bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management and Outcomes of 65 Quadruplet Pregnancies: Sixteen Years' Experience in France
Authors: Pons J.C. , Nekhlyudov L. , Dephot N. , Moal S. Le , Papiernik E. 
Published: July 2016

AbstractObjective: data on the prognosis and management of multifetal pregnancies are of vital importance, particularly when the option of selective termination is considered. The present study details the obstetric management, neonatal outcome, and follow-up data of 65 quadruplet pregnancies in France.Methods: to conduct the study, a questionnaire was sent to families registered with the National Association Helping Parents of Multiple Births (Association National d'Entraide des Parents de Naissance Multiples, A.N.E.P.N.M.).Results: of 116 questionnaires sent to families of quadruplets born between 1972 and 1988, 65 were received. Of these pregnancies, 58 were obtained with ovulation induction agents, 2 with IVF (in vitro fertilization) and GIFT (gamete intrafallopian transfer) and 5 were spontaneous. Diagnosis was made prior to 13 weeks gestation in 87.2% of cases. Most mothers were hospitalized prior to delivery – mean duration of 47 days. The mean gestational age at delivery was 31.2 ± 3 weeks with a prematurity rate of 97%. Cesarean sections were performed in 51 cases and vaginal deliveries in 14. Neonatal and perinatal mortality rates were 68 and 104 per 1000, respectively. Birthweights of quadruplets ranged from 760 to 2455g with a mean of 1615 g.Conclusion: management of quadruplet pregnancies in France consists of early diagnosis, echographical and clinical monitoring, early reduction of maternal activity and cesarean deliveries. Our management of such pregnancies is of high quality as reflected by our obstetrical results. Lack of adequate management, as perceived by families of quadruplets, exists at two levels: a psychological (lack of psychological support) and a financial (lack of specific help).
Parental Imprinting on Mouse Chromosome 7
Authors: Ferguson-Smith A.C. 
Published: July 2016

Genetic studies have shown that both a maternally and paternally inherited copy of mouse chromosome 7 are essential for normal embryogenesis. When the parental dosage is altered, such as in maternal or paternal uniparental disomy for chromosome 7 (UPD7), the resulting embryos die. This is due to the altered dosage of imprinted genes which are normally expressed only from the paternally or maternally inherited chromosome homologue. Several genes on mouse chromosome 7 are subject to parental imprinting. Mutant phenotypes seen in UPD7 embryos and chimaeras can be explained by the altered dosage of some of these genes.The mechanism(s) that causes genes to be expressed in a parental origin specific manner has not yet been determined but is believed to involve germline specific modifications to DNA and/or chromatin which are acted upon after fertilisation to affect the activity of imprinted genes. Two genes, H19 and Igf2, are located 90kb apart on the distal end of chromosome 7 and are imprinted reciprocally with the maternally inherited allele of HI9 and paternally inherited allele of Igf2 being expressed. We have used UPD7 embryos to identify epigenetic modifications that distinguish the two parental alleles in the H19 and Igf2 domain by comparing DNA and chromatin from normal and maternal UPD cobceptuses. Clear cut differences in DNA methylation and chromatin compaction were observed for the H19 gene with the paternal allele exhibiting promoter methylation and nuclease insensitivity. These were not found in sperm. In addition, no major differences were noted for the Igf2 gene, although subtle parental origin specific modifications were found. These studies suggest that the two genes may share a common regulatory mechanism which controls their reciprocal imprinting.
An Introduction to Genomic Imprinting and Parent of Origin Effects
Authors: Hall J.G. , Lopez-Rangel E. 
Published: July 2016

Recent developments in molecular genetics and cytogenetics have allowed for better understanding of the inheritance and expression of genes. Many newly recognized mechanisms such as genomic imprinting, mosaicism, allelic expansion, cytoplasmic inheritance and uniparental disomy have been recognized to play an important role in human heredity.Genomic imprinting refers to differences in the phenotype which are observed depending on whether the gene was inherited from the father or from the mother. Genomic imprinting is a difficult concept to understand because imprinting has been used loosely to refer to a number of different mechanisms including psychological development, endocrinological actions of cells and protein-protein interactions. Genomic imprinting produces parent-of-origin effects. Parent-of-origin effects is a term that encompasses many of the non-traditional types of inheritance and other genetic and non-genetic mechanisms which show an effect depending on whether they were paternally or maternally derived.
Why is There No Diploid Overdose Effect in Prader-Willi Syndrome Due to Uniparental Disomy?
Authors: Smith A. 
Published: July 2016

AbstractDue to DNA technology, it is now apparent that the mechanisms of genetic disease are more complex than the model of a gene with biallelic expression in the diploid state. If a gene is imprinted, monoallelic expression is the norm when the chromosomes of a pair are inherited normally from each parent. Uniparental disomy (UPD) is the abnormal situation where both chromosomes of a pair come from the same parent. When the chromosome contains an imprinted gene, UPD may result in nullisomy or disomy for a functional copy of that gene. If there are two imprinted loci on the same chromosome, UPD for that chromosome results in nullisomy for one imprinted gene but functional disomy for the other a “diploid overdose” (DO). This situation has been well demonstrated in the Prader-Willi syndrome (PWS) which is the nullisomic phenotype for the PWS gene(s) on chromosome 15q 11-13. Chromosome 15q11-13 also contains the gene for Angelman syndrome (AS) which has a phenotype distinct from PWS. Both loci are subject to imprinting – in PWS, the imprint is on the maternal chromosome 15, in AS it is on the paternal chromosome 15. All individuals with PWS due to maternal UPD, while functionally nullisomic for the PWS locus, are functionally disomic for the AS locus – a DO situation. Assuming that biallelic expression of an imprinted gene is harmful, one would expect DO for an imprinted gene to produce a phenotypic effect. Cases of PWS due to UPD do not appear to differ from those due to deletion (hypopigmentation in deletional cases can be explained by loss of D15S12 downstream from the critical region). There is no good evidence of DO for the AS locus in PWS due to UPD. Why then was it ‘necessary’ in evolutionary terms to imprint the AS locus and maintain the imprint faithfully for life. A similar situation of two imprinted genes on the same chromosome occurs with IGF2 and H19 on chromosome 11p15. Maternal imprinting for IGF2 and paternal imprinting for H19 is the norm. Paternal UPD in this situation does lead to a DO effect, namely Beckwith-Wiedemann syndrome. The possibility of a DO effect needs to be considered when assessing the phenotypic spectrum of UPD for other chromosomes currently under investigation.
Asynchronous Replication Patterns of Imprinted Genes in Triploid Cells
Authors: Argyriou-Tirita A. , Romanakis K. , Kroisel P. , Haas O. A. 
Published: July 2016

Several unique features distinguish imprinted from nonimprinted genes, including the unusual replication behavior the unequal methylation and the differential expression of imprinted alleles [1]. The replication timing in S phase of the two homologous alleles of a normal, nonimprinted gene is highly synchronous [2, 3]. Housekeeping genes replicate early, constitutive heterochromatic regions replicate late and tissue-specific genes replicate earlier when they are expressed than when they are not [2-4]. In contrast, imprinted genes which, by definition, display allele-specific expression replicate asynchronously [2-5].The relative order of replication of homologous alleles as well as that of different loci can be elegantly compared with fluorescence in situ hybridization (FISH) on interphase nuclei [2-5]. Unreplicated DNA segments give singlet hybridization signals in normal diploid cells, while replicated loci are characterized by doublets. The distribution of these two patterns can be used to determine the S phase replication time of any DNA sequence. Moreover, determination of the singlet/doublet ratio allows a good estimation of the degree of replication asynchrony of two homologous alleles [2-5].Using cell lines with deletions, disomies or associated FISH-detectable centromeric satellite polymorphisms, Kitsberg et al. [4] found that the paternal allele was the early replicating one in all the imprinted genes which they had analyzed. Subsequently, however, Knoll et al. [5] detected genes in the imprinted Prader-Willi region on chromosome 15, which also displayed other patterns. Therefore, it seems necessary to specify the relative timing of maternally and paternally derived alleles for each individual asynchronously replicating gene. Unfortunately, this is so far only feasible with a very restricted number of sequences.
Influence of Mouse-Strain-Specific Factors on Position-Dependent Transgene DNA Methylation Patterns
Authors: Koetsier P.A. , Doerfler W. 
Published: July 2016

In previous work from this laboratory, an inverse dependence was established for the adenovirus type 2 E2A late promoter between sequence-specific DNA methylation and promoter activity [1-5; for reviews see ref. 6, 7]. The effect of DNA methylation on promoter activity was also assessed in the transgenic mice, which were obtained from microinjections of unmethylated or in vitroHpaII-premethylated pAd2E2AL-CAT DNA [1] into F2zygotes from B6D2F, (C57BL/6 × DBA/2) hybrid mice. In CAT assays carried out on organ extracts from the pAd2E2AL-CAT mice, the inverse relationship was confirmed [2].We studied the stability of the pAd2E2AL-CAT DNA methylation patterns in up to eight mouse generations and assessed the influence of the strain-specific genetic background. Three pAd2E2AL-CAT mouse lines were crossed with inbred DBA/2, C57BL/6 or B6D2F, mice. Parent-of-origin effects were controlled by exclusive hemizygous transgene transmission either via females or males. The founder animal of line 7-1 carried two groups of transgenes (A and B) on separate chromosomes. The transgene methylation patterns of the 7-1B transgenes and those of the lines 5-8 and 8-1 were stably transmitted.Southern blot hybridization experiments [8, 9] revealed that the 7-1A transgene methylation pattern was a cellular mosaic. In mixed-genetic-background offspring from 7-1A animals, 10% carried transgenes withHpaII-DNA methylation levels that were reduced from 40 to 10-15%. This finding suggested that in this background the factors that supported high methylation levels were dominant. When inbred DBA/2 mice were the mates, 40% of the siblings carried demethylated transgenes, whereas this ratio amounted to only 10% in C57BL/6 offspring (comparable to B6D2F1crossings). Transgene methylation patterns were not detectably influenced by the parent-of-origin.
Unusual Clinical Findings in Prader-Willi Syndrome Patients with Uniparental Disomy
Authors: Schulze A. , Petersen M.B. , Horn N. , Kastrup K.W. , Brøndum-Nielsen K. 
Published: July 2016

Eight patients with Prader-Willi syndrome (PWS), 3 males and 5 females, who were shown to have uniparental maternal disomy after investigation with polymorphic DNA marker spanning chromosome 15, were investigated clinically.Four patients displayed in addition to the clinical signs, some unusual clinical feature: two patients showed a hairshaft anomaly, one of whom, a female, suggested a Menkes'-like condition-an investigation of copper uptake showed slightly increased values. Further investigations are in progress. One patient died unexpectedly at the age of 1 year 4 months and adenovirus was isolated postmortem in the airway secretion. Two patients presented a seizure disorder.The mean birth weight was 2,122 (1,195-3,170) g and the gestational age was 37.1 (32-42) weeks for this group, lower than expected for PWS. Mean maternal age was elevated [31.9 (25-39) year].Since the recent report [1] of a case of Bloom syndrome in a PWS patient led to the mapping of the Bloom syndrome gene to chromosome 15, it has been suggested that isodisomy could lead to homozygosity for recessive genes. This opens up the possibility of mapping genes in a new way. We suggest that uniparental disomy PWS patients should be investigated for unusual features to identify other monogenic disorders with a locus on chromosome 15. Isodisomy defined by multiple DNA markers indicates potential regions of candidate genes.
Fingernail, as an Alternative Source of DNA for Forensic Investigations and Medical Diagnostics A new technique to obtain template DNA in critical situations
Authors: Ricci U. , Uzielli M.L. Giovannucci 
Published: July 2016

The use of PCR (polymerase chain reaction) is having a profound impact on forensic science and medical diagnostics.Limited amounts of biological material and/or degraded low molecular weight DNA can be anticipated for forensic identification and often also for diagnostic investigations in fetuses, stillbirths and children with birth defects.In vitro amplification of DNA, via PCR, represents an important tool for overcoming some of the limitations. Nevertheless, the problem of availability of biological samples as DNA source is often critic.In order to obtain a useful and rapid procedure of DNA analysis in such difficult situations, we have recently developed a simple DNA extraction method using Chelex 100 and a PCR based amplification technique, and using fingernail as an alternative source of DNA.Chelex 100 procedures result in denaturated DNA samples, not suitable for RFLPS analysis. Nevertheless we demonstrated that no differences are detectable between the genotypes obtained by PCR amplification using the conventional phenol-chlorophorm or saline extraction and the Chelex based procedure.A DNA sample of 3-5 micrograms weight was easily obtained from fingernail clippings, and enabled us to perform several tests by using DNA typing methodologies, both for personal identification (in various forensic, medical and social situations) and in disputed parentage.Our laboratory uses as polymorphic markers a set of several VNTRs (variable number of tandem repeats) and, more recently, a series of unlinked STRs (short tandem repeats). The use of DNA typing with STR loci provides an accurate, highly sensitive and rapid assay for parentage testing, forensic identification and medical applications.
Slow Twin Conception at First Birth and Subsequent Maternal Twin Proneness in a Natural Fertility Population
Authors: Nonaka K. , Desjardins B. , Charbonneau H. , Légaré J. , Miura T. 
Published: July 2016

AbstractTo study whether apparently more fecund women having delivered twins at first birth have traits of higher twin-proneness, we performed a retrospective cohort study on population-based historical vital records of the 17-18th century French Canadian immigrants and their descendants under natural fertility conditions. Among 24896 mothers who had at least one child, 248 had twin maternities at their first birth (twinning rate = 1.0%). Among 21508 mothers with a valid marriage-first birth interval, twinning rate was 0.97% among prompt conceptions (7.0-11.0 months), with a particularly high rate at the interval of 7.0-8.0 months (2.2%). Marriages in August-October resulted in a higher twinning rate particularly for the slow conceptions than those in the other seasons. Promptly-conceived mothers of twins at the first delivery may seem to have higher fecundity, but subsequent births from these mothers (n = 88) show a lower twinning rate (1.7%) particularly at younger maternal age than from the other mothers who had slowly conceived twins at their first birth (n = 112). The latter show a 4.5% twinning rate as a whole among their second or later births. So-called twin-proneness of a mother, whether genetic or acquired, was not connected to higher conception rate of twin's mothers immediately after marriage. Reduced fecundity, which may have been imposed by some environmental factors, could raise the chance of twinning.
Use of Single- and Multi-Locus and Polymerase Chain Reaction Systems for Zygosity Determination - Clinical Application in Twins with Clefts of the Lip and Palate
Authors: Eufinger H. , Rand S.P. , Schütte U. 
Published: July 2016

AbstractPrecision of zygosity determination in twins can be improved by the use of modern methods of DNA analysis. The clinical application of 4 single- (SLS) and 2 multi-locus (MLS), and 6 PCR (polymerase chain reaction) systems for zygosity determination in 12 twin pairs with oral clefts was compared with regard to the quality and quantity of sample material required and the probability of error in monozygosity determination. PCR systems proved to be superior to SLS or MLS, as DNA sampling is much more convenient, while its level of accuracy still fulfils clinical requirements. For this reason, PCR systems should be considered a basic method in modern clinical twin research.
Analysis of the Effect of Hormones on Opposite-Sex Twin Attitudes
Authors: Miller E.M. , Martin N. 
Published: July 2016

AbstractNumerous reports in the literature suggest that hormones may transfer from one fetus to another, in humans as in animals. In a large sample of over seven thousand Australian adult twins, it was found that opposite-sex females showed a statistically significant tendency to hold more masculine attitudes than did same-sex female twins. This may be due to post-natal social interaction, but could also be caused by the transfer of testosterone from the male to the female fetus in opposite-sex twins.
Discordant Twin Pairs: The Relation Between Gestational Age and Neonatal Temperament Differences in Cotwins
Authors: Riese M.L. 
Published: July 2016

AbstractTemperament differences between cotwins at least 15% discordant for birth-weight were compared for a group of 66 preterm twin pairs and a group of 70 fullterm twin pairs, assessed in the neonatal period. The assessment focused on irritability, resistance to soothing, activity, reactivity, and reinforcement value. For the most part, significant differences were not obtained between discordant preterm cotwins. Previous research [10] had demonstrated that the larger fullterm twin of discordant pairs was more irritable, more difficult to soothe, more active while awake and during sleep, less reactive to visual and auditory stimuli, and less reinforcing to the examiner than the smaller cotwin. It was concluded that, for the behavioral variables measured, the fullterm group is at higher risk than the preterm group, and that both the lighter and the heavier discordant twins displayed signs of early behavioral risk. The findings suggested that the continued gestation for cotwins discordant in weight may be a risk period for early temperament development of the twins.
The Epidemiology of Genetic Epidemiology
Authors: Hopper J.L. 
Published: July 2016

AbstractFamilial aggregation for disease is important; strong familial risk factors must exist even if the increased risk to a relative of an affected individual is modest. It is in practice difficult, however, to conduct studies in genetic epidemiology which conform to strict epidemiological principles. For twin studies there are two major questions: Are twins ‘no different’ from the population on which inference is to be made? Are study twins ‘no different’ to twins in the population? The importance of each question of bias depends on the scientific question, the trait(s) studied, and sampling issues. The strength of the twin design is its ability to refute the null hypothesis that genetic factors do not explain variation in a trait. Following the Popperian paradigm, alternate hypotheses should be considered in depth (both theoretically and empirically), with a design and sample size sufficient to exclude not just naive explanations. More sophisticated statistical techniques are now being applied, so the philosophy, assumptions, and limitations of statistical modelling must be appreciated. The concept of ‘heritability’ has, in the past, been misunderstood and misused. New advances in DNA technology promise to revolutionise epidemiological thinking, and so case-control-pedigree designs may well become standard tools. The strengths and limitations of studies based on related individuals as the sampling unit are discussed.
The Effects of Two EFL (English as a Foreign Language) Teaching Approaches Studied by the Cotwin Control Method: A Comparative Study of the Communicative and the Grammatical Approaches
Authors: Ando J. 
Published: July 2016

AbstractThe present study compared two different types of English-language teaching approaches, the grammatical approach (GA) and the communicative approach (CA), by the cotwin control method. This study has two purposes: to study the effects of teaching approaches and to estimate genetic influences upon learning aptitudes. Seven pairs of identical twins (MZ) and 4 pairs of fraternal twins (DZ) participated in the experiment along with 68 other nontwin fifth graders. Each cotwin was assigned to the GA and CA respectively and received 20 hours of lessons over a 10-day period. The behavioral similarities between MZ cotwins were statistically and descriptively depicted. No major effect of either teaching approach was noted, but the genetic influence upon individual differences of learning achievement was obvious. Furthermore, an interesting interaction between the teaching approaches and intelligence was found, that is, that the GA capitalises on and CA compensates for intelligence. This interactional pattern could be interpreted as an example of genotype-environment interaction. The relationship between genetic factors and learning aptitudes is discussed.
A Study of Maternity Provision in the UK in Response to the Needs of Families Who Have a Multiple Birth
Authors: Spillman J.R. 
Published: July 2016

Multiple pregnancy is NEVER planned. A few years ago one could categorically make such a statement. Perhaps nowadays one cannot be so sure. Although parents are still unlikely to be able to plan such an event, it does seem that current infertility treatments may allow or even encourage practitioners to use methods which predispose to a multiple pregnancy. The practice of returning several fertilised embryos to the uterus in the hope of achieving a successful result has meant that many parents who longed for a baby have had to adjust to the realisation of a multiple pregnancy with all the effects such an occurrence has on family physical, social and emotional resources.The Study of Triplets and Higher Order Births by the Office of Population Censuses and Surveys [1] highlighted the striking increase in Multiple Births in recent years. This was particularly evident in the case of triplets and higher order births. (Fig. 1) Care of these high-risk infants is costly in resources and no increased funding has been given to the National Health Service or Social Services budgets to provide care and support for the families.This study endeavours to ascertain the needs of such families preconceptually, antenatally, intra-partum, postnatally and in the early months following the birth. It also tries to assess how appropriate current practice is in meeting these needs.