfarction left ventricular dysfunction. However, limited cell viability after transplantation into the myocardium has restricted its regenerative capacity. In this study, we genetically modified MSCs with an antiapoptotic Bcl-2 gene and evaluated cell survival, engraftment, revascularization, and functional improvement in a rat left anterior descending ligation model via intracardiac injection. Rat MSCs were manipulated to overexpress the Bcl-2 gene. In vitro, the antiapoptotic and paracrine effects were assessed under hypoxic conditions. In vivo, the Bcl-2 gene-modified MSCs (Bcl-2-MSCs) were injected after myocardial infarction. The surviving cells were tracked after transplantation. Capillary density was quantified after 3 weeks. The left ventricular function was evaluated by pressure-volume loops. The Bcl-2 gene protected MSCs against apoptosis. In vitro, Bcl-2 overexpression reduced MSC apoptosis by 32% and enhanced vascular endothelial growth factor secretion by more than 60% under hypoxic conditions. Transplantation with Bcl-2-MSCs increased 2.2-fold, 1.9-fold, and 1.2-fold of the cellular survival at 4 days, 3 weeks, and 6 weeks, respectively, compared with the vector-MSC group. Capillary density in the infarct border zone was 15% higher in Bcl-2-MSC transplanted animals than in vector-MSC treated animals. Furthermore, Bcl-2-MSC transplanted animals had 17% smaller infarct size than vector-MSC treated animals and exhibited functional recovery remarkably. Our current findings support the premise that transplantation of antiapoptotic gene-modified MSCs may have values for mediating substantial functional recovery after acute myocardial infarction.
Bone Marrow Contributes to Epithelial Cancers in Mice and Humans as Developmental Mimicry
Authors: Cogle Christopher R. , Theise Neil D. , Fu DongTao , Ucar Deniz , Lee Sean , Guthrie Steven M. , Lonergan Jean , Rybka Witold , Krause Diane S. , Scott Edward W. 
Published: May 2007

Abstract
Bone marrow cells have the capacity to contribute to distant organs. We show that marrow also contributes to epithelial neoplasias of the small bowel, colon, and lung, but not the skin. In particular, epithelial neoplasias found in patients after hematopoietic cell transplantations demonstrate that human marrow incorporates into neoplasias by adopting the phenotype of the surrounding neoplastic environment. To more rigorously evaluate marrow contribution to epithelial cancer, we employed mouse models of intestinal and lung neoplasias, which revealed specifically that the hematopoietic stem cell and its progeny incorporate within cancer. Furthermore, this marrow involvement in epithelial cancer does not appear to occur by induction of stable fusion. Whereas previous claims have been made that marrow can serve as a direct source of epithelial neoplasia, our results indicate a more cautionary note, that marrow contributes to cancer as a means of developmental mimicry.
Disclosure of Potential Conflicts of Interest is found at the end of this article.
Emergency Endovascular Stent Grafting for Thoracic Aortic Pathology
Authors: Bos Wendy T.G.J. , Verhoeven Eric L.G. , Zeebregts Clark J.A.M. , Tielliu Ignace F.J. , Prins Ted R. , Oranen Bjorn I. , van den Dungen Jan J.A.M. 
Published: May 2007

Our aim was to report single-center results of emergency endovascular treatment for thoracic aortic disease. From March 1998 to January 2006, 30 acute thoracic EVAR procedures were carried out in 29 patients. One patient received two procedures in different settings. Four patients died before treatment could be initiated. The pathology of aortic lesions included atherosclerotic aneurysm ( n = 13), pseudoaneurysm ( n = 6), aortic rupture ( n = 5), type B dissection ( n = 5), aortobronchial or aortoesophageal fistula ( n = 4), and intramural hematoma ( n = 1). The surgical mortality rate was 21%. Three patients died as a result of technical complications, and three patients died after technically successful procedures. The mean follow-up was 31 ± 23 months. The late mortality rate was 40% (8 of 20). Four patients died of causes unrelated to the procedure; two patients died at home without autopsy. Two patients died as a consequence of graft infections. Three late nonfatal complications occurred. Two of these resulted in additional treatment: one patient developed a mycotic aneurysm that was treated with additional stent grafting, and one patient developed a type 3 endoleak after 6 years of follow-up and was successfully treated with a bridging stent graft. Endovascular treatment for acute thoracic disease is feasible and associated with a reasonable outcome. In selected cases, it may be considered as a first option.