Alderson, P; Aro, A R; Dragonas, T
Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...
Jyothi Kiran Kohli
Full Text Available BACKGROUND Genetic diseases are one of the major causes of hospital admissions due to disability and mortality particularly among children (1:5 children of hospital admission either partially/completely as distribution of genetic diseases is not related to socioeconomic background, which implies that developing world has a large number of genetic diseases largely left uncared for, i.e. overall incidence of foetal/neonatal loss due to genetic/genetic environmental causes are as follows: 1:50 newborns have major congenital abnormality, 1:100 have a unifactorial disorder, 1:200 have a major chromosomal abnormality before birth. Diagnosis of chromosomal anomalies in foetus is one of the most important challenges in modern perinatology as invasive or noninvasive methods. The aim of the study is to review on cytogenetic evaluation of CVS obtained (transcervically during first trimester of pregnancy by direct karyotyping of tissue. MATERIALS AND METHODS This study was conducted in 2001 in Department of Anatomy along with Obstetrics and Gynaecology Department, LNJP Hospital. 37 healthy cases with 6-12 weeks of gestational age coming for medical termination of pregnancy were included in the study. After written informed consent for procedure, ultrasound-guided transcervical chorionic villus sampling was done (Brambati’s method. Tissue procured was then processed for direct karyotyping and studied. Metaphase spreads were photographed and karyotypes prepared and studied. RESULTS Out of 37 pregnant females, 30 samples were successfully prepared and processed by Direct method out of which 23 were normal female (46, XX and 7 were normal male (46, XY. No normal anomaly was detected. Best biopsies were obtained with 8-12 weeks gestation. G Banding could not be performed as chromosome obtained were found to be resistant to banding. CONCLUSIONS To summarise chromosome preparations obtained from CVS by Direct method has advantage of providing sufficient number
Full Text Available The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF embryos. Preimplantation genetic diagnosis (PGD or screening (PGS involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future.
The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF) embryos. Preimplantation genetic diagnosis (PGD) or screening (PGS) involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND) require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future. PMID:24783200
... Videos for Educators Search English Español Prenatal Genetic Counseling KidsHealth / For Parents / Prenatal Genetic Counseling What's in ... can they help your family? What Is Genetic Counseling? Genetic counseling is the process of: evaluating family ...
In this thesis we studied the efficacy and utilization of prenatal screening and prenatal diagnosis in the Netherlands and the increasing options for prenatal genetic diagnosis in general. In chapter 1 background information on prenatal screening and diagnosis in pregnancies conceived through
Takyi, Afua; Santolaya-Forgas, Joaquin
Obstetricians offer prenatal screening for most common chromosomal abnormalities to all pregnant women including those that had in vitro fertilization (IVF) and preimplantation genetic screening/diagnosis (PGS/D). We propose that free fetal DNA in maternal circulation together with the second trimester maternal serum alfa feto protein (MSAFP) and ultrasound imaging is the best prenatal screening test for chromosomal abnormalities and congenital anomalies in IVF-PGD/S patients because risk estimations from all other prenatal screening algorithms for chromosomal abnormalities depend heavily on maternal age which is irrelevant in PGS/D patients.
Down's Syndrome prenatal diagnostic and screening techniques have spread widely in France over the last 30 years and are now part of the routine clinical practice of prenatal care. These techniques, which originated in the field of genetics, ultrasonography and biochemistry, were the first to provide the possibility of choosing the features of the foetus, or at least to reject some of its characteristics. They lead to new norms of healthy foetuses and a progressive acceptance of medical abortions. The aim of this paper is to understand how the use of these tests has been generalised in France despite scientific controversies about their risks and ethical questioning about a potential renewal of eugenics. It analyses the representations of public needs that have been articulated by key players in the scientific and medical fields. This research explores political and administrative decision making processes to understand how progressively widening public access to prenatal testing has been organised and funded. The results highlight the scientific and political role of biomedical researchers, the forms of involvement of health authorities and politicians, and the passive participation of the vast majority of the users. The paper also examines the characteristics of the French health system that facilitated the generalised use of the technology.
Twisk, Moniek; Haadsma, Maaike L.; van der Veen, Fulco; Repping, Sjoerd; Mastenbroek, Sebastiaan; Heineman, Maas-Jan; Bossuyt, Patrick M. M.; Korevaar, Johanna C.
Objective: Although the primary goal of preimplantation genetic screening (PGS) is to increase pregnancy rates in women undergoing IVF/intracytoplasmic sperm injection treatment, it has been suggested that it may also be used as an alternative to prenatal testing for Down syndrome. Design: Trade-off
Twisk, Moniek; Haadsma, Maaike L.; van der Veen, Fulco; Repping, Sjoerd; Mastenbroek, Sebastiaan; Heineman, Maas-Jan; Bossuyt, Patrick M. M.; Korevaar, Johanna C.
Objective: Although the primary goal of preimplantation genetic screening (PGS) is to increase pregnancy rates in women undergoing IVF/intracytoplasmic sperm injection treatment, it has been suggested that it may also be used as an alternative to prenatal testing for Down syndrome. Design: Trade-off
Full Text Available Maternal markers are widely used to screen for fetal neural tube defects (NTDs, chromosomal abnormalities and cardiac defects. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia. The methods initially developed for NTDs using a single marker have since been built upon to develop high performance multi-maker tests for chromosomal abnormalities. Although cell-free DNA testing is still too expensive to be considered for routine application in public health settings, it can be cost-effective when used in combination with existing multi-maker marker tests. The established screening methods can be readily applied in the first trimester to identify pregnancies at high risk of pre-eclampsia and offer prevention though aspirin treatment. Prenatal screening for fragile X syndrome might be adopted more widely if the test was to be framed as a form of maternal marker screening.
%) of 61 AMA women reached genetic counselling in tertiary care: reasons included late initiation of antenatal care and low referral rates from primary care. Conclusion. Prenatal screening and diagnosis for DS based on AMA is working ...
Harper, Joyce C
Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selecting chromosomally normal embryos will lead to higher implantation and decreased miscarriage rates. This procedure, preimplantation genetic screening, was initially performed using fluorescent in situ hybridisation, but 11 randomised controlled trials of screening using this technique showed no improvement in in vitro fertilisation delivery rates. Progress in genetic testing has led to the introduction of array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing for preimplantation genetic screening, and three small randomised controlled trials of preimplantation genetic screening using these new techniques indicate a modest benefit. Other trials are still in progress but, regardless of their results, preimplantation genetic screening is now being offered globally. In the near future, it is likely that sequencing will be used to screen the full genetic code of the embryo.
... Inherited disorders include sickle cell disease , cystic fibrosis , Tay–Sachs disease , and many others. In most cases, both parents ... pain. It occurs most often in African Americans. Tay–Sachs Disease: An inherited birth defect that causes intellectual disability, ...
This paper is a review of the economics of prenatal screening as seen from a medical point of view. The difficulties and controversies over the economic analysis are examined with specific reference to screening for Down syndrome. The aims and principles of prenatal screening are set out and discussed before reviewing the attempts that have been made to assess the costs and benefits of screening for Down syndrome. The major problem identified is the measurement and valuation of benefits. This...
Full Text Available The frequency of inherited malformations as well as genetic disorders in newborns account for around 3-5%. These frequency is much higher in early stages of pregnancy, because serious malformations and genetic disorders usually lead to spontaneous abortion. Prenatal diagnosis allowed identification of malformations and/or some genetic syndromes in fetuses during the first trimester of pregnancy. Thereafter, taking into account the severity of the disorders the decision should be taken in regard of subsequent course of the pregnancy taking into account a possibilities of treatment, parent's acceptation of a handicapped child but also, in some cases the possibility of termination of the pregnancy. In prenatal testing, both screening and diagnostic procedures are included. Screening procedures such as first and second trimester biochemical and/or ultrasound screening, first trimester combined ultrasound/biochemical screening and integrated screening should be widely offered to pregnant women. However, interpretation of screening results requires awareness of both sensitivity and predictive value of these procedures. In prenatal diagnosis ultrasound/MRI searching as well as genetic procedures are offered to pregnant women. A variety of approaches for genetic prenatal analyses are now available, including preimplantation diagnosis, chorion villi sampling, amniocentesis, fetal blood sampling as well as promising experimental procedures (e.g. fetal cell and DNA isolation from maternal blood. An incredible progress in genetic methods opened new possibilities for valuable genetic diagnosis. Although karyotyping is widely accepted as golden standard, the discussion is ongoing throughout Europe concerning shifting to new genetic techniques which allow obtaining rapid results in prenatal diagnosis of aneuploidy (e.g. RAPID-FISH, MLPA, quantitative PCR.
... poses no physical risks for you or your baby. While prenatal cell-free DNA screening might cause anxiety, it might help you avoid the need for more invasive tests, treatment or monitoring during your pregnancy. Keep in mind, however, that ...
Chandrasekharan, Subhashini; McGuire, Amy L.; Van den Veyver, Ignatia B.
Thousands of patents have been awarded that claim human gene sequences and their uses, and some have been challenged in court. In a recent high-profile case, Association for Molecular Pathology, et al. vs. Myriad Genetics, Inc., et al., the United States Supreme Court ruled that genes are natural occurring substances and therefore not patentable through “composition of matter” claims. The consequences of this ruling will extend well beyond ending Myriad's monopoly over BRCA testing, and may affect similar monopolies of other commercial laboratories for tests involving other genes. It could also simplify intellectual property issues surrounding genome-wide clinical sequencing, which can generate results for genes covered by intellectual property. Non-invasive prenatal testing (NIPT) for common aneuploidies using cell-free fetal (cff) DNA in maternal blood is currently offered through commercial laboratories and is also the subject of ongoing patent litigation. The recent Supreme Court decision in the Myriad case has already been invoked by a lower district court in NIPT litigation and resulted in invalidation of primary claims in a patent on currently marketed cffDNA-based testing for chromosomal aneuploidies. PMID:24989832
Chandrasekharan, Subhashini; McGuire, Amy L; Van den Veyver, Ignatia B
Thousands of patents have been awarded that claim human gene sequences and their uses, and some have been challenged in court. In a recent high-profile case, Association for Molecular Pathology, et al. v. Myriad Genetics, Inc., et al., the US Supreme Court ruled that genes are natural occurring substances and therefore not patentable through 'composition of matter' claims. The consequences of this ruling will extend well beyond ending Myriad's monopoly over BRCA testing and may affect similar monopolies of other commercial laboratories for tests involving other genes. It could also simplify intellectual property issues surrounding genome-wide clinical sequencing, which can generate results for genes covered by intellectual property. Non-invasive prenatal testing (NIPT) for common aneuploidies using cell-free fetal (cff) DNA in maternal blood is currently offered through commercial laboratories and is also the subject of ongoing patent litigation. The recent Supreme Court decision in the Myriad case has already been invoked by a lower district court in NIPT litigation and resulted in invalidation of primary claims in a patent on currently marketed cffDNA-based testing for chromosomal aneuploidies. © 2014 John Wiley & Sons, Ltd.
Chitayat, David; Langlois, Sylvie; Douglas Wilson, R
To develop a Canadian consensus document on maternal screening for fetal aneuploidy (e.g., Down syndrome and trisomy 18) in singleton pregnancies. Pregnancy screening for fetal aneuploidy started in the mid 1960s, using maternal age as the screening test. New developments in maternal serum and ultrasound screening have made it possible to offer all pregnant patients a non-invasive screening test to assess their risk of having a fetus with aneuploidy to determine whether invasive prenatal diagnostic testing is necessary. This document reviews the options available for non-invasive screening and makes recommendations for Canadian patients and health care workers. To offer non-invasive screening for fetal aneuploidy (trisomy 13, 18, 21) to all pregnant women. Invasive prenatal diagnosis would be offered to women who screen above a set risk cut-off level on non-invasive screening or to pregnant women whose personal, obstetrical, or family history places them at increased risk. Currently available non-invasive screening options include maternal age combined with one of the following: (1) first trimester screening (nuchal translucency, maternal age, and maternal serum biochemical markers), (2) second trimester serum screening (maternal age and maternal serum biochemical markers), or (3) 2-step integrated screening, which includes first and second trimester serum screening with or without nuchal translucency (integrated prenatal screen, serum integrated prenatal screening, contingent, and sequential). These options are reviewed, and recommendations are made. Studies published between 1982 and 2009 were retrieved through searches of PubMed or Medline and CINAHL and the Cochrane Library, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational
Petersen, Andrea K; Cheung, Sau Wai; Smith, Janice L; Bi, Weimin; Ward, Patricia A; Peacock, Sandra; Braxton, Alicia; Van Den Veyver, Ignatia B; Breman, Amy M
Since its debut in 2011, cell-free fetal DNA screening has undergone rapid expansion with respect to both utilization and coverage. However, conclusive data regarding the clinical validity and utility of this screening tool, both for the originally included common autosomal and sex-chromosomal aneuploidies as well as the more recently added chromosomal microdeletion syndromes, have lagged behind. Thus, there is a continued need to educate clinicians and patients about the current benefits and limitations of this screening tool to inform pre- and posttest counseling, pre/perinatal decision making, and medical risk assessment/management. The objective of this study was to determine the positive predictive value and false-positive rates for different chromosomal abnormalities identified by cell-free fetal DNA screening using a large data set of diagnostic testing results on invasive samples submitted to the laboratory for confirmatory studies. We tested 712 patient samples sent to our laboratory to confirm a cell-free fetal DNA screening result, indicating high risk for a chromosome abnormality. We compiled data from all cases in which the indication for confirmatory testing was a positive cell-free fetal DNA screen, including the common trisomies, sex chromosomal aneuploidies, microdeletion syndromes, and other large genome-wide copy number abnormalities. Testing modalities included fluorescence in situ hybridization, G-banded karyotype, and/or chromosomal microarray analysis performed on chorionic villus samples, amniotic fluid, or postnatally obtained blood samples. Positive predictive values and false-positive rates were calculated from tabulated data. The positive predictive values for trisomy 13, 18, and 21 were consistent with previous reports at 45%, 76%, and 84%, respectively. For the microdeletion syndrome regions, positive predictive values ranged from 0% for detection of Cri-du-Chat syndrome and Prader-Willi/Angelman syndrome to 14% for 1p36 deletion
Dondorp, W J; Page-Christiaens, G C M L; de Wert, G M W R
The practice of prenatal screening is undergoing important changes as a result of the introduction of genomic testing technologies at different stages of the screening trajectory. It is expected that eventually it will become possible to routinely obtain a comprehensive 'genome scan' of all fetuses. Although this will still take several years, there are clear continuities between present developments and this future scenario. As this review shows, behind the still limited scope of screening for common aneuploidies, a rapid widening of the range of conditions tested for is already taking shape at the invasive testing stage. But the continuities are not just technical; they are also ethical. If screening for Down's syndrome is a matter of providing autonomous reproductive choice, then why would providing the choice to have a full fetal genome scan be something entirely different? There is a clear need for a sustainable normative framework that will have to answer three challenges: the indeterminateness of the autonomy paradigm, the need to acknowledge the future child as an interested stakeholder, and the prospect of broad-scope genomic prenatal screening with a double purpose: autonomy and prevention. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Kleinveld, J.H.; van den Berg, M.; van Eijk, J.T.; van Vugt, J.M.G.; van der Wal, G.; Timmermans, D.R.M.
Objectives: This study aims to find out whether offering prenatal screening for Down syndrome and neural tube defects influences pregnant women's attitudes toward having a screening test. Methods: Women were randomised into a group that was offered prenatal screening and a group that was not offered
Santavy, J.; Janouskova, M.; Fingerova, H.; Krikal, Z.
Prenatal medicine strives to reveal hereditary disorders and congenital malformations before delivery. The application of RIA significantly widened the spectrum of available diagnostic possibilities. We first focused our attention on determining alpha-1-fetoprotein in the amniotic fluid and the serum. We used the results of 33 examinations of the amniotic fluid and 100 samples of the blood serum to compile a graph of physiological values during pregnancy. The graph is used in assessing clinical samples in suspect congenital disorders of neural tube closure and other malformations. In the last two years we have tested testosterone determination in the amniotic fluid to ascertain prenatally the fetal sex in early pregnancy. The results were satisfactory and agreed in 70.6%. (author)
Full Text Available To evaluate the impact of prenatal screening and genetic testing for trisomy 21 (T21 on the prevalence of T21 in Slovenia.Data about all prenatally and postnatally confirmed cases of T21 in Slovenia between 1981 and 2012 were collected retrospectively from all genetic laboratories in Slovenia. The expected number of babies with T21 according to maternal age was calculated.The primary outcomes measures were number of fetuses and newborn infants with T21 diagnosed prenatally and postnatally and the impact of advances in screening and genetic diagnostics on the prevalence of newborns with T21 in Slovenia.Despite a significantly increased mean maternal age from 25.4 years in year 1981 to 30.3 years in year 2012 the prevalence of newborn infants with T21 was 0.51 per 1000 births compared to 0.55 per 1000 births, respectively. The prevalence of prenatally diagnosed cases increased from 0.03 per 1000 births to 2.06 per 1000. The detection rate of T21 in year 2012 was 78,9%. The total number of prenatal invasive procedures (chorionic villous sampling and amniocenteses carried out during that period was rising until 2002, since when it is stable at around 7%.The advancement and implementation of screening tests and prenatal diagnostic procedures in Slovenia caused an important improvement in the efficiency of the prenatal detection of T21.
Rudolf, Gorazd; Tul, Nataša; Verdenik, Ivan; Volk, Marija; Brezigar, Anamarija; Kokalj Vokač, Nadja; Jeršin, Nataša; Prosenc, Bernarda; Premru Sršen, Tanja; Peterlin, Borut
To evaluate the impact of prenatal screening and genetic testing for trisomy 21 (T21) on the prevalence of T21 in Slovenia. Data about all prenatally and postnatally confirmed cases of T21 in Slovenia between 1981 and 2012 were collected retrospectively from all genetic laboratories in Slovenia. The expected number of babies with T21 according to maternal age was calculated. The primary outcomes measures were number of fetuses and newborn infants with T21 diagnosed prenatally and postnatally and the impact of advances in screening and genetic diagnostics on the prevalence of newborns with T21 in Slovenia. Despite a significantly increased mean maternal age from 25.4 years in year 1981 to 30.3 years in year 2012 the prevalence of newborn infants with T21 was 0.51 per 1000 births compared to 0.55 per 1000 births, respectively. The prevalence of prenatally diagnosed cases increased from 0.03 per 1000 births to 2.06 per 1000. The detection rate of T21 in year 2012 was 78,9%. The total number of prenatal invasive procedures (chorionic villous sampling and amniocenteses) carried out during that period was rising until 2002, since when it is stable at around 7%. The advancement and implementation of screening tests and prenatal diagnostic procedures in Slovenia caused an important improvement in the efficiency of the prenatal detection of T21.
Murphy, Timothy F
Jürgen Habermas has argued against prenatal genetic interventions used to influence traits on the grounds that only biogenetic contingency in the conception of children preserves the conditions that make the presumption of moral equality possible. This argument fails for a number of reasons. The contingency that Habermas points to as the condition of moral equality is an artifact of evolutionary contingency and not inviolable in itself. Moreover, as a precedent for genetic interventions, parents and society already affect children's traits, which is to say there is moral precedent for influencing the traits of descendants. A veil-of-ignorance methodology can also be used to justify prenatal interventions through its method of advance consent and its preservation of the contingency of human identities in a moral sense. In any case, the selection of children's traits does not undermine the prospects of authoring a life since their future remains just as contingent morally as if no trait had been selected. Ironically, the prospect of preserving human beings as they are--to counteract genetic drift--might even require interventions to preserve the ability to author a life in a moral sense. In light of these analyses, Habermas' concerns about prenatal genetic interventions cannot succeed as objections to their practice as a matter of principle; the merits of these interventions must be evaluated individually. © 2012 John Wiley & Sons Ltd.
Santalahti, P; Aro, A R; Hemminki, E
, and diagnostic tests and their risks. Knowledge was poorer among women without a high school education. When counselling women about prenatal screening tests, more emphasis should be given to the sensitivity of serum screening, all of its screening uses, and the possible diagnostic tests and their risks...... of a procedure. The aim of this study was to examine Finnish women's knowledge and perceptions of, and stated reasons to participate in, two prenatal screening tests: serum screening and mid-trimester ultrasound screening. Subjects (n=1035) for the serum screening survey were catered for in the maternity care...... centres of two Finnish towns, where serum screening is available for all pregnant women. After one reminder, 88 per cent returned the questionnaire. Subjects (n=497) for the mid-trimester ultrasound screening survey were catered for in the obstetrical and gynaecological outpatient clinic of the city...
HIVThe influence of HIV status on prenatal genetic diagnosis choices. JS Bee, M Glass, JGR Kromberg. Abstract. Background. At-risk women of advanced maternal age (AMA) can choose to have second-trimester invasive testing for a prenatal genetic diagnosis on the fetus. Being HIV-positive can complicate the ...
Although the philosophical literature on the ethics of human prenatal genetic alteration (PGA) purports to inform us about how to act, it rarely explicitly recognizes the perspective of those who will be making the PGA decision in practice. Here I approach the ethics of PGA from a distinctly virtue-based perspective, taking seriously what it means to be a good parent making this decision for one's child. From this perspective, I generate a sound verdict on the moral standing of human PGA (research): given the current state of the art, good parents have compelling reason not to consent to PGA (research) for their child, especially as part of the first wave(s) of PGA research participants and especially for non-medically oriented purposes. This is because doing otherwise is inconsistent with a plausible and defensible understanding of virtuous parenting and parental virtues, founded on a genuine concern for promoting the overall flourishing of the eventual child. In essence, given the current and foreseeable state of the art, parents who allow prenatal genetic alteration of their children are less-than-virtuous parents to those children, even in cases where they have a right to do so and even if PGA turns out to be beneficial to the eventual child.
van Schendel, Rachèl V.; Kleinveld, Johanna H.; Dondorp, Wybo J.; Pajkrt, Eva; Timmermans, Danielle R. M.; Holtkamp, Kim C. A.; Karsten, Margreet; Vlietstra, Anne L.; Lachmeijer, Augusta M. A.; Henneman, Lidewij
Non-invasive prenatal testing (NIPT) and its potential to test for multiple disorders has received much attention. This study explores attitudes of women and men towards NIPT, and their views on widening the scope of prenatal testing in a country with a low uptake of prenatal screening (The
Seven, Memnun; Eroglu, Kafiye; Akyüz, Aygül; Ingvoldstad, Charlotta
The latest advances in genetics/genomics have significantly impacted prenatal screening and diagnostic tests. This cross-sectional descriptive study was conducted in inpatient and outpatient obstetric clinics in 24 hospitals in Turkey to determine knowledge of genetics related to prenatal care and the educational needs of perinatal nurses. A total of 116 nurses working in these clinics agreed to participate. The results included the level of knowledge among nurses was not affected by sociodemographic factors. Also, there is a lack of knowledge and interest in genetics among prenatal nurses and in clinical practice to provide education and counseling related to genetics in prenatal settings as a part of prenatal care. © 2017 John Wiley & Sons Australia, Ltd.
Skjøth, Mette Maria; Draborg, Eva; Pedersen, Claus Duedal
BACKGROUND: In recent decades there have been advances in the options for prenatal screening. Screening programmes for Down syndrome are well established in many countries. It is important that pregnant women are well informed about the benefits and risks of screening. A variety of interventions...... screening for Down syndrome. DESIGN: SYSTEMATIC REVIEW: METHODS: A systematic search was performed using the PUBMED and EMBASE databases. The search terms included MeSH terms and free text and were combined by Boolean terms (AND, OR) with no restriction on language or time. MAIN OUTCOME MEASURES: Main...... information about prenatal screening for Down syndrome can improve their ability to make an informed choice. This article is protected by copyright. All rights reserved....
de Jong, Antina; Maya, Idit; van Lith, Jan M M
Prenatal screening pathways, as nowadays offered in most Western countries consist of similar tests. First, a risk-assessment test for major aneuploides is offered to pregnant women. In case of an increased risk, invasive diagnostic tests, entailing a miscarriage risk, are offered. For decades, only conventional karyotyping was used for final diagnosis. Moreover, several foetal ultrasound scans are offered to detect major congenital anomalies, but the same scans also provide relevant information for optimal support of the pregnancy and the delivery. Recent developments in prenatal screening include the application of microarrays that allow for identifying a much broader range of abnomalities than karyotyping, and non-invasive prenatal testing (NIPT) that enables reducing the number of invasive tests for aneuploidies considerably. In the future, broad NIPT may become possible and affordable. This article will briefly address the ethical issues raised by these technological developments. First, a safe NIPT may lead to routinisation and as such challenge the central issue of informed consent and the aim of prenatal screening: to offer opportunity for autonomous reproductive choice. Widening the scope of prenatal screening also raises the question to what extent 'reproductive autonomy' is meant to expand. Finally, if the same test is used for two different aims, namely detection of foetal anomalies and pregnancy-related problems, non-directive counselling can no longer be taken as a standard. Our broad outline of the ethical issues is meant as an introduction into the more detailed ethical discussions about prenatal screening in the other articles of this special issue. © 2014 John Wiley & Sons Ltd.
... your own sperm and eggs, and then use preimplantation genetic diagnosis to see if the fertilized egg has CF ... that can be passed from parent to child. Preimplantation Genetic Diagnosis: A type of genetic testing that can be ...
Wilson, R Douglas
To provide obstetrical and genetic health care practitioners with guidelines and recommendations for prenatal screening, diagnosis, and obstetrical management of fetal open and closed neural tube defects (OCNTD). This review includes prenatal screening and diagnostic techniques currently being used for the detection of OCNTD including maternal serum alpha fetoprotein screening, ultrasound, fetal magnetic resonance imaging, and amniocentesis. To improve prenatal screening, diagnosis, and obstetrical management of OCNTD while taking into consideration patient care, efficacy, cost, and care procedures. Published literature was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in November, 2013, using appropriate controlled vocabulary and key words (e.g., prenatal screening, congenital anomalies, neural tube defects, alpha fetoprotein, ultrasound scan, magnetic resonance imaging). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from 1977 to 2012. Searches were updated on a regular basis and incorporated in the guideline to November 30, 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. An online survey of health care practitioners was also reviewed. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). This review will provide health care practitioners with a better understanding of the available prenatal screening methods for OCNTD and the benefits and risks associated with each technique to allow evidenced-based decisions on OCNTD screening, diagnosis, and obstetrical management.
Non‐invasive prenatal screening for chromosomal abnormalities using circulating cell-free fetal DNA in maternal plasma: Current applications, limitations and ... fetal DNAtesting is a matter of concern, because of the low positive predictive value for these changes, and the associated significant cumulative false-positive rate.
Weldner, B M; Persson, P H; Ivarsson, S A
In a general, ultrasound screening programme, 12 453 women were examined at 16 and 32 weeks of pregnancy. The screening detected all limb deformities in the population during the study period. The seeming prevalence of dwarfism in the population was 750 per million.
Weldner, B M; Persson, P H; Ivarsson, S A
In a general, ultrasound screening programme, 12 453 women were examined at 16 and 32 weeks of pregnancy. The screening detected all limb deformities in the population during the study period. The seeming prevalence of dwarfism in the population was 750 per million. PMID:3907507
Audibert, Francois; De Bie, Isabelle; Johnson, Jo-Ann; Okun, Nanette; Wilson, R Douglas; Armour, Christine; Chitayat, David; Kim, Raymond
To review the available prenatal screening options in light of the recent technical advances and to provide an update of previous guidelines in the field of prenatal screening. Health care providers involved in prenatal screening, including general practitioners, obstetricians, midwives, maternal fetal medicine specialists, geneticists, and radiologists. All pregnant women receiving counselling and providing informed consent for prenatal screening. Published literature was retrieved through searches of Medline, PubMed, and the Cochrane Library in and prior to March 2016 using an appropriate controlled vocabulary (prenatal diagnosis, amniocentesis, chorionic villi sampling, non-invasive prenatal screening) and key words (prenatal screening, prenatal genetic counselling). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English and published from January 1985 to May 2016. Searches were updated on a regular basis and incorporated in the guideline. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical speciality societies. Evidence will be reviewed 5 years after publication to determine whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations. Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.
Dahdouh, Elias M; Balayla, Jacques; Audibert, François; Wilson, R Douglas; Audibert, François; Brock, Jo-Ann; Campagnolo, Carla; Carroll, June; Chong, Karen; Gagnon, Alain; Johnson, Jo-Ann; MacDonald, William; Okun, Nanette; Pastuck, Melanie; Vallée-Pouliot, Karine
technologies. Preimplantation genetic diagnosis is an alternative to prenatal diagnosis for the detection of genetic disorders in couples at risk of transmitting a genetic condition to their offspring. Preimplantation genetic screening is being proposed to improve the effectiveness of in vitro fertilization by screening for embryonic aneuploidy. Though FISH-based PGS showed adverse effects on IVF success, emerging evidence from new studies using comprehensive chromosome screening technology appears promising. Recommendations 1. Before preimplantation genetic diagnosis is performed, genetic counselling must be provided by a certified genetic counsellor to ensure that patients fully understand the risk of having an affected child, the impact of the disease on an affected child, and the benefits and limitations of all available options for preimplantation and prenatal diagnosis. (III-A) 2. Couples should be informed that preimplantation genetic diagnosis can reduce the risk of conceiving a child with a genetic abnormality carried by one or both parents if that abnormality can be identified with tests performed on a single cell or on multiple trophectoderm cells. (II-2B) 3. Invasive prenatal or postnatal testing to confirm the results of preimplantation genetic diagnosis is encouraged because the methods used for preimplantation genetic diagnosis have technical limitations that include the possibility of a false result. (II-2B) 4. Trophectoderm biopsy has no measurable impact on embryo development, as opposed to blastomere biopsy. Therefore, whenever possible, trophectoderm biopsy should be the method of choice in embryo biopsy and should be performed by experienced hands. (I-B) 5. Preimplantation genetic diagnosis of single-gene disorders should ideally be performed with multiplex polymerase chain reaction coupled with trophectoderm biopsy whenever available. (II-2B) 6. The use of comprehensive chromosome screening technology coupled with trophectoderm biopsy in preimplantation
Hu, Hao; Wang, Hua; Jia, Zhengjun; Xie, Qiong
To perform genotyping analysis and subsequent prenatal genetic diagnosis for two families affected with oculocutaneous albinism (OCA). Direct sequencing of TYR and P genes was performed in two albino probands. Family members were screened for corresponding mutant alleles. Prenatal genetic diagnoses were performed at early pregnancy by chorionic villus sampling (CVS) at mid-pregnancy through amniocentesis. No mutations were detected in the TYR gene in either probands, whereas 4 heterozygous mutations of the P gene were found, namely c.406C>T, c.535A>G, c.808-2A>G and c.2180T>C, among which c.535A>G and c.808-2A>G were novel. In the first round prenatal genetic testing, both fetuses were found to have the same genotypes as the probands. Both families had decided to terminate the pregnancy after genetic counseling. In the second round testing, neither of the fetuses was found to be affected by genotyping. The pregnancies continued and two healthy fetuses were born. OCA can be classified by genotyping, with which reliable prenatal diagnosis and feasible genetic counseling may be provided.
Portocarrero, M.E.; Giguere, A.M.; Lepine, J.; Garvelink, M.M.; Robitaille, H.; Delanoe, A.; Levesque, I.; Wilson, B.J.; Rousseau, F.; Legare, F.
BACKGROUND: Patient decision aids (PtDAs) help people make difficult, values-sensitive decisions. Prenatal screening for assessing the risk of genetic conditions in the fetus is one such decision and patient decision aids are rarely used in this clinical context. We sought to identify factors
Portocarrero, Maria Esther Leiva; Giguère, Anik M C; Lépine, Johanie; Garvelink, Mirjam M; Robitaille, Hubert; Delanoë, Agathe; Lévesque, Isabelle; Wilson, Brenda J; Rousseau, François; Légaré, France
Patient decision aids (PtDAs) help people make difficult, values-sensitive decisions. Prenatal screening for assessing the risk of genetic conditions in the fetus is one such decision and patient decision aids are rarely used in this clinical context. We sought to identify factors influencing pregnant women's use of a patient decision aid for deciding about prenatal screening for Down syndrome (DS). This qualitative study was embedded in a sequential mixed-methods research program whose main aim is to implement shared decision-making (SDM) in the context of prenatal screening for DS in the province of Quebec, Canada. We planned to recruit a purposive sample of 45 pregnant women with low-risk pregnancy consulting for prenatal care at three clinical sites. Participating women watched a video depicting a prenatal care follow-up during which a pregnant woman, her partner and a health professional used a PtDA to decide about prenatal screening for DS. The women were then interviewed about factors that would influence the use of this PtDA using questions based on the Theoretical Domains Framework (TDF). We performed content analysis of transcribed verbatim interviews. Out of 216 eligible women, 100 agreed to participate (46% response rate) and 46 were interviewed. Regarding the type of health professional responsible for their prenatal care, 19 participants (41%) reported having made a decision about prenatal screening for DS with an obstetrician-gynecologist, 13 (28%) with a midwife, 12 (26%) with a family physician, and two (4%) decided on their own. We identified 54 factors that were mapped onto nine of the 12 TDF domains. The three most frequently-mentioned were: opinion of the pregnant woman's partner (n = 33, 72%), presentation of the PtDA by health professional and a discussion (n = 27, 72%), and not having encountered a PtDA (n = 26, 57%). This study allowed us to identify factors influencing pregnant women's use of a PtDA for prenatal screening for
After agreeing to host over 200 students on a daylong genetics field trip, the author needed an easy-to-prepare genetics experiment to accompany the DNA-necklace and gel-electrophoresis activities already planned. One of the student's mothers is a pediatric physician at the local hospital, and she suggested exploring genetic-disease screening…
Background: Down Syndrome (DS) is a common genetic disorder that is associated with high intrauterine lethality. Morbidity for the survivors includes congenital anomalies and Intellectual Disability (ID). Genetic screening for DS is an ever evolving field with remarkable progress made over the years. Health care workers ...
Tóth, Adél; Szabó, János
Giving detailed information on prenatal screening for Down's syndrome is considered as paramount since this medical procedure intends to enhance the patient's self-governance in reproductive issues. Not only the respect for autonomy, but also the increased maternal anxiety and the reproductive decisions following the positive test result demand from the genetic professional to offer the test through genetic counselling. The counsellor's awareness about the expectations of pregnant women and the clarification of her own attitude concerning the screening can contribute to the effectiveness of counselling. The content of information embraces the technical aspects of screening and its consequences, like the description of Down's syndrome, the method of screening, the way of risk assessment, the detection rate, the false positive and false negative test results, the diagnostic procedures, and the termination of pregnancy. Written information leaflets should be completed by personal communication as the combination of these two forms has proved to be the most useful. The process of consultation is influenced by the communication skill of the genetic professional and the information seeking activity of the patient, so doctors should be trained to communicate better and patients should be encouraged to get more information about the screening.
Fransen, Mirjam P.; Wildschut, Hajo; Vogel, Ineke; Mackenbach, Johan; Steegers, Eric; Essink-Bot, Marie-Louise
To evaluate the provision of information about prenatal screening for Down syndrome to women of Dutch, Turkish and Surinamese origins, and to examine the effects of this provision on ethnic differences in knowledge about Down syndrome and prenatal screening. The study population consisted of 105
Garcia, E.; Timmermans, D.R.; Leeuwen, E. van
OBJECTIVES: Answering the question: Does the offer of prenatal screening impede women in making autonomous choices? METHODS: Semi-structured interviews with 59 women to whom a prenatal screening test was offered and who were in the process of taking a decision. RESULTS: Women described the offer as
Garcia Gonzalez, M.E.; Timmermans, D.R.M.; van Leeuwen, E.
Objectives: Answering the question: Does the offer of prenatal screening impede women in making autonomous choices? Methods: Semi-structured interviews with 59 women to whom a prenatal screening test was offered and who were in the process of taking a decision. Results: Women described the offer as
Sullivan-Pyke, Chantae; Dokras, Anuja
Preimplantation genetic testing encompasses preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). PGS improves success rates of in vitro fertilization by ensuring the transfer of euploid embryos that have a higher chance of implantation and resulting in a live birth. PGD enables the identification of embryos with specific disease-causing mutations and transfer of unaffected embryos. The development of whole genome amplification and genomic tools, including single nucleotide polymorphism microarrays, comparative genomic hybridization microarrays, and next-generation sequencing, has led to faster, more accurate diagnoses that translate to improved pregnancy and live birth rates. Copyright © 2017 Elsevier Inc. All rights reserved.
Men's involvement in prenatal screening is becoming increasingly important. However, despite the potentially significant role of fathers in haemoglobinopathy screening, their participation is under researched. Furthermore, the portrayal of Black and minority ethnic (BME) fathers tends to be based on persisting stereotypes of men as either absentee parents with limited roles in screening or as controlling decision-makers. To describe the influence of ethnicity and gender on the process of participation of men in antenatal screening for sickle cell and thalassaemia. A qualitative study, using in-depth interviews and focus groups with 22 pregnant women from a range of socio-economic and ethnic backgrounds, 16 male partners and 15 midwives in a northern city in the UK. Men from BME groups take a pragmatic and equitable role in screening with their partners. White British men on the other hand, while willing to participate in screening, take a more casual view of their own direct participation. Accounts from hospital midwives supported these findings. While acknowledging the importance of material connections between certain BME groups and blood disorders, two key issues are raised. First, BME men's involvement contribute a challenge towards existing assumptions often made about BME fathers. Second, White British men's participation can be useful in determining the genetic status of the foetus and therefore their role should not be neglected. Screening research and practice need to broaden out their focus on issues of gender, ethnicity and screening.
Full Text Available Counseling parents of a fetus with trisomy 13 mosaicism remains difficult because of the phenotypic variability associated with the condition; some patients exhibit the typical phenotype of complete trisomy 13 with neonatal death, while others have few dysmorphic features and prolonged survival. This article provides a comprehensive review of the prenatal diagnosis and genetic counseling for mosaic trisomy 13, including confined placental mosaicism 13, mosaic trisomy 13 diagnosed at amniocentesis, and phylloid hypomelanosis in association with mosaic trisomy 13.
Group B streptococcus (GBS) is a leading cause of neonatal morbidity and mortality in the United States. Intrapartum antibiotics administered to women at risk for transmitting GBS to their newborns are effective in preventing perinatal GBS infection. In 2002, CDC, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists recommended universal prenatal screening for vaginal and rectal GBS colonization at 35-37 weeks' gestation. To examine prenatal GBS screening among pregnant women in North Carolina, CDC analyzed 2002 and 2003 data from the North Carolina Pregnancy Risk Assessment Monitoring System (PRAMS). The proportions of women reporting prenatal screening for GBS were similar in 2002 and 2003 (70% and 74%, respectively); however, for both years, women of Hispanic ethnicity and women who received prenatal care at a hospital or health department clinic were less likely to report prenatal screening for GBS. These findings underscore the need to increase GBS-related education and prevention activities targeted to these populations.
Dahl, Katja; Hvidman, Lone; Jørgensen, Finn Stener
well-being respectively worries in pregnancy. METHODS: A population-based cross-sectional study with 6,427 pregnant women consecutively included before the time of a nuchal translucency scan. Participants were recruited from three Danish obstetric departments offering prenatal screening free of charge....... The results presented are based on 4,111 pregnant women (64%). Knowledge was measured by 15 knowledge questions. The primary outcomes were measured by use of pre-existing validated scales i.e. The Decisional Conflict Scale, the WHO well-being index, and the Cambridge Worry Scale. Associations were analysed...... associated with higher levels of well-being (adjusted linear coefficient 0.51 (0.26 to 0.75), p
Jun, Myunghee; Thongpriwan, Vipavee; Choi, Jeeyae; Sook Choi, Kyung; Anderson, Gwen
to understand the prenatal genetic testing decision-making processes among pregnant Korean-American women. a qualitative, descriptive research design. referrals and snowball sampling techniques were used to recruit 10 Korean-American women who had been recommended for amniocentesis during pregnancy in the United States (U.S.). All participants were born in Korea and had immigrated to the U.S. The number of years living in the U.S. ranged from 4 to 11 (M=5.7). various regional areas of the U.S. the researchers conducted face-to-face or phone interviews using semi-structured interview guides. The interviews were conducted in the Korean language and lasted approximately 50-100minutes. The interview guides focused on the decision-making process and experiences with prenatal genetic testing, as well as reflections on the decisions. Four core themes emerged related to the participants' decision-making processes, according to their descriptions. These themes are (1) facing the challenges of decision-making, (2) seeking support, (3) determining one's preferred role in the decision-making process, and (4) feeling uncomfortable with the degree of patient autonomy in U.S. health care. researchers concluded that many distinctive factors influence the decision-making processes used by pregnant Korean-American women. The results have the potential to improve shared decision-making practices regarding prenatal genetic testing. clinicians need to understand the sociocultural underpinnings of pregnant Korean-American immigrants regarding prenatal genetic screening and testing as an initial step to engage these patients in shared decision-making. Published by Elsevier Ltd.
Besser, Andria G; Mounts, Emily L
The evolution of preimplantation genetic screening (PGS) for aneuploidy to blastocyst biopsy and more sensitive 24-chromosome screening techniques has resulted in a new diagnostic category of PGS results: those classified as mosaic. This diagnosis presents significant challenges for clinicians in developing policies regarding transfer and storage of such embryos, as well as in providing genetic counselling for patients prior to and following PGS. Given the high frequency of mosaic PGS results and the wide range of possible associated outcomes, there is an urgent need to understand how to appropriately counsel patients regarding such embryos. This is the first commentary to thoroughly address pre- and post-test genetic counselling recommendations, as well as considerations regarding prenatal screening and diagnosis. Current data on mosaic PGS results are summarized along with embryo selection considerations and potential outcomes of embryos diagnosed as mosaic. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Lewando Hundt, Gillian; Bryanston, Claudette; Lowe, Pam; Cross, Saul; Sandall, Jane; Spencer, Kevin
Background The role of applied theatre in engaging both lay and professional publics with debate on health policy and practice is an emergent field. This paper discusses the development, production performance and discussion of ‘Inside View’.\\ud \\ud Objectives The objectives were to produce applied theatre from research findings of a completed study on genetic prenatal screening, exploring the dilemmas for women and health professionals of prenatal genetic screening, and to engage audiences i...
Wang, Li; Qin, Litao; Li, Tao; Liu, Hongjian; Ma, Lingcao; Li, Wan; Wu, Dong; Wang, Hongdan; Guo, Qiannan; Guo, Liangjie; Liao, Shixiu
Waardenburg syndrome (WS) is an auditory-pigmentary disorder with varying combinations of sensorineural hearing loss and abnormal pigmentation. The present study aimed to investigate the underlying molecular pathology and provide a method of prenatal diagnosis of WS in Chinese families. A total of 11 patients with WS from five unrelated Chinese families were enrolled. A thorough clinical examination was performed on all participants. Furthermore, patients with WS underwent screening for mutations in the following genes: Paired box 3 (PAX3), melanogenesis associated transcription factor (MITF), SRY-box 10, snail family transcriptional repressor 2 and endothelin receptor type B using polymerase chain reaction sequencing. Array-based comparative genomic hybridization was used for specific patients whose sequence results were normal. Following identification of the genotype of the probands and their parents, prenatal genetic diagnosis was performed for family 01 and 05. According to the diagnostic criteria for WS, five cases were diagnosed as WS1, while the other six cases were WS2. Genetic analysis revealed three mutations, including a nonsense mutation PAX3 c.583C>T in family 01, a splice-site mutation MITF c.909G>A in family 03 and an in-frame deletion MITF c.649_651delGAA in family 05. To the best of the authors' knowledge the mutations (c.583C>T in PAX3 and c.909G>A in MITF) were reported for the first time in Chinese people. Mutations in the gene of interest were not identified in family 02 and 04. The prenatal genetic testing of the two fetuses was carried out and demonstrated that the two babies were normal. The results of the present study expanded the range of known genetic mutations in China. Identification of genetic mutations in these families provided an efficient way to understand the causes of WS and improved genetic counseling. PMID:29115496
Chitty, Lyn S; Hudgins, Louanne; Norton, Mary E
Noninvasive prenatal testing (NIPT) using cell-free DNA (cfDNA) from maternal serum has been clinically available since 2011. This technology has revolutionized our ability to screen for the common aneuploidies trisomy 21 (Down syndrome), trisomy 18, and trisomy 13. More recently, clinical laboratories have offered screening for other chromosome abnormalities including sex chromosome abnormalities and copy number variants (CNV) without little published data on the sensitivity, specificity, and positive predictive value. In this debate, the pros and cons of performing prenatal screening via cfDNA for all chromosome abnormalities is discussed. At the time of the debate in 2017, the general consensus was that the literature does not yet support using this technology to screen for all chromosome abnormalities and that education is key for both providers and the patients so that the decision-making process is as informed as possible. © 2018 John Wiley & Sons, Ltd.
Potter, B K; Avard, D; Entwistle, V; Kennedy, C; Chakraborty, P; McGuire, M; Wilson, B J
Prenatal/preconceptional and newborn screening programs have been a focus of recent policy debates that have included attention to ethical, legal, and social issues (ELSIs). In parallel, there has been an ongoing discussion about whether and how ELSIs may be addressed in health technology assessment (HTA). We conducted a knowledge synthesis study to explore both guidance and current practice regarding the consideration of ELSIs in HTA for prenatal/preconceptional and newborn screening. As the concluding activity for this project, we held a Canadian workshop to discuss the issues with a diverse group of stakeholders. Based on key workshop themes integrated with our study results, we suggest that population-based genetic screening programs may present particular types of ELSIs and that a public health ethics perspective is potentially highly relevant when considering them. We also suggest that approaches to addressing ELSIs in HTA for prenatal/preconceptional and newborn screening may need to be flexible enough to respond to diversity in HTA organizations, cultural values, stakeholder communities, and contextual factors. Finally, we highlight a need for transparency in the way that HTA producers move from evidence to conclusions and the ways in which screening policy decisions are made. Copyright © 2008 S. Karger AG, Basel.
de la Fe Rodríguez-Muñoz, María; Le, Huynh-Nhu; de la Cruz, Ivette Vargas; Crespo, María Eugenia Olivares; Méndez, Nuria Izquierdo
Prenatal depression is a significant public health problem and one of the main risk factors for postpartum depression. Limited research in perinatal depression has been conducted in Spain. The objectives of this study was to: (1) examine the feasibility of integrating a screening program for prenatal depression in an obstetrics setting in a large urban hospital in Spain; and (2) provide an initial estimate of the prevalence rate of the severity of depressive symptoms during pregnancy. Screening for prenatal depression was conducted during the first trimester in an obstetrics setting in an urban hospital in Madrid, Spain 2014-2015. The Patient Health Questionnaire (PHQ-9) was used as the main screener. Of the 730 women asked to complete the screening protocol, 445 (60.9%) completed the PHQ-9 during the first trimester. Those who did not complete the screening were more likely to be immigrants and did not read Spanish. The prevalence of moderate to high severity of prenatal depressive symptoms prenatal depressive is 14.8% (PHQ-9≥10). It is possible to integrate screening for prenatal depression in an urban obstetrics setting, but there are significant structural barriers to implementation. The prevalence of significant prenatal depressive symptoms is similar to previous research in Spain and adds to the limited research in this area. Copyright © 2017 Elsevier B.V. All rights reserved.
Martin, L.; Gitsels-van der Wal, J.T.; Pereboom, M.T.R.; Spelten, E.R.; Hutton, E.K.; Dulmen, S. van
Objectives: This study focuses on facilitation of clients’ psychosocial communication during prenatal counseling for fetal anomaly screening. We assessed how psychosocial communication by clients is related to midwives’ psychosocial and affective communication, client-directed gaze and counseling
Hixson, Lucas; Goel, Srishti; Schuber, Paul; Faltas, Vanessa; Lee, Jessica; Narayakkadan, Anjali; Leung, Ho; Osborne, Jim
This article is a review of current and emerging methods used for prenatal detection of chromosomal aneuploidies. Chromosomal anomalies in the developing fetus can occur in any pregnancy and lead to death prior to or shortly after birth or to costly lifelong disabilities. Early detection of fetal chromosomal aneuploidies, an atypical number of certain chromosomes, can help parents evaluate their pregnancy options. Current diagnostic methods include maternal serum sampling or nuchal translucency testing, which are minimally invasive diagnostics, but lack sensitivity and specificity. The gold standard, karyotyping, requires amniocentesis or chorionic villus sampling, which are highly invasive and can cause abortions. In addition, many of these methods have long turnaround times, which can cause anxiety in mothers. Next-generation sequencing of fetal DNA in maternal blood enables minimally invasive, sensitive, and reasonably rapid analysis of fetal chromosomal anomalies and can be of clinical utility to parents. This review covers traditional methods and next-generation sequencing techniques for diagnosing aneuploidies in terms of clinical utility, technological characteristics, and market potential. © 2015 Society for Laboratory Automation and Screening.
Fransen, Mirjam P; Essink-Bot, Marie-Louise; Vogel, Ineke; Mackenbach, Johan P; Steegers, Eric A P; Wildschut, Hajo I J
The aim of this study was to assess ethnic variations in informed decision-making about prenatal screening for Down's syndrome and to examine the contribution of background and decision-making variables. Pregnant women of Dutch, Turkish and Surinamese origin were recruited between 2006 and 2008 from community midwifery or obstetrical practices in The Netherlands. Each woman was personally interviewed 3 weeks (mean) after booking for prenatal care. Knowledge, attitude and participation in prenatal screening were assessed following the 'Multidimensional Measure of Informed Choice' that has been developed and applied in the UK. In total, 71% of the Dutch women were classified as informed decision-makers, compared with 5% of the Turkish and 26% of the Surinamese women. Differences between Surinamese and Dutch women could largely be attributed to differences in educational level and age. Differences between Dutch and Turkish women could mainly be attributed to differences in language skills and gender emancipation. Women from ethnic minority groups less often made an informed decision whether or not to participate in prenatal screening. Interventions to decrease these ethnic differences should first of all be aimed at overcoming language barriers and increasing comprehension among women with a low education level. To further develop diversity-sensitive strategies for counselling, it should be investigated how women from different ethnic backgrounds value informed decision-making in prenatal screening, what decision-relevant knowledge they need and what they take into account when considering participation in prenatal screening.
Vanstone, Meredith; Kinsella, Elizabeth Anne; Nisker, Jeff
The 2011 SOGC clinical practice guideline "Prenatal Screening for Fetal Aneuploidy in Singleton Pregnancies" recommends that clinicians offer prenatal screening to all pregnant women and provide counselling in a non-directive manner. Non-directive counselling is intended to facilitate autonomous decision-making and remove the clinician's views regarding a particular course of action. However, recent research in genetic counselling raises concerns that non-directive counselling is neither possible nor desirable, and that it may not be the best way to facilitate informed choice. We propose an alternative model of information-sharing specific to prenatal screening that combines attributes of the models of informative decision-making and shared decision-making. Our proposed model is intended to provide clinicians with a strategy to communicate information about prenatal screening in a way that facilitates a shared deliberative process and autonomous decision-making. Our proposed model may better prepare a pregnant woman to make an informed choice about participating in prenatal screening on the basis of her consideration of the medical information provided by her clinician and her particular circumstances and values.
Santalahti, P; Hemminki, E; Aro, A R
AIMS: The study examined how prenatal screening tests are presented to women, factors associated with women's participation in screening, their experience of decision-making and intentions concerning pregnancy termination, and hospital data on rates of selective terminations. METHODS: Questionnai......AIMS: The study examined how prenatal screening tests are presented to women, factors associated with women's participation in screening, their experience of decision-making and intentions concerning pregnancy termination, and hospital data on rates of selective terminations. METHODS...... as a routine procedure. Most women (92%) underwent serum screening and most (86%) found the decision to participate or not easy. In almost every aspect of presentation and participation studied, serum and ultrasound screening differed from each other. 85% of respondents to ultrasound screening answered...... in screening and with intentions about selective termination, women's perceptions of lives of the disabled should receive more attention in future studies....
Full Text Available Current ethical and legal issues with regard to abortion, prenatal genetic testing and managing pregnancy are discussed in this paper. These problems are considered from the legal theory point of view as well as from the standpoint of the Serbian Law, the European Convention for the Protection of Human Rights and Fundamental Freedoms, European Court of Human Rights, legal regulations of several EU countries, the USA, Japan, and their judicial practice. First, the pregnancy termination standards that exist in Serbia are introduced. Then the following issues are explained separately: the pro life and pro choice approaches to abortion; abortion according to the legal approach as a way of survival; the moral and legal status of the fetus; prenatal genetic testing, and finally matters regarding managing pregnancy today. Moral and legal principals of autonomy, namely freedom of choice of the individual, privacy and self-determination give women the right to terminate unwanted pregnancies. In addition, the basic question is whether the right of the woman to abortion clashes with the rights of others. Firstly, with the right of the "fetus to life". Secondly, with the right of the state to intervene in the interest of protecting "the life of the fetus". Third, with the rights of the woman’s partner. The fetus has the moral right to life, but less in relation to the same right of the woman as well as in relation to her right to control her life and her physical and moral integrity. On the other hand, the value of the life of the fetus increases morally and legally with the maturity of gestation; from the third trimester, the interest of the state prevails in the protection of the "life of the fetus" except when the life or health of the pregnant woman are at risk. As regards the rights of the woman’s partner, namely the husband’s opinion, there is no legal significance. The law does not request his participation in the decision on abortion because
Posner, S. F.; Learman, L. A.; Gates, E. A.; Washington, A. E.; Kuppermann, M.
Background: Prenatal screening for chromosomal abnormalities is routinely offered to all pregnant women who present for care by their 20th gestational week. Not all women, however, choose to undergo one of these tests, and choice of which test(s) to undergo also vary. The reasons for variation in screening test behavior have not been fully…
Prusa, Andrea-Romana; Kasper, David C; Sawers, Larry; Walter, Evelyn; Hayde, Michael; Stillwaggon, Eileen
Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario. We retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric long-term follow-up until May 2013. We constructed a decision-analytic model to compare lifetime societal costs of prenatal screening with lifetime societal costs estimated in a No-Screening scenario. We included costs of treatment, lifetime care, accommodation of injuries, loss of life, and lost earnings that would have occurred in a No-Screening scenario and compared them with the actual costs of screening, treatment, lifetime care, accommodation, loss of life, and lost earnings. We replicated that analysis excluding loss of life and lost earnings to estimate the budgetary impact alone. Our model calculated total lifetime costs of €103 per birth under prenatal screening as carried out in Austria, saving €323 per birth compared with No-Screening. Without screening and treatment, lifetime societal costs for all affected children would have been €35 million per year; the implementation costs of the Austrian program are less than €2 million per year. Calculating only the budgetary impact, the national program was still cost-saving by more than €15 million per year and saved €258 million in 17 years. Cost savings under a national program of prenatal screening for toxoplasma infection and treatment are
Guo, Yi-bin; Ai, Yang; Zhao, Yan; Tang, Jia; Jiang, Wei-ying; Du, Min-lian; Ma, Hua-mei; Zhong, Yan-fang
To provide rapid and accurate prenatal genetic diagnosis for a fetus with high risk of Morquio A syndrome. Based on ascertained etiology of the proband and genotypes of the parents, particular mutations of the GALNS gene were screened at 10th gestational week with amplification refractory mutation system (ARMS), denaturing high performance liquid chromatography (DHPLC), and direct DNA sequencing. DHPLC screening has identified abnormal double peaks in the PCR products of exons 1 and 10, whilst only a single peak was detected in normal controls. Amplification of ARMS specific primers derived a specific product for the fetus's gene, whilst no similar product was detected in normal controls. Sequencing of PCR products confirmed that exons 1 and 10 of the GALNS gene from the fetus contained a heterozygous paternal c.106-111 del (p.L36-L37 del) deletion and a heterozygous maternal c.1097 T>C (p.L366P) missense mutation, which resulted in a compound heterozygote status. The fetus was diagnosed with Morquio A syndrome and a genotype similar to the proband. Termination of the pregnancy was recommended. Combined ARMS, DHPLC and DNA sequencing are effective for rapid and accurate prenatal diagnosis for fetus with a high risk for Morquio A syndrome. Such methods are particularly suitable for early diagnosis when pathogenesis is clear. Furthermore, combined ARMS and DHPLC are suitable for rapid processing of large numbers of samples for the identification of new mutations.
Tsai, Ginger J; Cameron, Carrie A; Czerwinski, Jennifer L; Mendez-Figueroa, Hector; Peterson, Susan K; Noblin, Sarah Jane
Recognizing the heterogeneity of the Asian population with regards to acculturation, education, health awareness, and cultural values is vital for tailoring culturally sensitive and appropriate care. Prior studies show that cultural values influence perceptions of genetics within Asian populations. The reputation of the family unit factors into decisions such as pregnancy termination and disclosure of family medical history, and the nondirective model of American genetic counseling may conflict with the historical Asian model of paternalistic health care. Previous studies also provide conflicting evidence regarding correlations between education, acculturation, age, and awareness and perceptions of genetic testing. The aims of this study were to describe attitudes towards prenatal genetics among Southeast and East Asian women living in the United States for varying amounts of time and to explore sociocultural factors influencing those attitudes. Twenty-three Asian women who were members of Asian cultural organizations in the United States were interviewed via telephone about their attitudes towards prenatal genetic counseling, prenatal genetic testing, and termination of pregnancy. Responses were transcribed and coded for common themes using a thematic analysis approach. Four major themes emerged. In general, participants: (1) had diverse expectations for genetic counselors; (2) tended to weigh risks and benefits with regards to genetic testing decisions; (3) had mixed views on termination for lethal and non-lethal genetic conditions; and (4) identified cultural factors which influenced testing and termination such as lack of available resources, societal shame and stigma, and family pressure. These findings may allow prenatal genetic counselors to gain a richer, more nuanced understanding of their Asian patients and to offer culturally tailored prenatal genetic counseling.
László, Aranka; Endreffy, Emoke; Tümer, Zeynep
Menkes disease (MD) is an X-linked recessive multisystemic lethal, heredodegenerative disorder. Progressive neurodegeneration and connective tissue disturbances with microscopically kinky hair are the main symptoms. Molecular genetic mutation analysis was made at a Hungarian male infant suffering...... from MD and prenatal diagnosis was done in this MD loaded family. METHOD: The 12th exon of ATP7A gene has been analyzed by dideoxy-finger printing (DDF), polymerase chain reaction (PCR), direct sequencing of exon 12. The specific mutation was screened from chorionic villi of the maternal aunt at the 14......th gestational week. RESULTS: In the exon 12th a basic pair substitution with Arg 844 His change was detected leading to very severe fatal missense mutation....
Sutherland, Sharon; Farrell, Ruth M; Lockwood, Charles
The State of Ohio is implementing an episode-based payment model for perinatal care. All costs of care will be tabulated for each live birth and assigned to the delivering provider, creating a three-tiered model for reimbursement for care. Providers will be reimbursed as usual for care that is average in cost and quality, while instituting rewards or penalties for those outside the expected range in either domain. There are few exclusions, and all methods of genetic screening and diagnostic testing are included in the episode cost calculation as proposed. Prenatal ultrasonography, genetic screening, and diagnostic testing are critical components of the delivery of high-quality, evidence-based prenatal care. These tests provide pregnant women with key information about the pregnancy, which, in turn, allows them to work closely with their health care provider to determine optimal prenatal care. The concepts of informed consent and decision-making, cornerstones of the ethical practice of medicine, are founded on the principles of autonomy and respect for persons. These principles recognize that patients' rights to make choices and take actions are based on their personal beliefs and values. Given the personal nature of such decisions, it is critical that patients have unbarred access to prenatal genetic tests if they elect to use them as part of their prenatal care. The proposed restructuring of reimbursement creates a clear conflict between patient autonomy and physician financial incentives.
Full Text Available Abstract Background Recent developments have made screening tests for foetal abnormalities available earlier in pregnancy and women have a range of testing options accessible to them. It is now recommended that all women, regardless of their age, are provided with information on prenatal screening tests. General Practitioners (GPs are often the first health professionals a woman consults in pregnancy. As such, GPs are well positioned to inform women of the increasing range of prenatal screening tests available. The aim of this study was to explore GPs experience of informing women of prenatal genetic screening tests for foetal abnormality. Methods A qualitative study consisting of four focus groups was conducted in metropolitan and rural Victoria, Australia. A discussion guide was used and the audio-taped transcripts were independently coded by two researchers using thematic analysis. Multiple coders and analysts and informant feedback were employed to reduce the potential for researcher bias and increase the validity of the findings. Results Six themes were identified and classified as 'intrinsic' if they occurred within the context of the consultation or 'extrinsic' if they consisted of elements that impacted on the GP beyond the scope of the consultation. The three intrinsic themes were the way GPs explained the limitations of screening, the extent to which GPs provided information selectively and the time pressures at play. The three extrinsic factors were GPs' attitudes and values towards screening, the conflict they experienced in offering screening information and the sense of powerlessness within the screening test process and the health care system generally. Extrinsic themes reveal GPs' attitudes and values to screening and to disability, as well as raising questions about the fundamental premise of testing. Conclusion The increasing availability and utilisation of screening tests, in particular first trimester tests, has expanded GPs
Fransen, Mirjam P.; Essink-Bot, Marie-Louise; Vogel, Ineke; Mackenbach, Johan P.; Steegers, Eric A. P.; Wildschut, Hajo I. J.
BACKGROUND: The aim of this study was to assess ethnic variations in informed decision-making about prenatal screening for Down's syndrome and to examine the contribution of background and decision-making variables. METHODS: Pregnant women of Dutch, Turkish and Surinamese origin were recruited
Wätterbjörk, Inger; Blomberg, Karin; Nilsson, Kerstin; Sahlberg-Blom, Eva
Pregnant women are often faced with having to decide about prenatal screening for Down's syndrome. However, the decision to participate in or refrain from prenatal screening can be seen as an important decision not only for the pregnant woman but also for both the partners. The aim of this study was to explore the couples' processes of decision making about prenatal screening. A total of 37 semi-structured interviews conducted at two time points were analysed using the interpretive description. The study was carried out in Maternal health-care centres, Örebro County Council, Sweden. Fifteen couples of different ages and with different experiences of pregnancy and childbirth were interviewed. Three different patterns of decision making were identified. For the couples in 'The open and communicative decision-making process', the process was straightforward and rational, and the couples discussed the decision with each other. 'The closed and personal decision-making process' showed an immediate and non-communicative decision making where the couples decided each for themselves. The couples showing 'The searching and communicative decision-making process' followed an arduous road in deciding whether to participate or not in prenatal screening and how to cope with the result. The decision-making process was for some couples a fairly straightforward decision, while for others it was a more complex process that required a great deal of consideration. © 2013 John Wiley & Sons Ltd.
Gammon, B L; Kraft, S A; Michie, M; Allyse, M
The recent introduction of cell-free DNA-based non-invasive prenatal screening (cfDNA screening) into clinical practice was expected to revolutionize prenatal testing. cfDNA screening for fetal aneuploidy has demonstrated higher test sensitivity and specificity for some conditions than conventional serum screening and can be conducted early in the pregnancy. However, it is not clear whether and how clinical practices are assimilating this new type of testing into their informed consent and counselling processes. Since the introduction of cfDNA screening into practice in 2011, the uptake and scope have increased dramatically. Prenatal care providers are under pressure to stay up to date with rapidly changing cfDNA screening panels, manage increasing patient demands, and keep up with changing test costs, all while attempting to use the technology responsibly and ethically. While clinical literature on cfDNA screening has shown benefits for specific patient populations, it has also identified significant misunderstandings among providers and patients alike about the power of the technology. The unique features of cfDNA screening, in comparison to established prenatal testing technologies, have implications for informed decision-making and genetic counselling that must be addressed to ensure ethical practice. This study explored the experiences of prenatal care providers at the forefront of non-invasive genetic screening in the United States to understand how this testing changes the practice of prenatal medicine. We aimed to learn how the experience of providing and offering this testing differs from established prenatal testing methodologies. These differences may necessitate changes to patient education and consent procedures to maintain ethical practice. We used the online American Congress of Obstetricians and Gynecologists Physician Directory to identify a systematic sample of five prenatal care providers in each U.S. state and the District of Columbia. Beginning
Probably the main purpose of reproductive technologies is to enable people who choose to do so to avoid the birth of a baby with a disabling condition. However the conditions women want information about and the 'price' they are willing to pay for obtaining that information vary enormously. Individual women have to arrive at their own prenatal testing choices by 'trading off' means and ends in order to resolve the dilemmas facing them. We know very little about how individuals make these trade-offs, so it is difficult to predict how new technologies will affect their choices and preferences. Uptake decisions can be expected to change, especially in the group of women who now are put off by some aspect of the current screening approach, where the avoidance of miscarriage risk may have provided a kind of 'psychological shelter', protecting a lot of people from having to make other decisions. Technologies such as Pre-implantation Genetic Diagnosis may remove a second 'psychological shelter' because they offer the means of avoiding the birth of an affected child without terminating a pregnancy. Even if new technologies will make some decisions easier in terms of their cognitive demands, they will also create new dilemmas and decision making will not necessarily become less stressful in emotional terms. Key challenges concern information and decision-making. © 2014 John Wiley & Sons Ltd.
Full Text Available Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario.We retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric long-term follow-up until May 2013. We constructed a decision-analytic model to compare lifetime societal costs of prenatal screening with lifetime societal costs estimated in a No-Screening scenario. We included costs of treatment, lifetime care, accommodation of injuries, loss of life, and lost earnings that would have occurred in a No-Screening scenario and compared them with the actual costs of screening, treatment, lifetime care, accommodation, loss of life, and lost earnings. We replicated that analysis excluding loss of life and lost earnings to estimate the budgetary impact alone. Our model calculated total lifetime costs of €103 per birth under prenatal screening as carried out in Austria, saving €323 per birth compared with No-Screening. Without screening and treatment, lifetime societal costs for all affected children would have been €35 million per year; the implementation costs of the Austrian program are less than €2 million per year. Calculating only the budgetary impact, the national program was still cost-saving by more than €15 million per year and saved €258 million in 17 years.Cost savings under a national program of prenatal screening for toxoplasma infection and
Prusa, Andrea-Romana; Kasper, David C.; Sawers, Larry; Walter, Evelyn; Hayde, Michael
Background Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario. Methodology/Principal findings We retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric long-term follow-up until May 2013. We constructed a decision-analytic model to compare lifetime societal costs of prenatal screening with lifetime societal costs estimated in a No-Screening scenario. We included costs of treatment, lifetime care, accommodation of injuries, loss of life, and lost earnings that would have occurred in a No-Screening scenario and compared them with the actual costs of screening, treatment, lifetime care, accommodation, loss of life, and lost earnings. We replicated that analysis excluding loss of life and lost earnings to estimate the budgetary impact alone. Our model calculated total lifetime costs of €103 per birth under prenatal screening as carried out in Austria, saving €323 per birth compared with No-Screening. Without screening and treatment, lifetime societal costs for all affected children would have been €35 million per year; the implementation costs of the Austrian program are less than €2 million per year. Calculating only the budgetary impact, the national program was still cost-saving by more than €15 million per year and saved €258 million in 17 years. Conclusions/Significance Cost savings under a national program of
García, Elisa; Timmermans, Danielle R M; van Leeuwen, Evert
Answering the question: Does the offer of prenatal screening impede women in making autonomous choices? Semi-structured interviews with 59 women to whom a prenatal screening test was offered and who were in the process of taking a decision. Women described the offer as confronting but expressed a positive attitude towards screening and considered the offer as an opportunity for making up their minds about testing. Participants stated that they took decisions freely to follow their individual perspectives. Nevertheless, they preferred to share the responsibility of taking decisions, and its consequences for other family members, with their partner and close persons. The active offer of an unsolicited prenatal test need not be considered as an impediment for making an autonomous choice. The moral significance of prenatal testing is inseparably bound with the social context in which it is practiced. Influence from other persons and emotional reactions due to the test offer can be interpreted as supportive for making a choice. In clinical practice, testing should be timely offered in order to give women the opportunity of discussing their views with significant others. Caregivers should care for the emotions experienced by women so as to help them decide according to their values.
Wang, Li; Qin, Litao; Li, Tao; Liu, Hongjian; Ma, Lingcao; Li, Wan; Wu, Dong; Wang, Hongdan; Guo, Qiannan; Guo, Liangjie; Liao, Shixiu
Waardenburg syndrome (WS) is an auditory‑pigmentary disorder with varying combinations of sensorineural hearing loss and abnormal pigmentation. The present study aimed to investigate the underlying molecular pathology and provide a method of prenatal diagnosis of WS in Chinese families. A total of 11 patients with WS from five unrelated Chinese families were enrolled. A thorough clinical examination was performed on all participants. Furthermore, patients with WS underwent screening for mutations in the following genes: Paired box 3 (PAX3), melanogenesis associated transcription factor (MITF), SRY‑box 10, snail family transcriptional repressor 2 and endothelin receptor type B using polymerase chain reaction sequencing. Array‑based comparative genomic hybridization was used for specific patients whose sequence results were normal. Following identification of the genotype of the probands and their parents, prenatal genetic diagnosis was performed for family 01 and 05. According to the diagnostic criteria for WS, five cases were diagnosed as WS1, while the other six cases were WS2. Genetic analysis revealed three mutations, including a nonsense mutation PAX3 c.583C>T in family 01, a splice‑site mutation MITF c.909G>A in family 03 and an in‑frame deletion MITF c.649_651delGAA in family 05. To the best of the authors' knowledge the mutations (c.583C>T in PAX3 and c.909G>A in MITF) were reported for the first time in Chinese people. Mutations in the gene of interest were not identified in family 02 and 04. The prenatal genetic testing of the two fetuses was carried out and demonstrated that the two babies were normal. The results of the present study expanded the range of known genetic mutations in China. Identification of genetic mutations in these families provided an efficient way to understand the causes of WS and improved genetic counseling.
Abbing, H R
Screening activities in health care are not always useful and sometimes harmful. The mere offer of a screening test puts the individual's autonomy under constraint. With genetic (predictive and risk assessment) tests, the right to free, informed consent and to protection of privacy and medical confidentiality is even more warranted. Screening evokes many questions from the perspective of the right to health care as well as (in particular with genetic screening) from the perspective of respect for individual human rights. Fear of liability puts pressure on professional restraint not to offer every screening test available. States have to take legislative measures for guaranteeing that only those screening activities become available that can significantly contribute to individual and public health. They also should consider additional rules for protecting individual rights where those that are generally accepted in the "ordinary" medical setting (the individual patient-doctor relationship), offer insufficient protection.
Marceau, Kristine; Ram, Nilam; Neiderhiser, Jenae M; Laurent, Heidemarie K; Shaw, Daniel S; Fisher, Phil; Natsuaki, Misaki N; Leve, Leslie D
Developmental plasticity models hypothesize the role of genetic and prenatal environmental influences on the development of the hypothalamic-pituitary-adrenal (HPA) axis and highlight that genes and the prenatal environment may moderate early postnatal environmental influences on HPA functioning. This article examines the interplay of genetic, prenatal and parenting influences across the first 4.5 years of life on a novel index of children's cortisol variability. Repeated measures data were obtained from 134 adoption-linked families, adopted children and both their adoptive parents and birth mothers, who participated in a longitudinal, prospective US domestic adoption study. Genetic and prenatal influences moderated associations between inconsistency in overreactive parenting from child age 9 months to 4.5 years and children's cortisol variability at 4.5 years differently for mothers and fathers. Among children whose birth mothers had high morning cortisol, adoptive fathers' inconsistent overreactive parenting predicted higher cortisol variability, whereas among children with low birth mother morning cortisol adoptive fathers' inconsistent overreactive parenting predicted lower cortisol variability. Among children who experienced high levels of prenatal risk, adoptive mothers' inconsistent overreactive parenting predicted lower cortisol variability and adoptive fathers' inconsistent overreactive parenting predicted higher cortisol variability, whereas among children who experienced low levels of prenatal risk there were no associations between inconsistent overreactive parenting and children's cortisol variability. Findings supported developmental plasticity models and uncovered novel developmental, gene × environment and prenatal × environment influences on children's cortisol functioning.
García, Elisa; Timmermans, Danielle R M; van Leeuwen, Evert
in debates around prenatal screening, it is frequently argued that responsible parenthood implies the acquisition of all available medical information about the health of a fetus, and use of this information to benefit the future child. to analyse whether an offer of a prenatal test leads women to believe that they are morally obliged to control the health of their fetus. a substudy within a randomised controlled trial (RCT) aimed to assess the decision-making process of women when confronted with an offer of a prenatal screening test. 111 women participating in an RCT were retrospectively asked their views on the meaning of testing within their parental duties. testing was described as a personal option that goes beyond the normal parental responsibilities. Participants did not believe that they ought to control the health of the fetus or to avoid disability. A duty to test was only reported when the birth of a disabled child would have a negative impact on family life. women's accounts suggest that two main factors are involved in making testing morally obligatory: (1) the woman's views on her moral duties to her family; and (2) the expected burden of a disabled child on the well-being of the family. A family-centred approach would be more suitable to assess the moral imperative character of testing than women's ethical views about their moral duties towards their unborn child. a test offer should not be limited to communication of the characteristics of screening and the meaning of the test results. In helping women to assess the meaning of testing within their parental duties, counselling should include the family situation in which women have to decide, the women's expectations about living with a child with Down's syndrome or any other disability, and the women's views on their commitments towards their family. Copyright © 2011 Elsevier Ltd. All rights reserved.
Yan, LiYing; Wei, Yuan; Huang, Jin; Zhu, XiaoHui; Shi, XiaoDan; Xia, Xi; Yan, Jie; Lu, CuiLing; Lian, Ying; Li, Rong; Liu, Ping; Qiao, Jie
Preimplantation genetic diagnosis (PGD) gives couples who have a high risk of transmitting genetic disorders to their baby the chance to have a healthy offspring through embryo genetic analysis and selection. Preimplantation genetic screening (PGS) is an effective method to select euploid embryos that may prevent repeated implantation failure or miscarriage. However, how and to whom PGS should be provided is a controversial topic. The first successful case of PGD of a human being was reported in 1990, and there have been tremendous improvements in this technology since then. Both embryo biopsy and genetic technologies have been improved dramatically, which increase the accuracy and expand the indications of PGD/PGS.
Han, Ming-yu; Huang, Sha-sha; Wang, Guo-jian; Yuan, Yong-yi; Kang, Dong-yang; Zhang, Xin; Dai, Pu
Analyzed the molecular pathogenesis of probands by means of genetic test and assisted the local Family Planning Institute by providing prenatal genetic counseling and instruction for deaf families who eager to have more baby. Total of forty-three deaf families were recruited by two institutes for family planning from Guangzhou and Weifang. Forty-two families had one deaf child with normal hearing parents. One family was that parents and their child were all deaf. Genetic testing of GJB2, SLC26A4 and mitochondrial DNA (mtDNA) 12SrRNA were firstly performed in probands and their parents, following medical history, physical examination, auditory test and CT scan of temporal bone were completed. And then the genetic information and instruction were provided to each deaf family. Fifteen of these 43 families had positive results of genetic test. In fifteen families, one family was confirmed that the parents and their child all carried homozygous GJB2 mutations and the recurrence risk was 100%. Twelve families were confirmed that the probands carried homozygous/compound GJB2 or SLC26A4 mutations while their parents were GJB2 or SLC26A4 carriers, and the recurrence risk was 25%. One family was confirmed that the proband, diagnosed with enlarged vestibular aqueduct syndrome (EVAS) by CT scan, carried heterozygous SLC26A4 mutation from the mother, and the recurrence risk was still 25% based on the hereditary pattern of EVAS although another SLC26A4 mutation from the father was not found. One family was confirmed that the proband carried a heterozygous GJB2 mutation from the mother and the possibility to be GJB2 carrier for offsprings was 50%. The rest 28 families were that all probands and their parents did not carry GJB2, SLC26A4 and mtDNA 12SrRNA pathological mutation. Genetic testing can provide more accurate and useful prenatal genetic counseling and instruction to deaf families. Meanwhile, it is an ideal way to develop a cooperative relationship with the institute for
Zhang, Di; Ng, Vincent H; Wang, Zhaochen; Zhai, Xiaomei; Lie, Reidar K
The application of genetic technologies in China, especially in the area of prenatal genetic testing, is rapidly increasing in China. In the wealthy regions of China, prenatal genetic testing is already very widely adopted. We argue that the government should actively promote prenatal genetic testing to the poor areas of the country. In fact, the government should prioritize resources first to make prenatal genetic testing a standard routine care with an opt-out model in these area. Healthcare professions would be required to inform pregnant women about the availability of genetic testing and provide free testing on a routine basis unless the parents choose not to do so. We argue that this proposal will allow parents to make a more informed decision about their reproductive choices. Secondarily, this proposal will attract more healthcare professionals and other healthcare resources to improve the healthcare infrastructures in the less-developed regions of the country. This will help to reduce the inequity of accessing healthcare services between in different regions of China. We further argue that this policy proposal is not practicing eugenics. © 2015 John Wiley & Sons Ltd.
Full Text Available Japan, known as a pro-choice country in terms of abortion, is currently facing the increase of “selective abortions” thanks to new prenatal screening. Efforts to restrict proliferation of new technology has not been successful and it is likely that Japan will turn pro-life by strictly enforcing the Maternity Protection Act (MPA, which prohibits abortions due to “fetal cause”.
Gagnon, Susie; Labrecque, Michel; Njoya, Merlin; Rousseau, François; St-Jacques, Sylvie; Légaré, France
To assess the extent to which family physicians (FPs) involve women in decisions about prenatal screening for Down syndrome. Based on transcripts of consultations between 41 FPs and 128 women, two raters independently assessed clinician's efforts to involve women in decisions about prenatal screening for Down syndrome using the French-language version of OPTION. Descriptive statistics of OPTION scores were calculated. Construct validity was assessed by performing a principal factor analysis and by measuring association with consultation duration and FPs sociodemograhics. Internal consistency was assessed with Cronbach's alpha and inter-rater reliability with the intraclass correlation coefficient. The overall mean OPTION score was low: 19 +/- 7 (range = 0 [no involvement] to 100 [high involvement]). One factor accounted for 80% of the variance. Both internal consistency and inter-rater reliability were very good (Cronbach's alpha = 0.73; ICC = 0.76). OPTION scores were lower for residents than for licensed FPs (17 +/- 5 vs 21 +/- 4; p = 0.02) and were positively associated with duration of consultation (r = 0.56; p women in decisions about prenatal screening for Down syndrome. (c) 2009 John Wiley & Sons, Ltd.
Lee, Hwa Jeen; Park, Seungman; Kang, Hyoung Jin; Jun, Jong Kwan; Lee, Jung Ae; Lee, Dong Soon; Park, Sung Sup; Seong, Moon-Woo
Fanconi anemia (FA) is a rare genetic disorder affecting multiple body systems. Genetic testing, including prenatal testing, is a prerequisite for the diagnosis of many clinical conditions. However, genetic testing is complicated for FA because there are often many genes that are associated with its development, and large deletions, duplications, or sequence variations are frequently found in some of these genes. This study describes successful genetic testing for molecular diagnosis, and subsequent prenatal diagnosis, of FA in a patient and his family in Korea. We analyzed all exons and flanking regions of the FANCA, FANCC, and FANCG genes for mutation identification and subsequent prenatal diagnosis. Multiplex ligation-dependent probe amplification analysis was performed to detect large deletions or duplications in the FANCA gene. Molecular analysis revealed two mutations in the FANCA gene: a frameshift mutation c.2546delC and a novel splice-site mutation c.3627-1G>A. The FANCA mutations were separately inherited from each parent, c.2546delC was derived from the father, whereas c.3627-1G>A originated from the mother. The amniotic fluid cells were c.3627-1G>A heterozygotes, suggesting that the fetus was unaffected. This is the first report of genetic testing that was successfully applied to molecular diagnosis of a patient and subsequent prenatal diagnosis of FA in a family in Korea.
Leve, Leslie D; DeGarmo, David S; Bridgett, David J; Neiderhiser, Jenae M; Shaw, Daniel S; Harold, Gordon T; Natsuaki, Misaki N; Reiss, David
Poor executive functioning has been implicated in children's concurrent and future behavioral difficulties, making work aimed at understanding processes related to the development of early executive function (EF) critical for models of developmental psychopathology. Deficits in EF have been associated with adverse prenatal experiences, genetic influences, and temperament characteristics. However, our ability to disentangle the predictive and independent effects of these influences has been limited by a dearth of genetically informed research designs that also consider prenatal influences. The present study examined EF and language development in a sample of 361 toddlers who were adopted at birth and reared in nonrelative adoptive families. Predictors included genetic influences (as inherited from birth mothers), prenatal risk, and growth in child negative emotionality. Structural equation modeling indicated that the effect of prenatal risk on toddler effortful attention at age 27 months became nonsignificant once genetic influences were considered in the model. In addition, genetic influences had unique effects on toddler effortful attention. Latent growth modeling indicated that increases in toddler negative emotionality from 9 to 27 months were associated with poorer delay of gratification and poorer language development. Similar results were obtained in models incorporating birth father data. Mechanisms of intergenerational transmission of EF deficits are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved
Gekas, Jean; Gagné, Geneviève; Bujold, Emmanuel; Douillard, Daniel; Forest, Jean-Claude; Reinharz, Daniel; Rousseau, François
To assess and compare the cost effectiveness of three different strategies for prenatal screening for Down's syndrome (integrated test, sequential screening, and contingent screenings) and to determine the most useful cut-off values for risk. Computer simulations to study integrated, sequential, and contingent screening strategies with various cut-offs leading to 19 potential screening algorithms. The computer simulation was populated with data from the Serum Urine and Ultrasound Screening Study (SURUSS), real unit costs for healthcare interventions, and a population of 110 948 pregnancies from the province of Québec for the year 2001. Cost effectiveness ratios, incremental cost effectiveness ratios, and screening options' outcomes. The contingent screening strategy dominated all other screening options: it had the best cost effectiveness ratio ($C26,833 per case of Down's syndrome) with fewer procedure related euploid miscarriages and unnecessary terminations (respectively, 6 and 16 per 100,000 pregnancies). It also outperformed serum screening at the second trimester. In terms of the incremental cost effectiveness ratio, contingent screening was still dominant: compared with screening based on maternal age alone, the savings were $C30,963 per additional birth with Down's syndrome averted. Contingent screening was the only screening strategy that offered early reassurance to the majority of women (77.81%) in first trimester and minimised costs by limiting retesting during the second trimester (21.05%). For the contingent and sequential screening strategies, the choice of cut-off value for risk in the first trimester test significantly affected the cost effectiveness ratios (respectively, from $C26,833 to $C37,260 and from $C35,215 to $C45,314 per case of Down's syndrome), the number of procedure related euploid miscarriages (from 6 to 46 and from 6 to 45 per 100,000 pregnancies), and the number of unnecessary terminations (from 16 to 26 and from 16 to 25 per 100
van El, C.G.; Pieters, T.; Cornel, M.C.
Recent decades have witnessed increasing possibilities for genetic testing and screening. In clinical genetics, the doctor's office defined a secluded space for discussion of sensitive reproductive options in cases of elevated risk for genetic disorders in individuals or their offspring. When
McDonald, Sheila; Wall, Jennifer; Forbes, Kaitlin; Kingston, Dawn; Kehler, Heather; Vekved, Monica; Tough, Suzanne
Post-partum depression (PPD) is the most common complication of pregnancy in developed countries, affecting 10-15% of new mothers. There has been a shift in thinking less in terms of PPD per se to a broader consideration of poor mental health, including anxiety after giving birth. Some risk factors for poor mental health in the post-partum period can be identified prenatally; however prenatal screening tools developed to date have had poor sensitivity and specificity. The objective of this study was to develop a screening tool that identifies women at risk of distress, operationalized by elevated symptoms of depression and anxiety in the post-partum period using information collected in the prenatal period. Using data from the All Our Babies Study, a prospective cohort study of pregnant women living in Calgary, Alberta (N = 1578), we developed an integer score-based prediction rule for the prevalence of PPD, as defined as scoring 10 or higher on the Edinburgh Postnatal Depression Scale (EPDS) at 4-months postpartum. The best fit model included known risk factors for PPD: depression and stress in late pregnancy, history of abuse, and poor relationship quality with partner. Comparison of the screening tool with the EPDS in late pregnancy showed that our tool had significantly better performance for sensitivity. Further validation of our tool was seen in its utility for identifying elevated symptoms of postpartum anxiety. This research heeds the call for further development and validation work using psychosocial factors identified prenatally for identifying poor mental health in the post-partum period. © 2012 Blackwell Publishing Ltd.
Pick, Joel L; Ebneter, Christina; Hutter, Pascale; Tschirren, Barbara
Organizational processes during prenatal development can have long-term effects on an individual's phenotype. Because these early developmental stages are sensitive to environmental influences, mothers are in a unique position to alter their offspring's phenotype by differentially allocating resources to their developing young. However, such prenatal maternal effects are difficult to disentangle from other forms of parental care, additive genetic effects, and/or other forms of maternal inheritance, hampering our understanding of their evolutionary consequences. Here we used divergent selection lines for high and low prenatal maternal investment and their reciprocal line crosses in a precocial bird-the Japanese quail (Coturnix japonica)-to quantify the relative importance of genes and prenatal maternal effects in shaping offspring phenotype. Maternal but not paternal origin strongly affected offspring body size and survival throughout development. Although the effects of maternal egg investment faded over time, they were large at key life stages. Additionally, there was evidence for other forms of maternal inheritance affecting offspring phenotype at later stages of development. Our study is among the first to successfully disentangle prenatal maternal effects from all other sources of confounding variation and highlights the important role of prenatal maternal provisioning in shaping offspring traits closely linked to fitness.
Mastenbroek, Sebastiaan; Repping, Sjoerd
All agree that in hindsight the rapid adoption of preimplantation genetic screening (PGS) using cleavage stage biopsy and fluorescence in situ hybridization (FISH) in routine clinical practice without proper evaluation of (cost-)effectiveness basically resulted in couples paying more money for a
Rasmussen, Maria; Olsen, Morten Smærup; Sunde, Lone
ObjectivesTo estimate the prevalence of kidney anomalies at second trimester ultrasound screening, and furthermore, to investigate pregnancy outcomes and the pattern of additional malformations. MethodsWe previously identified all women attending second-trimester ultrasound scans in Denmark between...... of non-urinary malformations, comparing the prevalences in infants with and without prenatally diagnosed kidney anomalies. ResultsThe prevalence of fetuses with kidney anomalies at second trimester scans was 11.4 per 10000 fetuses. Among the 412 fetuses identified, 127 pregnancies were terminated....... For live born children the prevalence of additional non-urinary malformations was four times higher (95% CI: 3-5) compared with the prevalence among children without prenatal kidney anomalies. Digestive system anomalies were particularly prevalent. ConclusionThese population-based data provide additional...
Cuturilo, Goran; Vucinic, Olivera Kontic; Novakovic, Ivana; Ignjatovic, Svetlana; Mijovic, Marija; Sulovic, Nenad; Vukolic, Dusan; Komnenic, Milica; Tadic, Jasmina; Cetkovic, Aleksandar; Belic, Aleksandra; Ljubic, Aleksandar
This is the first study in Serbia and the region of South-East Europe dedicated to clients' perception of outcome and efficiency of prenatal and reproductive genetic counseling. The primary aim of this study was to assess overall value and success of genetic counseling in prenatal and reproductive care with regard to perceived personal control of clients, reflecting also in a part patient comprehension, knowledge retention, and empowerment in decision-making. The standardized Perceived Personal Control questionnaire (PPC) was used for the assessment of 239 female participants. First, we performed a complete validation of the psychometric characteristics of the Serbian-language version of the PPC questionnaire. The validation of the questionnaire permits other researchers from Serbian-speaking regions of South-East Europe to use this standard instrument to assess the effectiveness of prenatal genetic counseling in their communities and analyze advantages and disadvantages of their counseling models. We also measured social and demographic characteristics of participants. Further, we analyzed effects of our team-based prenatal and reproductive genetic counseling model through (a) calculation of PPC scores at three different stages (before initial, after initial, and before second counseling session), and (b) by assessing participants' responses by indication for referral (advanced maternal age, abnormal biochemical screening, family history of hereditary disorders, maternal exposure to drugs, exposure to radiation, exposure to infective agents, infertility or recurrent abortions, and miscellaneous). The results indicate that participants' knowledge after initial counseling increased significantly and after that remained stable and sustainable. A satisfactory level of confidence among participants had been achieved, in that many felt an increased sense of control over their situation and emotional response to it. Indirectly, these results indicate the success of a
van der Schoot CE
Full Text Available Abstract Background Since July 1998 all Dutch women (± 200,000/y are screened for red cell antibodies, other than anti-RhesusD (RhD in the first trimester of pregnancy, to facilitate timely treatment of pregnancies at risk for hemolytic disease of the fetus and newborn (HDFN. Evidence for benefits, consequences and costs of screening for non-RhD antibodies is still under discussion. The screening program was evaluated in a nation-wide study. As a part of this evaluation study we investigated, according to the sixth criterium of Wilson and Jüngner, the acceptance by pregnant women of the screening program for non-RhD antibodies. Methods Controlled longitudinal survey, including a prenatal and a postnatal measurement by structured questionnaires. Main outcome measures: information satisfaction, anxiety during the screening process (a.o. STAI state inventory and specific questionnaire modules, overall attitude on the screening program. Univariate analysis was followed by standard multivariate analysis to identify significant predictors of the outcome measures. Participants: 233 pregnant women, distributed over five groups, according to the screening result. Results Satisfaction about the provided information was moderate in all groups. All screen- positive groups desired more supportive information. Anxiety increased in screen- positives during the screening process, but decreased to basic levels postnatally. All groups showed a strongly positive balance between perceived utility and burden of the screening program, independent on test results or background characteristics. Conclusion Women highly accept the non-RhD antibody screening program. However, satisfaction about provided information is moderate. Oral and written information should be provided by obstetric care workers themselves, especially to screen-positive women.
Gitsels-van der Wal, Janneke T; Manniën, Judith; Gitsels, Lisanne A; Reinders, Hans S; Verhoeven, Pieternel S; Ghaly, Mohammed M; Klomp, Trudy; Hutton, Eileen K
In the Netherlands, prenatal screening follows an opting in system and comprises two non-invasive tests: the combined test to screen for trisomy 21 at 12 weeks of gestation and the fetal anomaly scan to detect structural anomalies at 20 weeks. Midwives counsel about prenatal screening tests for congenital anomalies and they are increasingly having to counsel women from religious backgrounds beyond their experience. This study assessed midwives' perceptions and practices regarding taking client's religious backgrounds into account during counseling. As Islam is the commonest non-western religion, we were particularly interested in midwives' knowledge of whether pregnancy termination is allowed in Islam. This exploratory study is part of the DELIVER study, which evaluated primary care midwifery in The Netherlands between September 2009 and January 2011. A questionnaire was sent to all 108 midwives of the twenty practices participating in the study. Of 98 respondents (response rate 92%), 68 (69%) said they took account of the client's religion. The two main reasons for not doing so were that religion was considered irrelevant in the decision-making process and that it should be up to clients to initiate such discussions. Midwives' own religious backgrounds were independent of whether they paid attention to the clients' religious backgrounds. Eighty midwives (82%) said they did not counsel Muslim women differently from other women. Although midwives with relatively many Muslim clients had more knowledge of Islamic attitudes to terminating pregnancy in general than midwives with relatively fewer Muslim clients, the specific knowledge of termination regarding trisomy 21 and other congenital anomalies was limited in both groups. While many midwives took client's religion into account, few knew much about Islamic beliefs on prenatal screening for congenital anomalies. Midwives identified a need for additional education. To meet the needs of the changing client population
The aim of this work is to summarize the current knowledge about preimplantation genetic screening and diagnostics. A review article. Department of Gynecology and Obstetrics, District Hospital Šternberk, IVF Clinic, Olomouc. Preimplantation genetic testing is a complex of genetic and molecular cytogenetic examinations, which can help to detect abnormalities in embryos before transfer into the uterus of the mother. These specialized examinations are based on the latest findings in genetics and assisted reproduction. The preimplantation genetic testing is necessarily associated with a method of in vitro fertilization. It is performed on isolated blastomeres on the third day of embryo cultivation. Nowadays, it is preferred trophectoderm examination of cells from the five-day blastocysts. Generally speaking, after preimplantation genetic testing, we can select only embryos without genetic load to transfer into uterus. Preimplantation genetic testing is an important part of treatment of infertility. Complex diagnostics and treatment of infertile couples are increasingly influenced by the development and use of advanced genomic technologies. Further development and application of these modern methods require close cooperation between the field of assisted reproduction and clinical genetics.
Garcia, E.; Timmermans, D.R.; Leeuwen, E. van
In contrast to most Western countries, routine offer of prenatal screening is considered problematic in the Netherlands. The main argument against offering it to every pregnant woman is that women would be brought into a moral dilemma when deciding whether to use screening or not. This paper
Garcia Gonzalez, M.E.; Timmermans, D.R.M.; Leeuwen, van E.
In contrast to most Western countries, routine offer of prenatal screening is considered problematic in the Netherlands. The main argument against offering it to every pregnant woman is that women would be brought into a moral dilemma when deciding whether to use screening or not. This paper
Minear, Mollie A; Alessi, Stephanie; Allyse, Megan; Michie, Marsha; Chandrasekharan, Subhashini
Noninvasive prenatal genetic testing (NIPT) for chromosomal aneuploidy involving the analysis of cell-free fetal DNA became commercially available in 2011. The low false-positive rate of NIPT, which reduces unnecessary prenatal invasive diagnostic procedures, has led to broad clinician and patient adoption. We discuss the ethical, legal, and social issues raised by rapid and global dissemination of NIPT. The number of women using NIPT is anticipated to expand, and the number of conditions being tested for will continue to increase as well, raising concerns about the routinization of testing and negative impacts on informed decision making. Ensuring that accurate and balanced information is available to all pregnant women and that access to NIPT is equitable will require policy guidance from regulators, professional societies, and payers. Empirical evidence about stakeholders' perspectives and experiences will continue to be essential in guiding policy development so that advances in NIPT can be used effectively and appropriately to improve prenatal care.
Anne Cathrine, Gjerris; Tabor, Ann; Loft, Anne
BACKGROUND Prenatal screening and diagnosis of chromosomal abnormalities especially Down's syndrome in IVF pregnancies are complicated by higher maternal age, a high multiple pregnancy rate, a high risk of a vanishing twin and an increased risk of chromosomal abnormalities, particularly in pregna......BACKGROUND Prenatal screening and diagnosis of chromosomal abnormalities especially Down's syndrome in IVF pregnancies are complicated by higher maternal age, a high multiple pregnancy rate, a high risk of a vanishing twin and an increased risk of chromosomal abnormalities, particularly...... in pregnancies after ICSI. The aim of the present systematic review was to evaluate the findings of first trimester screening for chromosomal abnormalities in IVF/ICSI singleton and twin pregnancies. METHODS A systematic MESH-term search in MEDLINE using PubMed and the Cochrane Library was performed until May...... 2011, with no earlier date limit. RESULTS The electronic search retrieved 562 citations, 96 of which were evaluated in detail and 57 were then excluded for not meeting the selection criteria. A total of 61 articles were finally selected for review. Our analysis of the data shows that, for IVF...
Traeger-Synodinos, Joanne; Harteveld, Cornelis L
Hemoglobinopathies constitute the most common severe monogenic disorders worldwide, with an increasing global burden each year. The benefit of applying programmes for preconception carrier screening, with the option of prenatal diagnosis, to minimize the incidence of new cases is recognized in many countries. Areas covered: The challenges associated with identifying carrier couples using hematology-based screening, along with DNA diagnosis and prenatal diagnosis were addressed, based on a literature search and the authors expertise. Expert commentary: The hemoglobinopathies are extremely heterogeneous at the haematological, molecular and clinical level, requiring appropriately equipped and staffed laboratories with experience to support comprehensive screening and diagnosis. However complete services with adequate infrastructure to address the associated technical challenges do not exist widely, especially in low-income countries that, coincidentally, are often those with the highest frequency of hemoglobinopathies in their population. Additionally, overcoming limited public awareness, education and absence of systematic dissemination of information also constitutes a challenge. This article aims to highlight these challenges and to evaluate potential future developments that may address at least some of them, focusing mainly on the technical challenges related to molecular diagnostics.
Khaled R. Gaber
Conclusion: Early prenatal screening and diagnosis, through a systematic multidisciplinary approach, to all cases of mucopolysaccharidoses are recommended, to improve the quality of life and to avoid the presence of other associated fetal developmental malformations.
Balcom, Jessica R; Veach, Patricia McCarthy; Bemmels, Heather; Redlinger-Grosse, Krista; LeRoy, Bonnie S
A limited amount of research indicates patient requests play a major role in genetic counselors' self-disclosure decisions and that disclosure and non-disclosure responses to patient requests may differentially affect genetic counseling processes. Studies further suggest patient requests may be more common in prenatal settings, particularly when counselors are pregnant. Empirical evidence is limited however, concerning the nature of patient requests. This study explored genetic counselors' experiences of prenatal patients' requests for self-disclosure. Four major research questions were: (1) What types of questions do prenatal patients ask that invite self-disclosure?; (2) Do pregnant genetic counselors have unique experiences with prenatal patient disclosure requests?; (3) How do genetic counselors typically respond to disclosure requests?; and (4) What strategies are effective and ineffective in responding to disclosure requests? One hundred seventy-six genetic counselors completed an online survey and 40 also participated in telephone interviews. Inductive analysis of 21 interviews revealed patient questions vary, although questions about counselor demographics are most common, and patients are more likely to ask pregnant counselors questions about their personal pregnancy decisions. Participants reported greater discomfort with self-disclosure requests during pregnancy, yet also disclosing more frequently during pregnancy. Counselor responses included personal self-disclosure, professional self-disclosure, redirection, and declining to disclose. Factors perceived as influencing disclosure included: topic, patient motivations, timing of request, quality of counseling relationship, patient characteristics, and ethical/legal responsibilities. Disclosure practices changed over time for most counselors. Additional findings, practice implications, and research recommendations are discussed.
Lépine, Johanie; Leiva Portocarrero, Maria Esther; Delanoë, Agathe; Robitaille, Hubert; Lévesque, Isabelle; Rousseau, François; Wilson, Brenda J; Giguère, Anik M C; Légaré, France
Health professionals are expected to engage pregnant women in shared decision making to help them make informed values-based decisions about prenatal screening. Patient decision aids (PtDAs) foster shared decision-making, but are rarely used in this context. Our objective was to identify factors that could influence health professionals to use a PtDA for decisions about prenatal screening for Down syndrome during a clinical pregnancy follow-up. We planned to recruit a purposive sample of 45 health professionals (obstetrician-gynecologists, family physicians and midwives) involved in the care of pregnant women in three clinical sites (15 per site). Participating health professionals first watched a video showing two simulated consecutive prenatal follow-up consultations during which a pregnant woman, her partner and a health professional used a PtDA about Down syndrome prenatal screening. Participants were then interviewed about factors that would influence their use of the PtDA. Questions were based on the Theoretical Domains Framework. We performed content analyses of transcribed verbatim interviews. Out of 42 eligible health professionals approached, 36 agreed to be interviewed (86 % response rate). Of these, 27 were female (75 %), nine were obstetrician-gynecologists (25 %), 15 were family physicians (42 %), and 12 were midwives (33 %), with a mean age of 42.1 ± 11.6 years old. We identified 35 distinct factors reported by 20 % or more participants that were mapped onto 10 of the 12 of the Theoretical Domains Framework domains. The six most frequently mentioned factors influencing use of the PtDA were: 1) a positive appraisal (n = 29, 81 %, beliefs about consequences domain); 2) its availability in the office (n = 27, 75 %, environmental context and resources domain); 3) colleagues' approval (n = 27, 75 %, social influences domain); 4) time constraints (n = 26, 72 %, environmental context and resources domain); 5) finding it a
Talebi, Farah; Ghanbari Mardasi, Farideh; Mohammadi Asl, Javad; Lashgari, Ali; Farhadi, Freidoon
Norrie disease (ND) is a rare X-linked recessive disorder, which is characterized by congenital blindness and, in several cases, accompanied with mental retardation and deafness. ND is caused by mutations in NDP, located on the proximal short arm of the X chromosome (Xp11.3). The disease has been observed in many ethnic groups worldwide, however, no such case has been reported from Iran. In this study, we present the molecular analysis of two patients with ND and the subsequent prenatal diagnosis. Screening of NDP identified a hemizygous missense mutation (p.Ser133Cys) in the affected male siblings of the family. The mother was the carrier for the mutation (p.Ser133Cys). In a subsequent chorionic amniotic pregnancy, we carried out prenatal diagnosis by sequencing NDP in the chorionic villi sample at 11 weeks of gestation. The fetus was carrying the mutation and thus unaffected. This is the first mutation report and prenatal diagnosis of an Iranian family with ND, and highlights the importance of prenatal diagnostic screening of this congenital disorder and relevant genetic counseling. Copyright© by Royan Institute. All rights reserved.
Botkin, Jeffrey R; Rothwell, Erin; Anderson, Rebecca A; Rose, Nancy C; Dolan, Siobhan M; Kuppermann, Miriam; Stark, Louisa A; Goldenberg, Aaron; Wong, Bob
Research clearly indicates that current approaches to newborn blood spot screening (NBS) education are ineffective. Incorporating NBS education into prenatal care is broadly supported by lay and professional opinion. To determine the efficacy and effect of prenatal education about newborn screening and use of residual dried blood spots (DBS) in research on parental knowledge, attitudes, and behaviors. A randomized clinical trial of prenatal educational interventions, with outcomes measured by survey at 2 to 4 weeks postpartum. Participants were recruited from obstetric clinics in Salt Lake City, Utah; San Francisco, California; and the Bronx, New York. Eligible women were English- or Spanish-speaking adults and did not have a high-risk pregnancy. A total of 901 women were enrolled. Participants who completed the follow-up survey included 212 women in the usual care group (70% retention), 231 in the NBS group (77% retention), and 221 women in the NBS + DBS group (75% retention). Those who completed the survey were similar across the 3 groups with respect to age, ethnicity, race, education, marital status, income, obstetric history, and language. Participants were randomized into 1 of 3 groups: usual care (n = 305), those viewing an NBS movie and brochure (n = 300), and those viewing both the NBS and DBS movies and brochures (n = 296). Two to four weeks postpartum, women completed a 91-item survey by telephone, addressing knowledge, attitudes, and behavior with respect to opting out of NBS or DBS for their child. A total of 901 women (mean age, 31 years) were randomized and 664 completed the follow-up survey. The total correct responses on the knowledge instrument in regard to NBS were 69% in the usual care group, 79% in the NBS group, and 75% in the NBS + DBS group, a significant between-group difference (P Educational interventions can be implemented in the prenatal clinic, using multimedia tools and electronic platforms. Prenatal education is
Alvarenga Fernandes Sin, Olga; Michels, Helen; Nollen, Ellen A. A.
Caenorhabditis elegans comprises unique features that make it an attractive model organism in diverse fields of biology. Genetic screens are powerful to identify genes and C. elegans can be customized to forward or reverse genetic screens and to establish gene function. These genetic screens can be
Rietzler, Jennifer L; Birkeland, Laura E; Petty, Elizabeth M
The impact of practicing as a prenatal genetic counselor while pregnant is unclear given the limited amount of published literature on this issue. To address this gap in knowledge, a total of 215 current and past prenatal genetic counselors provided insights regarding this personal yet professional juncture through completion of an online survey that allowed for both close-ended and open-ended responses. While participants agreed that experiencing pregnancy affected their perspectives and counseling in several ways, this paper focuses on one particular finding-that of the changes in their own obstetric care perceived by genetic counselors while working within the prenatal setting and being pregnant themselves. As a result of these changes, considerations about when to disclose a pregnancy to colleagues along with how to integrate personal and professional needs as a pregnant prenatal genetic counselor surfaced. Additional findings, practice implications, and research recommendations are discussed.
Menezes, Melody A; Hodgson, Jan M; Sahhar, Margaret A; Aitken, Maryanne; Metcalfe, Sylvia A
Prenatal genetic counselors work with clients who are at risk of having a child with a fetal anomaly, or who have been diagnosed with a fetal anomaly. This can raise challenging ethical, moral and legal issues for both clients and counselors. Few studies have explored whether this type of work impacts on genetic counselors themselves. Interviews were conducted with 15 prenatal genetic counselors, five from Toronto, Canada and ten from Melbourne, Australia. A qualitative approach was used to allow for an in-depth exploration of the experiences of genetic counselors working in the prenatal setting. While participants reported that working in a prenatal setting affected them in several ways, this paper focuses on one particular unanticipated finding--that of the impact experienced by counselors from both countries while working when pregnant.
Harrison, Patricia A; Godecker, Amy; Sidebottom, Abbey C
The purpose of the study was to validate the Prenatal Risk Overview (PRO) Alcohol use domain against a structured diagnostic interview. The PRO was developed to screen for 13 psychosocial risk factors associated with poor birth outcomes. After clinic staff administered the PRO to prenatal patients, they asked for consent to administration of selected modules of the structured clinical interview for DSM-IV (SCID) by a research assistant. To assess the criterion validity of the PRO, low and moderate/high risk classifications from the alcohol use domain were cross-tabulated with SCID Alcohol Use Disorder variables. The study sample included 744 women. Based on PRO responses, 48.7% reported alcohol use during the 12 months before they learned they were pregnant; 5.4% reported use post pregnancy awareness. The typical quantity consumed pre-pregnancy was four or more drinks per occasion. Based on the SCID, 7.4% met DSM-IV criteria for either Alcohol Abuse or Dependence. Sensitivity and specificity of the PRO for Alcohol Use Disorders were 83.6 and 80.3%, respectively. Negative predictive value was 98.4% and positive predictive value was 25.3%. The results indicate the PRO effectively identified pregnant women with Alcohol Use Disorders. However, prenatal screening must also detect consumption patterns that do not meet diagnostic thresholds but may endanger fetal development. The PRO also identified women who continued to drink after they knew they were pregnant, as well as those whose previous drinking habits put them at risk for resumption of hazardous use.
Hubbard, R; Henifin, M S
Genetic screening programs are based on assumptions and values that reflect the history of racial and social eugenics in the United States and Europe. They stigmatize individuals by shifting the focus from social, economic, and political decisions that affect the health of prospective parents, newborns, and workers to "bad genes," that is, intrapersonal factors that are given the status of "causes" of disease. Prenatal screening, at best, can help the relatively few individuals who know that their future children are at risk for a particular inherited disease or disability; it has little positive value for the average person. Workplace genetic screening has not been shown to reduce occupational disease, but it has led to employment discrimination and has drawn attention away from controlling exposures to toxic chemicals in the workplace.
Nicholas J Wald
Full Text Available BACKGROUND: Prenatal screening for Down's syndrome is performed using biochemical and ultrasound markers measured in early pregnancy such as the Integrated test using first and second trimester markers. Recently, DNA sequencing methods have been introduced on free DNA in maternal plasma, yielding a high screening performance. These methods are expensive and there is a test failure rate. We determined the screening performance of merging the Integrated test with the newer DNA techniques in a protocol that substantially reduces the cost compared with universal DNA testing and still achieves high screening performance with no test failures. METHODS: Published data were used to model screening performance of a protocol in which all women receive the first stage of the Integrated test at about 11 weeks of pregnancy. On the basis of this higher risk women have reflex DNA testing and lower risk women as well as those with a failed DNA test complete the Integrated test at about 15 weeks. RESULTS: The overall detection rate was 95% with a 0.1% false-positive rate if 20% of women were selected to receive DNA testing. If all women had DNA testing the detection rate would be 3 to 4 percentage points higher with a false-positive rate 30 times greater if women with failed tests were treated as positive and offered a diagnostic amniocentesis, or 3 times greater if they had a second trimester screening test (Quadruple test and treated as positive only if this were positive. The cost per women screened would be about one-fifth, compared with universal DNA testing, if the DNA test were 20 times the cost of the Integrated test. CONCLUSION: The proposed screening protocol achieves a high screening performance without programme test failures and at a substantially lower cost than offering all women DNA testing.
Afroze, B.; Jehan, F.
Objective: To assess the needs related to prenatal genetic counselling in a developing country. Methods: The prospective observational study was conducted at the Prenatal-Genetic Counselling Clinic of Aga Khan University Hospital, Karachi, from October 2007 to September 2010. In-depth interviews were conducted and the data was stored in the form of patient charts. Information was then extracted from the charts and entered into a structured questionnaire. Results: Of the 93 couples in the study, 49(53%) were in the self-referral group and 44(47%) were in the physician-referral group. Diagnosis was not given for previously affected children by the paediatrician or by obstetrician for recurrent miscarriages in 68(73%)cases. Besides, 20(22%) couples had voluntarily terminated a pregnancy without any tests because of the fear of having a diseased child. Eleven (12%) couples were looking for amniocentensis or chorionic villus sampling. Death in previous children was the main reason to seek genetic counselling and was seen in 57(61%) couples. Consanguinity was seen in 77(83%) couples. Conclusion: A clear deficiency of knowledge of genetics was seen among the non-genetic healthcare providers. Demand of antenatal genetic testing among the public was also seen, highlighting the need of diagnostic facility for genetic and metabolic disorders. However, this needs to be explored in the context of the existing healthcare infrastructure. (author)
Wätterbjörk, Inger; Sahlberg-Blom, Eva; Nilsson, Kerstin; Blomberg, Karin
A two-step model on information on prenatal screening consists of brief information at the first visit at the Maternal Health Care Centre and an offer of extended information at a separate visit. There is a lack of knowledge why some pregnant women and their partners refrain from the extended information visit. The aim of this study was to explore their reasons. Eight qualitative interviews were analyzed using Interpretive Description. In the first theme 'From an individual view', the interviewees saw the invitation from their own points of view. They refrained because they did not want to receive any more information or had taken an individual position against chromosomal testing. In the theme, 'From a societal view', the interviewees perceived the offer as part of a societal view on prenatal screening that they could not support. The findings show that these interviewees' reasons of declining an extended information visit are multidimensional and influenced by different views, from both an individual perspective and a more societal one. Health care professionals should be aware that some persons could have a different view on health care services and could be reluctant to accept offered services. © 2015 John Wiley & Sons, Ltd.
Faber, H. H.; Bouman, K.; Walle, H. E. K.
OBJECTIVES: There has been much discussion about the relatively high perinatal mortality seen in the Netherlands (Buitendijk 2004, Europeristat 2009), for which congenital anomalies (CA) are known to be one of the four main risk factors. There was no nationwide routine prenatal screening for CA...... in the Netherlands until 2007. We have analysed data for a 14-year period from the EUROCAT registries to investigate the effect of the introduction of screening for CA on the perinatal mortality rate in the Netherlands and compared the results with those from other European registries. METHODS: We used data from...... of 1.35 per 1000 births in the period 1998-2006 to 1.15 per 1000 births in the period 2007-2011. In the northern Netherlands, it dropped from 1.73 per 1000 births in the period 1998-2006 to 1.00 per 1000 births in the period 2007- 2011. In 2011, the perinatal mortality associated with CA...
Clausen, F. Banch; Steffensen, R.; Christiansen, M.
Objective: Prenatal and postnatal RhD prophylaxis reduces the risk of RhD immunization in pregnancies of RhD-negative women. Based on the result from prenatal screening for the fetal RHD gene, prenatal RhD prophylaxis in Denmark is targeted to RhD-negative women who carry an RhD-positive fetus...... of newborns in 12,668 pregnancies. Early compliance was assessed for 690 pregnancies. Results: The sensitivity for the detection of fetal RHD was 99.9% (95% CI: 99.7-99.9%). Unnecessary recommendation of prenatal RhD prophylaxis was avoided in 97.3% of the women carrying an RhD-negative fetus. Fetuses...... that were seropositive for RhD were not detected in 11 pregnancies (0.087%). The sample uptake percentage was 84.2%, and the compliance for prenatal anti-D administration was 93.2%. Conclusion: The high sensitivity, maintained over 2years, underlines the reliability of routine prenatal fetal RHD screening...
Background. Fragile X syndrome (FXS), the most common inherited cause of intellectual disability (ID) worldwide, is caused by the expansion of a CGG repeat in the fragile X mental retardation gene (FMR-1) gene. Objectives. To review, retrospectively, the genetic services for FXS and other FMR-1-related disorders ...
Kreiner-Møller, Eskil; Bisgaard, Hans; Bønnelykke, Klaus
BACKGROUND: It is unknown to what extent adult lung function genes affect lung function development from birth to childhood. OBJECTIVE: Our aim was to study the association of candidate genetic variants with neonatal lung function and lung function development until age 7 years. METHODS: Lung fun...
Vendrell, Xavier; Bautista-Llácer, Rosa
The genetic diagnosis and screening of preimplantation embryos generated by assisted reproduction technology has been consolidated in the prenatal care framework. The rapid evolution of DNA technologies is tending to molecular approaches. Our intention is to present a detailed methodological view, showing different diagnostic strategies based on molecular techniques that are currently applied in preimplantation genetic diagnosis. The amount of DNA from one single, or a few cells, obtained by embryo biopsy is a limiting factor for the molecular analysis. In this sense, genetic laboratories have developed molecular protocols considering this restrictive condition. Nevertheless, the development of whole-genome amplification methods has allowed preimplantation genetic diagnosis for two or more indications simultaneously, like the selection of histocompatible embryos plus detection of monogenic diseases or aneuploidies. Moreover, molecular techniques have permitted preimplantation genetic screening to progress, by implementing microarray-based comparative genome hybridization. Finally, a future view of the embryo-genetics field based on molecular advances is proposed. The normalization, cost-effectiveness analysis, and new technological tools are the next topics for preimplantation genetic diagnosis and screening. Concomitantly, these additions to assisted reproduction technologies could have a positive effect on the schedules of preimplantation studies.
Nahar, Risha; Puri, Ratna D; Saxena, Renu; Verma, Ishwar C
Surveys of attitudes of individuals with deafness and their families towards genetic testing or prenatal diagnosis have mostly been carried out in the West. It is expected that the perceptions and attitudes would vary amongst persons of different cultures and economic background. There is little information on the prevailing attitudes for genetic testing and prenatal diagnosis for deafness in developing countries. Therefore, this study evaluates the motivations of Indian people with inherited hearing loss towards such testing. Twenty-eight families with history of congenital hearing loss (23 hearing parents with child/family member with deafness, 4 couples with both partners having deafness and 1 parent and child with deafness) participated in a semi-structured survey investigating their interest, attitudes, and intentions for using genetic and prenatal testing for deafness. Participants opinioned that proper management and care of individuals with deafness were handicapped by limited rehabilitation facilities with significant financial and social burden. Nineteen (68%) opted for genetic testing. Twenty-six (93%) expressed high interest in prenatal diagnosis, while 19 (73%) would consider termination of an affected fetus. Three hearing couples, in whom the causative mutations were identified, opted for prenatal diagnosis. On testing, all the three fetuses were affected and the hearing parents elected to terminate the pregnancies. This study provides an insight into the contrasting perceptions towards hearing disability in India and its influence on the desirability of genetic testing and prenatal diagnosis. Copyright © 2012 Wiley Periodicals, Inc.
Halliday, Jane; Collins, Veronica; Riley, Merilyn; Youssef, Danielle; Muggli, Evelyne
With this study we aimed to compare survival rates for children with Down syndrome in 2 time periods, 1 before prenatal screening (1988-1990) and 1 contemporaneous with screening (1998-2000), and to examine the frequency of comorbidities and their influence on survival rates. Record-linkage was performed between the population-based Victorian Birth Defects Register and records of deaths in children up to 15 years of age collected under the auspice of the Consultative Council on Obstetric and Pediatric Mortality and Morbidity. Cases of Down syndrome were coded according to the presence or absence of comorbidities by using the International Classification of Diseases, Ninth Revision classification of birth defects. Kaplan-Meier survival functions and log rank tests for equality of survival distributions were performed. Of infants liveborn with Down syndrome in 1998-2000, 90% survived to 5 years of age, compared with 86% in the earlier cohort. With fetal deaths excluded, the proportion of isolated Down syndrome cases in the earlier cohort was 48.7% compared with 46.1% in the most recent cohort. In 1988-1990 there was at least 1 cardiac defect in 41.1% of cases and in 45.4% in 1998-2000. There was significant variation in survival rates for the different comorbidity groupings in the 1988-1990 cohort, but this was not so evident in the 1998-2000 cohort. Survival of children with Down syndrome continues to improve, and there is an overall survival figure of 90% to at least 5 years of age. It is clear from this study that prenatal screening technologies are not differentially ascertaining fetuses with Down syndrome and additional defects, because there has been no proportional increase in births of isolated cases with Down syndrome.
Chen, Chun-Kai; Yu, Hsing-Tse; Soong, Yung-Kuei; Lee, Chyi-Long
Preimplantation genetic diagnosis is a procedure that involves the removal of one or more nuclei from oocytes (a polar body) or embryos (blastomeres or trophectoderm cells) in order to test for problems in genome sequence or chromosomes of the embryo prior to implantation. It provides new hope of having unaffected children, as well as avoiding the necessity of terminating an affected pregnancy for genetic parents who carry an affected gene or have balanced chromosomal status. Polymerase chain reaction-based molecular techniques are the methods used to detect gene defects with a known sequence and X-linked diseases. The indication for using this approach has expanded for couples who are prevented from having babies because they carry a serious genetic disorder to couples with conditions that are not immediately life threatening, such as cancer predisposition genes and Huntington disease. In addition, fluorescent in situ hybridization (FISH) has been widely applied for the detection of chromosome abnormalities. FISH allows the evaluation of many chromosomes at the same time, up to 15 chromosome pairs in a single cell. Preimplantation genetic screening, defined as a test that screens for aneuploidy, has been most commonly used in situations of advanced maternal age, a history of recurrent miscarriage, a history of repeated implantation failure, or a severe male factor. Unfortunately, randomized controlled trials have as yet shown no benefit with respect to preimplantation genetic screening using cleavage stage biopsy, which is probably attributable to the high levels of mosaicism at early cleavage stages and the limitations of FISH. Recently, two main types of array-based technology combined with whole genome amplification have been developed for use in preimplantation genetic diagnosis; these are comparative genomic hybridization and single nucleotide polymorphism-based arrays. Both allow the analysis of all chromosomes, and the latter also allows the haplotype of
Full Text Available Preimplantation genetic diagnosis is a procedure that involves the removal of one or more nuclei from oocytes (a polar body or embryos (blastomeres or trophectoderm cells in order to test for problems in genome sequence or chromosomes of the embryo prior to implantation. It provides new hope of having unaffected children, as well as avoiding the necessity of terminating an affected pregnancy for genetic parents who carry an affected gene or have balanced chromosomal status. Polymerase chain reaction-based molecular techniques are the methods used to detect gene defects with a known sequence and X-linked diseases. The indication for using this approach has expanded for couples who are prevented from having babies because they carry a serious genetic disorder to couples with conditions that are not immediately life threatening, such as cancer predisposition genes and Huntington disease. In addition, fluorescent in situ hybridization (FISH has been widely applied for the detection of chromosome abnormalities. FISH allows the evaluation of many chromosomes at the same time, up to 15 chromosome pairs in a single cell. Preimplantation genetic screening, defined as a test that screens for aneuploidy, has been most commonly used in situations of advanced maternal age, a history of recurrent miscarriage, a history of repeated implantation failure, or a severe male factor. Unfortunately, randomized controlled trials have as yet shown no benefit with respect to preimplantation genetic screening using cleavage stage biopsy, which is probably attributable to the high levels of mosaicism at early cleavage stages and the limitations of FISH. Recently, two main types of array-based technology combined with whole genome amplification have been developed for use in preimplantation genetic diagnosis; these are comparative genomic hybridization and single nucleotide polymorphism-based arrays. Both allow the analysis of all chromosomes, and the latter also allows
Swift, Oscar; Vilar, Enric; Rahman, Belinda; Side, Lucy; Gale, Daniel P
No recommendations currently exist regarding implementation of both prenatal diagnosis and preimplantation genetic diagnosis (PGD) for autosomal dominant polycystic kidney disease (ADPKD). This study evaluated attitudes in ADPKD patients with either chronic kidney disease (CKD) stages I-IV or end-stage renal failure (ESRF) toward prenatal diagnosis and PGD. Ninety-six ADPKD patients were recruited from an outpatient clinic, wards, and dialysis units. Thirty-eight patients had ESRF and 58 had CKD stages I-IV. Participants were given an information sheet on prenatal diagnosis and PGD and subsequently completed a questionnaire. The median age of participants was 51.5 years. Seventeen percent of ADPKD patients with CKD and 18% of ADPKD patients with ESRF would consider prenatal diagnosis and termination of pregnancy for ADPKD. Fifty percent with CKD would have opted for PGD (or might consider it in the future) were it available and funded by the UK National Health Service, compared to 63% in the ESRF group (p = 0.33). Sixty-nine percent in the CKD group and 68% in the ESRF group believed that PGD should be offered to other patients. There was a spectrum of attitudes among this cohort. A proportion of patients believe that PGD should be made available to prospective parents with this disease. The discrepancy between the low proportion (17% CKD, 18% ESRF) who would consider prenatal diagnosis and termination of pregnancy and the higher number who hypothetically express an intention or wish to access PGD (50% CKD and 63% ESRF) indicates far greater acceptability for diagnostic methods that occur before embryo implantation. It is not known how the development of methods to identify patients whose renal function is likely to decline rapidly and treatments altering the natural history of ADPKD will affect these attitudes.
Martin, Linda; Gitsels-van der Wal, Janneke T; Pereboom, Monique T R; Spelten, Evelien R; Hutton, Eileen K; van Dulmen, Sandra
This study focuses on facilitation of clients' psychosocial communication during prenatal counseling for fetal anomaly screening. We assessed how psychosocial communication by clients is related to midwives' psychosocial and affective communication, client-directed gaze and counseling duration. During 184 videotaped prenatal counseling consultations with 20 Dutch midwives, verbal psychosocial and affective behavior was measured by the Roter Interaction Analysis System (RIAS). We rated the duration of client-directed gaze. We performed multilevel analyses to assess the relation between clients' psychosocial communication and midwives' psychosocial and affective communication, client-directed gaze and counseling duration. Clients' psychosocial communication was higher if midwives' asked more psychosocial questions and showed more affective behavior (β=0.90; CI: 0.45-1.35; pcommunication was not related to midwives" client-directed gaze. Additionally, psychosocial communication by clients was directly, positively related to the counseling duration (β=0.59; CI: 0.20-099; p=0.004). In contrast with our expectations, midwives' client-directed gaze was not related with psychosocial communication of clients. In addition to asking psychosocial questions, our study shows that midwives' affective behavior and counseling duration is likely to encourage client's psychosocial communication, known to be especially important for facilitating decision-making. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Benn, Peter A
The acceptability of prenatal screening and diagnosis of Down syndrome is dependent, in part, on the gestational age at which the testing is offered. First trimester screening could be advantageous if it has sufficient efficacy and can be effectively delivered. Two first trimester maternal serum screening markers, pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG), are useful for identifying women at increased risk for fetal Down syndrome. In addition, measurement of an enlarged thickness of the subcutaneous fluid-filled space at the back of the neck of the developing fetus (referred to as nuchal translucency or NT) has been demonstrated to be an indicator for these high-risk pregnancies. When these three parameters are combined, estimates for Down syndrome efficacy exceed those currently attainable in the second trimester. Women who are screen-positive in the first trimester can elect to receive cytogenetic testing of a chorionic villus biopsy. The first trimester tests could also, theoretically, be combined with the second trimester maternal serum screening tests (integrated screening) to obtain even higher levels of efficacy. There are, however, several practical limitations to first trimester and integrated screening. These include scheduling of testing within relatively narrow gestational age intervals, availability of appropriately trained ultrasonographers for NT measurement, risks associated with chorionic villus biopsy, and costs. There is also increasing evidence that an enlarged NT measurement is indicative of a high risk for spontaneous abortion and for fetal abnormalities that are not detectable by cytogenetic analysis. Women whose fetuses show enlarged NT, therefore, need first trimester counseling regarding their Down syndrome risks and the possibility of other adverse pregnancy outcomes. Follow-up ultrasound and fetal echocardiography in the second trimester are also indicated. First trimester
Filoche, Sara; Cram, Fiona; Lawton, Bev; Beard, Angela; Stone, Peter
Non-invasive prenatal testing (NIPT) is a relatively new screen for congenital conditions - specifically, common fetal aneuploidies including Down Syndrome. The test is based on isolating freely circulating fragments of fetal-placental DNA that is present in the mother's blood. NIPT has a superior clinical performance compared to current screening, and has been available privately in Aotearoa New Zealand for the last 4 years. The proposed implementation of NIPT as a publicly funded service may widen the inequity in access to optional antenatal screening that already exists in this country. This paper discusses precautions that can be taken at the health system, organisation, and personnel levels to ensure that access to NIPT is equitable, that services are culturally responsive, and women's informed choice is promoted and protected. The adoption of NIPT into publicly funded services is an example of how genetic screening is becoming mainstreamed into health services; as such our approach may also have relevance around the introduction of other genetic and genomic screening initiatives.
Geraedts, Joep; Collins, John; Gianaroli, Luca; Goossens, Veerle; Handyside, Alan; Harper, Joyce; Montag, Markus; Repping, Sjoerd; Schmutzler, Andreas
Screening of human preimplantation embryos for numerical chromosome abnormalities has been conducted mostly at the preimplantation stage using fluorescence in situ hybridization. However, it is clear that preimplantation genetic screening (PGS) as it is currently practiced does not improve live
This paper focuses on the pre-natal genetic testing and reproductive decision-making around thalassaemia in China. Findings are based on fieldwork conducted in hospitals and research institutions, interviews with families with thalassaemia-affected children, interviews with geneticists and genetic
Lou, Stina; Petersen, Olav B.; Jørgensen, Finn Stener
INTRODUCTION: Denmark was the first country in the world to implement a national, free-for-all offer of prenatal screening for Down syndrome to all pregnant women. It has a high uptake (> 90%) compared to other countries. Thus, Denmark offers an interesting case for investigating the consequences...... of implementing a comprehensive, national prenatal screening guideline. The aim of this study was to describe the historical developments in invasive procedures, pre-/postnatal diagnoses of Down syndrome and Down syndrome live births in the period 1973-2016 in Denmark MATERIAL AND METHODS: Data on invasive...... procedures, pre- and postnatal Down syndrome diagnoses were retrieved from the Danish Cytogenetic Central Registry RESULTS: From 1973-1993 screening based on maternal age and high-risk indications resulted in a constant increase in invasive procedures. After the introduction of the triple test in 1994...
Zhao, Y; Edington, S; Fleenor, J; Sinkovskaya, E; Porche, L; Abuhamad, A
To compare prenatal findings, associated genetic anomalies and postnatal outcome in fetuses with tetralogy of Fallot (TOF) with normal cardiac axis (CAx) and those with abnormal CAx. In this retrospective cohort study, 85 cases diagnosed with TOF by prenatal ultrasound at our clinic between 2005 and 2015 were reviewed. Follow-up ultrasound and postnatal outcome were available for 68 cases. One case complicated with absent pulmonary valve syndrome and a further seven cases diagnosed postnatally with anomalies other than TOF were excluded from the study. The remaining 60 cases of postnatally confirmed TOF were divided according to CAx into two groups: those with normal CAx (n = 33) and those with abnormal CAx (n = 27). CAx was defined as the angle between the interventricular septum and midline of the fetal thorax at the level of the four-chamber view. CAx > 65° or < 25° was considered abnormal. Prenatal sonographic findings, associated genetic anomalies and postnatal outcome were compared between the two groups. Fetuses with TOF and abnormal CAx were more likely to have pulmonary atresia (40.7% vs 15.2%; P = 0.026) and right-sided aortic arch (48.1% vs 21.2%; P = 0.028) than those with normal CAx. Postnatal death occurred in 30.4% of infants with abnormal CAx vs 6.5% with normal CAx (P = 0.028). Incidence of tested genetic anomalies was similar between the two groups. In fetuses with TOF, abnormal CAx is associated with the presence of pulmonary atresia, right-sided aortic arch and a higher risk of postnatal death. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Fisher, Celia B
The pressing need for empirically informed public policies aimed at understanding and promoting children's health has challenged environmental scientists to modify traditional research paradigms and reevaluate their roles and obligations toward research participants. Methodologic approaches to children's environmental health research raise ethical challenges for which federal regulations may provide insufficient guidance. In this article I begin with a general discussion of privacy concerns and informed consent within pediatric environmental health research contexts. I then turn to specific ethical challenges associated with research on genetic determinants of environmental risk, prenatal studies and maternal privacy, and data causing inflicted insight or affecting the informational rights of third parties.
We used the Allin 2.0 GMO screening system from Biosmart, Switzerland to screen for the presence of genetically modified food sequences in maize meal samples, fresh fruit and vegetables from some retailers around Gaborone, Botswana. The Allin 2.0 is a multiplex PCR system for the detection of genetically modified ...
Wang, C-W; Hui, E C
With the progress in cancer genetics and assisted reproductive technologies, it is now possible for cancer gene mutation carriers not only to reduce cancer mortality through the targeting of surveillance and preventive therapies, but also to avoid the birth of at-risk babies through the choice of different means of reproduction. Thus, the incidence of hereditary cancer syndromes may be decreased in the future. The integration of cancer genetic testing and assisted reproductive technologies raises certain ethical, legal and social issues beyond either genetic testing or assisted reproductive technology itself. In this paper, the reproductive decisions/choices of at-risk young couples and the ethical, legal and social concerns of prenatal genetic testing and preimplantation genetic diagnosis for susceptibility to hereditary cancer syndromes are discussed. Specifically, three ethical principles related to the integration of cancer genetic testing and assisted reproductive technologies, i.e. informed choice, beneficence to children and social justice, and their implications for the responsible translation of these medical techniques into common practice of preventive medicine are highlighted.
Full Text Available In up to 5% of pregnancies, ultrasound screening detects a "soft marker" (SM that places the foetus at risk for a severe abnormality. In most cases, prenatal diagnostic work-up rules out a severe defect. We aimed to study the effects of false positive SM on maternal emotional status, maternal representations of the infant, and mother-infant interaction.Utilizing an extreme-case prospective case control design, we selected from a group of 244 women undergoing ultrasound, 19 pregnant women whose foetus had a positive SM screening and a reassuring diagnostic work up, and 19 controls without SM matched for age and education. In the third trimester of pregnancy, within one week after delivery, and 2 months postpartum, we assessed anxiety, depression, and maternal representations. Mother-infant interactions were videotaped during feeding within one week after delivery and again at 2 months postpartum and coded blindly using the Coding Interactive Behavior (CIB scales. Anxiety and depression scores were significantly higher at all assessment points in the SM group. Maternal representations were also different between SM and control groups at all study time. Perturbations to early mother-infant interactions were observed in the SM group. These dyads showed greater dysregulation, lower maternal sensitivity, higher maternal intrusive behaviour and higher infant avoidance. Multivariate analysis showed that maternal representation and depression at third trimester predicted mother-infant interaction.False positive ultrasound screenings for SM are not benign and negatively affect the developing maternal-infant attachment. Medical efforts should be directed to minimize as much as possible such false diagnoses, and to limit their psychological adverse consequences.
Sui, Suli; Sleeboom-Faulkner, Margaret
This paper focuses on the pre-natal genetic testing and reproductive decision-making around thalassaemia in China. Findings are based on fieldwork conducted in hospitals and research institutions, interviews with families with thalassaemia-affected children, interviews with geneticists and genetic researchers and a literature review conducted between September and November 2007. The paper aims to provide insight into the ways in which those who carry thalassaemia decide to have a test for the condition and the choices available to prospective parents. The paper also analyses factors affecting reproductive choices and the decision to produce a 'saviour sibling', including financial implications, state family planning policy, images and information conveyed through the media and propaganda, advice and counselling from doctors, psychological pressure from the community and social discrimination. The paper concludes with a discussion on the issues involved in the creation of saviour siblings, some of which are particular to China.
Forum T. Shah
Full Text Available Until recently, maternal serum analyte levels paired with sonographic fetal nuchal translucency measurement was the most accurate prenatal screen available for Trisomies 18 and 21, (91% and 94% detection and false positive rates of 0.31% and 4.5% respectively. Women with positive California Prenatal Screening Program (CPSP results have the option of diagnostic testing to determine definitively if the fetus has a chromosomal abnormality. Cell-free fetal (cff- DNA screening for Trisomies 13, 18, and 21 was first offered in 2012, allowing women with positive screens to choose additional screening before diagnostic testing. Cff-DNA sensitivity rates are as high as 99.9% and 99.1%, with false positive rates of 0.4% and 0.1%, for Trisomies 18 and 21, respectively. A retrospective chart review was performed in 2012 on 500 CPSP referrals at the University of California, San Diego Thornton Hospital. Data were collected prior to and after the introduction of cff-DNA. There was a significant increase in the number of participants who chose to pursue additional testing and a decrease in the number of invasive procedures performed after cff-DNA screening was available. We conclude that as fetal aneuploidy screening improves, the number of invasive procedures will continue to decrease.
Gardiner, Helena M; Kovacevic, Alexander; van der Heijden, Laila B; Pfeiffer, Patricia W; Franklin, Rodney Cg; Gibbs, John L; Averiss, Ian E; Larovere, Joan M
Determine maternity hospital and lesion-specific prenatal detection rates of major congenital heart disease (mCHD) for hospitals referring prenatally and postnatally to one Congenital Cardiac Centre, and assess interhospital relative performance (relative risk, RR). We manually linked maternity data (3 hospitals prospectively and another 16 retrospectively) with admissions, fetal diagnostic and surgical cardiac data from one Congenital Cardiac Centre. This Centre submits verified information to National Institute for Cardiovascular Outcomes Research (NICOR-Congenital), which publishes aggregate antenatal diagnosis data from infant surgical procedures. We included 120 198 unselected women screened prospectively over 11 years in 3 maternity hospitals (A, B, C). Hospital A: colocated with fetal medicine, proactive superintendent, on-site training, case-review and audit, hospital B: on-site training, proactive superintendent, monthly telemedicine clinics, and hospital C: sonographers supported by local obstetrician. We then studied 321 infants undergoing surgery for complete transposition (transposition of the great arteries (TGA), n=157) and isolated aortic coarctation (CoA, n=164) screened in hospitals A, B, C prospectively, and 16 hospitals retrospectively. 385 mCHD recorded prospectively from 120 198 (3.2/1000) screened women in 3 hospitals. Interhospital relative performance (RR) in Hospital A:1.68 (1.4 to 2.0), B:0.70 (0.54 to 0.91), C:0.65 (0.5 to 0.8). Standardised prenatal detection rates (funnel plots) demonstrating inter-hospital variation across 19 hospitals for TGA (37%, 0.00 to 0.81) and CoA (34%, 0.00 to 1.06). Manually linking data sources produced hospital-specific and lesion-specific prenatal mCHD detection rates. More granular, rather than aggregate, data provides meaningful feedback to improve screening performance. Automatic maternal and infant record linkage on a national scale, requires verified, prospective maternity audit and integration of
Bozdar, M.; Hanif, T.B.
To compare the response towards prenatal diagnosis (PND) of b-thalassaemia, in individuals who had not received genetic counselling and a genetically counselled population. Study Design: Cross-sectional survey. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from March 2009 to December 2010. Methodology: Using non-probability consecutive sampling, a total of 176 individuals having thalassaemic children, were interviewed regarding PND of thalassaemia, by using a structured questionnaire. Forty two individuals were taken as controls as they had received genetic counselling for PND, whereas the remaining 134 were taken as cases. Responses towards PND were compared using chi-square test. Odds ratio was also calculated for subsequent PND utilization. Results: Seventy (52.2%) cases and 42 (100%) controls were aware of the availability of PND in Pakistan. This difference in awareness was statistically significant (p < 0.001). In the controls, 40 (95.3%) individuals were aware of the appropriate timing of the test, in contrast to 52 (39%) cases (p < 0.001). PND was used in subsequent pregnancies by 50 (37.3%) cases and 32 (80%) controls (p < 0.001). The calculated odds ratio for subsequent PND utilization was 5.37. Conclusion: The study reflects a very positive attitude of genetically counselled thalassaemia affected families towards PND. For better utilization of PND, genetic counselling services should be available at all health strata. (author)
Eastwood, Ashley; Webster, Dianne; Taylor, Juliet; Mckay, Richard; McEwen, Alison; Sullivan, Jan; Pope-Couston, Rachel; Stone, Peter
To gauge clinical opinion about the current system and possible changes as well as providing a forum for education about Non-Invasive Prenatal Testing (NIPT). A series of workshops for doctors and midwives, supported by the National Screening Unit of the Ministry of Health and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, were held in the main centres of New Zealand. Following a brief education session, a structured evaluation of current screening and future possibilities was undertaken by questionnaire. One hundred and eight maternity carers participated in 5 workshops. Over 40% identified barriers to current screening. More than 60% would support NIPT in the first trimester. The majority of carers provided their own counselling support for women. The survey has shown general enthusiasm for the introduction of publically funded NIPT into prenatal screening in New Zealand. Barriers to utilisation of the current system have been identified and enhancements to screening performance with guidelines around conditions to be screened for would be supported.
S. S. Deryabina
Full Text Available The article considers philosophical questions of neonatal screening technology. The main focus is on ethical and methodological issues that inevitably arise when expanding the number of scanned nosologies and applying genetic research methods. Questions concerning the existing discrepancy between technical capacity and the practical level of healthcare delivery and the probabilistic nature of results obtained by molecular testing are analyzed in terms of methodology. Access to information about the DNA-testing of newborns and the linkage between neonatal screening and prenatal diagnostics are among the most topical ethical problems raised within this article. One of the purposes of this article is to draw the attention of the public — especially it concerns current and prospective parents and volunteer organizations — to these contemporary problems.
Kang, M Agnes; Zayts, Olga A
In this paper, we examine the interactional means by which non-native English speaking patients in Hong Kong participate in prenatal screening sessions. Using interactional sociolinguistics as the theoretical framework, we apply the concept of contextualization cues to illustrate that patients indicate their participation in the consultation through verbal and non-verbal modes. We find that non-native English speaking patients participate: (1) by displaying the interactional difficulties they are encountering and (2) by coordinating their displays of interactional difficulties with the activities of the healthcare provider. We conclude that the notion of patient participation must be expanded to take into account non-native speaking contexts; in particular, that collaborative displays of knowledge (or lack thereof) must be included as part of the definition of patient participation. While verbal contributions represent an important mode of participation in consultations, patients also participate by contextualizing their lack of understanding, which then can serve as a resource to healthcare providers in pursuing meaningful consultations. Our analysis illustrates how health care professionals' awareness of the modes of patient participation and what these modes may signal in non-native consultations can help to establish what the patient knows in the consultation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Vintzileos, A M; Ananth, C V; Fisher, A J; Smulian, J C; Day-Salvatore, D; Beazoglou, T; Knuppel, R A
The objective of this study was to perform an economic evaluation of second-trimester genetic ultrasonography for prenatal detection of Down syndrome. More specifically, we sought to determine the following: (1) the diagnostic accuracy requirements (from the cost-benefit point of view) of genetic ultrasonography versus genetic amniocentesis for women at increased risk for fetal Down syndrome and (2) the possible economic impact of second-trimester genetic ultrasonography for the US population on the basis of the ultrasonographic accuracies reported in previously published studies. A cost-benefit equation was developed from the hypothesis that the cost of universal genetic amniocentesis of patients at increased risk for carrying a fetus with Down syndrome should be at least equal to the cost of universal genetic ultrasonography with amniocentesis used only for those with abnormal ultrasonographic results. The main components of the equation included the diagnostic accuracy of genetic ultrasonography (sensitivity and specificity for detecting Down syndrome), the costs of the amniocentesis package and genetic ultrasonography, and the lifetime cost of Down syndrome cases not detected by the genetic ultrasonography. After appropriate manipulation of the equation a graph was constructed, representing the balance between sensitivity and false-positive rate of genetic ultrasonography; this was used to examine the accuracy of previously published studies from the cost-benefit point of view. Sensitivity analyses included individual risks for Down syndrome ranging from 1:261 (risk of a 35-year-old at 18 weeks' gestation) to 1:44 (risk of a 44-year-old at 18 weeks' gestation). This economic evaluation was conducted from the societal perspective. Genetic ultrasonography was found to be economically beneficial only if the overall sensitivity for detecting Down syndrome was >74%. Even then, the cost-benefit ratio depended on the corresponding false-positive rate. Of the 7
Hercher, Laura; Uhlmann, Wendy R; Hoffman, Erin P; Gustafson, Shanna; Chen, Kelly M
Advances in genetic testing and the availability of such testing in pregnancy allows prospective parents to test their future child for adult-onset conditions. This ability raises several complex ethical issues. Prospective parents have reproductive rights to obtain information about their fetus. This information may or may not alter pregnancy management. These rights can be in conflict with the rights of the future individual, who will be denied the right to elect or decline testing. This paper highlights the complexity of these issues, details discussions that went into the National Society of Genetic Counselors (NSGC) Public Policy Task Force's development of the Prenatal testing for Adult-Onset Conditions position statement adopted in November 2014, and cites relevant literature on this topic through December 2015. Issues addressed include parental rights and autonomy, rights of the future child, the right not to know, possible adverse effects on childhood and the need for genetic counseling. This paper will serve as a reference to genetic counselors and healthcare professionals when faced with this situation in clinical practice.
Ozge Ozalp Yuregir
Full Text Available Prenatal diagnosis is the process of determining the health or disease status of the fetus or embryo before birth. The purpose is early detection of diseases and early intervention when required. Prenatal genetic tests comprise of cytogenetic (chromosome assessment and molecular (DNA mutation analysis tests. Prenatal testing enables the early diagnosis of many diseases in risky pregnancies. Furthermore, in the event of a disease, diagnosing prenatally will facilitate the planning of necessary precautions and treatments, both before and after birth. Upon prenatal diagnosis of some diseases, termination of the pregnancy could be possible according to the family's wishes and within the legal frameworks. [Archives Medical Review Journal 2012; 21(1.000: 80-94
McDougall, William M; Perreira, Jill M; Reynolds, Erin C; Brass, Abraham L
Viruses impose an immense burden on human health. With the goal of treating and preventing viral infections, researchers have carried out genetic screens to improve our understanding of viral dependencies and identify potential anti-viral strategies. The emergence of CRISPR genetic screening tools has facilitated this effort by enabling host-virus screens to be undertaken in a more versatile and fidelitous manner than previously possible. Here we review the growing number of CRISPR screens which continue to increase our understanding of host-virus interactions. Copyright © 2018 Elsevier B.V. All rights reserved.
Stajner, Tijana; Bobic, Branko; Klun, Ivana; Nikolic, Aleksandra; Srbljanovic, Jelena; Uzelac, Aleksandra; Rajnpreht, Irena; Djurkovic-Djakovic, Olgica
Abstract To determine the risk of congenital toxoplasmosis (CT) and provide early (pre- or postnatal) identification of cases of CT in the absence of systematic screening in pregnancy. In the presented cross-sectional study, serological criteria were used to date Toxoplasma gondii infection versus conception in 80 pregnant women with fetal abnormalities or referred to as suspected of acute infection, and in 16 women after delivery of symptomatic neonates. A combination of serological, molecular (qPCR), and biological (bioassay) methods was used for prenatal and/or postnatal diagnosis of CT. Most (77.5%) pregnant women were examined in advanced pregnancy. Of all the examined seropositive women (n = 90), infection could not be ruled out to have occurred during pregnancy in 93.3%, of which the majority (69%) was dated to the periconceptual period. CT was diagnosed in 25 cases, of which 17 prenatally and 8 postnatally. Molecular diagnosis proved superior, but the diagnosis of CT based on bioassay in 7 instances and by Western blot in 2 neonates shows that other methods remain indispensable. In the absence of systematic screening in pregnancy, maternal infection is often diagnosed late, or even only when fetal/neonatal infection is suspected. In such situations, use of a complex algorithm involving a combination of serological, biological, and molecular methods allows for prenatal and/or early postnatal diagnosis of CT, but lacks the preventive capacity provided by early maternal treatment. PMID:26945416
Harvey J. Stern
Full Text Available Preimplantation genetic diagnosis was developed nearly a quarter-century ago as an alternative form of prenatal diagnosis that is carried out on embryos. Initially offered for diagnosis in couples at-risk for single gene genetic disorders, such as cystic fibrosis, spinal muscular atrophy and Huntington disease, preimplantation genetic diagnosis (PGD has most frequently been employed in assisted reproduction for detection of chromosome aneuploidy from advancing maternal age or structural chromosome rearrangements. Major improvements have been seen in PGD analysis with movement away from older, less effective technologies, such as fluorescence in situ hybridization (FISH, to newer molecular tools, such as DNA microarrays and next generation sequencing. Improved results have also started to be seen with decreasing use of Day 3 blastomere biopsy in favor of polar body or Day 5 trophectoderm biopsy. Discussions regarding the scientific, ethical, legal and social issues surrounding the use of sequence data from embryo biopsy have begun and must continue to avoid concern regarding eugenic or inappropriate use of this technology.
Stern, Harvey J.
Preimplantation genetic diagnosis was developed nearly a quarter-century ago as an alternative form of prenatal diagnosis that is carried out on embryos. Initially offered for diagnosis in couples at-risk for single gene genetic disorders, such as cystic fibrosis, spinal muscular atrophy and Huntington disease, preimplantation genetic diagnosis (PGD) has most frequently been employed in assisted reproduction for detection of chromosome aneuploidy from advancing maternal age or structural chromosome rearrangements. Major improvements have been seen in PGD analysis with movement away from older, less effective technologies, such as fluorescence in situ hybridization (FISH), to newer molecular tools, such as DNA microarrays and next generation sequencing. Improved results have also started to be seen with decreasing use of Day 3 blastomere biopsy in favor of polar body or Day 5 trophectoderm biopsy. Discussions regarding the scientific, ethical, legal and social issues surrounding the use of sequence data from embryo biopsy have begun and must continue to avoid concern regarding eugenic or inappropriate use of this technology. PMID:26237262
Timms, Richard T.; Menzies, Sam A.; Tchasovnikarova, Iva A.
The application of forward genetic screens to cultured human cells represents a powerful method to study gene function. The repurposing of the bacterial CRISPR/Cas9 system provides an effective method to disrupt gene function in mammalian cells, and has been applied to genome-wide screens. Here, we...... compare the efficacy of genome-wide CRISPR/Cas9-mediated forward genetic screens versus gene-trap mutagenesis screens in haploid human cells, which represent the existing ‘gold standard’ method. This head-to-head comparison aimed to identify genes required for the endoplasmic reticulum....../3-associated disulphide reductase. Genome-wide CRISPR/Cas9-mediated screens together with haploid genetic screens provide a powerful addition to the forward genetic toolbox....
Epidemiologists and geneticists claim that genetics has an increasing role to play in public health policies and programs in the future. Within this perspective, genetic testing and screening are instrumental in avoiding the birth of children with serious, costly or untreatable disorders. This paper
Smeets, Hubert J M; Sallevelt, Suzanne C E H; Dreesen, Jos C F M; de Die-Smulders, Christine E M; de Coo, Irenaeus F M
Mitochondrial disorders are among the most common inborn errors of metabolism; at least 15% are caused by mitochondrial DNA (mtDNA) mutations, which occur de novo or are maternally inherited. For familial heteroplasmic mtDNA mutations, the mitochondrial bottleneck defines the mtDNA mutation load in offspring, with an often high or unpredictable recurrence risk. Oocyte donation is a safe option to prevent the transmission of mtDNA disease, but the offspring resulting from oocyte donation are genetically related only to the father. Prenatal diagnosis (PND) is technically possible but usually not applicable because of limitations in predicting the phenotype. For de novo mtDNA point mutations, recurrence risks are low and PND can be offered to provide reassurance regarding fetal health. PND is also the best option for female carriers with low-level mutations demonstrating skewing to 0% or 100%. A fairly new option for preventing the transmission of mtDNA diseases is preimplantation genetic diagnosis (PGD), in which embryos with a mutant load below a mutation-specific or general expression threshold of 18% can be transferred. PGD is currently the best reproductive option for familial heteroplasmic mtDNA point mutations. Nuclear genome transfer and genome editing techniques are currently being investigated and might offer additional reproductive options for specific mtDNA disease cases. © 2015 New York Academy of Sciences.
Bhogal, Ashvinder K; Brunger, Fern
To help family physicians practise effective genetic counseling and offer practical strategies for cross-cultural communication in the context of prenatal genetic counseling. PubMed and the Cochrane Database of Systematic Reviews were searched. Most evidence was level II and some was level III. The values and beliefs of practitioners, no less than those of patients, are shaped by culture. In promoting a patient's best interest, the assumptions of both the patient and the provider must be held up for examination and discussed in the attempt to arrive at a consensus. Through the explicit discussion and formation of trust, the health professionals, patients, and family members who are involved can develop a shared understanding of appropriate therapeutic goals and methods. Reflecting on the cultural nature of biomedicine's ideas about risk, disability, and normality helps us to realize that there are many valid interpretations of what is in a patient's best interest. Self-reflection helps to ensure that respectful communication with the specific family and patient is the basis for health care decisions. Overall, this helps to improve the quality of care.
Full Text Available This chapter is an overview of the current status of the law in the United States regarding prenatal genetic testing with an emphasis on issues related to professional liability and other challenges affecting patient access to prenatal genetic testing. The chapter discusses the roles that federal regulations, promulgated by the Centers for Medicare and Medicaid Services (CMS, the Food and Drug Administration (FDA and the Federal Trade Commission (FTC, play in the regulation of prenatal genetic tests. The chapter discusses tort litigation based on allegations of malpractice in the provision of prenatal genetic testing and how courts have analyzed issues related to causation, damages and mitigation of damages. The chapter provides reference information regarding how individual states address causes of action under the tort theories of wrongful birth and wrongful life. The chapter concludes with a discussion of future legal issues that may affect clinical prenatal genetic testing services arising from the continued expansion of prenatal genetic testing, legal restrictions on access to abortion and the potential development of embryonic treatments.
Ferry, P; Massias, C; Salzard, C; Anguill, C; Olleac, A; Quentin, M
We report a case of isolated truncus arteriosis diagnosed prenatally which recurred during a subsequent pregnancy. This observation would suggest an increased risk of recurrent single trunk malformation as compared with other congenital heart diseases, in agreement with our understanding of the genetic processes involved. A prenatal screening can be achieved with a systematic examination of the fetal morphology. Prognosis is severe and prenatal diagnosis is difficult.
Boyd, P A; Devigan, C; Khoshnood, B
tube defects (NTDs) using the EUROCAT database. MAIN OUTCOME MEASURES: Existence of national prenatal screening policies, legal gestation limit for TOPFA, prenatal detection and termination rates for Down's syndrome and NTD. RESULTS: Ten of the 18 countries had a national country-wide policy for Down...... cases. Six of the 18 countries had a legal gestational age limit for TOPFA, and in two countries, termination of pregnancy was illegal at any gestation. CONCLUSIONS: There are large differences in screening policies between countries in Europe. These, as well as organisational and cultural factors...
Hamilton, Jada G.; Edwards, Heather M.; Khoury, Muin J.; Taplin, Stephen H.
The long-standing medical tradition to “first do no harm” is reflected in population-wide evidence-based recommendations for cancer screening tests that focus primarily on reducing morbidity and mortality. The conventional cancer screening process is predicated on finding early-stage disease that can be treated effectively; yet emerging genetic and genomic testing technologies have moved the target earlier in the disease development process to identify a probabilistic predisposition to diseas...
Bart A Ellenbroek
Full Text Available There is ample evidence that prenatal exposure to valproate (or valproic acid, VPA enhances the risk of developing Autism Spectrum Disorders (ASD. In line with this, a single injection of VPA induces a multitude of ASD-like symptoms in animals such as rats and mice. However, there is equally strong evidence that genetic factors contribute significantly to the risk of ASD and indeed, like most other psychiatric disorders, ASD is now generally thought to results from an interaction between genetic and environmental factors. Given that VPA significantly impacts on the serotonergic system, and serotonin has strong biochemical and genetic links to ASD, we aimed to investigate the interaction between genetic reduction in the serotonin transporter and prenatal valproate administration. More specifically, we exposed both wildtype (SERT+/+ rats and rats heterozygous for the serotonin transporter deletion (SERT+/- to a single injection of 400 mg/kg VPA at gestational day (GD 12. The offspring, in adulthood, was assessed in four different tests: Elevated Plus Maze and Novelty Suppressed Feeding as measures for anxiety and prepulse inhibition (PPI and latent inhibition as measures for cognition and information processing. The results show that prenatal VPA significantly increased anxiety in both paradigm, reduced PPI and reduced conditioning in the latent inhibition paradigm. However, we failed to find a significant gene – environment interaction. We propose that this may be related to the timing of the VPA injection and suggest that whereas GD12 might be optimal for affecting normal rat, rats with a genetically compromised serotonergic system may be more sensitive to VPA at earlier time points during gestation. Overall our data are the first to investigate gene * environmental interactions in a genetic rat model for ASD suggest that timing may be of crucial importance to the long-term outcome.
Pivetti, Monica; Montali, Lorenzo; Simonetti, Giorgia
This study explores the underlying values and beliefs that guide women's reasoning on prenatal genetic test (PGT) uptake, as framed by their own words, during a group discussion, in a Catholic country such as Italy. Women's reasoning was explored by means of five focus group consisting of seven pregnant women and 13 new mothers. The focus group material content was analysed using the Nudist software. The discourse around PGT was rooted into four frames of reference: The usefulness dimension was used to express the positions in favour of PGT, whereas morality, risk and trust were used to express negative evaluations on such a technology. Participants advocated for themselves the choice of being tested, besides giving some credit to the partner's opinion. Moreover, participants reported little knowledge on PGT. The research shed some light on the frames of reference used by participants to build their positions on PGT uptake, confirming the public's ability to translate scientific accounts into personally meaningful information. A more complete understanding of the reasons for decisions to test would help counsellors to better communicate with women and couples, and to better assist them to make a better informed testing decision. © 2012 John Wiley & Sons, Ltd.
Full Text Available The incidence of inborn errors of metabolisms (IEMs varies dramatically in different countries and regions. Expanded newborn screening for IEMs by tandem mass spectrometry (MS/MS is an efficient approach for early diagnosis and presymptomatic treatment to prevent severe permanent sequelae and death. To determine the characteristics of IEMs and IEMs-associated mutations in newborns in Jining area, China, 48,297 healthy neonates were recruited for expanded newborn screening by MS/MS. The incidence of IEMs was 1/1178 in Jining, while methylmalonic acidemia, phenylketonuria, and primary carnitine deficiency ranked the top 3 of all detected IEMs. Thirty mutations in nine IEMs-associated genes were identified in 28 confirmed cases. As 19 cases with the mutations in phenylalanine hydroxylase (PAH, solute carrier family 22 member 5 (SLC22A5, and methylmalonic aciduria (cobalamin deficiency cblC type with homocystinuria (MMACHC genes, respectively, it suggested that mutations in the PAH, SLC22A5, and MMACHC genes are the predominant causes of IEMs, leading to the high incidence of phenylketonuria, primary carnitine deficiency, and methylmalonic acidemia, respectively. Our work indicated that the overall incidence of IEMs is high and the mutations in PAH, SLC22A5, and MMACHC genes are the leading causes of IEMs in Jining area. Therefore, it is critical to increase the coverage of expanded newborn screening by MS/MS and prenatal genetic consulting in Jining area.
Yanet Hernández Triguero
Full Text Available Introducción: la creación de centros para el desarrollo de la Genética comunitaria, en todos los municipios del país, ha hecho posible el incremento de la cobertura de atención de los servicios de genética médica en la atención primaria. Objetivo: evaluar los resultados obtenidos en el funcionamiento prenatal del Programa Cubano de Diagnóstico, Manejo y Prevención de Enfermedades Genéticas y Defectos Congénitos. Material y métodos: se realizó un estudio descriptivo, retrospectivo y de corte longitudinal que incluyó el total de gestantes captadas desde el 1ro. de enero de 2007 hasta el 31 de diciembre de 2011, en el municipio La Palma. Resultados: de 2016 gestantes, el 51.7% fueron clasificadas como riesgo genético incrementado. En este grupo, la adolescencia (29.4% y la edad materna avanzada (15.8% fueron los principales factores de riesgo genético encontrados. Se realizaron 1720 exámenes de ecografía, entre las 11 y 13.6 semanas, examen que logra una cobertura del 94.8%. Se detectaron 47 portadoras de hemoglobina AS o AC. Se determinó el valor de la alfafetoproteína en suero materno, el 7.1 % mostró cifras elevadas y la amenaza de aborto constituyó la primera causa de esta alteración. Se diagnosticaron prenatalmente, por ecografía del segundo trimestre, 20 gestantes que presentaron fetos con defectos congénitos, lográndose una cobertura de 99,5%. Conclusiones: el enfoque comunitario de la genética y el trabajo coordinado con la atención primaria de salud permiten confeccionar estrategias dirigidas al control y disminución de los riesgos de defectos congénitos y enfermedades comunes en la población.Introduction: the creation of centers to the development of community genetics all over the municipalities of the country has made possible an increased coverage of medical genetics services in Primary Health Care. Objective: to assess the results obtained in the establishment of Cuban Prenatal Diagnosis, Management and
Kujat, Annegret; Veith, Veit-Peter; Faber, Renaldo; Froster, Ursula G
Waardenburg syndrome type I (WS I) is an autosomal dominant inherited disorder with an incidence of 1:45,000 in Europe. Mutations within the PAX3 gene are responsible for the clinical phenotype ranging from mild facial features to severe malformations detectable in prenatal diagnosis. Here, we report a four-generation family with several affected members showing various symptoms of WS I. We diagnosed the syndrome first in a pregnant young woman; she was referred because of a spina bifida in prenatal diagnosis. We performed clinical genetic investigations and molecular genetic analysis in all available family members. The phenotype displays a wide intra-familial clinical variability of pigmentary disturbances, facial anomalies and developmental defects. Molecular studies identified a novel splice site mutation within the PAX3 gene in intron 5 in all affected family members, but in none of the unaffected relatives. This case demonstrates the prenatal diagnosis of spina bifida in a fetus which leads to the initial diagnosis of WS I. Further studies could identify a private splice site mutation within the PAX3 gene responsible for the phenotype in this family.
Shao, Yunru; Liu, Shuling; Grinzaid, Karen
Improvements in genetic testing technologies have led to the development of expanded carrier screening panels for the Ashkenazi Jewish population; however, there are major inconsistencies in current screening practices. A 2-year pilot program was launched in Atlanta in 2010 to promote and facilitate screening for 19 Jewish genetic diseases. We analyzed data from this program, including participant demographics and outreach efforts. This retrospective analysis is based on a de-identified dataset of 724 screenees. Data were obtained through medical chart review and questionnaires and included demographic information, screening results, response to outreach efforts, and follow-up behavior and preferences. We applied descriptive analysis, chi-square tests, and logistic regression to analyze the data and compare findings with published literature. The majority of participants indicated that they were not pregnant or did not have a partner who was pregnant were affiliated with Jewish organizations and reported 100 % AJ ancestry. Overall, carrier frequency was 1 in 3.9. Friends, rabbis, and family members were the most common influencers of the decision to receive screening. People who were older, had a history of pregnancy, and had been previously screened were more likely to educate others (all p influencers who then encouraged screening in the target population. Educating influencers and increasing overall awareness were the most effective outreach strategies.
Notch signaling controls a wide range of developmental processes, including proliferation, apoptosis, and cell fate specification during both development and adult tissue homeostasis. The functional versatility of the Notch signaling pathway is tightly linked with the complexity of its regulation in different cellular contexts. To unravel the complexity of Notch signaling, it is important to identify the different components of the Notch signaling pathway. A powerful strategy to accomplish this task is based on genetic screens. Given that the developmental context of signaling is important, these screens should be customized to specific cell populations or tissues. Here, I describe how to perform F1 clonal forward genetic screens in Drosophila to identify novel components of the Notch signaling pathway. These screens combine a classical EMS (ethyl methanesulfonate) chemical mutagenesis protocol along with clonal analysis via FRT-mediated mitotic recombination. These F1 clonal screens allow rapid phenotypic screening within clones of mutant cells induced at specific developmental stages and in tissues of interest, bypassing the pleiotropic effects of isolated mutations. More importantly, since EMS mutations have been notoriously difficult to map to specific genes in the past, I briefly discuss mapping methods that allow rapid identification of the causative mutations.
Delanoë, Agathe; Lépine, Johanie; Leiva Portocarrero, Maria Esther; Robitaille, Hubert; Turcotte, Stéphane; Lévesque, Isabelle; Wilson, Brenda J; Giguère, Anik M C; Légaré, France
It has been suggested that health literacy may impact the use of decision aids (DAs) among patients facing difficult decisions. Embedded in the pilot test of a questionnaire, this study aimed to measure the association between health literacy and pregnant women's intention to use a DA to decide about prenatal screening. We recruited a convenience sample of 45 pregnant women in three clinical sites (family practice teaching unit, birthing center and obstetrical ambulatory care clinic). We asked participating women to complete a self-administered questionnaire assessing their intention to use a DA to decide about prenatal screening and assessed their health literacy levels using one subjective and two objective scales. Two of the three scales discriminated between levels of health literacy (three numeracy questions and three health literacy questions). We found a positive correlation between pregnant women's intention to use a DA and subjective health literacy (Spearman coefficient, Rho 0.32, P = 0.04) but not objective health literacy (Spearman coefficient, Rho 0.07, P = 0.65). Hence subjective health literacy may affect the intention to use a DA among pregnant women facing a decision about prenatal screening. Special attention should be given to pregnant women with lower health literacy levels to increase their intention to use a DA and ensure that every pregnant women can give informed and value-based consent to prenatal screening.
Spyridou, Andria; Schauer, Maggie; Ruf-Leuschner, Martina
Prenatal stress and other prenatal risk factors (e.g. intimate partner violence) have a negative impact on mother's health, fetal development as well as enduring adverse effects on the neuro-cognitive, behavioral and physical health of the child. Mothers of low socio-economic status and especially those living in crime-ridden areas are even more exposed to a host of risk factors. Societies of extreme violence, poverty and inequalities, often present difficulties to provide adequate mental health care to the most needed populations. The KINDEX, a brief standardized instrument that assesses 11 different risk factors was used by midwives to identify pregnant women at-risk, in a suburban area with one of the highest levels of domestic violence in Lima. The instrument was designed to be used by medical staff to identify high-risk child-bearing women and, based on the results, to refer them to the adequate psychological or social support providers. The aim of this study is to assess the feasibility of psychosocial screening using the KINDEX in a Latin American Country for the first time, and to explore the relationship of the KINDEX with thee major risk areas, maternal psychopathology, perceived stress and traumatic experiences. The study was conducted in cooperation with the gynecological department of a general hospital in a suburban area of Lima. Nine midwives conducted interviews using the KINDEX of ninety-five pregnant women attending the gynecological unit of the hospital. From these, forty pregnant women were re-interviewed by a clinical psychologist using established instruments in order to assess the feasibility of the prenatal assessment in public health settings and the relationship of the KINDEX with maternal perceived stress, psychopathology symptoms and trauma load during pregnancy. We found high rates of risk factors in the examined pregnant women comparable with those found in the general population. Significant correlations were found between the KINDEX
Wallon, M; Peyron, F; Cornu, C; Vinault, S; Abrahamowicz, M; Kopp, C Bonithon; Binquet, C
Toxoplasma infection during pregnancy exposes the fetus to risks of congenital infection and sequelae that depend heavily on gestational age (GA) at time of infection. Accurate risk estimates by GA are necessary to counsel parents and improve clinical decisions. We analyzed data from pregnant women diagnosed with acute Toxoplasma infection in Lyon (France) from 1987 to 2008 and assessed how the risks of congenital toxoplasmosis and of clinical signs at age 3 years vary depending on GA at the time of maternal infection. Among 2048 mother-infant pairs, 93.2% of mothers received prenatal treatment and 513 (24.7%) fetuses were infected. Because of a significant reduction in risk since 1992 when monthly screening was introduced (59.4% vs 46.6% at 26 GA weeks; P = .038), probabilities of infection were estimated on the basis of maternal infections diagnosed after mid-1992 (n = 1624). Probabilities of congenital infection were <10% for maternal infections before 12 weeks of gestation, rose to 20.0% at 19 weeks, and then continued increasing to 52.3% and almost 70% at 28 and 39 GA weeks, respectively. Because of a significant reduction in risk of clinical signs of congenital toxoplasmosis in infected children born from mothers diagnosed after 1995 when polymerase chain reaction testing on amniotic fluid was initiated (87/794 vs 46/1150; P = .012), probabilities of clinical signs at 3 years were estimated based on 1015 maternal infections diagnosed after 1995 including 207 infected children, with symptoms in 46 (22.2%). These analyses demonstrated that introduction of monthly prenatal screening and improvement in antenatal diagnosis were associated with a significant reduction in the rate of congenital infection and a better outcome at 3 years of age in infected children. Our updated estimates will improve individual management and counseling in areas where genotype II Toxoplasma is predominant.
Arjunan, Aishwarya; Litwack, Karen; Collins, Nick; Charrow, Joel
The Center for Jewish Genetics provides genetic education and carrier screening to individuals of Jewish descent. Carrier screening has traditionally been performed by targeted mutation analysis for founder mutations with an enzyme assay for Tay-Sachs carrier detection. The development of next-generation sequencing (NGS) allows for higher detection rates regardless of ethnicity. Here, we explore differences in carrier detection rates between genotyping and NGS in a primarily Jewish population. Peripheral blood samples or saliva samples were obtained from 506 individuals. All samples were analyzed by sequencing, targeted genotyping, triplet-repeat detection, and copy-number analysis; the analyses were carried out at Counsyl. Of 506 individuals screened, 288 were identified as carriers of at least 1 condition and 8 couples were carriers for the same disorder. A total of 434 pathogenic variants were identified. Three hundred twelve variants would have been detected via genotyping alone. Although no additional mutations were detected by NGS in diseases routinely screened for in the Ashkenazi Jewish population, 26.5% of carrier results and 2 carrier couples would have been missed without NGS in the larger panel. In a primarily Jewish population, NGS reveals a larger number of pathogenic variants and provides individuals with valuable information for family planning.Genet Med 18 12, 1214-1217.
Full Text Available Background & Objectives : Bacterial vaginosis is a condition which is determined by changes in microbial ecosystem of vagina and is considered as a preventable risk factor for preterm delivery. This study was conducted to assess the effectiveness of bacterial vaginosis screening program in routine prenatal care and its effect on decreasing preterm labor. Methods: This clinical trial study was conducted on 474 pregnant women at gestational stage between 2007 and 2008. The participants were randomly divided into 2 groups: intervention group and control group. Screening was performed in intervention group with Amsel's criteria (3 of 4 needed for diagnosis. Positive cases were given clindamycin cream (2% for one week. The outcome of the delivery was assessed in both groups afterward. Data were analyzed by SPSS11 software using descriptive statistics. Results: There was no significant difference between two groups regarding pregnancy rank, wanted and unwanted pregnancy, insufficient weight gain, mother vaccination and complication of pregnancy. Bacterial vaginosis was observed in 17 out of 216 (8% in the intervention group and then treated. Prevalence of preterm delivery in the intervention and control groups were 3 (1.4% and 12 (4.7%, respectively. The relative risk was protective (RR: 0.3, DR: 0.033, NNT: 30. Conclusion: Screening and treatment of bacterial vaginosis in pregnant women could significantly decrease the rate of preterm delivery.
Full Text Available Abstract Background Genome-wide screening in human and mouse cells using RNA interference and open reading frame over-expression libraries is rapidly becoming a viable experimental approach for many research labs. There are a variety of gene expression modulation libraries commercially available, however, detailed and validated protocols as well as the reagents necessary for deconvolving genome-scale gene screens using these libraries are lacking. As a solution, we designed a comprehensive platform for highly multiplexed functional genetic screens in human, mouse and yeast cells using popular, commercially available gene modulation libraries. The Gene Modulation Array Platform (GMAP is a single microarray-based detection solution for deconvolution of loss and gain-of-function pooled screens. Results Experiments with specially constructed lentiviral-based plasmid pools containing ~78,000 shRNAs demonstrated that the GMAP is capable of deconvolving genome-wide shRNA "dropout" screens. Further experiments with a larger, ~90,000 shRNA pool demonstrate that equivalent results are obtained from plasmid pools and from genomic DNA derived from lentivirus infected cells. Parallel testing of large shRNA pools using GMAP and next-generation sequencing methods revealed that the two methods provide valid and complementary approaches to deconvolution of genome-wide shRNA screens. Additional experiments demonstrated that GMAP is equivalent to similar microarray-based products when used for deconvolution of open reading frame over-expression screens. Conclusion Herein, we demonstrate four major applications for the GMAP resource, including deconvolution of pooled RNAi screens in cells with at least 90,000 distinct shRNAs. We also provide detailed methodologies for pooled shRNA screen readout using GMAP and compare next-generation sequencing to GMAP (i.e. microarray based deconvolution methods.
Primary amenorrhea should be investigated by karyotype analysis and selected mutation screening according to the patient's clinical features. Karyotype analyses and FMR1 gene screening is recommended in cases of POF. At present the infertility of patients with POF cannot be restored if the diagnosis is made after complete follicular depletion, but in some cases, early diagnosis by genetic investigation may instead lead to the advice of early conception or oocyte harvesting and preservation. In addition, the accumulation and annotation of array comparative genomic hybridization data might, in the near future, lead to the identification of pathogenetic copy number variations and genes involved in POF. Karyotype analysis of both partners is recommended in all couples with recurrent pregnancy loss. No routine genetic test can be recommended so far in patients with PCOS.
Full Text Available The incidence of β-thalassemia in Sardinia is high and β-39 is the most common mutation. The prevention campaign started in 1977 and was performed in a single center (Microcitemico Hospital, Cagliari, Sardinia, Italy. It was based on educational programs, population screening by hematological and molecular identification of the carriers. Prenatal and pre-implantation diagnosis was offered to couples at risk. 8564 fetal diagnosis procedures using different invasive approaches and analysis techniques were performed in the last 40 years. Trans-abdominal chorionic villous sampling was preferred due to lower complication risks and early diagnosis. Chorionic villous DNA was analyzed by PCR technique. 2138 fetuses affected by β-thalassemia were diagnosed. Women opted for termination of the pregnancy (TOP in 98.2% of these cases. Pre-implantation genetic diagnosis (PGD was proposed to couples at risk to avoid TOP. A total of 184 PGD were performed. Initially, the procedure was exclusively offered to infertile couples, according to the law in force. The success rate of pregnancies increased from 11.1% to 30.8% when, crucial law changes were enacted, and PGD was offered to fertile women as well. Forty years of β-thalassemia prevention programs in Sardinia have demonstrated the important decrease of this severe genetic disorder.
Monni, Giovanni; Peddes, Cristina; Iuculano, Ambra; Ibba, Rosa Maria
The incidence of β-thalassemia in Sardinia is high and β-39 is the most common mutation. The prevention campaign started in 1977 and was performed in a single center (Microcitemico Hospital, Cagliari, Sardinia, Italy). It was based on educational programs, population screening by hematological and molecular identification of the carriers. Prenatal and pre-implantation diagnosis was offered to couples at risk. 8564 fetal diagnosis procedures using different invasive approaches and analysis techniques were performed in the last 40 years. Trans-abdominal chorionic villous sampling was preferred due to lower complication risks and early diagnosis. Chorionic villous DNA was analyzed by PCR technique. 2138 fetuses affected by β-thalassemia were diagnosed. Women opted for termination of the pregnancy (TOP) in 98.2% of these cases. Pre-implantation genetic diagnosis (PGD) was proposed to couples at risk to avoid TOP. A total of 184 PGD were performed. Initially, the procedure was exclusively offered to infertile couples, according to the law in force. The success rate of pregnancies increased from 11.1% to 30.8% when, crucial law changes were enacted, and PGD was offered to fertile women as well. Forty years of β-thalassemia prevention programs in Sardinia have demonstrated the important decrease of this severe genetic disorder.
WU Ting; DING Xin-sheng; LI Wen-lei; YAO Juan; DENG Xiao-xuan
Background Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of anterior horn cells of the spinal cord.The survival motor neuron gene is SMA-determining gene deleted in approximately 95% of SMA patients.This study was undertaken to predict prenatal SMA efficiently and rapidly in families with previously affected child.Methods Prenatal diagnosis was made in 8 fetuses with a family history of SMA.Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used for the detection of the survival motor neuron gene.Results The survival motor neuron gene was not found in 6 fetuses, ruling out the diagnosis of SMA.Two fetuses were detected positive and the pregnancies were terminated.Conclusion Our method is effective and convenient in prenatal diagnosis of SMA.
Huai, Lei; Leng, Jianhang; Ma, Shenglin; Huang, Fang; Shen, Junya; Ding, Yu
This study aimed to investigate the serum concentration of alpha-fetoprotein (AFP)-L3 in midterm pregnancies and its potential application in prenatal trisomy screening. The serum samples from 27 women with trisomy 21 fetuses and 800 women with normal fetuses were examined to measure the concentrations of AFP, AFP-L3, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and inhibin-A. The screening results of various tests consisting of these markers were analyzed. In normal pregnancies within 15-20 weeks of gestation, the medians of serum AFP-L3 were 4.63, 5.70, 5.78, 6.58, 7.03, and 7.25 pg/mL. The median of AFP-L3 MoM in the trisomy 21 group was 0.46, which was significantly lower than the value of 1 in the normal group (P < 0.05). When using a cutoff value of 1/270, the sensitivity of the triple marker test (AFP, hCG, uE3) was improved from 74% to 81% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 5.4% to 6.8%. Similarly, the sensitivity of the quad marker test (AFP, hCG, uE3, inhibin-A) was improved from 81% to 89% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 4.6% to 5.6%. Serum AFP-L3 concentration increases along with more weeks of gestation in the midterm pregnancies. Trisomy 21 screening tests with AFP replaced by AFP-L3 have higher sensitivities at the expense of slightly increased false-positive rates. This improvement in screening may help to better prepare the parents and caregivers for the special needs of newborns with trisomy 21.
Walder, Deborah J; Faraone, Stephen V; Glatt, Stephen J; Tsuang, Ming T; Seidman, Larry J
The familial ("genetic") high-risk (FHR) paradigm enables assessment of individuals at risk for schizophrenia based on a positive family history of schizophrenia in first-degree, biological relatives. This strategy presumes genetic transmission of abnormal traits given high heritability of the illness. It is plausible, however, that adverse environmental factors are also transmitted in these families. Few studies have evaluated both biological and environmental factors within a FHR study of adolescents. We conceptualize four precursors to psychosis pathogenesis: two biological (genetic predisposition, prenatal health issues (PHIs)) and two environmental (family environment, stressful life events (SLEs)). Participants assessed between 1998 and 2007 (ages 13-25) included 40 (20F/20M) adolescents at FHR for schizophrenia (FHRs) and 55 (31F/24M) community controls. 'Genetic load' indexed number of affected family members relative to pedigree size. PHI was significantly greater among FHRs, and family cohesion and expressiveness were less (and family conflict was higher) among FHRs; however, groups did not significantly differ in SLE indices. Among FHRs, genetic liability was significantly associated with PHI and family expressiveness. Prenatal and family environmental disruptions are elevated in families with a first-degree relative with schizophrenia. Findings support our proposed 'polygenic neurodevelopmental diathesis-stress model' whereby psychosis susceptibility (and resilience) involves the independent and synergistic confluence of (temporally-sensitive) biological and environmental factors across development. Recognition of biological and social environmental influences across critical developmental periods points to key issues relevant for enhanced identification of psychosis susceptibility, facilitation of more precise models of illness risk, and development of novel prevention strategies. Copyright © 2014 Elsevier B.V. All rights reserved.
Khaled R. Gaber
Feb 21, 2015 ... revealed 36.8% (14/33) affected fetuses. During the final .... uated during the course of the study, making them 37 pregnan- cies evaluated and .... Prenatal diagnostic techniques have rendered decision mak- ing about ... This, in addition to the feeling of guilt experienced by many couples for termi- nation of ...
Martin, L.; Dulmen, S. van; Spelten, E.; Hutton, E.
OBJECTIVES: Counseling about prenatal testing for congenital abnormalities has become an increasing part of obstetric care in the Netherlands (Wiegers and Hingstman, 2008). During the past decade many changes have taken place in medical-technical and social-cultural areas as well as in health care
Erickson, B.H.; Martin, P.G.
The stem germ cells of the prenatal pig are highly vulnerable to the cytotoxic effects of ionizing irradiation. This study was conducted to determine whether sensitivity to killing was also marked by a sensitivity to mutation and how prenatal depletion of the germ-cell population affects reproductive performance. Germ-cell populations were reduced by continuously irradiating sows at dose rates of either 0.25 or 1.0 rad/day for the first 108 days of gestation. The prenatally irradiated boars were tested for sperm-producing ability, sperm abnormalities, dominant lethality, reciprocal translocations, and fertility. Prenatally irradiated females were allowed to bear and nurture one litter, then tested for dominant lethality in a second litter; germ cell survival and follicular development were assessed in their serially sectioned ovaries. Sperm production was not significantly affected in the 0.25-rad boars, but boars irradiated with 1.0 rad per day produced sperm at only 17% of the control level. Incidence of defective sperm was 4.9% and 11.1% in the 0.25 and 1.0 groups, respectively. Four of the 1.0-rad boars were infertile, but prenatal irradiation apparently caused neither dominant lethality nor reciprocal translocations in fertile males. Number of oocytes was reduced to 66 +/- 7% of control in the 0.25-rad gilts, but reproductive performance was unaffected and no dominant lethality was observed. Only 7 +/- 1% of the oocytes survived in the 1.0-rad group. Reproductive performance was normal for the first litter, but four of the 23 sows tested were infertile at the second litter and a significant incidence of dominant lethality was observed
Palomaki, Glenn E; Lee, Jo Ellen S; Canick, Jacob A; McDowell, Geraldine A; Donnenfeld, Alan E
This statement is intended to augment the current general ACMG Standards and Guidelines for Clinical Genetics Laboratories and to address guidelines specific to first-trimester screening for Down syndrome. The aim is to provide the laboratory the necessary information to ensure accurate and reliable Down syndrome screening results given a screening protocol (e.g., combined first trimester and integrated testing). Information about various test combinations and their expected performance are provided, but other issues such as availability of reagents, patient interest in early test results, access to open neural tube defect screening, and availability of chorionic villus sampling are all contextual factors in deciding which screening protocol(s) will be selected by individual health care providers. Individual laboratories are responsible for meeting the quality assurance standards described by the Clinical Laboratory Improvement Act, the College of American Pathologists, and other regulatory agencies, with respect to appropriate sample documentation, assay validation, general proficiency, and quality control measures. These guidelines address first-trimester screening that includes ultrasound measurement and interpretation of nuchal translucency thickness and protocols that combine markers from both the first and second trimesters. Laboratories can use their professional judgment to make modification or additions.
Conclusion: In prenatal diagnosis of Down syndrome noninvasive screening methods are important for estimation of individual risks, in both, young population of woman and older mothers, while conventional and molecular cytogenetic methods are essential for definite diagnosis and proper genetic counseling.
Koelewijn, Joke M.; Vrijkotte, Tanja G. M.; de Haas, Masja; van der Schoot, C. E.; Bonsel, Gouke J.
ABSTRACT: BACKGROUND: Since July 1998 all Dutch women (+/- 200,000/y) are screened for red cell antibodies, other than anti-RhesusD (RhD) in the first trimester of pregnancy, to facilitate timely treatment of pregnancies at risk for hemolytic disease of the fetus and newborn (HDFN). Evidence for
J. Koelewijn; T.G.M. Vrijkotte (Tanja); M. de Haas; C.E. van der Schoot (Ellen); G.J. Bonsel (Gouke)
textabstractBackground: Since July 1998 all Dutch women (± 200,000/y) are screened for red cell antibodies, other than anti-RhesusD (RhD) in the first trimester of pregnancy, to facilitate timely treatment of pregnancies at risk for hemolytic disease of the fetus and newborn (HDFN). Evidence for
Pelham, Trena L.; DeJong, Allan R.
A survey of 81 pediatric and 81 obstetric training programs from 42 states determined that respondents favored screening pregnant patients for cocaine abuse by maternal history (81 percent) and urine toxicology (36 percent), though many fewer reported these as established policy. Physicians favored such interventions as voluntary drug…
Lu, Lina; Lv, Bo; Huang, Kevin; Xue, Zhigang; Zhu, Xianmin; Fan, Guoping
Preimplantation genetic diagnosis/screening (PGD/PGS) aims to help couples lower the risks of transmitting genetic defects to their offspring, implantation failure, and/or miscarriage during in vitro fertilization (IVF) cycles. However, it is still being debated with regard to the practicality and diagnostic accuracy of PGD/PGS due to the concern of invasive biopsy and the potential mosaicism of embryos. Recently, several non-invasive and high-throughput assays have been developed to help overcome the challenges encountered in the conventional invasive biopsy and low-throughput analysis in PGD/PGS. In this mini-review, we will summarize the recent progresses of these new methods for PGD/PGS and discuss their potential applications in IVF clinics.
ClÃ¡udia Amorim Costa
Aug 27, 2016 ... The Egyptian Journal of Medical Human Genetics (2017) 18, 1–7. HOSTED BY ... Despite several reports describing a 1% increase in cffDNA ..... In the large multicentric study conducted by Norton et al., no results on cffDNA ...
Mersereau, Jennifer E; Plunkett, Beth A; Cedars, Marcelle I
To compare the strategy of traditional IVF with prenatal diagnosis versus IVF with preimplantation genetic screening (IVF/PGS) to prevent aneuploid births in women with advanced maternal age. A decision tree analytic model was created to compare IVF alone versus IVF/PGS to evaluate which strategy is the least costly per healthy (euploid) infant. Outpatient IVF practices. Infertile women, 38-40 and >40 years old. IVF or IVF/PGS. Cost per healthy infant. Using base-case estimates of costs and probabilities in women aged 38-40 years, after a maximum of two fresh IVF cycles and two frozen cycles, the chance of having a healthy infant was 37.8% with IVF alone versus 21.7% with IVF/PGS. The average cost for each strategy is $25,700, but the cost per healthy infant is substantially higher when IVF/PGS is applied as opposed to IVF alone ($118,713 vs. $68,026). To assess the robustness of the model, all probabilities were varied simultaneously in a Monte Carlo simulation, and in 96.2% of trials, IVF alone proved to be the most cost-effective option. Conversely, our data demonstrate that in women aged >40, IVF and IVF/PGS are essentially equal in terms of cost-effectiveness ($122,000 vs. $118,713). IVF alone is less costly per healthy infant than IVF/PGS in women ages 38-40.
Full Text Available Background: there are many reasons why a couple may seek specialist genetic counselling about foetal risk. The referral for prenatal genetic counselling of women with a known risk factor during pregnancy has many disadvantages. Despite this, 10-20% of women seek counselling when already pregnant.Methods: data on 804 pregnant women out of 2 158 (37.3% referred for genetic counselling in 2010 to three Clinical Genetic Services were retrospectively analysed. Patients referred only for advanced maternal age were analysed in a separate study.Results: the 804 pregnant women were referred for 932 counselling issues. 325 issues (34.9% were identified during pregnancy and 607 (65.1% were pre-existing. 81.2% of Italians compared to 41.8% of the non-Italians (P<0.01 had access to counselling before 13 weeks of gestation for risk factors present before pregnancy. An accurate genetic diagnosis was available in 25.0% of cases. In 21.7% of the cases an elevated a priori risk of >10% for the unborn child was established.Conclusions: genetic services provide 37.3% of counselling to pregnant women. Referral for genetic counselling during pregnancy can require considerable resources and pose significant ethical and organizational challenges. New models of pregnancy care in the community need to be developed. General practitioners and gynaecologists have an important role in the referral and in the defence of equity of access and a more structured approach to the participation of medical geneticists to primary practice should be considered.
Huang, Mei-Chih; Lin, Shio-Jean; Chen, Chih-Ling; Huang, Tzu-Jung
The biomedical technology related to prenatal screen/diagnosis has developed rapidly in recent decades. Many prenatal genetic examinations are now available to assist pregnant women to better understand the status and development of their fetus. Moreover, many commercial advertisements for innovative prenatal examinations are now shown in the media. Cell-free DNA Screening (cfDNA screening), a non-invasive prenatal testing (NIPT) procedure, is a safe and high accuracy test that may be done at an earlier gestational age to screen for fetal aneuploidy. The following questions should be considered when applying cfDNA screening in clinical practice: 1. what is cfDNA screening, 2. who are its potential users, and 3. what ethical and policy considerations are associated with this examination? This article provides relevant information, clinical practice guidelines, and ethical / policy considerations related to cfDNA screening. Discussing cases involving different clinical situations helps promote understanding of cfDNA screening and maternal-care quality.
Nshimyumukiza, Léon; Beaumont, Jean-Alexandre; Duplantie, Julie; Langlois, Sylvie; Little, Julian; Audibert, François; McCabe, Christopher; Gekas, Jean; Giguère, Yves; Gagné, Christian; Reinharz, Daniel; Rousseau, François
Yearly, 450 000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. Different screening strategies select approximately 4% of women for invasive fetal chromosome testing. Non-invasive prenatal testing (NIPT) using maternal blood cell-free DNA could reduce those invasive procedures but is expensive. This study evaluated the cost-effectiveness of NIPT strategies compared with conventional strategies. This study used a decision analytic model to estimate the cost-effectiveness of 13 prenatal screening strategies for fetal aneuploidies: six frequently used strategies, universal NIPT, and six strategies incorporating NIPT as a second-tier test. The study considered a virtual cohort of pregnant women of similar size and age as women in Quebec. Model data were obtained from published sources and government databases. The study predicted the number of chromosomal anomalies detected (trisomies 21, 13, and 18), invasive procedures and euploid fetal losses, direct costs, and incremental cost-effectiveness ratios. Of the 13 strategies compared, eight identified fewer cases at a higher cost than at least one of the remaining five strategies. Integrated serum screening with conditional NIPT had the lowest cost, and the cost per case detected was $63 139, with a 90% reduction of invasive procedures. The number of cases identified was improved with four other screening strategies, but with increasing of incremental costs per case (from $61 623 to $1 553 615). Results remained robust, except when NIPT costs and risk cut-offs varied. NIPT as a second-tier test for high-risk women is likely to be cost-effective as compared with screening algorithms not involving NIPT. Copyright © 2018 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.
Stepanova, Ye I; Vdovenko, V Yu; Misharina, Zh A; Kolos, V I; Mischenko, L P
To study the genetic effects in children exposed to radiation in utero as a result of the Chornobyl nuclear power plant accident accounting the total radiation doses and equivalent radiation doses to the red bone marrow. Incidence of minor developmental anomalies was studied in children exposed to radiation in utero (study group) and in the control group (1144 subjects surveyed in total). Cytogenetic tests using the method of differential G-banding of chromosomes were conducted in 60 children of both study and control groups (10-12-year-olds) and repeatedly in 39 adolescents (15-17-year-olds). A direct correlation was found between the number of minor developmental anomalies and fetal dose of radiation, and a reverse one with fetal gestational age at the time of radiation exposure. Incidence of chromosomal damage in somatic cells of 10-12-year-old children exposed prenatally was associated with radiation dose to the red bone marrow. The repeated testing has revealed that an increased level of chromosomal aberrations was preserved in a third of adolescents. The persons exposed to ionizing radiation at prenatal period should be attributed to the group of carcinogenic risk due to persisting increased levels of chromosome damage. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".
Jørgensen, Ditte E S; Vejlstrup, Niels; Jørgensen, Connie
OBJECTIVES: The prenatal detection rate of congenital heart disease (CHD) is low compared with other fetal malformations. Our aim was to evaluate the prenatal detection of CHD in Eastern Denmark. METHODS: Fetuses and infants diagnosed with CHD in the period 01.01.2008-31.12.2010 were assessed...
Full Text Available Preimplantation genetic diagnosis (PGD is a clinically feasible technology to prevent the transmission of monogenic inherited disorders in families afflicted the diseases to the future offsprings. The major technical hurdle is it does not have a general formula for all mutations, thus different gene locus needs individualized, customized design to make the diagnosis accurate enough to be applied on PGD, in which the quantity of DNA is scarce, whereas timely result is sometimes requested if fresh embryo transfer is desired. On the other hand, preimplantation genetic screening (PGS screens embryo with aneuploidy and was also known as PGD-A (A denotes aneuploidy in order to enhance the implantation rates as well as livebirth rates. In contrasts to PGD, PGS is still under ferocious debate, especially recent reports found that euploid babies were born after transferring the aneuploid embryos diagnosed by PGS back to the womb and only very few randomized trials of PGS are available in the literature. We have been doing PGD and/or PGS for more than 10 years as one of the core PGD/PGS laboratories in Taiwan. Here we provide a concise review of PGD/PGS regarding its current status, both domestically and globally, as well as its future challenges.
Yachie, Nozomu; Petsalaki, Evangelia; Mellor, Joseph C; Weile, Jochen; Jacob, Yves; Verby, Marta; Ozturk, Sedide B; Li, Siyang; Cote, Atina G; Mosca, Roberto; Knapp, Jennifer J; Ko, Minjeong; Yu, Analyn; Gebbia, Marinella; Sahni, Nidhi; Yi, Song; Tyagi, Tanya; Sheykhkarimli, Dayag; Roth, Jonathan F; Wong, Cassandra; Musa, Louai; Snider, Jamie; Liu, Yi-Chun; Yu, Haiyuan; Braun, Pascal; Stagljar, Igor; Hao, Tong; Calderwood, Michael A; Pelletier, Laurence; Aloy, Patrick; Hill, David E; Vidal, Marc; Roth, Frederick P
High-throughput binary protein interaction mapping is continuing to extend our understanding of cellular function and disease mechanisms. However, we remain one or two orders of magnitude away from a complete interaction map for humans and other major model organisms. Completion will require screening at substantially larger scales with many complementary assays, requiring further efficiency gains in proteome-scale interaction mapping. Here, we report Barcode Fusion Genetics-Yeast Two-Hybrid (BFG-Y2H), by which a full matrix of protein pairs can be screened in a single multiplexed strain pool. BFG-Y2H uses Cre recombination to fuse DNA barcodes from distinct plasmids, generating chimeric protein-pair barcodes that can be quantified via next-generation sequencing. We applied BFG-Y2H to four different matrices ranging in scale from ~25 K to 2.5 M protein pairs. The results show that BFG-Y2H increases the efficiency of protein matrix screening, with quality that is on par with state-of-the-art Y2H methods. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.
Singh, Manish Pratap; Rai, Sandhya; Suyal, Shradha; Singh, Sunil Kumar; Singh, Nand Kumar; Agarwal, Akash; Srivastava, Sameer
Colorectal cancer (CRC) is a heterogenous disease which develops from benign intraepithelial lesions known as adenomas to malignant carcinomas. Acquired alterations in Wnt signaling, TGFβ, MAPK pathway genes and clonal propagation of altered cells are responsible for this transformation. Detection of adenomas or early stage cancer in asymptomatic patients and better prognostic and predictive markers is important for improving the clinical management of CRC. Area covered: In this review, the authors have evaluated the potential of genetic and epigenetic alterations as markers for early detection, prognosis and therapeutic predictive potential in the context of CRC. We have discussed molecular heterogeneity present in CRC and its correlation to prognosis and response to therapy. Expert commentary: Molecular marker based CRC screening methods still fail to gain trust of clinicians. Invasive screening methods, molecular heterogeneity, chemoresistance and low quality test samples are some key challenges which need to be addressed in the present context. New sequencing technologies and integrated omics data analysis of individual or population cohort results in GWAS. MPE studies following a GWAS could be future line of research to establish accurate correlations between CRC and its risk factors. This strategy would identify most reliable biomarkers for CRC screening and management.
Dagan, Efrat; Gershoni-Baruch, Ruth; Kurolap, Alina; Goldberg, Yael; Fried, Georgeta
This article presents the complexity of prenatal genetic diagnosis and preimplantation genetic diagnosis for hereditary breast-ovarian cancer syndrome. These issues are discussed using a case report to highlight the genetic counseling process, together with decision-making considerations, in light of the clinical, psychological, and ethical perspectives, of both the mutation carriers and health professionals; and the health policy regarding these procedures in Israel compared to several European countries.
Fantini, C; Pedinielli, J-L; Manouvrier, S
Introduction. The development of a DNA based diagnostic test has allowed for the genetic screening of many hereditary diseases. In addition to the identification of the deleterious gene, this screening process has led to the recognition of developing illnesses at high risk. In recent years, a number of genes predisposing to an inherited cancer syndrome have been identified. Our purpose in this study was to determine whether subjects at risk who test for inherited colorectal cancer, are likely to develop a higher level of psychological distress than the norm, taking into consideration the particular history of this familial disease. The demographic and psychosocial aspects of our population was described using: 1) the State Trait Anxiety Inventory (STAI), 2) the Center for Epidemiologic Studies Depression (CES-D), 3) a perceived risk for the gene carrier, 4) subjective perception of personal vulnerability and 5) the role of the medical status (affected or not), which places the subject in either predisposition or predictive testing. Results show that our population had a higher predisposition for depressive disorders (chi2=9,3. p=0.002) and a significantly higher state of anxiety (chi2=9,3. p=0.002), prior to genetic counselling, compared with other populations. We found no evidence in the medical status, nor the perceived risk. However, the assessment of one's own personal vulnerability is related to psychological distress. These results highlight the particular vulnerability of subjects undergoing genetic testing as well as showing the pertinence of proposing psychological help throughout the process of these new specific diagnoses.
Yonkers, Kimberly A; Gotman, Nathan; Kershaw, Trace; Forray, Ariadna; Howell, Heather B; Rounsaville, Bruce J
To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into "training" (n=1,610) and "validation" (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike's Information Criterion=579.75, Nagelkerke R=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. III.
Plaga, Stacey L; Demarco, Kristin; Shulman, Lee P
We sought to evaluate the prenatal decision-making of pregnant adolescents identified at increased risk for identifiable fetal genetic abnormalities. A retrospective review of records of gravid women 19 years old or younger undergoing genetic counseling from 2001-2003 (inclusive) was undertaken. Hospital-based academic center. Thirty-seven women were identified; four cases did not meet inclusion criteria. None. Decision to undergo or forgo invasive prenatal testing. Of the 33 women included in this study, the average age was 17.6 years (range: 15-19). Eighteen were Latinas, eight were African-Americans, and seven were Caucasians. Sixteen women had positive maternal serum screening outcomes; nine women sought counseling because of personal/family histories of genetic abnormalities, seven sought counseling after fetal structural anomalies were detected by ultrasound, and one woman sought counseling because she and her partner were positive for Mendelian disorder screening (sickle cell disease). Sixteen of the women (48.5%) chose to undergo invasive testing (15 amniocenteses, one chorionic villus sampling) whereas 17 (51.5%) chose to forgo invasive testing. Adolescents offered invasive prenatal diagnosis will chose to undergo or forgo such testing based on diagnostic and personal criteria as do adult women. Nonetheless, unique adolescent issues may make the process by which information is obtained and communicated during counseling to be different from counseling provided to adults. The development of new genetic screening and diagnostic protocols has and will increase the number of pregnant adolescent women who will be offered genetic counseling during their pregnancies. Such an increase in numbers will place considerably more pressure on an already taxed genetic counseling system; accordingly, new counseling paradigms will need to be developed to provide service to an expanded patient population seeking information for an increasing number of genetic issues.
Seoud, Muheiddine; Nassar, Anwar H; Zalloua, Pierre; Boghossian, Nansi; Ezeddine, Jihad; Fakhoury, Hassan; Abboud, Joseph; Melki, Imad; Araj, George; Nacouzi, Ghinwa; Sanyoura, May; Yunis, Khalid
The study aimed at determining the prevalence, risk factors, perinatal transmission, and serotypes of Group B Streptococcus (GBS) among pregnant women and their newborns in Beirut, Lebanon. This was a cross-sectional study of all pregnant women admitted from February to September 2006 to three major hospitals. Overall, 137 of 775 (17.7%) mothers and 50 of 682 newborns (7.3%) tested positive for GBS. Maternal colonization was not associated with maternal age, household income, gravidity, intrapartum fever, preterm labor, or premature rupture of membrane. Transmission rate was 40/120 (30%). Serotype 5 (24.1%) was the most common followed by serotype 1a (15.0%), 3 (14.4%), 2 (11.8%) and 1b (7.5%). Pregnant women in Lebanon appear to have a relatively high prevalence of GBS colonization with no identifiable risk factors for its acquisition. These results could provide basis for the institution of a national policy for universal maternal GBS screening to reduce neonatal morbidity and mortality.
Mallia, Pierre; ten Have, Henk
Catholic movements within the centre of Roman Catholic doctrine recently have discussed Trinitarian theology as applied to sciences, arts, economics, health and other social areas. We explore the possibilities Trinitarian theology offers to bioethical debate, concentrating particularly on genetic screening and testing. It is important therefore to analyse the philosophical implications of this approach onto the bioethical world, where much disagreement occurs on fundamental issues. It is Catholic basic teaching to recognize and see God's hand in plurality, not merely as a cliche and then doing what we feel is right, but to recognize how to live in a pluralistic world. We recognize, in agreement with these theologians, that in order for a Trinitarian mode of understanding to be used by those doing bioethical debate, there is a need to depart from fundamentalism.
Boyle, B; Morris, J K; McConkey, R
OBJECTIVE: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome. DESIGN: Population-based prevalence study based on EUROCAT congenital anomaly registries. SETTING: Eight European countries. POPULATION: 14...
Vintzileos, A M; Ananth, C V; Fisher, A J; Smulian, J C; Day-Salvatore, D; Beazoglou, T
To determine 1) the diagnostic accuracy requirements of first-trimester genetic sonography from the cost-benefit point of view and 2) the economic impact of first-trimester genetic sonography for the United States on the basis of the accuracy of previously published studies. A cost-benefit equation was developed on the basis of the hypothesis that the cost of chorionic villus sampling (CVS) in pregnant women with advanced maternal age (at least 35 years old) should be at least equal to the cost of genetic sonography with CVS used only for those with abnormal ultrasound results. The components of the equation included the diagnostic accuracy of genetic ultrasound (sensitivity and specificity for detecting Down syndrome), the costs of the CVS package and genetic ultrasound, and the lifetime cost of Down syndrome cases. First-trimester genetic sonography was found to be beneficial if the overall sensitivity for detecting Down syndrome was greater than 70%, and even then, the cost-benefit ratio depended on the corresponding false-positive rate. The required minimum ultrasound sensitivity varied according to the maternal age-specific prevalence of Down syndrome and ranged between 40% (for women 35 years old) to 96% (for women 44 years old). Of eight published cohorts using nuchal translucency thickness for genetic sonography, five had accuracies of genetic ultrasound compatible with net benefits. The benefits of first-trimester genetic sonography depend on its diagnostic accuracy. First-trimester genetic sonography has the potential for annual savings of 22 million dollars in the United States.
McLennan, Andrew; Palma-Dias, Ricardo; da Silva Costa, Fabricio; Meagher, Simon; Nisbet, Debbie L; Scott, Fergus
There are limited data regarding noninvasive prenatal testing (NIPT) in low-risk populations, and the ideal aneuploidy screening model for a pregnant population has yet to be established. To assess the implementation of NIPT into clinical practice utilising both first- and second-line screening models. Three private practices specialising in obstetric ultrasound and prenatal diagnosis in Australia offered NIPT as a first-line test, ideally followed by combined first-trimester screening (cFTS), or as a second-line test following cFTS, particularly in those with a calculated risk between 1:50 and 1:1000. NIPT screening was performed in 5267 women and as a first-line screening method in 3359 (63.8%). Trisomies 21 and 13 detection was 100% and 88% for trisomy 18. Of cases with known karyotypes, the positive predictive value (PPV) of the test was highest for trisomy 21 (97.7%) and lowest for monosomy X (25%). Ultrasound detection of fetal structural abnormality resulted in the detection of five additional chromosome abnormalities, two of which had high-risk cFTS results. For all chromosomal abnormalities, NIPT alone detected 93.4%, a contingent model detected 81.8% (P = 0.097), and cFTS alone detected 65.9% (P < 0.005). NIPT achieved 100% T21 detection and had a higher DR of all aneuploidy when used as a first-line test. Given the false-positive rate for all aneuploidies, NIPT is an advanced screening test, rather than a diagnostic test. The benefit of additional cFTS was the detection of fetal structural abnormalities and some unusual chromosomal abnormalities. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.
Holtzman, N A
Pressures to lower health-care costs remain an important stimulus to eugenic approaches. Prenatal diagnosis followed by abortion of affected fetuses has replaced sterilization as the major eugenic technique. Voluntary acceptance has replaced coercion, but subtle pressures undermine personal autonomy. The failure of the old eugenics to accurately predict who will have affected offspring virtually disappears when prenatal diagnosis is used to predict Mendelian disorders. However, when prenatal diagnosis is used to detect inherited susceptibilities to adult-onset, common, complex disorders, considerable uncertainty is inherent in the prediction. Intolerance and the resurgence of genetic determinism are current pressures for a eugenic approach. The increasing use of carrier screening (to identify those at risk of having affected offspring) and of prenatal diagnosis could itself generate intolerance for those who refuse the procedures. Genetic determinism deflects society from social action that would reduce the burden of disease far more than even the maximum use of eugenics.
Huang, Jin; Li, Rong; Lian, Ying; Chen, Lixue; Shi, Xiaodan; Qiao, Jie; Liu, Ping
To investigate the single blastocyst transfer in preimplantation genetic diagnosis (PGD)/preimplantation genetic screening (PGS) cycles. 80 PGD/PGS cycles undergoing blastocyst biopsy were studied. There were 88 warming cycles during the study period. Only one warmed blastocyst was transferred per cycle. The outcomes were followed up to the infants were born. The embryo implantation rate was 54.55% (48/88). The clinical pregnancy rate was 54.55% (48/88) per transfer cycle and 60% (48/80) per initial PGD/PGS cycle. There was no multi-pregnant in this study. The live birth rate was 42.05% (37/88) per transfer cycle and 46.25% (37/80) per initial PGD/PGS cycle. In PGD/PGS cycles, single blastocyst transfer reduces the multiple pregnancy rate without affecting the clinical outcomes.
Zlocha, J; Kovács, L; Pozgayová, S; Kupcová, V; Durínová, S
identified through biochemical testing for iron overload using serum transferrin saturation and genetic testing for C282Y homozygosity. DNA analysis is recommended in patients whose transferrin saturation is 45% or more on a repeated test. General population screening has been waived in preference to targeting high-risk groups such as first-degree relatives of affected individuals and those with secondary iron overload, especially patients with chronic liver disorders and chronic anemia. This screening strategy is likely to continue until uncertainties regarding the natural history of the disease, age-related penetrance, and management of asymptomatic individuals are clarified.
Wilson, R Douglas; De Bie, Isabelle; Armour, Christine M; Brown, Richard N; Campagnolo, Carla; Carroll, June C; Okun, Nan; Nelson, Tanya; Zwingerman, Rhonda; Audibert, Francois; Brock, Jo-Ann; Brown, Richard N; Campagnolo, Carla; Carroll, June C; De Bie, Isabelle; Johnson, Jo-Ann; Okun, Nan; Pastruck, Melanie; Vallée-Pouliot, Karine; Wilson, R Douglas; Zwingerman, Rhonda; Armour, Christine; Chitayat, David; De Bie, Isabelle; Fernandez, Sara; Kim, Raymond; Lavoie, Josee; Leonard, Norma; Nelson, Tanya; Taylor, Sherry; Van Allen, Margot; Van Karnebeek, Clara
This guideline was written to update Canadian maternity care and reproductive healthcare providers on pre- and postconceptional reproductive carrier screening for women or couples who may be at risk of being carriers for autosomal recessive (AR), autosomal dominant (AD), or X-linked (XL) conditions, with risk of transmission to the fetus. Four previous SOGC- Canadian College of Medical Geneticists (CCMG) guidelines are updated and merged into the current document. All maternity care (most responsible health provider [MRHP]) and paediatric providers; maternity nursing; nurse practitioner; provincial maternity care administrator; medical student; and postgraduate resident year 1-7. Fertile, sexually active females and their fertile, sexually active male partners who are either planning a pregnancy or are pregnant (preferably in the first trimester of pregnancy, but any gestational age is acceptable). Women and their partners will be able to obtain appropriate genetic carrier screening information and possible diagnosis of AR, AD, or XL disorders (preferably pre-conception), thereby allowing an informed choice regarding genetic carrier screening and reproductive options (e.g., prenatal diagnosis, preimplantation genetic diagnosis, egg or sperm donation, or adoption). Informed reproductive decisions related to genetic carrier screening and reproductive outcomes based on family history, ethnic background, past obstetrical history, known carrier status, or genetic diagnosis. SOGC REPRODUCTIVE CARRIER SCREENING SUMMARY STATEMENT (2016): Pre-conception or prenatal education and counselling for reproductive carrier screening requires a discussion about testing within the three perinatal genetic carrier screening/diagnosis time periods, which include pre-conception, prenatal, and neonatal for conditions currently being screened for and diagnosed. This new information should be added to the standard reproductive carrier screening protocols that are already being utilized by
Zhao, Yili; Abuhamad, Alfred; Fleenor, Jonathan; Guo, Yajun; Zhang, Wangshu; Cao, Danming; Zeng, Shi; Sinkovskaya, Elena; Zhou, Qichang
The aim of this systematic review was to compare the postnatal outcomes, genetic testing results, and sonographic findings in 3 subtypes of tetralogy of Fallot. Thirty-six articles from the MEDLINE and EMBASE databases were selected for this review. The postnatal outcomes, karyotyping results, and sonographic findings of fetal tetralogy of Fallot with pulmonary stenosis, tetralogy of Fallot with pulmonary atresia, and tetralogy of Fallot with an absent pulmonary valve were collected and compared. The survival rates (termination of pregnancy was considered fetal death) for prenatally diagnosed tetralogy of Fallot with pulmonary atresia and tetralogy of Fallot with an absent pulmonary valve at the end of neonatal period were significantly lower than the rate for tetralogy of Fallot with pulmonary stenosis (P tetralogy of Fallot with pulmonary atresia was also lower at birth (P tetralogy of Fallot with pulmonary stenosis (Ptetralogy of Fallot with pulmonary atresia and tetralogy of Fallot with an absent pulmonary valve (P tetralogy of Fallot with pulmonary stenosis, a right aortic arch was more associated with tetralogy of Fallot with pulmonary atresia (32.6%; P tetralogy of Fallot with an absent pulmonary valve (87.5%; P tetralogy of Fallot. Documenting those details at diagnosis can help specialists better counsel their patients. © 2016 by the American Institute of Ultrasound in Medicine.
Gonzalez-Bulnes, Antonio; Ovilo, Cristina
Obesity and type-2 diabetes are currently considered global pandemics. A large set of epidemiological evidences are addressing both the importance of a genetic predisposition -starting with the thrifty genotype hypothesis- and the determinant role of the maternal nutrition during pregnancy -starting with longitudinal studies of individuals born during the Dutch famine- on the adult onset of the disease. Compelling evidences suggest that both over- and undernutrition may modify the intrauterine environment of the conceptus and may alter the expression of its genome, predisposing to disease in the adult life. However, the most recent data indicate that the consequences of this phenomenon, termed as prenatal programming, are influenced both by timing, degree and duration of the challenge and by the adaptive response of the mother and the conceptus; thus, the information acquired by interventional studies modifying these parameters is becoming increasingly important. Obviously, interventional research in human beings is limited by ethical issues; hence, investigations need to be conducted on animal models, either rodents or large animals. This review summarizes the results of epidemiological human studies and translational animal research in unraveling the interaction between genome, nutritional status and adaptive response on the establishment of postnatal obesity, insulin resistance and type-2 diabetes. © 2012 Bentham Science Publishers
Gielen, Marij; Pinto-Sietsma, Sara-Joan; Zeegers, Maurice P.; Loos, Ruth J.; Fagard, Robert; de Leeuw, Peter W.; Beunen, Gaston; Derom, Catherine; Vlietinck, Robert
Previous studies have shown that low birth weight (LBW) is a risk factor for renal impairment in adult life. The effects of LBW and renal function were studied by using twins, which allows distinguishing among fetoplacental, maternal, and genetic influences. Perinatal data were obtained at birth,
Adhikari, Emily H; Nelson, David B; Johnson, Kathryn A; Jacobs, Sara; Rogers, Vanessa L; Roberts, Scott W; Sexton, Taylor; McIntire, Donald D; Casey, Brian M
Zika virus infection during pregnancy is a known cause of congenital microcephaly and other neurologic morbidities. We present the results of a large-scale prenatal screening program in place at a single-center health care system since March 14, 2016. Our aims were to report the baseline prevalence of travel-associated Zika infection in our pregnant population, determine travel characteristics of women with evidence of Zika infection, and evaluate maternal and neonatal outcomes compared to women without evidence of Zika infection. This is a prospective, observational study of prenatal Zika virus screening in our health care system. We screened all pregnant women for recent travel to a Zika-affected area, and the serum was tested for those considered at risk for infection. We compared maternal demographic and travel characteristics and perinatal outcomes among women with positive and negative Zika virus tests during pregnancy. Comprehensive neurologic evaluation was performed on all infants delivered of women with evidence of possible Zika virus infection during pregnancy. Head circumference percentiles by gestational age were compared for infants delivered of women with positive and negative Zika virus test results. From March 14 through Oct. 1, 2016, a total of 14,161 pregnant women were screened for travel to a Zika-affected country. A total of 610 (4.3%) women reported travel, and test results were available in 547. Of these, evidence of possible Zika virus infection was found in 29 (5.3%). In our population, the prevalence of asymptomatic or symptomatic Zika virus infection among pregnant women was 2/1000. Women with evidence of Zika virus infection were more likely to have traveled from Central or South America (97% vs 12%, P Zika virus infection. Additionally, there was no difference in mean head circumference of infants born to women with positive vs negative Zika virus testing. No microcephalic infants born to women with Zika infection were identified
Légaré, France; St-Jacques, Sylvie; Gagnon, Susie; Njoya, Merlin; Brisson, Michel; Frémont, Pierre; Rousseau, François
To assess the willingness of women and their family physicians (FPs) to engage in shared decision-making (SDM) as regards prenatal Down-syndrome screening and the factors that might influence their willingness to do so. We conducted a survey of participants in Québec City, Canada, using the theory of planned behavior. We used a general linear model and multilevel approach that took the fact that some women consulted the same FP into account. This study comprised 109 pregnant women and 41 FPs. On a scale of - 3 to + 3, the pregnant women's and FPs' response scores were, respectively, 2.11 ± 1.38 and 2.66 ± 0.40. In women, attitude, significant others, self-efficacy, perceived moral correctness, and their FP's attitude influenced their willingness to engage in SDM. However, women without a post-secondary education were less likely to engage in SDM than women with a post-secondary education, mostly because the former lacked a sense of self-efficacy. In FPs, only attitude and significant others influenced their willingness to engage in SDM. Overall, the women and their FPs wished to engage in SDM as regards prenatal Down-syndrome screening. Only a few factors influenced this desire which therefore may be modifiable. Copyright © 2011 John Wiley & Sons, Ltd.
Kenen, R H; Schmidt, R M
Possible latent psychological and social consequences ensuing from genetic screening programs need to be investigated during the planning phase of national genetic screening programs. The relatively few studies which have been performed to determine psychological, social, and economic consequences resulting from a genetic screening program are reviewed. Stigmatization of carrier-status, having major psychosocial implications in heterozygote genetic screening programs, is discussed and related to Erving Goffman's work in the area of stigmatization. Questions are raised regarding the relationship between such variables as religiosity and sex of the individual and acceptance of the status of newly identified carrier of a mutant gene. Severity of the deleterious gene and visibility of the carrier status are two important factors to consider in an estimation of potential stigma. Specific implications are discussed for four genetic diseases: Tay-Sachs, Sickle-Cell Anemia, Huntington's disease and Hemophilia. PMID:152585
Jonas, Susanna; Wild, Claudia; Schamberger, Chantal
mastectomy (PM) reduces the relative breast cancer risk by approximately 90%. The question is if PM has an impact on mortality. The acceptance of PM is culture-dependent. Colectomy can be used as a prophylactic (FAP) and therapeutic method. After surgery, the cancer risk remains high and so early detection examinations are still necessary. EVIDENCE-BASED STATEMENTS: The evidence is often fragmentary and of limited quality. For objective test result presentation information about sensitivity, specificity, positive predictive value, and number needed to screen and treat, respectively, are necessary. New identification of mutations and demand will lead to an increase of predictive genetic counselling and testing. There is a gap between predictive genetic diagnosis and prediction, prevention, early detection and surgical interventions. These circumstances require a basic strategy. Since predictive genetic diagnosis is a very sensitive issue it is important to deal with it carefully in order to avoid inappropriate hopes. Thus, media, experts and politicians need to consider opportunities and limitations in their daily decision-making processes.
Canter, E F
The emergence of genetic screening techniques will permit employers to exclude hypersusceptible individuals from potentially hazardous workplace environments. The denial of employment opportunities to these individuals, however, may constitute discrimination. This Note analyzes genetic screening cases with respect to currently available remedies contained in Title VII of the Civil Rights Act of 1964 and the Rehabilitation Act of 1973. The Note concludes that Title VII claims may succeed but only in limited circumstances and that Rehabilitation Act claims will encounter numerous obstacles to relief. Additionally, the Note discusses some of the implications of the use of genetic screening in the workplace.
Pediatric Vesicoureteral Reflux Guidelines Panel Summary Report: Clinical Practice Guidelines for Screening Siblings of Children With Vesicoureteral Reflux and Neonates/Infants With Prenatal Hydronephrosis.
Skoog, Steven J; Peters, Craig A; Arant, Billy S; Copp, Hillary L; Elder, Jack S; Hudson, R Guy; Khoury, Antoine E; Lorenzo, Armando J; Pohl, Hans G; Shapiro, Ellen; Snodgrass, Warren T; Diaz, Mireya
The American Urological Association established the Vesicoureteral Reflux Guideline Update Committee in July 2005 to update the management of primary vesicoureteral reflux in children guideline. The Panel defined the task into 5 topics pertaining to specific vesicoureteral reflux management issues, which correspond to the management of 3 distinct index patients and the screening of 2 distinct index patients. This report summarizes the existing evidence pertaining to screening of siblings and offspring of index patients with vesicoureteral reflux and infants with prenatal hydronephrosis. From this evidence clinical practice guidelines are developed to manage the clinical scenarios insofar as the data permit. The Panel searched the MEDLINE(R) database from 1994 to 2008 for all relevant articles dealing with the 5 chosen guideline topics. The database was reviewed and each abstract segregated into a specific topic area. Exclusions were case reports, basic science, secondary reflux, review articles and not relevant. The extracted article to be accepted should have assessed a cohort of children, clearly stating the number of children undergoing screening for vesicoureteral reflux. Vesicoureteral reflux should have been diagnosed with a cystogram and renal outcomes assessed by nuclear scintigraphy. The screening articles were extracted into data tables developed to evaluate epidemiological factors, patient and renal outcomes, and results of treatment. The reporting of meta-analysis of observational studies elaborated by the MOOSE group was followed. The extracted data were analyzed and formulated into evidence-based recommendations regarding the screening of siblings and offspring in index cases with vesicoureteral reflux and infants with prenatal hydronephrosis. In screened populations the prevalence of vesicoureteral reflux is 27.4% in siblings and 35.7% in offspring. Prevalence decreases at a rate of 1 screened person every 3 months of age. The prevalence is the same
Prenatal diagnostics of congenital malformations, the most efficient way to decrease genetic consequences of Chernobyl accident; Perinatal'naya diagnostika vrozhdennykh porokov razvitiya - naibolee ehffektivnyj metod minimizatsii geneticheskikh posledstvij Chernobyl'skoj katastrofy
Lazjuk, G I; Zatsepin, I O; Kravchuk, Zn P; Khmel, R D
in the last 5 years about 500 pregnancies were terminated annually for genetic reasons. Over 100 pregnancies were terminated in Gomel region, which considerably reduced (by 1-3%) perinatal mortality, children's morbidity and disability. The number of children, born with the anomalies of the central nervous system, renal polycystosis and agenesis, omphalocele, reduction limb defects, is decreasing most considerably. The potentialities of prenatal diagnostics of CM are far from being used adequately in the Republic. With sufficient financing, present-day techniques allow prenatal diagnosing of 1000 cases instead of 600 diagnosed each year. The program will be productive, if prenatal biochemical screening and invasive prenatal procedures are financed regularly and interregional centres for prenatal diagnostics are created. These measures will not only reduce the proportion of children, born with congenital malformations, but increase the birth rate in Belarus, since the future mothers will not be scared to give birth to a malformed child, which is especially essential for the population exposed to radiation due to Chernobyl accident (authors)
... Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...
Bain, Luchuo Engelbert; Dierickx, Kris; Hens, Kristien
Prevention of mother to child transmission of HIV remains a key public health priority in most developing countries. The provider Initiated Opt - Out Prenatal HIV Screening Approach, recommended by the World Health Organization (WHO) lately has been adopted and translated into policy in most Sub - Saharan African countries. To better ascertain the ethical reasons for or against the use of this approach, we carried out a literature review of the ethics literature. Papers published in English and French Languages between 1990 and 2015 from the following data bases were searched: Pubmed, Cochrane literature, Embase, Cinhal, Web of Science and Google Scholar. After screening from 302 identified relevant articles, 21 articles were retained for the critical review. Most authors considered this approach ethically justifiable due to its potential benefits to the mother, foetus and society (Beneficence). The breaching of respect for autonomy was considered acceptable on the grounds of libertarian paternalism. Most authors considered the Opt - Out approach to be less stigmatizing than the Opt - In. The main arguments against the Opt - Out approach were: non respect of patient autonomy, informed consent becoming a meaningless concept and the HIV test becoming compulsory, risk of losing trust in health care providers, neglect of social and psychological implications of doing an HIV test, risk of aggravation of stigma if all tested patients are not properly cared for and neglect of sociocultural peculiarities. The Opt - Out approach could be counterproductive in case gender sensitive issues within the various sociocultural representations are neglected, and actions to offer holistic care to all women who shall potentially test positive for HIV were not effectively ascertained. The Provider Initiated Opt - Out Prenatal HIV Screening option remains ethically acceptable, but deserves caution, active monitoring and evaluation within the translation of this approach into to practice.
Rosenmann, Ada; Bejarano-Achache, Idit; Eli, Dalia; Maftsir, Genia; Mizrahi-Meissonnier, Liliana; Blumenfeld, Anat
To present our accumulated data on prenatal molecular diagnosis of oculocutaneous albinism (OCA) in a large cohort of Israeli albino families. Albinism consists of variable phenotypes, but only families with predicted severely handicapped albino offspring, who declared their wish to terminate a pregnancy of such a fetus, are eligible for prenatal testing. Prenatal testing is not offered otherwise. Following detailed genetic investigation and counseling, molecular prenatal testing was performed using the combination of mutation screening, direct sequencing, and haplotype analysis. A total of 55 prenatal tests were performed in 37 families; in 26 families the propositus was the child, and in 11, a parent or a close relative. In 32 families tyrosinase (TYR) mutations were diagnosed. In 5 families a P gene mutation was detected. Twelve albino fetuses were diagnosed. Following further genetic counseling, all couples elected to terminate the pregnancy. Three additional pregnancies were terminated for other reasons. Families with increased risk for an albino child with severe visual handicap, seek premarital and prenatal genetic counseling and testing, for the prevention of affected offspring. Our combined methods of molecular genetic testing enable a nationwide approach for prevention of albinism. The same paradigm can be applied to other populations affected with albinism.
Dick, P T
To make recommendations to physicians providing prenatal care on (1) whether prenatal screening for and diagnosis of Down syndrome (DS) is advisable and (2) alternative screening and diagnosis manoeuvres. "Triple-marker" screening of maternal serum levels of alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol; fetal ultrasonographic examination; amniocentesis; and chorionic villus sampling (CVS). Accuracy of detection of DS in fetuses, and risks to the mother, including psychologic distress, and to the fetus from the screening and diagnostic interventions. A MEDLINE search for relevant articles published from Jan. 1, 1966, to Mar. 31, 1994, with the use of MeSH terms "Down syndrome," "prenatal diagnosis," "screening," "prevention," "amniocentesis," "chorionic villus sampling," "ultrasonography," "anxiety," "depression" and "psychological stress" and a manual search of bibliographies, recent issues of key journals and Current Contents. The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examination were used. A high value was placed on providing pregnant women with the opportunity to determine whether they are carrying a fetus with DS and to make choices concerning the termination of the pregnancy. The economic issues involved are complex and were not considered. Triple-marker screening identifies an estimated 58% of fetuses with DS, but it has an estimated rate of true-positive results of 0.1% and of false-positive results of 3.7% (given a risk cut-off of one chance in 190 of DS). These rates vary with maternal age and the risk cut-off chosen. Women with a known risk of having a fetus with DS (e.g., those who have had a previous child with DS) may benefit from a reduction in anxiety after confirmation that their fetus does not have DS. Screening allows women at low risk of having a child with DS to detect fetuses with the syndrome, but may cause psychologic distress if there is a false-positive screening test
Holtkamp, Kim C. A.; Lakeman, Phillis; Hader, Hind; Jans, Suze M. J. P.; Hoenderdos, Maria; Playfair, Henna A. M.; Cornel, Martina C.; Peters, Marjolein; Henneman, Lidewij
Carrier screening for hemoglobinopathies (HbPs; sickle cell disease and thalassemia) aims to facilitate autonomous reproductive decision-making. In the absence of a Dutch national HbP carrier screening program, some primary care midwives offer screening on an ad hoc basis. This qualitative
Agarwal, Ashwin; Sayres, Lauren C; Cho, Mildred K; Cook-Deegan, Robert; Chandrasekharan, Subhashini
Cell-free fetal DNA-based noninvasive prenatal testing (NIPT) could significantly change the paradigm of prenatal testing and screening. Intellectual property (IP) and commercialization promise to be important components of the emerging debate about clinical implementation of these technologies. We have assembled information about types of testing, prices, turnaround times, and reimbursement of recently launched commercial tests in the United States from the trade press, news articles, and scientific, legal, and business publications. We also describe the patenting and licensing landscape of technologies underlying these tests and ongoing patent litigation in the United States. Finally, we discuss how IP issues may affect clinical translation of NIPT and their potential implications for stakeholders. Fetal medicine professionals (clinicians and researchers), genetic counselors, insurers, regulators, test developers, and patients may be able to use this information to make informed decisions about clinical implementation of current and emerging noninvasive prenatal tests. © 2013 John Wiley & Sons, Ltd.
Tonni, Gabriele; Ida, Vito; Alessandro, Ventura; Bonasoni, Maria Paola
Prune-belly syndrome (PBS) is a rare congenital syndrome characterized by deficient abdominal muscles, urinary tract malformation, and in males, cryptorchidism and has an estimated incidence of 1 in 35,000 to 1 in 50,000 live births. The syndrome might be due to severe bladder outlet obstruction or to abdominal muscle deficiency secondary to a migrational defect of the lateral mesoblast between weeks 6 and 7 of pregnancy. The current review of the medical record reports a special focus on epidemiology, genetic factors, early prenatal diagnosis clusters, treatment, and prognosis of PBS.
Dondorp, W; De Wert, G; Pennings, G; Shenfield, F; Devroey, P; Tarlatzis, B; Barri, P; Diedrich, K; Eichenlaub-Ritter, U; Tüttelmann, F; Provoost, V
This Task Force document explores the ethical issues involved in the debate about the scope of genetic screening of gamete donors. Calls for expanded donor screening arise against the background of both occasional findings of serious but rare genetic conditions in donors or donor offspring that were not detected through present screening procedures and the advent of new genomic technologies promising affordable testing of donors for a wide range of conditions. Ethical principles require that all stakeholders' interests are taken into account, including those of candidate donors. The message of the profession should be that avoiding all risks is impossible and that testing should remain proportional.
Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair.
Sapiro, Anne L.; Ihry, Robert J.; Buhr, Derek L.; Konieczko, Kevin M.; Ives, Sarah M.; Engstrom, Anna K.; Wleklinski, Nicholas P.; Kopish, Kristin J.; Bashirullah, Arash
Mutagenesis screens are a staple of classical genetics. Chemical-induced mutations, however, are often difficult and time-consuming to identify. Here, we report that recombination analysis with pairs of dominant visible markers provides a rapid and reliable strategy to map mutations in Drosophila melanogaster. This method requires only two generations and a total of six crosses in vials to estimate the genetic map position of the responsible lesion with high accuracy. This genetic map positio...
Burton, Sarah K; Withrow, Kara; Arnos, Kathleen S; Kalfoglou, Andrea L; Pandya, Arti
Progress in identifying genes for deafness together with implementation of universal audiologic screening of newborns has provided the opportunity for more widespread use of molecular tests to detect genetic forms of hearing loss. Efforts to assess consumer attitudes toward these advances have lagged behind. Consumer focus groups were held to explore attitudes toward genetic advances and technologies for hearing loss, views about newborn hearing screening, and reactions to the idea of adding molecular screening for hearing loss at birth. Focus group discussions were recorded, transcribed and analyzed. Five focus groups with 44 participants including hearing parents of deaf children, deaf parents and young deaf adults were held. Focus group participants supported the use of genetic tests to identify the etiology of hearing loss but were concerned that genetic information might influence reproductive decisions. Molecular newborn screening was advocated by some; however, others expressed concern about its effectiveness. Documenting the attitudes of parents and other consumers toward genetic technologies establishes the framework for discussions on the appropriateness of molecular newborn screening for hearing loss and informs specialists about potential areas of public education necessary prior to the implementation of such screening.
... Testing CLINSEQ®: A Large-Scale Medical Sequencing Clinical Research Pilot Study Prenatal Screening - Prenatal testing information, including ultrasound, amniocentesis, and chorionic villus sampling ( ...
Mallia, P.; Have, H.A.M.J. ten
Catholic movements within the centre of Roman Catholic doctrine recently have discussed Trinitarian theology as applied to sciences, arts, economics, health and other social areas. We explore the possibilities Trinitarian theology offers to bioethical debate, concentrating particularly on genetic
Dixon, M.L.; Mortimer, R.K.
Mutation, recombination, and mitochondrial deficiencies have been proposed to have roles in the carcinogenic process. The authors describe a diploid strain of the yeast Saccharomyces cerevisiae capable of detecting this wide spectrum of genetic changes. The markers used for monitoring these events have been especially well characterized genetically. Ultraviolet light was chosen as a model carcinogenic agent to test this system. In addition to highly significant increases in the frequencies of each genetic change, increases in the absolute numbers of each change indicated induction and not selective survival. The relative amounts of each type of genetic change varied with dose. The wide spectrum of endpoints monitored in the XD83 yeast system may allow the detection of certain carcinogens and other genetically toxic agents which have escaped detection in more limited systems. Since only one strain is required to simultaneously monitor these genetic changes, this assay system should facilitate comparisons of the induced changes and be more efficient than using multiple strains to monitor the same endpoints. (Auth.)
The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.
Frøslev-Friis, Christina; Hjort-Pedersen, Karina; Henriques, Carsten U
Prenatal screening for karyotype anomalies takes place in most European countries. In Denmark, the screening method was changed in 2005. The aim of this study was to study the trends in prevalence and prenatal detection rates of chromosome anomalies and Down syndrome (DS) over a 22-year period....
Pick, J L; Hutter, P; Tschirren, B
Maternal effects are an important force in nature, but the evolutionary dynamics of the traits that cause them are not well understood. Egg size is known to be a key mediator of prenatal maternal effects with an established genetic basis. In contrast to theoretical expectations for fitness-related traits, there is a large amount of additive genetic variation in egg size observed in natural populations. One possible mechanism for the maintenance of this variation is through genetic constraints caused by a shared genetic basis among traits. Here we created replicated, divergent selection lines for maternal egg investment in Japanese quail (Coturnix japonica) to quantify the role of genetic constraints in the evolution of egg size. We found that egg size responds rapidly to selection, accompanied by a strong response in all egg components. Initially, we observed a correlated response in body size, but this response declined over time, showing that egg size and body size can evolve independently. Furthermore, no correlated response in fecundity (measured as the proportion of days on which a female laid an egg) was observed. However, the response to selection was asymmetrical, with egg size plateauing after one generation of selection in the high but not the low investment lines. We attribute this pattern to the presence of genetic asymmetries, caused by directional dominance or unequal allele frequencies. Such asymmetries may contribute to the evolutionary stasis in egg size observed in natural populations, despite a positive association between egg size and fitness.
Yau, Mabel; Khattab, Ahmed; New, Maria I
Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is a monogenic disorder of adrenal steroidogenesis. To prevent genital ambiguity, in girls, prenatal dexamethasone treatment is administered early in the first trimester. Prenatal genetic diagnosis of CAH and fetal sex determination identify affected female fetuses at risk for genital virilization. Advancements in prenatal diagnosis are owing to improved understanding of the genetic basis of CAH and improved technology. Cloning of the CYP21A2 gene ushered in molecular genetic analysis as the current standard of care. Noninvasive prenatal diagnosis allows for targeted treatment and avoids unnecessary treatment of males and unaffected females. Copyright © 2016 Elsevier Inc. All rights reserved.
M.G.F. van Lier (Margot); S.E. Korsse (Susanne); E.M.H. Mathus-Vliegen (Elisabeth); E.J. Kuipers (Ernst); A.M.W. van den Ouweland (Ans); K. Vanheusden (Kathleen); M.E. van Leerdam (Monique); A. Wagner (Anja)
textabstractPeutz-Jeghers syndrome (PJS) is a hereditary disorder caused by LKB1 gene mutations, and is associated with considerable morbidity and decreased life expectancy. This study was conducted to assess the attitude of PJS patients towards family planning, prenatal diagnosis (PND) and
van Lier, Margot G. F.; Korsse, Susanne E.; Mathus-Vliegen, Elisabeth M. H.; Kuipers, Ernst J.; van den Ouweland, Ans M. W.; Vanheusden, Kathleen; van Leerdam, Monique E.; Wagner, Anja
Peutz-Jeghers syndrome (PJS) is a hereditary disorder caused by LKB1 gene mutations, and is associated with considerable morbidity and decreased life expectancy. This study was conducted to assess the attitude of PJS patients towards family planning, prenatal diagnosis (PND) and pregnancy
... are available for many inherited disorders. The main disadvantage is that diagnostic testing carries a very small ... chromosomes, arranged in order of size. Microarray: A technology that examines all of a person’s genes to ...
Wu, L.; Luo, P.; Di, D.W.; Wang, L.; Wang, M.; Lu, C.K.; Wei, S.D.; Zhang, L.; Zhang, T.Z.; Amakorová, Petra; Strnad, Miroslav; Novák, Ondřej; Guo, G.Q.
Roč. 5, JUL 6 (2015) ISSN 2045-2322 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : ETHYLENE-INSENSITIVE MUTANTS * YUCCA FLAVIN MONOOXYGENASES * ARABIDOPSIS-THALIANA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.228, year: 2015
An exploration via an anonymous questionnaire of Australian public attitudes towards medical genetics and sample banking revealed the overwhelming majority views these developments with thoughtful confidence. Continued public education and awareness of these issues will allow the public to make informed decisions and enhance vigilance towards the sometimes misleading coverage in the press and media.
... discriminant power between the castor bean accesses, being the multivariate analysis efficient in this process. The castor bean accesses ACS-001 CRSP and ACS-001-MASP are promising for introduction in genetic improvement programs of this culture. Keywords: Ricinus communis L., genotype, multivariate statistics, ...
Full Text Available Jean Gekas,1,2 Sylvie Langlois,3 Vardit Ravitsky,4 François Audibert,5 David Gradus van den Berg,6 Hazar Haidar,4 François Rousseau2,7 1Prenatal Diagnosis Unit, Department of Medical Genetics and Pediatrics, Faculty of Medicine, Université Laval, Québec City, QC, Canada; 2Department of Medical Biology, CHU de Québec, Québec City, QC, Canada; 3Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada; 4Bioethics Program, Department of Social and Preventive Medicine, School of Public Health, University of Montreal, Montreal, QC, Canada; 5Department of Obstetrics and Gynecology, Hospital Sainte-Justine, Montreal, QC, Canada; 6Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Québec City, QC, Canada; 7Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Québec City, QC, Canada Abstract: Genomics-based non-invasive prenatal screening using cell-free DNA (cfDNA screening was proposed to reduce the number of invasive procedures in current prenatal diagnosis for fetal aneuploidies. We review here the clinical and ethical issues of cfDNA screening. To date, it is not clear how cfDNA screening is going to impact the performances of clinical prenatal diagnosis and how it could be incorporated in real life. The direct marketing to users may have facilitated the early introduction of cfDNA screening into clinical practice despite limited evidence-based independent research data supporting this rapid shift. There is a need to address the most important ethical, legal, and social issues before its implementation in a mass setting. Its introduction might worsen current tendencies to neglect the reproductive autonomy of pregnant women. Keywords: prenatal diagnosis, Down syndrome, non-invasive prenatal testing, cell-free fetal DNA, informed consent, reproductive autonomy
Gerlai, Robert; Poshusta, Tanya L; Rampersad, Mindy; Fernandes, Yohaan; Greenwood, Tammy M; Cousin, Margot A; Klee, Eric W; Clark, Karl J
The zebrafish enjoys several advantages over other model organisms. It is small, easy to maintain, prolific, and numerous genetic tools are available for it. For example, forward genetic screens have allowed investigators to identify important genes potentially involved in a variety of functions from embryogenesis to cancer. However, despite its sophisticated behavioral repertoire, behavioral methods have rarely been utilized in forward genetic screens. Here, we employ a two-tiered strategy, a proof of concept study, to explore the feasibility of behavioral screens. We generated mutant lines using transposon-based insertional mutagenesis, allowing us to bias mutant selection with target genes expressed within the brain. Furthermore, we employed an efficient and fast behavioral pre-selection in which we investigated the locomotory response of 5-day post-fertilization old larval fish to hyperosmotic shock. Based on this assay, we selected five lines for our lower throughput secondary adult behavioral screen. The latter screen utilized tests in which computer animated image presentation and video-tracking-based automated quantification of behavior allowed us to compare heterozygous zebrafish with their wild-type siblings on their responses to a variety of stimuli. We found significant mutation induced adult behavioral alterations in 4 out of the 5 lines analyzed, including changes in response to social or fear inducing stimuli, to handling and novelty, or in habituation to novelty. We discuss the pros and cons of behavioral phenotyping and of the use of different forward genetic methods in biomedical research with zebrafish.
Toiviainen, Hanna; Jallinoja, Piia; Aro, Arja R
The purpose of this study was to compare physicians', midwives' and lay people's attitudes towards genetic screening and testing to find out whether medical education and experience influence attitudes of genetic screening and testing. The study was based on comparison of answers to joint questions...... in three different cross-sectional postal surveys between October 1996 and April 1998 in Finland. Target groups were physicians (study base n=772, response rate 74%, including gynaecologists, paediatricians, general practitioners and clinical geneticists), midwives and public health nurses (collectively...
Breast cancer is in 5% of cases due to a genetic disposition. BRCA1 and BRCA2 are by far the most common breast cancer susceptibility genes. For a woman with a genetic predisposition, the individual risk of developing breast cancer sometime in her life is between 70 and 90%. Compared to the spontaneous forms of breast cancer, woman with a genetic predisposition often develop breast cancer at a much younger age. This is why conventional screening programs on the basis of mammography alone cannot be applied without modification to this high-risk group. In this article, an integrated screening concept for women with genetic prodisposition for breast cancer using breast self-examination, clinical examination, ultrasound, mammography and magnetic resonance imaging is introduced. (orig.) [de
Shraga, Roman; Yarnall, Sarah; Elango, Sonya; Manoharan, Arun; Rodriguez, Sally Ann; Bristow, Sara L; Kumar, Neha; Niknazar, Mohammad; Hoffman, David; Ghadir, Shahin; Vassena, Rita; Chen, Serena H; Hershlag, Avner; Grifo, Jamie; Puig, Oscar
Current professional society guidelines recommend genetic carrier screening be offered on the basis of ethnicity, or when using expanded carrier screening panels, they recommend to compute residual risk based on ethnicity. We investigated the reliability of self-reported ethnicity in 9138 subjects referred to carrier screening. Self-reported ethnicity gathered from test requisition forms and during post-test genetic counseling, and genetic ancestry predicted by a statistical model, were compared for concordance. We identified several discrepancies between the two sources of self-reported ethnicity and genetic ancestry. Only 30.3% of individuals who indicated Mediterranean ancestry during consultation self-reported this on requisition forms. Additionally, the proportion of individuals who reported Southeast Asian but were estimated to have a different genetic ancestry was found to depend on the source of self-report. Finally, individuals who reported Latin American demonstrated a high degree of ancestral admixture. As a result, carrier rates and residual risks provided for patient decision-making are impacted if using self-reported ethnicity. Our analysis highlights the unreliability of ethnicity classification based on patient self-reports. We recommend the routine use of pan-ethnic carrier screening panels in reproductive medicine. Furthermore, the use of an ancestry model would allow better estimation of carrier rates and residual risks.
Full Text Available Our goal was to test the hypothesis that inter-individual genomic copy number variation in control samples is a confounding factor in the non-invasive prenatal detection of fetal microdeletions via the sequence-based analysis of maternal plasma DNA. The database of genomic variants (DGV was used to determine the "Genomic Variants Frequency" (GVF for each 50kb region in the human genome. Whole genome sequencing of fifteen karyotypically normal maternal plasma and six CVS DNA controls samples was performed. The coefficient of variation of relative read counts (cv.RTC for these samples was determined for each 50kb region. Maternal plasma from two pregnancies affected with a chromosome 5p microdeletion was also sequenced, and analyzed using the GCREM algorithm. We found strong correlation between high variance in read counts and GVF amongst controls. Consequently we were unable to confirm the presence of the microdeletion via sequencing of maternal plasma samples obtained from two sequential affected pregnancies. Caution should be exercised when performing NIPT for microdeletions. It is vital to develop our understanding of the factors that impact the sensitivity and specificity of these approaches. In particular, benign copy number variation amongst controls is a major confounder, and their effects should be corrected bioinformatically.
Derks-Smeets, I A P; Gietel-Habets, J J G; Tibben, A; Tjan-Heijnen, V C G; Meijer-Hoogeveen, M; Geraedts, J P M; van Golde, R; Gomez-Garcia, E; van den Bogaart, E; van Hooijdonk, M; de Die-Smulders, C E M; van Osch, L A D M
How do couples with a BRCA1/2 mutation decide on preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) for hereditary breast and ovarian cancer syndrome (HBOC)? BRCA couples primarily classify PGD and/or PND as reproductive options based on the perceived severity of HBOC and moral considerations, and consequently weigh the few important advantages of PGD against numerous smaller disadvantages. Awareness of PGD is generally low among persons at high risk for hereditary cancers. Most persons with HBOC are in favour of offering PGD for BRCA1/2 mutations, although only a minority would consider this option for themselves. Studies exploring the motivations for using or refraining from PGD among well-informed BRCA carriers of reproductive age are lacking. We studied the reproductive decision-making process by interviewing a group of well-informed, reproductive aged couples carrying a BRCA1/2 mutation, regarding their decisional motives and considerations. This exploratory, qualitative study investigated the motives and considerations taken into account by couples with a BRCA1/2 mutation and who have received extensive counselling on PGD and PND and have made a well-informed decision regarding this option. Eighteen couples took part in focus group and dyadic interviews between January and September 2012. Semi-structured focus groups were conducted containing two to four couples, assembled based on the reproductive method the couple had chosen: PGD (n = 6 couples) or conception without testing (n = 8 couples). Couples who had chosen PND for BRCA (n = 4) were interviewed dyadically. Two of the women, of whom one had chosen PND and the other had chosen no testing, had a history of breast cancer. None of the couples who opted for PGD or conception without testing found the use of PND, with possible pregnancy termination, acceptable. PND users chose this method because of decisive, mainly practical reasons (natural conception, high chance of favourable outcome
Manotaya, S.; Xu, H.; Uerpairojkit, B.
-risk pregnancies, either with advanced maternal age or positive serum biochemical tests, and 1889 low-risk pregnancies without conventional indications; 99.9% (4732/4736) of the participants with a median maternal age of 35years old received reports, and 1.3% (63/4732) were classified as test positive, including...... testing (NIPT) has enabled efficient and accurate screening for T21, T18 and T13. Various professional societies suggested that NIPT could be considered as a second-tier screening test for women at high risk for aneuploidy. What does this study add? This study reports the performance of NIPT...
Full Text Available Prevention of Hemoglobinopathies has developed around the world based upon the experience done in pioneering endemic countries and is now facing a new phase in non-endemic areas with a recent immigration history. We describe two situations, taking Latium (central Italy and The Netherlands as two models for endemic and non-endemic countries both confronted with a large multi-ethnic immigrant society. We present prevention results and discuss aspects such as local knowledge and organization. We illustrate the importance of issues like information, carrier diagnostics, screening, counseling and prenatal diagnosis in particular situation of contrasting interest an different ethical opinions. We conclude by underlining the importance of implementing primary prevention at the European level, based upon better information, diagnostics and counseling.
Full Text Available The metabolic syndrome (MetS is described as a cluster of health conditions that are associated with an increased risk of cardiovascular disease. The clinical diagnosis of MetS in pediatrics is challenging due to differing criteria, although the estimated prevalence continues to rise. The increased prevalence of childhood obesity and insulin resistance, in both developed and developing countries, is believed to be a major contributor to MetS diagnosis in children. We review the current literature surrounding genetic predisposition, maternal influence, epigenetics, environmental and lifestyle factors pertaining to pediatric MetS with a specific emphasis on obesity and insulin resistance. We highlight and discuss recent, key studies in prenatal through to adolescent populations and review evidence suggesting that children may be pre-disposed to obesity and insulin resistance, prenatally. We also discuss several key lifestyle drivers of these conditions including poor nutrition and dietary habits, insufficient physical activity, use of electronic devices, over-consumption of caffeinated and/or sugar-sweetened beverages, as well as the importance of sleep during childhood and adolescence in relation to metabolic health. We conclude with recommendations for preventable methods to tackle this growing pediatric public health issue, which, if current trends continue, will undoubtedly compromise the health and longevity of the next adult generation.
Full Text Available Genetic tests frequently produce more information than is initially expected. Several documents have addressed this issue and offer suggestions regarding how this information should be managed and, in particular, concerning the expedience of revealing (or not revealing it to the persons concerned. While the approaches to the management of these incidental findings (IFs vary, it is usually recommended that the information be disclosed if there is confirmed clinical utility and the possibility of treatment or prevention. However, this leaves unsolved some fundamental issues such as the different ways of interpreting "clinical utility", countless sources of uncertainty and varying ways of defining the notion of "incidental". Guidelines and other reference documents can offer indications to those responsible for managing IFs but should not be allowed to relieve researchers and healthcare professionals of their responsibilities.
RESEARCH NOTE. Genetic screening of EXT1 and EXT2 in Cypriot families with hereditary .... on samples from the HMO patient's parents in an attempt to establish .... Intragenic deletions involving single or multiple EXT1 or. EXT2 exons are ...
Barad, David H; Darmon, Sarah K; Kushnir, Vitaly A; Albertini, David F; Gleicher, Norbert
Our objective was to estimate the contribution of preimplantation genetic screening to in vitro fertilization pregnancy outcomes in donor oocyte-recipient cycles. This was a retrospective cross-sectional study of US national data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System between 2005 and 2013. Society for Assisted Reproductive Technology Clinic Outcome Reporting relies on voluntarily annual reports by more than 90% of US in vitro fertilization centers. We evaluated pregnancy and live birth rates in donor oocyte-recipient cycles after the first embryo transfer with day 5/6 embryos. Statistical models, adjusted for patient and donor ages, number of embryos transferred, race, infertility diagnosis, and cycle year were created to compare live birth rates in 392 preimplantation genetic screening and 20,616 control cycles. Overall, pregnancy and live birth rates were significantly lower in preimplantation genetic screening cycles than in control cycles. Adjusted odds of live birth for preimplantation genetic screening cycles were reduced by 35% (odds ratio, 0.65, 95% confidence interval, 0.53-0.80; P cycles over the past 9 years, has not been associated with improved odds of live birth or reduction in miscarriage rates. Copyright © 2017 Elsevier Inc. All rights reserved.
Chow, J Fc; Yeung, W Sb; Lee, V Cy; Lau, E Yl; Ho, P C; Ng, E Hy
Preimplantation genetic screening has been proposed to improve the in-vitro fertilisation outcome by screening for aneuploid embryos or blastocysts. This study aimed to report the outcome of 133 cycles of preimplantation genetic diagnosis and screening by array comparative genomic hybridisation. This study of case series was conducted in a tertiary assisted reproductive centre in Hong Kong. Patients who underwent preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening between 1 April 2012 and 30 June 2015 were included. They underwent in-vitro fertilisation and intracytoplasmic sperm injection. An embryo biopsy was performed on day-3 embryos and the blastomere was subject to array comparative genomic hybridisation. Embryos with normal copy numbers were replaced. The ongoing pregnancy rate, implantation rate, and miscarriage rate were studied. During the study period, 133 cycles of preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening were initiated in 94 patients. Overall, 112 cycles proceeded to embryo biopsy and 65 cycles had embryo transfer. The ongoing pregnancy rate per transfer cycle after preimplantation genetic screening was 50.0% and that after preimplantation genetic diagnosis was 34.9%. The implantation rates after preimplantation genetic screening and diagnosis were 45.7% and 41.1%, respectively and the miscarriage rates were 8.3% and 28.6%, respectively. There were 26 frozen-thawed embryo transfer cycles, in which vitrified and biopsied genetically transferrable embryos were replaced, resulting in an ongoing pregnancy rate of 36.4% in the screening group and 60.0% in the diagnosis group. The clinical outcomes of preimplantation genetic diagnosis and screening using comparative genomic hybridisation in our unit were comparable to those reported internationally. Genetically transferrable embryos replaced in a natural cycle may improve the ongoing pregnancy rate
Kaback, Michael; Lopatequi, Jean; Portuges, Amin Riley; Quindipan, Cathy; Pariani, Mitchel; Salimpour-Davidov, Nilou; Rimoin, David L
Israeli investigators have identified several relatively frequent disorders due to founder point mutations in Persian (Iranian) Jews, who, for nearly three centuries up to the Islamic Revolution of 1979, were completely isolated reproductively. Using a community-based model previously employed with Tay-Sachs disease prevention, we developed a pilot program for the Persian Jewish community of greater Los Angeles. We screened for mutations responsible for four relatively frequent autosomal recessive conditions in Persian Jews in which effective interventions are available for each: Pseudocholinesterase deficiency (butyryl cholinesterase deficiency); Congenital hypoaldosteronism (corticosterone methyl oxidase II); Autoimmune polyendocrinopathy (autoimmune regulatory element); and Hereditary Inclusion Body myopathy. One thousand individuals volunteered. Mutations were assessed in saliva-derived DNA and were positive for 121/1000 butyryl cholinesterase deficiency; 92/1000 Hereditary Inclusion Body myopathy; 38/1000 corticosterone methyl oxidase II; and 37/1000 autoimmune regulatory element. Ten homozygous individuals (9 butyryl cholinesterase deficiency and 1 Hereditary Inclusion Body myopathy) and 10 "at-risk" couples (seven for butyryl cholinesterase deficiency and one each for the other three disorders) were identified. These frequencies are comparable with those in Israel and indicate an extraordinary level of inbreeding, as anticipated. A carefully planned effort can be delivered to an "increased risk" community if detailed attention is given to planning and organization. However, availability of an effective intervention for those found to be "at-risk" or possibly affected, is essential before embarking.
Hull, Danna; Davies, Gregory; Armour, Christine M
To explore prenatal practices related to aneuploidy screening, risk modification, and invasive diagnostic procedures across Canadian centres. We conducted a survey of members of the Canadian Association of Genetic Counsellors, the Canadian College of Medical Genetics, and the Canadian Society of Maternal Fetal Medicine, who provide direct counselling or management of prenatal patients in Canada. Eighty-two of 157 respondents indicated that their centre's definition of advanced maternal age was ≥ 35 years, with 33/157 respondents reporting an advanced maternal age definition of ≥ 40 years. The majority of respondents reported that prenatal serum screening for aneuploidy is provincially funded in their province or territory (121/147). The majority of respondents who reported that prenatal screening is not provincially funded (17/147) were from Quebec (14/17). Thirty-nine of 123 respondents reported that their centre defines increased nuchal translucency as ≥ 3.0 mm, whereas 49/123 reported a definition of ≥ 3.5 mm. Sixty-four of 150 respondents reported that the aneuploidy risk provided by serum screening is modified by a soft marker likelihood ratio, whereas 46/150 respondents reported that both age-related and serum screening risks are modified. Fifty-nine of 124 respondents reported that their centre will modify aneuploidy risk after a normal ultrasound; the most commonly cited negative likelihood ratio was 0.5. The most commonly reported procedure-related risk for chorionic villus sampling was 1/100 (123/147) and for amniocentesis was 1/200 (73/142). This study demonstrates inconsistencies in prenatal practices and access to screening programs across Canada. The information gained from this study will inform policy advisors developing prenatal practice guidelines at both the provincial and national levels.
... tests are considered routine — that is, almost all pregnant women receiving prenatal care get them. They include things like checking urine (pee) levels for protein, sugar, or signs of infection. Other non-routine ...
... Testing CLINSEQ®: A Large-Scale Medical Sequencing Clinical Research Pilot Study Prenatal Screening - Prenatal testing information, including ultrasound, amniocentesis, and chorionic villus sampling ( ...
Farrell, Ruth M; Dolgin, Natasha; Flocke, Susan A; Winbush, Victoria; Mercer, Mary Beth; Simon, Christian
The clinical introduction of first trimester aneuploidy screening uniquely challenges the informed consent process for both patients and providers. This study investigated key aspects of the decision-making process for this new form of prenatal genetic screening. Qualitative data were collected by nine focus groups that comprised women of different reproductive histories (N = 46 participants). Discussions explored themes regarding patient decision making for first trimester aneuploidy screening. Sessions were audio recorded, transcribed, coded, and analyzed to identify themes. Multiple levels of uncertainty characterize the decision-making process for first trimester aneuploidy screening. Baseline levels of uncertainty existed for participants in the context of an early pregnancy and the debate about the benefit of fetal genetic testing in general. Additional sources of uncertainty during the decision-making process were generated from weighing the advantages and disadvantages of initiating screening in the first trimester as opposed to waiting until the second. Questions of the quality and quantity of information and the perceived benefit of earlier access to fetal information were leading themes. Barriers to access prenatal care in early pregnancy presented participants with additional concerns about the ability to make informed decisions about prenatal genetic testing. The option of the first trimester aneuploidy screening test in early pregnancy generates decision-making uncertainty that can interfere with the informed consent process. Mechanisms must be developed to facilitate informed decision making for this new form of prenatal genetic screening.
Biochemical genetic testing and newborn screening are essential laboratory services for the screening, detection, diagnosis, and monitoring of inborn errors of metabolism or inherited metabolic disorders. Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is categorized on the basis of the level of testing complexity as either waived (i.e., from routine regulatory oversight) or nonwaived testing (which includes tests of moderate and high complexity). Laboratories that perform biochemical genetic testing are required by CLIA regulations to meet the general quality systems requirements for nonwaived testing and the personnel requirements for high-complexity testing. Laboratories that perform public health newborn screening are subject to the same CLIA regulations and applicable state requirements. As the number of inherited metabolic diseases that are included in state-based newborn screening programs continues to increase, ensuring the quality of performance and delivery of testing services remains a continuous challenge not only for public health laboratories and other newborn screening facilities but also for biochemical genetic testing laboratories. To help ensure the quality of laboratory testing, CDC collaborated with the Centers for Medicare & Medicaid Services, the Food and Drug Administration, the Health Resources and Services Administration, and the National Institutes of Health to develop guidelines for laboratories to meet CLIA requirements and apply additional quality assurance measures for these areas of genetic testing. This report provides recommendations for good laboratory practices that were developed based on recommendations from the Clinical Laboratory Improvement Advisory Committee, with additional input from the Secretary's Advisory Committee on Genetics, Health, and Society; the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; and representatives of newborn
Pressman, Sigal; Reinke, Catherine A; Wang, Xiaohong; Carthew, Richard W
A central goal of microRNA biology is to elucidate the genetic program of miRNA function and regulation. However, relatively few of the effectors that execute miRNA repression have been identified. Because such genes may function in many developmental processes, mutations in them are expected to be pleiotropic and thus are discarded in most standard genetic screens. Here, we describe a systematic screen designed to identify all Drosophila genes in ∼40% of the genome that function in the miRNA pathway. To identify potentially pleiotropic genes, the screen analyzed clones of homozygous mutant cells in heterozygous animals. We identified 45 mutations representing 24 genes, and we molecularly characterized 9 genes. These include 4 previously known genes that encode core components of the miRNA pathway, including Drosha, Pasha, Dicer-1, and Ago1. The rest are new genes that function through chromatin remodeling, signaling, and mRNA decapping. The results suggest genetic screens that use clonal analysis can elucidate the miRNA program and that ∼100 genes are required to execute the miRNA program.
Full Text Available Background: Selection of the best embryo for transfer is very important in assisted reproductive technology (ART. Using morphological assessment for this selection demonstrated that the correlation between embryo morphology and implantation potential is relatively weak. On the other hand, aneuploidy is a key genetic factor that can influence human reproductive success in ART. Objective: The aim of this lab trial study was to evaluate the incidence of aneuploidies in five chromosomes in the morphologically high-quality embryos from young patients undergoing ART for sex selection. Materials and Methods: A total of 97 high quality embryos from 23 women at the age of 37or younger years that had previously undergone preimplantation genetic screening for sex selection were included in this study. After washing, the slides of blastomeres from embryos of patients were reanalyzed by fluorescence in-situ hybridization for chromosomes 13, 18 and 21. Results: There was a significant rate of aneuploidy determination in the embryos using preimplantation genetic screening for both sex and three evaluated autosomal chromosomes compared to preimplantation genetic screening for only sex chromosomes (62.9% vs. 24.7%, p=0.000. The most frequent detected chromosomal aneuploidy was trisomy or monosomy of chromosome 13. Conclusion: There is considerable numbers of chromosomal abnormalities in embryos generated in vitro which cause in vitro fertilization failure and it seems that morphological characterization of embryos is not a suitable method for choosing the embryos without these abnormalities
Gong, Meng; Shi, Hua; Zhang, Yu-guo; Ming, Lei
To investigate whether assisted reproductive technology (ART) increases the risk of fetal chromosomal abnormalities. A total of 2034 singleton pregnant women were included in this retrospective study. They were divided into ART (574 fetuses) and control groups (1460 fetuses conceived naturally). All pregnant women received screening according to the Fetal Medicine Foundation, London 2004 Kypros H. Nicolaides guidelines at 11-13+6 weeks of gestation. Accordingly, women with value at risk of chromosomal abnormalities >1:250 underwent chorionic villus sampling or amniocentesis. Mean body mass index was 22.83 ± 3.27 versus 21.29 ± 2.81 kg/m(2) in the ART and control groups, respectively (P fetal chromosomal abnormalities. Additionally, fetus size in the ART group was bigger than that in the natural conception group. © 2015 Japan Society of Obstetrics and Gynecology.
Choi, Su-Lim; Rha, Eugene; Lee, Sang Jun; Kim, Haseong; Kwon, Kilkoang; Jeong, Young-Su; Rhee, Young Ha; Song, Jae Jun; Kim, Hak-Sung; Lee, Seung-Goo
Large-scale screening of enzyme libraries is essential for the development of cost-effective biological processes, which will be indispensable for the production of sustainable biobased chemicals. Here, we introduce a genetic circuit termed the Genetic Enzyme Screening System that is highly useful for high-throughput enzyme screening from diverse microbial metagenomes. The circuit consists of two AND logics. The first AND logic, the two inputs of which are the target enzyme and its substrate, is responsible for the accumulation of a phenol compound in cell. Then, the phenol compound and its inducible transcription factor, whose activation turns on the expression of a reporter gene, interact in the other logic gate. We confirmed that an individual cell harboring this genetic circuit can present approximately a 100-fold higher cellular fluorescence than the negative control and can be easily quantified by flow cytometry depending on the amounts of phenolic derivatives. The high sensitivity of the genetic circuit enables the rapid discovery of novel enzymes from metagenomic libraries, even for genes that show marginal activities in a host system. The crucial feature of this approach is that this single system can be used to screen a variety of enzymes that produce a phenol compound from respective synthetic phenyl-substrates, including cellulase, lipase, alkaline phosphatase, tyrosine phenol-lyase, and methyl parathion hydrolase. Consequently, the highly sensitive and quantitative nature of this genetic circuit along with flow cytometry techniques could provide a widely applicable toolkit for discovering and engineering novel enzymes at a single cell level.
Waiblinger, Hans-Ulrich; Grohmann, Lutz; Mankertz, Joachim; Engelbert, Dirk; Pietsch, Klaus
In routine analysis, screening methods based on real-time PCR are most commonly used for the detection of genetically modified (GM) plant material in food and feed. In this paper, it is shown that the combination of five DNA target sequences can be used as a universal screening approach for at least 81 GM plant events authorised or unauthorised for placing on the market and described in publicly available databases. Except for maize event LY038, soybean events DP-305423 and BPS-CV127-9 and cotton event 281-24-236 x 3006-210-23, at least one of the five genetic elements has been inserted in these GM plants and is targeted by this screening approach. For the detection of these sequences, fully validated real-time PCR methods have been selected. A screening table is presented that describes the presence or absence of the target sequences for most of the listed GM plants. These data have been verified either theoretically according to available databases or experimentally using available reference materials. The screening table will be updated regularly by a network of German enforcement laboratories.
Niimi, Hideki; Ogawa, Tomomi; Note, Rhougou; Hayashi, Shirou; Ueno, Tomohiro; Harada, Kenu; Uji, Yoshinori; Kitajima, Isao
In recent years, genetic diagnostics of pathogenic splicing abnormalities are increasingly recognized as critically important in the clinical genetic diagnostics. It is reported that approximately 10% of pathogenic mutations causing human inherited diseases are splicing mutations. Nonetheless, it is still difficult to identify splicing abnormalities in routine genetic diagnostic settings. Here, we studied two different kinds of cases with splicing abnormalities. The first case is a protein S deficiency. Nucleotide analyses revealed that the proband had a previously reported G to C substitution in the invariant AG dinucleotide at the splicing acceptor site of intronl/exon2, which produces multiple splicing abnormalities resulting in protein S deficiency. The second case is an antithrombin (AT) deficiency. This proband had a previously reported G to A substitution, at nucleotide position 9788 in intron 4, 14 bp in front of exon 5, which created a de novo exon 5 splice site and resulted in AT deficiency. From a practical standpoint, we discussed the pitfalls, attentions, and screening approaches in genetic diagnostics of pathogenic splicing abnormalities. Due to the difficulty with full-length sequence analysis of introns, and the lack of RNA samples, splicing mutations may escape identification. Although current genetic testing remains to be improved, to screen for splicing abnormalities more efficiently, it is significant to use an appropriate combination of various approaches such as DNA and/or RNA samples, splicing mutation databases, bioinformatic tools to detect splice sites and cis-regulatory elements, and in vitro and/or in vivo experimentally methods as needed.
Elmar W Tobi
Full Text Available Both the early environment and genetic variation may affect DNA methylation, which is one of the major molecular marks of the epigenome. The combined effect of these factors on a well-defined locus has not been studied to date. We evaluated the association of periconceptional exposure to the Dutch Famine of 1944-45, as an example of an early environmental exposure, and single nucleotide polymorphisms covering the genetic variation (tagging SNPs with DNA methylation at the imprinted IGF2/H19 region, a model for an epigenetically regulated genomic region. DNA methylation was measured at five differentially methylated regions (DMRs that regulate the imprinted status of the IGF2/H19 region. Small but consistent differences in DNA methylation were observed comparing 60 individuals with periconceptional famine exposure with unexposed same-sex siblings at all IGF2 DMRs (P(BH<0.05 after adjustment for multiple testing, but not at the H19 DMR. IGF2 DMR0 methylation was associated with IGF2 SNP rs2239681 (P(BH = 0.027 and INS promoter methylation with INS SNPs, including rs689, which tags the INS VNTR, suggesting a mechanism for the reported effect of the VNTR on INS expression (P(BH = 3.4 × 10(-3. Prenatal famine and genetic variation showed similar associations with IGF2/H19 methylation and their contributions were additive. They were small in absolute terms (<3%, but on average 0.5 standard deviations relative to the variation in the population. Our analyses suggest that environmental and genetic factors could have independent and additive similarly sized effects on DNA methylation at the same regulatory site.
In 1969, the field of human genetics was in its infancy. Amniocentesis was a new technique for prenatal diagnosis, and a newborn genetic screening program had been established in one state. There were also concerns about the potential hazards of genetic engineering. A research group at the Hastings Center and Paul Ramsey pioneered in the discussion of genetics and bioethics. Two principal techniques have emerged as being of enduring importance: human gene transfer research and genetic testing and screening. This essay tracks the development and use of these techniques and considers the ethical issues that they raise.
Ryu, Jung Kyu; Cho, Jeong Yeon; Lee, Young Ho; Kim, Ei Jeong; Chun, Yi Kyeong [Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)
Focal musculoskeletal anomalies are various and may be an isolated finding or may be found in conjunction with numerous associations, including genetic syndromes, Karyotype abnormals, central nervous system anomalies and other general musculoskeletal disorders. Early prenatal diagnosis of these focal musculoskeletal anomalies nor only affects prenatal care and postnatal outcome but also helps in approaching other numerous associated anomalies.
Ryu, Jung Kyu; Cho, Jeong Yeon; Lee, Young Ho; Kim, Ei Jeong; Chun, Yi Kyeong
Focal musculoskeletal anomalies are various and may be an isolated finding or may be found in conjunction with numerous associations, including genetic syndromes, Karyotype abnormals, central nervous system anomalies and other general musculoskeletal disorders. Early prenatal diagnosis of these focal musculoskeletal anomalies nor only affects prenatal care and postnatal outcome but also helps in approaching other numerous associated anomalies.
Ramos, Laia; Daina, Gemma; Del Rey, Javier; Ribas-Maynou, Jordi; Fernández-Encinas, Alba; Martinez-Passarell, Olga; Boada, Montserrat; Benet, Jordi; Navarro, Joaquima
To assess whether preimplantation genetic screening can successfully identify cytogenetically normal embryos in couples carrying balanced chromosome rearrangements in addition to increased sperm DNA fragmentation. Comprehensive preimplantation genetic screening was performed on three couples carrying chromosome rearrangements. Sperm DNA fragmentation was assessed for each patient. Academic center. One couple with the male partner carrying a chromosome 2 pericentric inversion and two couples with the male partners carrying a Robertsonian translocation (13:14 and 14:21, respectively). A single blastomere from each of the 18 cleavage-stage embryos obtained was analysed by metaphase comparative genomic hybridization. Single- and double-strand sperm DNA fragmentation was determined by the alkaline and neutral Comet assays. Single- and double-strand sperm DNA fragmentation values and incidence of chromosome imbalances in the blastomeres were analyzed. The obtained values of single-strand sperm DNA fragmentation were between 47% and 59%, and the double-strand sperm DNA fragmentation values were between 43% and 54%. No euploid embryos were observed in the couple showing the highest single-strand sperm DNA fragmentation. However, euploid embryos were observed in the other two couples: embryo transfer was performed, and pregnancy was achieved by the couple showing the lowest sperm DNA fragmentation values. Preimplantation genetic screening enables the detection of euploid embryos in couples affected by balanced chromosome rearrangements and increased sperm DNA fragmentation. Even though sperm DNA fragmentation may potentially have clinical consequences on fertility, comprehensive preimplantation genetic screening allows for the identification and transfer of euploid embryos. Copyright © 2015. Published by Elsevier Inc.
Sapiro, Anne L; Ihry, Robert J; Buhr, Derek L; Konieczko, Kevin M; Ives, Sarah M; Engstrom, Anna K; Wleklinski, Nicholas P; Kopish, Kristin J; Bashirullah, Arash
Mutagenesis screens are a staple of classical genetics. Chemical-induced mutations, however, are often difficult and time-consuming to identify. Here, we report that recombination analysis with pairs of dominant visible markers provides a rapid and reliable strategy to map mutations in Drosophila melanogaster. This method requires only two generations and a total of six crosses in vials to estimate the genetic map position of the responsible lesion with high accuracy. This genetic map position can then be reliably used to identify the mutated gene through complementation testing with an average of nine deficiencies and Sanger sequencing. We have used this approach to successfully map a collection of mutations from an ethyl methanesulfonate-based mutagenesis screen on the third chromosome. We propose that this method also may be used in conjunction with whole-genome sequencing, particularly when multiple independent alleles of the mutated locus are not available. By facilitating the rapid identification of mutated genes, our mapping strategy removes a primary obstacle to the widespread use of powerful chemical mutagenesis screens to understand fundamental biological phenomena.
Filkins, K.; Russo, R.J.
The multiauthor text is written as a ''guide to rationalize and clarify certain aspects of diagnosis, general counseling and intervention'' for ''health professionals who provide care to pregnant women.'' The text is not aimed at the ultrasonographer but rather at the physicians who are clinically responsible for patient management. Chapters of relevance to radiologists include an overview of prenatal screening and counseling, diagnosis of neural tube defects, ultrasonographic (US) scanning of fetal disorders in the first and second trimesters of pregnancy, US scanning in the third trimester, multiple gestation and selective termination, fetal echo and Doppler studies, and fetal therapy. Also included are overviews of virtually all currently utilized prenatal diagnostic techniques including amniocentesis, fetal blood sampling, fetoscopy, recombinant DNA detection of hemoglobinopathies, chorionic villus sampling, embryoscopy, legal issues, and diagnosis of Mendelian disorders by DNA analysis
Full Text Available One of the landmarks in clinical genetics is prenatal diagnosis of genetic disorders. The recent advances in the field have made it possible to diagnose the genetic conditions in the embryos before implantation in a setting of in vitro fertilization. Polymerase chain reaction and fluorescence in situ hybridization are the two common techniques employed on a single or two cells obtained via embryo biopsy. The couple who seek in vitro fertilization may screen their embryos for aneuploidy and the couple at risk for a monogenic disorder but averse to abortion of the affected fetuses after prenatal diagnosis, are likely to be the best candidates to undergo this procedure. This article reviews the technique, indications, benefits, and limitations of pre-implantation genetic testing in clinical practice.
Ring, Kari L; Garcia, Christine; Thomas, Martha H; Modesitt, Susan C
The world of hereditary cancers has seen exponential growth in recent years. While hereditary breast and ovarian cancer and Lynch syndrome account for the majority of mutations encountered by gynecologists, newly identified deleterious genetic mutations continue to be unearthed with their associated risks of malignancies. However, these advances in genetic cancer predispositions then force practitioners and their patients to confront the uncertainties of these less commonly identified mutations and the fact that there is limited evidence to guide them in expected cancer risk and appropriate risk-reduction strategies. Given the speed of information, it is imperative to involve cancer genetics experts when counseling these patients. In addition, coordination of screening and care in conjunction with specialty high-risk clinics, if available, allows for patients to have centralized management for multiple cancer risks under the guidance of physicians with experience counseling these patients. The objective of this review is to present the current literature regarding genetic mutations associated with gynecologic malignancies as well to propose screening and risk-reduction options for these high-risk patients. Copyright © 2017 Elsevier Inc. All rights reserved.
Graffigna, Guendalina; Leone, Daniela; Vegni, Elena
How do patients with thrombophilia experience a physician's request to undergo a genetic test? How do they experience the test outcome? To answer these questions, we conducted an interpretative phenomenological analysis study, based on 10 in-depth interviews with patients who underwent genetic testing for thrombophilia in Italy, half with positive and half with negative results. The experience of undergoing genetic screening for thrombophilia plays an important role in reconfiguring patients' signification of their illness experience. A positive outcome becomes a cue to reorganize in a more adaptive way the illness meaning at the cognitive and emotive levels, whereas a negative outcome appears more distressing and confusing. As a clinical implication of the study, clinicians should consider communicating carefully with the patients regardless from the positive/negative test results and they should explore the patient's specific reaction and understanding of test result.
Ossa, Diego F; Towse, Adrian
The potential use of genetic tests in insurance has raised concerns about discrimination and individuals losing access to health care either because of refusals to test for treatable diseases, or because test-positives cannot afford premiums. Governments have so far largely sought to restrict the use of genetic information by insurance companies. To date the number of tests available with significant actuarial value is limited. However, this is likely to change, raising more clearly the question as to whether the social costs of adverse selection outweigh the social costs of individuals not accessing health care for fear of the consequences of test information being used in insurance markets. In this contribution we set out the policy context and model the potential trade-offs between the losses faced by insurers from adverse selection by insurees (which will increase premiums reducing consumer welfare) and the detrimental health effects that may result from persons refusing to undergo tests that could identify treatable health conditions. It argues that the optimal public policy on genetic testing should reflect overall societal benefit, taking account of these trade-offs. Based on our model, the factors that influence the outcome include: the size of and value attached to the health gains from treatment; deterrent effects of a disclosure requirement on testing for health reasons; incidence of the disease; propensity of test-positives to adverse select; policy value adverse selectors buy in a non-disclosure environment; and price elasticity of demand for insurance. Our illustrative model can be used as a benchmark for developing other scenarios or incorporating real data in order to address the impact of different policies on disclosure and requirement to test.
Health Resources and Services Administration (DHHS/PHS), Rockville, MD. Office for Maternal and Child Health Services.
This booklet is the first in a series of publications designed to provide parents with useful information about childrearing. Contents are organized into three parts. Part I focuses on the pregnancy, prenatal care, development of the baby, pregnant lifestyles, nutrition, common discomforts, and problems of pregnancy. Part II provides information…
Bui, T H; Kristoffersson, U
Invasive prenatal diagnosis was introduced in Sweden in the early 1970s and is an integral part of the public health care system. Funding is provided by taxation; the patient only pays a consultation fee. Genetic analyses on a broad range of cytogenetic and molecular disorders are performed at the 6 university-affiliated hospitals and in 1 county hospital. About 6% of all newborns have been cytogenetically screened during pregnancy, and about 90% of the analyses are performed after amniocentesis. The main indication is chromosome analysis because of advanced maternal age.
Palmer, K T; Poole, J; Rawbone, R G; Coggon, D
Tests of genotype may enable workers at unusual risk of future ill-health to be identified. Using them to select for employment, however, entails gains and losses to employers and employees. Ensuring a fair balance between the rights and obligations of each group requires a value judgement, but the advantages and disadvantages to interested parties must first be quantified in a meaningful way. The purposes of pre-employment screening are reviewed, and several simple measures relevant to the separate interests of employers and job applicants proposed-number screened to prevent a single adverse outcome; number excluded to prevent a case; expected incidence of the adverse outcome in those excluded; and preventable fraction. The derivation of these measures is illustrated, and the factors that influence them (the prevalence of the prognostic trait, the relative risk that it carries for an adverse outcome, and the overall incidence of disease) are related algebraically and graphically, to aid judgement on the utility of screening under different circumstances. In sensitive areas such as genetic testing the onus should be on the employer to justify plans for pre-placement screening. Several quantitative measures can be used to inform the ethical and economic debate about screening and to evaluate alternative strategies for prevention.
Pei, Wuhong; Xu, Lisha; Huang, Sunny C; Pettie, Kade; Idol, Jennifer; Rissone, Alberto; Jimenez, Erin; Sinclair, Jason W; Slevin, Claire; Varshney, Gaurav K; Jones, MaryPat; Carrington, Blake; Bishop, Kevin; Huang, Haigen; Sood, Raman; Lin, Shuo; Burgess, Shawn M
Regenerative medicine holds great promise for both degenerative diseases and traumatic tissue injury which represent significant challenges to the health care system. Hearing loss, which affects hundreds of millions of people worldwide, is caused primarily by a permanent loss of the mechanosensory receptors of the inner ear known as hair cells. This failure to regenerate hair cells after loss is limited to mammals, while all other non-mammalian vertebrates tested were able to completely regenerate these mechanosensory receptors after injury. To understand the mechanism of hair cell regeneration and its association with regeneration of other tissues, we performed a guided mutagenesis screen using zebrafish lateral line hair cells as a screening platform to identify genes that are essential for hair cell regeneration, and further investigated how genes essential for hair cell regeneration were involved in the regeneration of other tissues. We created genetic mutations either by retroviral insertion or CRISPR/Cas9 approaches, and developed a high-throughput screening pipeline for analyzing hair cell development and regeneration. We screened 254 gene mutations and identified 7 genes specifically affecting hair cell regeneration. These hair cell regeneration genes fell into distinct and somewhat surprising functional categories. By examining the regeneration of caudal fin and liver, we found these hair cell regeneration genes often also affected other types of tissue regeneration. Therefore, our results demonstrate guided screening is an effective approach to discover regeneration candidates, and hair cell regeneration is associated with other tissue regeneration.
Prenatal diagnosis and molecular cytogenetic characterization of a derivative chromosome der(18;18(q10;q10del(18(q11.1q12.1del(18(q22.1q22.3 presenting as apparent isochromosome 18q in a fetus with holoprosencephaly
Conclusion: Concomitant monosomy 18p and trisomy 18q can be associated with holoprosencephaly and abnormal maternal serum screening results. Array-comparative genomic hybridization, fluorescence in situ hybridization, and quantitative fluorescent polymerase chain reaction are useful in genetic counseling of prenatally detected isochromosomes by providing information on the origin and genetic components of the isochromosome.
Baker, Jessica; Shuman, Cheryl; Chitayat, David; Wasim, Syed; Okun, Nan; Keunen, Johannes; Hofstedter, Renee; Silver, Rachel
The introduction of chromosomal microarray (CMA) into the prenatal setting has involved considerable deliberation due to the wide range of possible outcomes (e.g., copy number variants of uncertain clinical significance). Such issues are typically discussed in pre-test counseling for pregnant women to support informed decision-making regarding prenatal testing options. This research study aimed to assess the level of informed decision-making with respect to prenatal CMA and the factor(s) influencing decision-making to accept CMA for the selected prenatal testing procedure (i.e., chorionic villus sampling or amniocentesis). We employed a questionnaire that was adapted from a three-dimensional measure previously used to assess informed decision-making with respect to prenatal screening for Down syndrome and neural tube defects. This measure classifies an informed decision as one that is knowledgeable, value-consistent, and deliberated. Our questionnaire also included an optional open-ended question, soliciting factors that may have influenced the participants' decision to accept prenatal CMA; these responses were analyzed qualitatively. Data analysis on 106 participants indicated that 49% made an informed decision (i.e., meeting all three criteria of knowledgeable, deliberated, and value-consistent). Analysis of 59 responses to the open-ended question showed that "the more information the better" emerged as the dominant factor influencing both informed and uninformed participants' decisions to accept prenatal CMA. Despite learning about the key issues in pre-test genetic counseling, our study classified a significant portion of women as making uninformed decisions due to insufficient knowledge, lack of deliberation, value-inconsistency, or a combination of these three measures. Future efforts should focus on developing educational approaches and counseling strategies to effectively increase the rate of informed decision-making among women offered prenatal CMA.
Middleton, Anna; Patch, Chris; Wiggins, Jennifer; Barnes, Kathy; Crawford, Gill; Benjamin, Caroline; Bruce, Anita
The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest ‘opportunistic genomic screening' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), w...
Kerruish, Nicola J; Healey, Dione M; Gray, Andrew R
Little is known about the psychosocial consequences of testing newborns for genetic susceptibility to multifactorial diseases. This study reports quantitative psychosocial evaluations of parents and children 12 years after screening for type 1 diabetes (T1D). Two parent-child cohorts participated: children at increased genetic risk of T1D and children at low genetic risk. T1D risk status was determined at birth as part of a prospective study investigating potential environmental triggers of autoimmunity. Parent measures included ratings of children's emotional, behavioural and social functioning (Child Behaviour Checklist) and parenting style (Alabama Parenting Questionnaire). Child self-concept was assessed using the self-description questionnaire (SDQ1). Statistical analyses were conducted to test for differences between the groups. Twelve years after testing there was no evidence that knowledge of a child's increased genetic risk of T1D adversely affected parental ratings of their child's emotional, behavioural or social functioning, or impacted upon parenting style. There was no adverse effect upon the child's assessment of their self-concept. This study provides important preliminary data concerning longer-term psychosocial effects of incorporating tests for genetic risk of complex disorders into NBS panels. While it is reassuring that no significant adverse effects have been detected, more data will be required to adequately inform policy. PMID:28120838
Holton, Avery E; Canary, Heather E; Wong, Bob
A growing body of research has given attention to issues surrounding genetic testing, including expanded carrier screening (ECS), an elective medical test that allows planning or expecting parents to consider the potential occurrence of genetic diseases and disorders in their children. These studies have noted the role of the mass media in driving public perceptions about such testing, giving particular attention to ways in which coverage of genetics and genetic testing broadly may drive public attitudes and choices concerning the morality, legality, ethics, and parental well-being involved in genetic technologies. However, few studies have explored how mass media are covering the newer test, ECS. Drawing on health-related framing studies that have shown in varying degrees the impact particular frames such as gain/loss and thematic/episodic can have on the public, this study examines the frame selection employed by online media in its coverage of ECS. This analysis-combined with an analysis of the sources and topics used in such coverage and how they relate to selected frames-helps to clarify how mass media are covering an increasingly important medical test and offers considerations of how such coverage may inform mass media scholarship as well as health-related practices.
This review is based on literature on prenatal anxiety effects that was found on Pubmed and PsycINFO for the years 2010-2016. Prenatal anxiety is thought to have distinct features, although it has been measured both by specific prenatal anxiety symptoms as well as by standardized anxiety scales. Its prevalence has ranged from 21 to 25% and it has been predicted by a number of pregnancy - related variables such as unintended pregnancy, demographic variables such as low acculturation and income and psychosocial factors including pessimism and partner tension. Prenatal anxiety effects on pregnancy include increased cortisol levels, pro-inflammatory cytokines, obstetric problems and cesarean section. Effects on the neonate include lower gestational age, prematurity, less insulin-like growth factor in cord blood, less exclusive breast-feeding and less self-regulation during the heelstick procedure. Prenatal anxiety effects continue into infancy and childhood both on physiological development and emotional/mental development. Among the physiological effects are lower vagal activity across the first two years, and lower immunity, more illnesses and reduced gray matter in childhood. Prenatal anxiety effects on emotional/mental development include greater negative emotionality and in infants, lower mental development scores and internalizing problems. Anxiety disorders occur during childhood and elevated cortisol and internalizing behaviors occur during adolescence. Interventions for prenatal anxiety are virtually nonexistent, although stroking (massaging) the infant has moderated the pregnancy - specific anxiety effects on internalizing behaviors in the offspring. The limitations of this literature include the homogeneity of samples, the frequent use of anxiety measures that are not specific to pregnancy, and the reliance on self-report. Nonetheless, the literature highlights the negative, long-term effects of prenatal anxiety and the need for screening and early
van der Tol, L.; Smid, B. E.; Poorthuis, B. J. H. M.; Biegstraaten, M.; Deprez, R. H. Lekanne; Linthorst, G. E.; Hollak, C. E. M.
Screening for Fabry disease (FD) reveals a high prevalence of individuals with α-galactosidase A (GLA) genetic variants of unknown significance (GVUS). These individuals often do not express characteristic features of FD. A systematic review on FD screening studies was performed to interpret the
Full Text Available Amyotrophic lateral sclerosis (ALS is underpinned by an oligogenic rare variant architecture. Identified genetic variants of ALS include RNA-binding proteins containing prion-like domains (PrLDs. We hypothesized that screening genes encoding additional similar proteins will yield novel genetic causes of ALS. The most common genetic variant of ALS patients is a G4C2-repeat expansion within C9ORF72. We have shown that G4C2-repeat RNA sequesters RNA-binding proteins. A logical consequence of this is that loss-of-function mutations in G4C2-binding partners might contribute to ALS pathogenesis independently of and/or synergistically with C9ORF72 expansions. Targeted sequencing of genomic DNA encoding either RNA-binding proteins or known ALS genes (n = 274 genes was performed in ALS patients to identify rare deleterious genetic variants and explore genotype-phenotype relationships. Genomic DNA was extracted from 103 ALS patients including 42 familial ALS patients and 61 young-onset (average age of onset 41 years sporadic ALS patients; patients were chosen to maximize the probability of identifying genetic causes of ALS. Thirteen patients carried a G4C2-repeat expansion of C9ORF72. We identified 42 patients with rare deleterious variants; 6 patients carried more than one variant. Twelve mutations were discovered in known ALS genes which served as a validation of our strategy. Rare deleterious variants in RNA-binding proteins were significantly enriched in ALS patients compared to control frequencies (p = 5.31E-18. Nineteen patients featured at least one variant in a RNA-binding protein containing a PrLD. The number of variants per patient correlated with rate of disease progression (t-test, p = 0.033. We identified eighteen patients with a single variant in a G4C2-repeat binding protein. Patients with a G4C2-binding protein variant in combination with a C9ORF72 expansion had a significantly faster disease course (t-test, p = 0.025. Our data are
Burton-Chase, Allison M.; Hovick, Shelly R.; Peterson, Susan K.; Marani, Salma K.; Vernon, Sally W.; Amos, Christopher I.; Frazier, Marsha L.; Lynch, Patrick M.; Gritz, Ellen R.
Purpose This study examined colonoscopy adherence and attitudes towards colorectal cancer (CRC) screening in individuals who underwent Lynch syndrome genetic counseling and testing. Methods We evaluated changes in colonoscopy adherence and CRC screening attitudes in 78 cancer-unaffected relatives of Lynch syndrome mutation carriers before pre-test genetic counseling (baseline) and at 6 and 12 months post-disclosure of test results (52 mutation-negative, 26 mutation-positive). Results While both groups were similar at baseline, at 12 months post-disclosure, a greater number of mutation-positive individuals had had a colonoscopy compared with mutation-negative individuals. From baseline to 12 months post-disclosure, the mutation-positive group demonstrated an increase in mean scores on measures of colonoscopy commitment, self-efficacy, and perceived benefits of CRC screening, and a decrease in mean scores for perceived barriers to CRC screening. Mean scores on colonoscopy commitment decreased from baseline to 6 months in the mutation-negative group. Conclusion Adherence to risk-appropriate guidelines for CRC surveillance improved after genetic counseling and testing for Lynch syndrome. Mutation-positive individuals reported increasingly positive attitudes toward CRC screening after receiving genetic test results, potentially reinforcing longer term colonoscopy adherence. PMID:23414081
This Sixth volume in the series The Key Debates. Mutations and Appropriations in European Film Studies investigates the question of screens in the context both of the dematerialization due to digitalization and the multiplication of media screens. Scholars offer various infomations and theories of topics such as the archeology of screen, film and media theories, contemporary art, pragmatics of new ways of screening (from home video to street screening).
Doucette, Jaimee; Zhao, Ziyan; Geyer, Rory J; Barra, Melanie M; Balunas, Marcy J; Zweifach, Adam
Genetically encoded sensors based on intramolecular FRET between CFP and YFP are used extensively in cell biology research. Flow cytometry has been shown to offer a means to measure CFP-YFP FRET; we suspected it would provide a unique way to conduct multiplexed measurements from cells expressing different FRET sensors, which is difficult to do with microscopy, and that this could be used for screening. We confirmed that flow cytometry accurately measures FRET signals using cells transiently transfected with an ERK activity reporter, comparing responses measured with imaging and cytometry. We created polyclonal long-term transfectant lines, each expressing a different intramolecular FRET sensor, and devised a way to bar-code four distinct populations of cells. We demonstrated the feasibility of multiplexed measurements and determined that robust multiplexed measurements can be conducted in plate format. To validate the suitability of the method for screening, we measured responses from a plate of bacterial extracts that in unrelated experiments we had determined contained the protein kinase C (PKC)-activating compound teleocidin A-1. The multiplexed assay correctly identifying the teleocidin A-1-containing well. We propose that multiplexed cytometric FRET measurements will be useful for analyzing cellular function and for screening compound collections. © 2016 Society for Laboratory Automation and Screening.
Loosli, F; Köster, R W; Carl, M; Kühnlein, R; Henrich, T; Mücke, M; Krone, A; Wittbrodt, J
In a pilot screen, we assayed the efficiency of ethylnitrosourea (ENU) as a chemical mutagen to induce mutations that lead to early embryonic and larval lethal phenotypes in the Japanese medaka fish, Oryzias latipes. ENU acts as a very efficient mutagen inducing mutations at high rates in germ cells. Three repeated treatments of male fish in 3 mM ENU for 1 h results in locus specific mutation rates of 1.1-1.95 x10(-3). Mutagenized males were outcrossed to wild type females and the F1 offspring was used to establish F2 families. F2 siblings were intercrossed and the F3 progeny was scored 24, 48 and 72 h after fertilization for morphological alterations affecting eye development. The presented mutant phenotypes were identified using morphological criteria and occur during early developmental stages of medaka. They are stably inherited in a Mendelian fashion. The high efficiency of ENU to induce mutations in this pilot screen indicates that chemical mutagenesis and screening for morphologically visible phenotypes in medaka fish allows the genetic analysis of specific aspects of vertebrate development complementing the screens performed in other vertebrate model systems.
Sharon M Lutz
Full Text Available In genome wide association studies (GWAS, families based studies tend to have less power to detect genetic associations than population based studies, such as case-control studies. This can be an issue when testing if genes in a family based GWAS have a direct effect on the phenotype of interest or if the genes act indirectly through a secondary phenotype. When multiple SNPs are tested for a direct effect in the family based study, a screening step can be used to minimize the burden of multiple comparisons in the causal analysis. We propose a 2-stage screening step that can be incorporated into the family based association test (FBAT approach similar to the conditional mean model approach in the VanSteen-algorithm . Simulations demonstrate that the type 1 error is preserved and this method is advantageous when multiple markers are tested. This method is illustrated by an application to the Framingham Heart Study.
Chambliss, Allison B; Resnick, Molly; Petrides, Athena K; Clarke, William A; Marzinke, Mark A
Current methods for the detection of single nucleotide polymorphisms (SNPs) associated with aberrant drug-metabolizing enzyme function are hindered by long turnaround times and specialized techniques and instrumentation. In this study, we describe the development and validation of a high-resolution melting (HRM) curve assay for the rapid screening of variant genotypes for targeted genetic polymorphisms in the cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP3A5. Sequence-specific primers were custom-designed to flank nine SNPs within the genetic regions of aforementioned drug metabolizing enzymes. PCR amplification was performed followed by amplicon denaturation by precise temperature ramping in order to distinguish genotypes by melting temperature (Tm). A standardized software algorithm was used to assign amplicons as 'reference' or 'variant' as compared to duplicate reference sequence DNA controls for each SNP. Intra-assay (n=5) precision of Tms for all SNPs was ≤0.19%, while inter-assay (n=20) precision ranged from 0.04% to 0.21%. When compared to a reference method of Sanger sequencing, the HRM assay produced no false negative results, and overcall frequency ranged from 0% to 26%, depending on the SNP. Furthermore, HRM genotyping displayed accuracy over input DNA concentrations ranging from 10 to 200 ng/μL. The presented assay provides a rapid method for the screening for genetic variants in targeted CYP450 regions with a result of 'reference' or 'variant' available within 2 h from receipt of extracted DNA. The method can serve as a screening approach to rapidly identify individuals with variant sequences who should be further investigated by reflexed confirmatory testing for aberrant cytochrome P450 enzymatic activity. Rapid knowledge of variant status may aid in the avoidance of adverse clinical events by allowing for dosing of normal metabolizer patients immediately while identifying the need to wait for confirmatory testing in those patients who are
Kaufman, Thomas C
The purpose of this chapter in FlyBook is to acquaint the reader with the Drosophila genome and the ways in which it can be altered by mutation. Much of what follows will be familiar to the experienced Fly Pusher but hopefully will be useful to those just entering the field and are thus unfamiliar with the genome, the history of how it has been and can be altered, and the consequences of those alterations. I will begin with the structure, content, and organization of the genome, followed by the kinds of structural alterations (karyotypic aberrations), how they affect the behavior of chromosomes in meiotic cell division, and how that behavior can be used. Finally, screens for mutations as they have been performed will be discussed. There are several excellent sources of detailed information on Drosophila husbandry and screening that are recommended for those interested in further expanding their familiarity with Drosophila as a research tool and model organism. These are a book by Ralph Greenspan and a review article by John Roote and Andreas Prokop, which should be required reading for any new student entering a fly lab for the first time. Copyright © 2017 by the Genetics Society of America.
Full Text Available Background: The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC is the most common autosomal dominant inherited predisposition for colorectal cancer, accounting for 1–2% of all bowel cancer. The only way to diagnose HNPCC is by a family history consistent with the disease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II. The main molecular cause of HNPCC is a constitutional mutation in one of the mismatch repair (MMR genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria, molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is present in about 90% of cancers of HNPCC patients. However, of all MSI colorectal cancers 80– 90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H.Conclusions: The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSIL, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and management of colorectal cancer. In some studies we and others have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. Population screening includes also colonoscopy which is restricted only to the obligate carriers of the mutation. This enables that the disease is detected in earlier stages which would greatly decrease medical treatment costs and most importantly decrease mortality. In Slovenia we have started population screening based
de Koning-Ward Tania F
Full Text Available Abstract The ability to analyze gene function in malaria-causing Plasmodium parasites has received a boost with a recent paper in BMC Genomics that describes a genome-wide mutagenesis system in the rodent malaria species Plasmodium berghei using the transposon piggyBac. This advance holds promise for identifying and validating new targets for intervention against malaria. But further improvements are still needed for the full power of genome-wide molecular genetic screens to be utilized in this organism. See research article: http://www.biomedcentral.com/1471-2164/12/155
Song, Zhang-yue; Tian, Jing-luan; Fu, Wei-zhe; Li, Lin; Lu, Ling-hong; Zhou, Lian; Shan, Zhi-hui; Tang, Gui-xiang; Shou, Hui-xia
The Agrobacterium-mediated transformation system is the most commonly used method in soybean transformation. Screening of soybean genotypes favorable for Agrobacterium-infection and tissue regeneration is the most important step to establish an efficient genetic transformation system. In this study, twenty soybean genotypes that originated from different soybean production regions in China were screened for transient infection, regeneration capacity, and stable transgenic efficiency. Three genotypes, Yuechun 04-5, Yuechun 03-3, and Tianlong 1, showed comparable stable transgenic efficiencies with that of the previously reported American genotypes Williams 82 and Jack in our experimental system. For the Tianlong 1, the average stable transformation efficiency is 4.59%, higher than that of control genotypes (Jack and Williams 82), which is enough for further genomic research and genetic engineering. While polymerase chain reaction (PCR), LibertyLink strips, and β-glucuronidase (GUS) staining assays were used to detect the insertion and expression of the transgene, leaves painted with 135 mg/L Basta could efficiently identify the transformants. PMID:23549846
Full Text Available The recent success of derivation of mammalian haploid embryonic stem cells (haESCs has provided a powerful tool for large-scale functional analysis of the mammalian genome. However, haESCs rapidly become diploidized after differentiation, posing challenges for genetic analysis. Here, we show that the spontaneous diploidization of haESCs happens in metaphase due to mitotic slippage. Diploidization can be suppressed by small-molecule-mediated inhibition of CDK1 and ROCK. Through ROCK inhibition, we can generate haploid somatic cells of all three germ layers from haESCs, including terminally differentiated neurons. Using piggyBac transposon-based insertional mutagenesis, we generated a haploid neural cell library harboring genome-wide mutations for genetic screening. As a proof of concept, we screened for Mn2+-mediated toxicity and identified the Park2 gene. Our findings expand the applications of mouse haploid cell technology to somatic cell types and may also shed light on the mechanisms of ploidy maintenance.
Marker, Simone; Carradec, Quentin; Tanty, Véronique; Arnaiz, Olivier; Meyer, Eric
In most eukaryotes, small RNA-mediated gene silencing pathways form complex interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA interference (RNAi) mechanisms coexist, involving distinct but overlapping sets of protein factors and producing different types of short interfering RNAs (siRNAs). One is specifically triggered by high-copy transgenes, and the other by feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study, we designed a forward genetic screen for mutants deficient in dsRNA-induced silencing, and a powerful method to identify the relevant mutations by whole-genome sequencing. We present a set of 47 mutant alleles for five genes, revealing two previously unknown RNAi factors: a novel Paramecium-specific protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic diversity distinguish non-essential and essential genes and suggest that the screen is saturated for non-essential, single-copy genes. We show that non-essential genes are specifically involved in dsRNA-induced RNAi while essential ones are also involved in transgene-induced RNAi. One of the latter, the RNA-dependent RNA polymerase RDR2, is further shown to be required for all known types of siRNAs, as well as for sexual reproduction. These results open the way for the dissection of the genetic complexity, interconnection, mechanisms and natural functions of RNAi pathways in P. tetraurelia. PMID:24860163
Full Text Available The aim of this study was to examine if isolated fetal ventricular septal defect (VSD is associated with trisomy 21. One hundred twenty six cases with prenatal VSD diagnosed by a pediatric cardiologist were reviewed. Cases with known risk factors for congenital heart disease, the presence of other major anomalies, soft signs for trisomy 21 or a positive screen test for trisomy 21 were excluded. Ninety two cases formed the study group. None of the cases in the study group had trisomy 21. The upper limit of prevalence for trisomy 21 in isolated VSD is 3%. When prenatal VSD is not associated with other major anomalies, soft markers for trisomy 21 or a positive nuchal translucency or biochemical screen, a decision whether to perform genetic amniocentesis should be individualized. The currently unknown association between isolated VSD and microdeletions and microduplications should be considered when discussing this option.
Quarterman, Josh; Kim, Soo Rin; Kim, Pan-Jun; Jin, Yong-Su
In order to determine beneficial gene deletions for ethanol production by the yeast Saccharomyces cerevisiae, we performed an in silico gene deletion experiment based on a genome-scale metabolic model. Genes coding for two oxidative phosphorylation reactions (cytochrome c oxidase and ubiquinol cytochrome c reductase) were identified by the model-based simulation as potential deletion targets for enhancing ethanol production and maintaining acceptable overall growth rate in oxygen-limited conditions. Since the two target enzymes are composed of multiple subunits, we conducted a genetic screening study to evaluate the in silico results and compare the effect of deleting various portions of the respiratory enzyme complexes. Over two-thirds of the knockout mutants identified by the in silico study did exhibit experimental behavior in qualitative agreement with model predictions, but the exceptions illustrate the limitation of using a purely stoichiometric model-based approach. Furthermore, there was a substantial quantitative variation in phenotype among the various respiration-deficient mutants that were screened in this study, and three genes encoding respiratory enzyme subunits were identified as the best knockout targets for improving hexose fermentation in microaerobic conditions. Specifically, deletion of either COX9 or QCR9 resulted in higher ethanol production rates than the parental strain by 37% and 27%, respectively, with slight growth disadvantages. Also, deletion of QCR6 led to improved ethanol production rate by 24% with no growth disadvantage. The beneficial effects of these gene deletions were consistently demonstrated in different strain backgrounds and with four common hexoses. The combination of stoichiometric modeling and genetic screening using a systematic knockout collection was useful for narrowing a large set of gene targets and identifying targets of interest. Copyright © 2014 Elsevier B.V. All rights reserved.
Cagnon, Caroline; Mirabella, Boris; Nguyen, Hoa Mai; Beyly-Adriano, Audrey; Bouvet, Séverine; Cuiné, Stéphan; Beisson, Fred; Peltier, Gilles; Li-Beisson, Yonghua
Oils produced by microalgae are precursors to biodiesel. To achieve a profitable production of biodiesel from microalgae, identification of factors governing oil synthesis and turnover is desirable. The green microalga Chlamydomonas reinhardtii is amenable to genetic analyses and has recently emerged as a model to study oil metabolism. However, a detailed method to isolate various types of oil mutants that is adapted to Chlamydomonas has not been reported. We describe here a forward genetic approach to isolate mutants altered in oil synthesis and turnover from C. reinhardtii. It consists of a three-step screening procedure: a primary screen by flow cytometry of Nile red stained transformants grown in 96-deep-well plates under three sequential conditions (presence of nitrogen, then absence of nitrogen, followed by oil remobilization); a confirmation step using Nile red stained biological triplicates; and a validation step consisting of the quantification by thin layer chromatography of oil content of selected strains. Thirty-one mutants were isolated by screening 1,800 transformants generated by random insertional mutagenesis (1.7%). Five showed increased oil accumulation under the nitrogen-replete condition and 13 had altered oil content under nitrogen-depletion. All mutants were affected in oil remobilization. This study demonstrates that various types of oil mutants can be isolated in Chlamydomonas based on the method set-up here, including mutants accumulating oil under optimal biomass growth. The strategy conceived and the protocol set-up should be applicable to other microalgal species such as Nannochloropsis and Chlorella, thus serving as a useful tool in Chlamydomonas oil research and algal biotechnology.
Full Text Available We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs. New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products.
Fernandez, Anita G; Mis, Emily K; Lai, Allison; Mauro, Michael; Quental, Angela; Bock, Carly; Piano, Fabio
mel-28 (maternal-effect-lethal-28) encodes a conserved protein required for nuclear envelope function and chromosome segregation in Caenorhabditis elegans. Because mel-28 is a strict maternal-effect lethal gene, its function is required in the early embryo but appears to be dispensable for larval development. We wanted to test the idea that mel-28 has postembryonic roles that are buffered by the contributions of other genes. To find genes that act coordinately with mel-28, we did an RNA interference-based genetic interaction screen using mel-28 and wild-type larvae. We screened 18,364 clones and identified 65 genes that cause sterility in mel-28 but not wild-type worms. Some of these genes encode components of the nuclear pore. In addition we identified genes involved in dynein and dynactin function, vesicle transport, and cell-matrix attachments. By screening mel-28 larvae we have bypassed the requirement for mel-28 in the embryo, uncovering pleiotropic functions for mel-28 later in development that are normally provided by other genes. This work contributes toward revealing the gene networks that underlie cellular processes and reveals roles for a maternal-effect lethal gene later in development.
Datukishvili, Nelly; Kutateladze, Tamara; Gabriadze, Inga; Bitskinashvili, Kakha; Vishnepolsky, Boris
We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs). New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV) 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS) terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps) gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab) gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS) and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products.
Granberg, Candace F; Harrison, Steven M; Dajusta, Daniel; Zhang, Shaohua; Hajarnis, Sachin; Igarashi, Peter; Baker, Linda A
Although the cause of prune belly syndrome is unknown, familial evidence suggests a genetic component. Recently 2 nonfamilial cases of prune belly syndrome with chromosome 17q12 deletions encompassing the HNF1β gene have made this a candidate gene for prune belly syndrome. To date, there has been no large-scale screening of patients with prune belly syndrome for HNF1β mutations. We assessed the role of HNF1β in prune belly syndrome by screening for genomic mutations with functional characterization of any detected mutations. We studied patients with prune belly syndrome who were prospectively enrolled in our Pediatric Genitourinary DNA Repository since 2001. DNA from patient samples was amplified by polymerase chain reaction, sequenced for coding and splice regions of the HNF1β gene, and compared to control databases. We performed functional assay testing of the ability of mutant HNF1β to activate a luciferase construct with an HNF1β DNA binding site. From 32 prune belly syndrome probands (30 males, 2 females) HNF1β sequencing detected a missense mutation (V61G) in 1 child with prune belly syndrome. Absent in control databases, V61G was previously reported in 2 patients without prune belly syndrome who had congenital genitourinary anomalies. Functional testing showed similar luciferase activity compared to wild-type HNF1β, suggesting the V61G substitution does not disturb HNF1β function. One genomic HNF1β mutation was detected in 3% of patients with prune belly syndrome but found to be functionally normal. Thus, functionally significant HNF1β mutations are uncommon in prune belly syndrome, despite case reports of HNF1β deletions. Further genetic study is necessary, as identification of the genetic basis of prune belly syndrome may ultimately lead to prevention and improved treatments for this rare but severe syndrome. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Cappa, Claudia; Giulivi, Sara; Schilirò, Antonino; Bastiani, Luca; Muzio, Carlo; Meloni, Fabrizio
The aim of the present research is to investigate the prevalence of Specific Learning Disorders (SLD) in Ogliastra, an area of the island of Sardinia, Italy. Having experienced centuries of isolation, Ogliastra has become a high genetic homogeneity area, and is considered particularly interesting for studies on different kinds of pathologies. Here we are going to describe the results of a screening carried out throughout 2 consecutive years in 49 second grade classes (24 considered in the first year and 25 in the second year of the study) of the Ogliastra region. A total of 610 pupils (average age 7.54 years; 293 female, 317 male) corresponding to 68.69% of all pupils who were attending second grade in the area, took part in the study. The tool used for the screening was "RSR-DSA. Questionnaire for the detection of learning difficulties and disorders", which allowed the identification of 83 subjects at risk (13.61% of the whole sample involved in the study). These subjects took part in an enhancement training program of about 6 months. After the program, pupils underwent assessment for reading, writing and calculation abilities, as well as cognitive assessment. According to the results of the assessment, the prevalence of SLDs is 6.06%. For what concerns dyslexia, 4.75% of the total sample manifested this disorder either in isolation or in comorbidity with other disorders. According to the first national epidemiological investigation carried out in Italy, the prevalence of dyslexia is 3.1-3.2%, which is lower than the prevalence obtained in the present study. Given the genetic basis of SLDs, this result, together with the presence of several cases of SLD in isolation (17.14%) and with a 3:1 ratio of males to females diagnosed with a SLD, was to be expected in a sample coming from a high genetic homogeneity area. Copyright © 2015 Elsevier Ltd. All rights reserved.
Middleton, Anna; Patch, Chris; Wiggins, Jennifer; Barnes, Kathy; Crawford, Gill; Benjamin, Caroline; Bruce, Anita
The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest 'opportunistic genomic screening' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), which represents British and Irish genetic counsellors and nurses, feels strongly that the following must be considered (see article for complete list): (1) Following appropriate genetic counselling, patients should be allowed to consent to or opt out of opportunistic genomic screening. (2) If true IFs are discovered the AGNC are guided by the report from the Joint Committee on Medical Genetics about the sharing of genetic testing results. (3) Children should not be routinely tested for adult-onset conditions. (4) The formation of a list of variants should involve a representative from the AGNC as well as a patient support group. (5) The variants should be for serious or life-threatening conditions for which there are treatments or preventative strategies available. (6) There needs to be robust evidence that the benefits of opportunistic screening outweigh the potential harms. (7) The clinical validity and utility of variants should be known. (8) There must be a quality assurance framework that operates to International standards for laboratory testing. (9) Psychosocial research is urgently needed in this area to understand the impact on patients.
Anasagasti, Ander; Barandika, Olatz; Irigoyen, Cristina; Benitez, Bruno A; Cooper, Breanna; Cruchaga, Carlos; López de Munain, Adolfo; Ruiz-Ederra, Javier
Retinitis Pigmentosa (RP) involves a group of genetically determined retinal diseases caused by a large number of mutations that result in rod photoreceptor cell death followed by gradual death of cone cells. Most cases of RP are monogenic, with more than 80 associated genes identified so far. The high number of genes and variants involved in RP, among other factors, is making the molecular characterization of RP a real challenge for many patients. Although HRM has been used for the analysis of isolated variants or single RP genes, as far as we are concerned, this is the first study that uses HRM analysis for a high-throughput screening of several RP genes. Our main goal was to test the suitability of HRM analysis as a genetic screening technique in RP, and to compare its performance with two of the most widely used NGS platforms, Illumina and PGM-Ion Torrent technologies. RP patients (n = 96) were clinically diagnosed at the Ophthalmology Department of Donostia University Hospital, Spain. We analyzed a total of 16 RP genes that meet the following inclusion criteria: 1) size: genes with transcripts of less than 4 kb; 2) number of exons: genes with up to 22 exons; and 3) prevalence: genes reported to account for, at least, 0.4% of total RP cases worldwide. For comparison purposes, RHO gene was also sequenced with Illumina (GAII; Illumina), Ion semiconductor technologies (PGM; Life Technologies) and Sanger sequencing (ABI 3130xl platform; Applied Biosystems). Detected variants were confirmed in all cases by Sanger sequencing and tested for co-segregation in the family of affected probands. We identified a total of 65 genetic variants, 15 of which (23%) were novel, in 49 out of 96 patients. Among them, 14 (4 novel) are probable disease-causing genetic variants in 7 RP genes, affecting 15 patients. Our HRM analysis-based study, proved to be a cost-effective and rapid method that provides an accurate identification of genetic RP variants. This approach is effective for
Full Text Available To select cytogenetically normal embryos, preimplantation genetic diagnosis (PGD aneuploidy screening (AS is used in numerous centers around the world. Chromosomal abnormalities lead to developmental problems, implantation failure, and early abortion of embryos. The usefulness of PGD in identifying single-gene diseases, human leukocyte antigen typing, X-linked diseases, and specific genetic diseases is well-known. In this review, preimplantation embryo genetics, PGD research studies, and the European Society of Human Reproduction and Embryology PGD Consortium studies and reports are examined. In addition, criteria for embryo selection, technical aspects of PGD-AS, and potential noninvasive embryo selection methods are described. Indications for PGD and possible causes of discordant PGD results between the centers are discussed. The limitations of fluorescence in situ hybridization, and the advantages of the array comparative genomic hybridization are included in this review. Although PGD-AS for patients of advanced maternal age has been shown to improve in vitro fertilization outcomes in some studies, to our knowledge, there is not sufficient evidence to use advanced maternal age as the sole indication for PGD-AS. PGD-AS might be harmful and may not increase the success rates of in vitro fertilization. At the same time PGD, is not recommended for recurrent implantation failure and unexplained recurrent pregnancy loss.
Full Text Available Prenatal diagnosis of invasive and noninvasive tests can be done in a way (NIPT, but because of the invasive methods have risks of infection and abortion, diagnosing non-invasive procedure increasing day by day. One of the widespread cell free fetal DNA in maternal blood test (cffDNA that is increasing in clinical use has been drawing attention. The incidence of aneuploidy chromosomal anomaly of the kind in which all live births; Trisomy 21 (Down Syndrome 1/800, trisomy 13 (Patau syndrome 1 /10,000, trisomy 18 (Edwards syndrome is a form of 1/6000. Because of the high mortality and morbidity, it is vital that congenital anomalies should be diagnosed in prenatal period. Aneuploidy testing for high-risk pregnant women after the 10th week of pregnancy in terms of the blood sample is taken and free fetal DNA in maternal plasma is based on the measurement of the relative amount. Knowledge of the current criteria for use by healthcare professionals in the field test will allow the exclusion of maternal and fetal risks. In this study, it is aimed to demonstrate current international approaches related to the positive and negative sides of non-invasive that is one of the prenatal diagnostic methods of cffDNA test. J Clin Exp Invest 2015; 6 (4: 414-417
Charlotte L Ridgway
Full Text Available Low birth weight has been associated with reduced hand grip strength, which is a marker of future physical function and disease risk. The aim of this study was to apply a twin pair approach, using both 'individual' data and 'within-pair' differences, to investigate the influence of birth weight on hand grip strength and whether this association may be mediated through fat free mass (FFM. Participants from the East Flanders Prospective Twin Survey were included if born without congenital abnormalities, birth weight >500 g and ≥22 weeks of gestation. Follow up in adulthood (age: 18-34 year, included anthropometric measures and hand grip (n = 783 individuals, n = 326 same-sex twin pairs. Birth weight was positively associated with hand grip strength (β = 2.60 kg, 95% CI 1.52, 3.67, p<0.001 and FFM (β = 4.2, 95% CI 3.16, 5.24, p<0.001, adjusted for gestational age, sex and adult age. Using 'within-pair' analyses, the birth weight hand grip association was significant in DZ men only (β = 5.82, 95% CI 0.67, 10.97, p = 0.028, which was attenuated following adjustment for FFM. Within-pair birth weight FFM associations were most pronounced in DZ men (β = 11.20, 95% CI 7.18, 15.22, p<0.001. Our 'individual' analyses show that higher birth weight is associated with greater adult hand grip strength, which is mediated through greater adult FFM. The 'within-pair' analyses confirm this observation and furthermore show that, particularly in men, genetic factors may in part explain this association, as birth weight differences in DZ men result in greater differences in adult strength and FFM.
Malogajski, Jelena; Jansen, Marleen E; Ouburg, Sander; Ambrosino, Elena; Terwee, Caroline B; Morré, Servaas A
This study aims to identify elements perceived by Dutch fertility specialists as barriers and facilitators for the introduction of genetic testing, and their attitudes towards the use of genetic information. The genetic test would be implemented in routine screening for tubal pathology and identifies SNPs relevant for the immune response causing tubal pathology. Experienced reproductive specialists working in Dutch Academic Hospitals were interviewed. Based on the results of four interviews a questionnaire was developed and used to survey medical doctors in six out of eight Dutch Academic hospitals. 60.4% (n=91) stated that the addition of genetic markers to the Chlamydia trachomatis antibody test (CAT) in screening for tubal pathology would increase screening accuracy. 68.2% (n=90) agreed they would require additional training on clinical genetics. Clinical utility (91.2%, n=91) and cost-effectiveness (95.6%, n=91) were recognized by the respondents as important factors in gaining support for the new screening strategy. In summary, respondents showed a positive attitude towards the implementation of a genetic test combined with CAT for tubal factor infertility (TFI) screening. To gain their support the majority of respondents agreed that clinical utility, specifically cost-effectiveness, is an important factor. Comprehensive research about economic implications and utility regarding the introduction of genomic markers should be the next step in the implementation strategy. Furthermore, education and training would need to be developed and offered to fertility care professionals about genetic markers, their interpretation, and implications for clinical decision-making. Copyright © 2017 Elsevier B.V. All rights reserved.
Karaca, Emin; Aykut, Ayça; Ertürk, Biray; Durmaz, Burak; Güler, Ahmet; Büke, Barış; Yeniel, Ahmet Özgür; Ergenoğlu, Ahmet Mete; Özkınay, Ferda; Özeren, Mehmet; Kazandı, Mert; Akercan, Fuat; Sağol, Sermet; Gündüz, Cumhur; Çoğulu, Özgür
Down syndrome, which is the most common human chromosomal anomaly that can affect people of any race and age, can be diagnosed prenatally in most cases. Prenatal diagnosis via culture method is time-consuming; thus, genetic analysis has thus been introduced and is continually being developed for rapid prenatal diagnosis. For this reason, the effective use of microRNA profiling for the rapid analysis of prenatal amniotic fluid samples for the diagnosis of Down syndrome was investigated. To evaluate the expression levels of 14 microRNAs encoded by chromosome 21 in amniotic fluid samples and their utility for prenatal diagnosis of Down syndrome. Case-control study. We performed invasive prenatal testing for 56 pregnant women; 23 carried fetuses with Down syndrome, and 33 carried fetuses with a normal karyotype. Advanced maternal age and increased risk for Down syndrome in the screening tests were indications for invasive prenatal testing. The age of gestation in the study and control groups ranged between 17 and 18 weeks. The expression levels of microRNA were measured by real-time polymerase chain reaction. The expression levels of microRNA-125b-2, microRNA-155 , and microRNA-3156 were significantly higher in the study group than in the control group. The presence of significantly dysregulated microRNAs may be associated with either the phenotype or the result of abnormal development. Further large-scale comparative studies conducted in a variety of conditions may bring novel insights in the field of abnormal prenatal conditions.
Norwitz, Errol R; Levy, Brynn
Prenatal detection of chromosome abnormalities has been offered for more than 40 years, first by amniocentesis in the early 1970s and additionally by chorionic villus sampling (CVS) in the early 1980s. Given the well-recognized association between increasing maternal age and trisomy,1-3 the primary utilization of prenatal testing has been by older mothers. This has drastically reduced the incidence of aneuploid children born to older mothers.4 Although younger women have relatively low risks of conceiving a child with aneuploidy, the majority of pregnant women are in their late teens, 20s, and early 30s. As such, most viable aneuploid babies are born to these younger mothers.5 Invasive prenatal diagnosis (CVS and amniocentesis) is not a feasible option for all low-risk mothers, as these procedures carry a small but finite risk and would ultimately cause more miscarriages than they would detect aneuploidy. For this reason, a number of noninvasive tests have been developed-including first-trimester risk assessment at 11 to 14 weeks, maternal serum analyte (quad) screening at 15 to 20 weeks, and sonographic fetal structural survey at 18 to 22 weeks-all of which are designed to give a woman an adjusted (more accurate) estimate of having an aneuploid fetus using as baseline her a priori age-related risk. Ultrasound and maternal serum analysis are considered screening procedures and both require follow up by CVS or amniocentesis in screen-positive cases for a definitive diagnosis of a chromosome abnormality in the fetus. The ability to isolate fetal cells and fetal DNA from maternal blood during pregnancy has opened up exciting opportunities for improved noninvasive prenatal testing (NIPT). Direct analysis of fetal cells from maternal circulation has been challenging given the scarcity of fetal cells in maternal blood (1:10,000-1:1,000,000) and the focus has shifted to the analysis of cell-free fetal DNA, which is found at a concentration almost 25 times higher than that
This paper describes two studies about the determinants of attitudes to pre-implantation genetic screening in a multicultural sample of medical students from the United States. Sample sizes were 292 in study 1 and 1464 in study 2. Attitudes were of an undifferentiated nature, but respondents did make a major distinction between use for disease prevention and use for enhancement. No strong distinctions were made between embryo selection and germ line gene manipulations, and between somatic gene therapy and germ line gene manipulations. Religiosity was negatively associated with acceptance of "designer baby" technology for Christians and Muslims but not Hindus. However, the strongest and most consistent influence was an apparently moralistic stance against active and aggressive interference with natural processes in general. Trust in individuals and institutions was unrelated to acceptance of the technology, indicating that fear of abuse by irresponsible individuals and corporations is not an important determinant of opposition.
Vernet, Erik; Kotzsch, Alexander; Voldborg, Bjørn
Soluble expression of proteins in a relevant form for functional and structural investigations still often remains a challenge. Although many biochemical factors are known to affect solubility, a thorough investigation of yield-limiting factors is normally not feasible in high-throughput efforts....... Here we present a screening strategy for expression of biomedically relevant proteins in Escherichia coli using a panel of six different genetic variations. These include engineered strains for rare codon supplementation, increased disulfide bond formation in the cytoplasm and novel vectors...... for secretion to the periplasm or culture medium. Combining these variants with expression construct truncations design, we report on parallel cloning and expression of more than 300 constructs representing 24 selected proteins; including full-length variants of human growth factors, interleukins and growth...
Kauffman, Tia L.; Wilfond, Benjamin S.; Jarvik, Gail P.; Leo, Michael C.; Lynch, Frances L.; Reiss, Jacob A.; Richards, C. Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O.; Goddard, Katrina A.B.
Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results...
P. Susana Aguilera, DRA.
Full Text Available Los principales objetivos del control prenatal son identificar aquellos pacientes de mayor riesgo, con el fin de realizar intervenciones en forma oportuna que permitan prevenir dichos riesgos y así lograr un buen resultado perinatal. Esto se realiza a través de la historia médica y reproductiva de la mujer, el examen físico, la realización de algunos exámenes de laboratorio y exámenes de ultrasonido. Además es importante promover estilos de vida saludables, la suplementación de ácido fólico, una consejería nutricional y educación al respecto.
Jen, Freda E-C; Djoko, Karrera Y; Bent, Stephen J; Day, Christopher J; McEwan, Alastair G; Jennings, Michael P
Under conditions of low oxygen availability, Neisseria meningitidis and Neisseria gonorrhoeae are able to respire via a partial denitrification pathway in which nitrite is converted to nitrous oxide. In this process, nitrite reductase (AniA), a copper (Cu)-containing protein converts nitrite to NO, and this product is converted to nitrous oxide by nitric oxide reductase (NorB). NorB also confers protection against toxic NO, and so we devised a conditional lethal screen, using a norB mutant, to identify mutants that were resistant to nitrite-dependent killing. After random-deletion mutagenesis of N. meningitidis, this genetic screen identified a gene encoding a Cu chaperone that is essential for AniA function, AccA. Purified AccA binds one Cu (I) ion and also possesses a second binding site for Cu (II). This novel periplasmic Cu chaperone (AccA) appears to be essential for provision of Cu ions to AniA of pathogenic Neisseria to generate an active nitrite reductase. Apart from the Neisseria genus, AccA is distributed across a wide range of environmental Proteobacteria species. © FASEB.
Full Text Available Abstract Background Multiple endocrine neoplasia type 2 is an autosomal dominant disorder. MEN 2A is characterized by medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism; MEN 2B by medullary thyroid carcinoma, pheochromocytoma and characteristic stigmata. Activating germline mutations of the RET proto oncogene are responsible for this hereditary syndrome. Codon 634 mutations are the most common mutations occurring in MEN 2A families whereas a specific mutation at codon 918 is observed in the great majority of MEN 2B families. Analysis of these codons will provide a final diagnosis in the great majority of affected families making unnecessary further studies. To specifically study the codons 634 and 918 we used a minisequencing method as an alternative method to complete sequencing. Results Using this mutation detection method we were able to reproduce in all cases, representative of 7 families, the information previously obtained by direct sequencing of PCR products. Depending on the number of primers used in the minisequencing reaction, we were able to interrogate either only one nucleotide of the target codon or the three nucleotides simultaneously. Conclusions This technique appears as a simple, rapid and efficient method for genetic screening of MEN 2 families. It can be utilized to seek for unknown mutations at specific codons or to screen for previously identified mutations and is therefore of interest to study index cases or individuals at risk. Results suggest that complete sequencing is unnecessary.
Lebensohn, Andres M; Dubey, Ramin; Neitzel, Leif R; Tacchelly-Benites, Ofelia; Yang, Eungi; Marceau, Caleb D; Davis, Eric M; Patel, Bhaven B; Bahrami-Nejad, Zahra; Travaglini, Kyle J; Ahmed, Yashi; Lee, Ethan; Carette, Jan E; Rohatgi, Rajat
The comprehensive understanding of cellular signaling pathways remains a challenge due to multiple layers of regulation that may become evident only when the pathway is probed at different levels or critical nodes are eliminated. To discover regulatory mechanisms in canonical WNT signaling, we conducted a systematic forward genetic analysis through reporter-based screens in haploid human cells. Comparison of screens for negative, attenuating and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor adenomatous polyposis coli or casein kinase 1α uncovered new regulatory features at most levels of the pathway. These include a requirement for the transcription factor AP-4, a role for the DAX domain of AXIN2 in controlling β-catenin transcriptional activity, a contribution of glycophosphatidylinositol anchor biosynthesis and glypicans to R-spondin-potentiated WNT signaling, and two different mechanisms that regulate signaling when distinct components of the β-catenin destruction complex are lost. The conceptual and methodological framework we describe should enable the comprehensive understanding of other signaling systems. DOI: http://dx.doi.org/10.7554/eLife.21459.001 PMID:27996937
Khoury Muin J
Full Text Available Abstract Background Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM, a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies. Results The data source for this research was the HuGE Navigator, formerly known as the HuGE Pub Lit database. Weighted SVM feature selection based on a keyword list obtained by the two-way z score method demonstrated the best screening performance, achieving 97.5% recall, 98.3% specificity and 31.9% precision in performance testing. Compared with the traditional screening process based on a complex PubMed query, the SVM tool reduced by about 90% the number of abstracts requiring individual review by the database curator. The tool also ascertained 47 articles that were missed by the traditional literature screening process during the 4-week test period. We examined the literature on genetic associations with preterm birth as an example. Compared with the traditional, manual process, the GAPscreener both reduced effort and improved accuracy. Conclusion GAPscreener is the first free SVM-based application available for screening the human genetic association literature in PubMed with high recall and specificity. The user-friendly graphical user interface makes this a practical, stand-alone application. The software can be downloaded at no charge.
Full Text Available Somatic cell genetics is a powerful approach for unraveling the regulatory mechanism of cholesterol metabolism. However, it is difficult to identify the mutant gene(s due to cells are usually mutagenized chemically or physically. To identify important genes controlling cholesterol biosynthesis, an unbiased forward genetics approach named validation-based insertional mutagenesis (VBIM system was used to isolate and characterize the 25-hydroxycholesterol (25-HC-resistant and SR-12813-resistant mutants. Here we report that five mutant cell lines were isolated. Among which, four sterol-resistant mutants either contain a truncated NH2-terminal domain of sterol regulatory element-binding protein (SREBP-2 terminating at amino acids (aa 400, or harbor an overexpressed SREBP cleavage-activating protein (SCAP. Besides, one SR-12813 resistant mutant was identified to contain a truncated COOH-terminal catalytic domain of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase. This study demonstrates that the VBIM system can be a powerful tool to screen novel regulatory genes in cholesterol biosynthesis.
Koutsis, G; Karadima, G; Pandraud, A; Sweeney, M G; Paudel, R; Houlden, H; Wood, N W; Panas, M
Huntington’s disease (HD) is an autosomal dominant disorder characterized by a triad of chorea, psychiatric disturbance and cognitive decline. Around 1% of patients with HD-like symptoms lack the causative HD expansion and are considered HD phenocopies. Genetic diseases that can present as HD phenocopies include HD-like syndromes such as HDL1, HDL2 and HDL4 (SCA17), some spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA). In this study we screened a cohort of 21 Greek patients with HD phenocopy syndromes formutations causing HDL2, SCA17, SCA1, SCA2, SCA3,SCA8, SCA12 and DRPLA. Fifteen patients (71%) had a positive family history. We identified one patient (4.8% of the total cohort) with an expansion of 81 combined CTA/CTG repeats at the SCA8 locus. This falls within what is believed to be the high-penetrance allele range. In addition to the classic HD triad, the patient had features of dystonia and oculomotor apraxia. There were no cases of HDL2, SCA17, SCA1, SCA2, SCA3, SCA12 or DRPLA. Given the controversy surrounding the SCA8 expansion, the present finding may be incidental. However, if pathogenic, it broadens the phenotype that may be associated with SCA8 expansions. The absence of any other mutations in our cohort is not surprising, given the low probability of reaching a genetic diagnosis in HD phenocopy patients.
Afanas'eva, N A; Bychkova, A M; Livshits, L A; Bariliak, I R
The clinical and genetical characteristics of patients with phenylketonuria in the Crimean population is done in the present work. The comparison of clinical peculiarities of 28 patients, revealed by means of neonatal screening and that of 24 patients, the treatment of which was started late is presented. The prenatal diagnostics of 4 families with high phenylketonuria risk is conducted.
Eijzenga, W.; Bleiker, E.M.A.; Hahn, D.E.E.; Kluijt, I.; Sidharta, G.N.; Gundy, C.; Aaronson, N.K.
Background: Up to three-quarters of individuals who undergo cancer genetic counseling and testing report psychosocial problems specifically related to that setting. The objectives of this study were to develop and evaluate the screening properties of a questionnaire designed to assess specific
Full Text Available Syphilis in pregnancy still remains a challenge despite the availability of adequate diagnostic tests for serological screening and penicillin therapy. We report a case of 2 month old female infant who presented with runny nose, papulosquamous lesions over both palms and soles and perianal erosions since 1 month after birth. Cutaneous examination revealed moist eroded areas in the perianal region and fine scaly lesions over palms and soles. Radiograph of both upper limbs and limbs revealed early periosteal changes in lower end of humerus and lower end of tibia. Diagnosis of early pre-natal syphilis was confirmed by Child′s Serum Rapid Plasma Reagin Antibody test [S.RPR] being positive with 1:64 dilution while that of mother was 1:8.
... Testing CLINSEQ®: A Large-Scale Medical Sequencing Clinical Research Pilot Study Prenatal Screening - Prenatal testing information, including ultrasound, amniocentesis, and chorionic villus sampling ( ...
Ruth M. Farrell
Full Text Available Noninvasive prenatal testing (NIPT offers pregnant women a new risk assessment tool for fetal aneuploidy that is superior to conventional screening tests. We conducted focus groups with women who were currently pregnant or had recently delivered in the past year to characterize their perspectives about NIPT and to explore factors they would consider during decision making about its use. Women identified accuracy, early timing, testing ease, and determination of fetal sex as advantages of NIPT over other screens, and the noninvasive method of NIPT as an advantage over diagnostic tests. False positive and false negative results, anxiety, cost and insurance coverage were seen as disadvantages of NIPT. Women who do not want fetal aneuploidy information most likely will not undergo NIPT, despite its advantages over other screening tests. However, given its advantages, the decision to have NIPT is straightforward for women who want genetic information about the fetus. Women emphasized the need to make autonomous, private, and informed choices about NIPT, as they would with any prenatal genetic testing option. These perspectives may guide clinicians to conduct effective and clinically relevant counseling with pregnant women who consider utilizing this new genetic technology.
Kim, Hyun-Joong; Ryu, Ji-Oh; Song, Ji-Yeon; Kim, Hae-Yeong
In the detection of Shigella species using molecular biological methods, previously known genetic markers for Shigella species were not sufficient to discriminate between Shigella species and diarrheagenic Escherichia coli. The purposes of this study were to screen for genetic markers of the Shigella genus and four Shigella species through comparative genomics and develop a multiplex polymerase chain reaction (PCR) for the detection of shigellae and Shigella species. A total of seven genomic DNA sequences from Shigella species were subjected to comparative genomics for the screening of genetic markers of shigellae and each Shigella species. The primer sets were designed from the screened genetic markers and evaluated using PCR with genomic DNAs from Shigella and other bacterial strains in Enterobacteriaceae. A novel Shigella quintuplex PCR, designed for the detection of Shigella genus, S. dysenteriae, S. boydii, S. flexneri, and S. sonnei, was developed from the evaluated primer sets, and its performance was demonstrated with specifically amplified results from each Shigella species. This Shigella multiplex PCR is the first to be reported with novel genetic markers developed through comparative genomics and may be a useful tool for the accurate detection of the Shigella genus and species from closely related bacteria in clinical microbiology and food safety.
Hu, Huiying; Jiang, Yulin; Zhang, Minghui; Liu, Shanying; Hao, Na; Zhou, Jing; Liu, Juntao; Zhang, Xiaojin; Ma, Liangkun
To evaluate, side by side, the efficiency of dried blood spots (DBSs) against serum screening for Down's syndrome, and then, to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down's syndrome. One thousand eight hundred and thirty-seven low-risk Chinese women, with singleton pregnancy, were enrolled for the study. Alpha-fetoprotein and free beta human chorionic gonadotropin were measured for the serum as well as for the parallel DBS samples. Partial high-risk pregnant women identified by primary blood testing (n = 38) were also subject to the secondary cfDNA screening. Diagnostic amniocentesis was utilized to confirm the screening results. The true positive rate for Down's syndrome detection was 100% for both blood screening methods; however, the false-positive rate was 3.0% for DBS and 4.0% for serum screening, respectively. DBS correlated well with serum screening on Down's syndrome detection. Three out of 38 primary high-risk women displayed chromosomal abnormalities by cfDNA analysis, which were confirmed by amniocentesis. Either the true detection rate or the false-positive rate for Down's syndrome between DBS and the serum test is comparable. In addition, blood primary screening aligned with secondary cfDNA analysis, a "before and after" two-tier screening strategy, can massively decrease the false-positive rate, which, then, dramatically reduces the demand for invasive diagnostic operation. Impact statement Children born with Down's syndrome display a wide range of mental and physical disability. Currently, there is no effective treatment to ease the burden and anxiety of the Down's syndrome family and the surrounding society. This study is to evaluate the efficiency of dried blood spots against serum screening for Down's syndrome and to construct a two-tier strategy by topping up the fetal
Full Text Available A genetic screen to identify mutants that can increase flux in the isoprenoid pathway of yeast has been lacking. We describe a carotenoid-based visual screen built with the core carotenogenic enzymes from the red yeast Rhodosporidium toruloides. Enzymes from this yeast displayed the required, higher capacity in the carotenoid pathway. The development also included the identification of the metabolic bottlenecks, primarily phytoene dehydrogenase, that was subjected to a directed evolution strategy to yield more active mutants. To further limit phytoene pools, a less efficient version of GGPP synthase was employed. The screen was validated with a known flux increasing gene, tHMG1. New mutants in the TATA binding protein SPT15 were isolated using this screen that increased the yield of carotenoids, and an alternate isoprenoid, α-Farnesene confirming increase in overall flux. The findings indicate the presence of previously unknown links to the isoprenoid pathway that can be uncovered using this screen. Keywords: Metabolic engineering, Carotenoids, Isoprenoids, α-Farnesene, Rhodosporidium toruloides, SPT15
... Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...
Dunn, Stephen J.; Khan, Imran H.; Chan, Ursula A.; Scearce, Robin L.; Melara, Claudia L.; Paul, Amber M.; Sharma, Vikram; Bih, Fong-Yih; Holzmayer, Tanya A.; Luciw, Paul A.; Abo, Arie
Human immunodeficiency virus (HIV) drugs designed to interfere with obligatory utilization of certain host cell factors by virus are less likely to encounter development of resistant strains than drugs directed against viral components. Several cellular genes required for productive infection by HIV were identified by the use of genetic suppressor element (GSE) technology as potential targets for anti-HIV drug development. Fragmented cDNA libraries from various pools of human peripheral blood mononuclear cells (PBMC) were expressed in vitro in human immunodeficiency virus type 1 (HIV-1)-susceptible cell lines and subjected to genetic screens to identify GSEs that interfered with viral replication. After three rounds of selection, more than 15 000 GSEs were sequenced, and the cognate genes were identified. The GSEs that inhibited the virus were derived from a diverse set of genes including cell surface receptors, cytokines, signaling proteins, transcription factors, as well as genes with unknown function. Approximately 2.5% of the identified genes were previously shown to play a role in the HIV-1 life cycle; this finding supports the biological relevance of the assay. GSEs were derived from the following 12 cell surface proteins: CXCR4, CCR4, CCR7, CD11C, CD44, CD47, CD68, CD69, CD74, CSF3R, GABBR1, and TNFR2. Requirement of some of these genes for viral infection was also investigated by using RNA interference (RNAi) technology; accordingly, 10 genes were implicated in early events of the viral life cycle, before viral DNA synthesis. Thus, these cell surface proteins represent novel targets for the development of therapeutics against HIV-1 infection and AIDS
The ethical guidelines for prenatal diagnosis proposed by the World Health Organisation (WHO), as well as by national regulations, only refer to paternity and gender of the fetus as unacceptable, disease-unrelated criteria for prenatal selection, as no other such parameters are at hand so far. This perspective is too narrow because research on complex genetic systems such as cognition and ageing is about to provide clinically applicable tests for genetic constituents of potentially desirable properties such as intelligence or longevity which could be misused as parameters for prenatal diagnosis. Moreover, there is an increasing number of prenatally testable genetic traits, such as heritable deafness, which are generally regarded as pathological but desired by some prospective parents and taken into account as parameters for pro-disability selection. To protect prenatal diagnosis from ethically unacceptable genetic consumerism, guidelines must be clarified as soon as possible and updated towards a worldwide restriction of prenatal genetic testing to immediately disease-determining traits. Key Words: Genetics • prenatal diagnosis • ethics • consumerism PMID:11129845
Langlois, Sylvie; Ford, Jason C; Chitayat, David
To provide recommendations to physicians, midwives, genetic counsellors, and clinical laboratory scientists involved in pre-conceptional or prenatal care regarding carrier screening for thalassemia and hemoglobinopathies (e.g., sickle cell anemia and other qualitative hemoglobin disorders). To determine the populations to be screened and the appropriate tests to offer to minimize practice variations across Canada. The Medline database was searched for relevant articles published between 1986 and 2007 on carrier screening for thalassemia and hemoglobinopathies. Key textbooks were also reviewed. Recommendations were quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on Preventive Health Care. The evidence collected from the Medline search was reviewed by the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG) and the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC). Screening of individuals at increased risk of being carriers for thalassemia and hemoglobinopathies can identify couples with a 25% risk of having a pregnancy with a significant genetic disorder for which prenatal diagnosis is possible. Ideally, screening should be done pre-conceptionally. However, for a significant proportion of patients, the screening will occur during the pregnancy, and the time constraint for obtaining screening results may result in psychological distress. This guideline does not include a cost analysis. 1. Carrier screening for thalassemia and hemoglobinopathies should be offered to a woman if she and/or her partner are identified as belonging to an ethnic population whose members are at higher risk of being carriers. Ideally, this screening should be done pre-conceptionally or as early as possible in the pregnancy. (II-2A) 2. Screening should consist of a complete blood count, as well as hemoglobin electrophoresis or hemoglobin high performance liquid chromatography. This
González Salvat, Rosa María; González Labrador, Ignacio
El uso del diagnóstico prenatal en la práctica de la genética médica ha hecho que se recuerden teorías eugenésicas. Se realizó una revisión histórica de este término y se relacionó con el uso del diagnóstico prenatal (DPN) y el aborto selectivo a la luz de los conocimientos bioéticos actuales. The use of the prenatal diagnosis in the practice of medical genetics has led us to remember eugenic theories. A historical review of this term was made and it was connected with the use of prenatal ...
Kauffman, Tia L; Wilfond, Benjamin S; Jarvik, Gail P; Leo, Michael C; Lynch, Frances L; Reiss, Jacob A; Richards, C Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O; Goddard, Katrina A B
Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results are placed into the medical record for use by healthcare providers. Through quantitative and qualitative measures, including baseline and post result disclosure surveys, post result disclosure interviews, 1-2year follow-up interviews, and team journaling, we are obtaining data about the clinical and personal utility of genomic carrier screening in this population. Key outcomes include the number of reportable carrier and additional findings, and the comparative cost, utilization, and psychosocial impacts of usual care vs. genomic carrier screening. As the study progresses, we will compare the costs of genome sequencing and usual care as well as the cost of screening, pattern of use of genetic or mental health counseling services, number of outpatient visits, and total healthcare costs. This project includes novel investigation into human reactions and responses from would-be parents who are learning information that could both affect a future pregnancy and their own health. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Full Text Available Ring chromosomes are unusual abnormalities that are observed in prenatal diagnosis. A 23-year-old patient (gravida 1, para 0 referred for amniocentesis due to abnormal maternal serum screening result in the 16th week of second pregnancy. Cytogenetic analysis of cultured amniyotic fluid cells revealed out ring chromosome 4. Both maternal and paternal karyotypes were normal. Terminal deletion was observed in both 4p and 4q arms of ring chromosome 4 by fluorescence in situ hybridization (FISH. However deletion was not observed in the WHS critical region of both normal and ring chromosome 4 by an additional FISH study. These results were confirmed by means of array-CGH showing terminal deletions on 4p16.3 (130 kb and 4q35.2 (2.449 Mb. In the 21th week of pregnancy, no gross anomalia, except two weeks symmetric growth retardation, was present in the fetal ultrasonographic examination. According to our review of literature, this is the first prenatal case with 4p and 4q subtelomeric deletion of ring chromosome 4 without the involvement of WHS critical region. Our report describes the prenatal case with a ring chromosome 4 abnormality completely characterized by array-CGH which provided complementary data for genetic counseling of prenatal diagnosis.
Akbas, Halit; Cine, Naci; Erdemoglu, Mahmut; Atay, Ahmet Engin; Simsek, Selda; Turkyilmaz, Aysegul; Fidanboy, Mehmet
Ring chromosomes are unusual abnormalities that are observed in prenatal diagnosis. A 23-year-old patient (gravida 1, para 0) referred for amniocentesis due to abnormal maternal serum screening result in the 16th week of second pregnancy. Cytogenetic analysis of cultured amniyotic fluid cells revealed out ring chromosome 4. Both maternal and paternal karyotypes were normal. Terminal deletion was observed in both 4p and 4q arms of ring chromosome 4 by fluorescence in situ hybridization (FISH). However deletion was not observed in the WHS critical region of both normal and ring chromosome 4 by an additional FISH study. These results were confirmed by means of array-CGH showing terminal deletions on 4p16.3 (130 kb) and 4q35.2 (2.449 Mb). In the 21th week of pregnancy, no gross anomalia, except two weeks symmetric growth retardation, was present in the fetal ultrasonographic examination. According to our review of literature, this is the first prenatal case with 4p and 4q subtelomeric deletion of ring chromosome 4 without the involvement of WHS critical region. Our report describes the prenatal case with a ring chromosome 4 abnormality completely characterized by array-CGH which provided complementary data for genetic counseling of prenatal diagnosis.
terphase cells. Patients and Methods: Prenatal diagnosis was performed on 40 high risk ... Prenatal diagnosis of aneuploidy among a sample of Egyptian high risk pregnancies ..... of medical genetics. 9th ed.: Churchill. Livingstone; 1995. p. 23-45. Edwards and Beard: FISH studies of. 2. pre-implantation embryos and PGD.
Scott J. Neal
Full Text Available Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation.
Lynch, HT; Lynch, PM; Lanspa, SJ; Snyder, CL; Lynch, JF; Boland, CR
More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (~30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC’s proximal occurrence (70–80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40–60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir-Torre variant). LS explains only 10–25% of familial CRC. PMID:19659756
Fleron, Stina Lou; Dahl, Katja; Risør, Mette Bech
by the health care system offering it. By prenatal examinations the pregnant women want to be giving the choice of future management should there be something wrong with their child. Conclusions:Participation in prenatal examinations is not based on a thorough knowledge of pros and contra of the screening tests...... Background:In 2004 The Danish National Board of Health issued new guidelines on prenatal examinations. The importance of informed decision making is strongly emphasised and any acceptance of the screenings tests offered should be based on thorough and adequate information. Objective...... and hypothesis:To explore the influence of information in the decision-making process of prenatal screenings tests offered, the relation between information, knowledge and up-take rates and reasons for accepting or declining the screenings tests offered. Methods:The study is based on a qualitative approach...
Sinkey, Rachel G; Odibo, Anthony O
Cost-effectiveness analyses allow assessment of whether marginal gains from new technology are worth increased costs. Several studies have examined cost-effectiveness of Down syndrome (DS) screening and found it to be cost-effective. Noninvasive prenatal screening also appears to be cost-effective among high-risk women with respect to DS screening, but not for the general population. Chromosomal microarray (CMA) is a genetic sequencing method superior to but more expensive than karyotype. In light of CMAs greater ability to detect genetic abnormalities, it is cost-effective when used for prenatal diagnosis of an anomalous fetus. This article covers methodology and salient issues of cost-effectiveness. Copyright © 2016 Elsevier Inc. All rights reserved.
Rio Romero, Luskenia del; Blanco Figueredo, Nadia; Rodriguez Dominguez, Zulay
Omphalocele is an abdominal wall defect at the midline characterized by herniation of abdominal contents and covered by peritoneum and amnion. The aim of this paper is to present a case of omphalocele with gestational age of 23 weeks and prenatal diagnosis by ultrasonography. Using ultrasound diagnosis in a patient inquest made 40 years of age in the second trimester (gestational age 23 weeks) showed a level of the anterior fetal echogenic image that sticks through the abdominal wall and then locate the cord umbilical. Stomach is seen displaced and loss of normal anatomy of the abdominal circumference. Genetic counseling was conducted at the Municipal Center for Genetics of Manzanillo. Pathologically the fetus presented short and wide neck, low-set ears, defect omphalomesenteric of ductal closure, hernia sac occupied by the caudate lobe of the liver and gallbladder bed, wide base heart dissection showing cava-cava absence of interventricular septum was observed pulmonary valve stenosis most dilation of supravalvular pulmonary artery, large defect and aorta intraventricular septum ride, which speaks in favor of a heart rate troncoconal fallop trilogy over the omphalocele. Prenatal diagnosis by ultrasonography is an efficient and reliable method for prenatal diagnosis of omphalocele
Best, Sunayna; Wou, Karen; Vora, Neeta; Van der Veyver, Ignatia B; Wapner, Ronald; Chitty, Lyn S
Prenatal genetic diagnosis provides information for pregnancy and perinatal decision-making and management. In several small series, prenatal whole exome sequencing (WES) approaches have identified genetic diagnoses when conventional tests (karyotype and microarray) were not diagnostic. Here, we review published prenatal WES studies and recent conference abstracts. Thirty-one studies were identified, with diagnostic rates in series of five or more fetuses varying between 6.2% and 80%. Differences in inclusion criteria and trio versus singleton approaches to sequencing largely account for the wide range of diagnostic rates. The data suggest that diagnostic yields will be greater in fetuses with multiple anomalies or in cases preselected following genetic review. Beyond its ability to improve diagnostic rates, we explore the potential of WES to improve understanding of prenatal presentations of genetic disorders and lethal fetal syndromes. We discuss prenatal phenotyping limitations, counselling challenges regarding variants of uncertain significance, incidental and secondary findings, and technical problems in WES. We review the practical, ethical, social and economic issues that must be considered before prenatal WES could become part of routine testing. Finally, we reflect upon the potential future of prenatal genetic diagnosis, including a move towards whole genome sequencing and non-invasive whole exome and whole genome testing. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.
Takabatake, Reona; Onishi, Mari; Koiwa, Tomohiro; Futo, Satoshi; Minegishi, Yasutaka; Akiyama, Hiroshi; Teshima, Reiko; Kurashima, Takeyo; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi
A novel real-time polymerase chain reaction (PCR)-based quantitative screening method was developed for three genetically modified soybeans: RRS, A2704-12, and MON89788. The 35S promoter (P35S) of cauliflower mosaic virus is introduced into RRS and A2704-12 but not MON89788. We then designed a screening method comprised of the combination of the quantification of P35S and the event-specific quantification of MON89788. The conversion factor (Cf) required to convert the amount of a genetically modified organism (GMO) from a copy number ratio to a weight ratio was determined experimentally. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDR), respectively. The determined RSDR values for the method were less than 25% for both targets. We consider that the developed method would be suitable for the simple detection and approximate quantification of GMO.
Sean F Landrette
Full Text Available Somatic forward genetic screens have the power to interrogate thousands of genes in a single animal. Retroviral and transposon mutagenesis systems in mice have been designed and deployed in somatic tissues for surveying hematopoietic and solid tumor formation. In the context of cancer, the ability to visually mark mutant cells would present tremendous advantages for identifying tumor formation, monitoring tumor growth over time, and tracking tumor infiltrations and metastases into wild-type tissues. Furthermore, locating mutant clones is a prerequisite for screening and analyzing most other somatic phenotypes. For this purpose, we developed a system using the piggyBac (PB transposon for somatic mutagenesis with an activated reporter and tracker, called PB-SMART. The PB-SMART mouse genetic screening system can simultaneously induce somatic mutations and mark mutated cells using bioluminescence or fluorescence. The marking of mutant cells enable analyses that are not possible with current somatic mutagenesis systems, such as tracking cell proliferation and tumor growth, detecting tumor cell infiltrations, and reporting tissue mutagenesis levels by a simple ex vivo visual readout. We demonstrate that PB-SMART is highly mutagenic, capable of tumor induction with low copy transposons, which facilitates the mapping and identification of causative insertions. We further integrated a conditional transposase with the PB-SMART system, permitting tissue-specific mutagenesis with a single cross to any available Cre line. Targeting the germline, the system could also be used to conduct F1 screens. With these features, PB-SMART provides an integrated platform for individual investigators to harness the power of somatic mutagenesis and phenotypic screens to decipher the genetic basis of mammalian biology and disease.
Liao, Wei-Ching; Chuang, Min-Chieh; Ho, Ja-An Annie
Genetically modified (GM) technique, one of the modern biomolecular engineering technologies, has been deemed as profitable strategy to fight against global starvation. Yet rapid and reliable analytical method is deficient to evaluate the quality and potential risk of such resulting GM products. We herein present a biomolecular analytical system constructed with distinct biochemical activities to expedite the computational detection of genetically modified organisms (GMOs). The computational mechanism provides an alternative to the complex procedures commonly involved in the screening of GMOs. Given that the bioanalytical system is capable of processing promoter, coding and species genes, affirmative interpretations succeed to identify specified GM event in terms of both electrochemical and optical fashions. The biomolecular computational assay exhibits detection capability of genetically modified DNA below sub-nanomolar level and is found interference-free by abundant coexistence of non-GM DNA. This bioanalytical system, furthermore, sophisticates in array fashion operating multiplex screening against variable GM events. Such a biomolecular computational assay and biosensor holds great promise for rapid, cost-effective, and high-fidelity screening of GMO. Copyright © 2013 Elsevier B.V. All rights reserved.
Gallistel, C R; Balci, Fuat; Freestone, David; Kheifets, Aaron; King, Adam
We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the "cloud" and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopper-switching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in cabinet; two such cabinets (16 environments) may be
Gina M. Zastrow-Hayes
Full Text Available Molecular characterization of events is an integral part of the advancement process during genetically modified (GM crop product development. Assessment of these events is traditionally accomplished by polymerase chain reaction (PCR and Southern blot analyses. Southern blot analysis can be time-consuming and comparatively expensive and does not provide sequence-level detail. We have developed a sequence-based application, Southern-by-Sequencing (SbS, utilizing sequence capture coupled with next-generation sequencing (NGS technology to replace Southern blot analysis for event selection in a high-throughput molecular characterization environment. SbS is accomplished by hybridizing indexed and pooled whole-genome DNA libraries from GM plants to biotinylated probes designed to target the sequence of transformation plasmids used to generate events within the pool. This sequence capture process enriches the sequence data obtained for targeted regions of interest (transformation plasmid DNA. Taking advantage of the DNA adjacent to the targeted bases (referred to as next-to-target sequence that accompanies the targeted transformation plasmid sequence, the data analysis detects plasmid-to-genome and plasmid-to-plasmid junctions introduced during insertion into the plant genome. Analysis of these junction sequences provides sequence-level information as to the following: the number of insertion loci including detection of unlinked, independently segregating, small DNA fragments; copy number; rearrangements, truncations, or deletions of the intended insertion DNA; and the presence of transformation plasmid backbone sequences. This molecular evidence from SbS analysis is used to characterize and select GM plants meeting optimal molecular characterization criteria. SbS technology has proven to be a robust event screening tool for use in a high-throughput molecular characterization environment.
Full Text Available The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP. A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1, while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1. The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.
Seabra, Mariana; Felino, António; Nogueira, Rosete; Valente, Francisco; Braga, Ana Cristina; Vaz, Paula
Hypodontia is the most frequent developmental anomaly of the orofacial complex, and its detection in prenatal ultrasound may indicate the presence of congenital malformations, genetic syndromes and chromosomal abnormalities. To date, only a few studies have evaluated the histological relationship of human tooth germs identified by two-dimensional (2D) ultrasonography. In order to analyze whether two-dimensional ultrasonography of tooth germs may be successfully used for identifying genetic syndromes, prenatal ultrasound images of fetal tooth germs obtained from a Portuguese population sample were compared with histological images obtained from fetal autopsies. Observational, descriptive, transversal study. The study protocol followed the ethical principles outlined by the Helsinki Declaration and was approved by the Ethics Committee of the School of Dental Medicine, University of Porto (FMDUP, Porto, Portugal) and of the Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/EPE, Porto, Portugal) as well as by the CGC Genetics Embryofetal Pathology Laboratory. Eighty-five fetuses examined by prenatal ultrasound screening from May 2011 to August 2012 had an indication for autopsy following spontaneous fetal death or medical termination of pregnancy. Of the 85 fetuses, 37 (43.5%) were randomly selected for tooth germ evaluation by routine histopathological analysis. Fetuses who were up to 30 weeks of gestation, and whose histological pieces were not representative of all maxillary tooth germs was excluded. Twenty four fetus between the 13(th) and 30(th) weeks of gestation fulfilled the parameters to autopsy. Twenty four fetuses were submitted to histological evaluation and were determined the exact number, morphology, and mineralization of their tooth germs. All tooth germs were identifiable with ultrasonography as early as the 13(th) week of gestation. Of the fetuses autopsied, 41.7% had hypodontia (29.1% maxillary hypodontia and 20.9% mandibular hypodontia). This
Anna Elise Engell
Full Text Available Objectives: The biochemical serum markers free Î²-human chorionic gonadotropin (hCGÎ² and pregnancy associated plasma protein A (PAPP-A, used in screening for trisomy 21 (T21, trisomy 18 (T18, and trisomy 13 (T13 during the first trimester, can be measured on different laboratory instruments e.g. Kryptor (Brahms and Cobas (Roche. We compared the performance of these two analytical instruments when used for first trimester combined testing. Design and methods: Serum samples from 944 singleton pregnant women attending for first trimester combined testing were routinely assayed for hCGÎ² and PAPP-A on Kryptor, and re-analyzed on Cobas. In addition, serum samples from 70 pregnant women carrying a fetus affected by T21, T18 or T13, were re-assayed on Cobas. Results: For the screening population, the hCGÎ² and PAPP-A results in multiples of the median (MoM from Kryptor and Cobas were significantly lower on Cobas when compared to Kryptor. The number of pregnant women with a risk above 1:300 for T21 was 48 for both Cobas and Kryptor, although a few patients only had a high risk with one of the methods. Overall, the screen positive rate was 5.1% for both instruments. In the trisomy groups the calculated risks for T21, T18, and T13 agreed well between Cobas and Kryptor. Conclusions: The screen positive rate for T21 (5.1% did not differ between the two analytical platforms in our screening population, although PAPP-A measurements form Cobas were significantly lower than those from Kryptor. The calculated risks for the pregnancies affected by trisomies using hCGÎ² MoM and PAPP-A MoM from Kryptor agreed well with those from Cobas. Keywords: Aneuploidy, Combined first trimester screening, First trimester risk assessment, Free Î²-human chorionic gonadotropin (hCGÎ², Pregnancy associated plasma protein-A (PAPP-A, Trisomy screening
Cecelia A. Bellcross
Full Text Available Newborn screening (NBS follow-up protocols vary significantly by state, and there is a need to better understand the infrastructure and communication flow of NBS programs. In addition, assessment of the educational needs of families and providers with regard to the implications of NBS results is required to inform the development of appropriate informational resources and training opportunities. To begin to address these issues, we administered a web-based survey to state NBS coordinators within the Southeast Regional Newborn Screening & Genetics Collaborative (SERC. Fourteen coordinators responded to the survey, including at least one from each of the 10 SERC states/territories. Over one-third of respondents had never received formal training regarding the metabolic conditions identified on NBS. Most communicated results via telephone or fax, though two centers indicated use of a web-based platform. Only two programs were involved in directly reporting results to the family. Four programs reported a long-term follow-up protocol. Deficits were noted for primary care provider (PCP knowledge of metabolic disorders identified on NBS, and how to inform parents of abnormal results. Close to half indicated that the adequacy of the number of genetic counselors, dietitians, and medical/biochemical geneticists was minimal to insufficient. Respondents uniformly recognized the importance of providing additional educational and informational resources in multiple categories to NBS staff, PCPs, and families.
Lapaire, O; Holzgreve, W; Miny, P; Hösli, I; Hahn, S; Tercanli, S
During the last years, technical improvements have increased the possibilities in prenatal ultrasound. During the eighties and nineties, fetal malformations were increasingly detected and specified. Since a few years, the measurement of the fetal nuchal translucency between 11 and 14 weeks of gestation has been implemented to calculate the individual risk, in combination with most recent biochemical markers. Today, the sonographic measurement of the nuchal translucency is regarded as a valuable screening tool for chromosomal anomalies in prenatal medicine. Beside standardized examinations, a profound information and counseling of the pregnant women should be emphasized. With the improvement of the specific maternal risk calculation, using the sonographic measurement of the nuchal translucency, the biochemical markers and the maternal age, unnecessary invasive examinations may be prevented and their overall number can significantly be reduced. The same trend is seen in the whole field of prenatal medicine, illustrated by the detection of the fetal rhesus D status from the maternal blood and the use of Doppler ultrasound in the management of fetal anemia.
Luciane Alves Rocha
Full Text Available Objective. To describe the experience of a tertiary center in Brazil to which patients are referred whose fetuses are at increased risk for congenital heart diseases (CHDs. Methods. This was a cross-sectional observational study. The data was collected prospectively, during the year 2012, through a screening protocol of the fetal heart adapted from the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG guideline. We performed a fetal echocardiogram screening for all pregnant women who were referred to the fetal cardiology outpatient obstetrics clinic of a university hospital. The exams were classified as normal or abnormal. The cases considered abnormal were undergone to a postnatal echocardiogram. We categorized the abnormal fetal heart according to severity in “complex,” “significant,” “minor,” and “others.” Results. We performed 271 fetal heart screening. The incidence of abnormal screenings was 9.96% (27 fetuses. The structural CHD when categorized due to severity showed 48.1% (n=13 of “complex” cases, 18.5% (n=5 “significant” cases, and 7.4% (n=2 “minor” cases. The most common referral reason was by maternal causes (67% followed by fetal causes (33%. The main referral indication was maternal metabolic disease (30%, but there was just one fetus with CHD in such cases (1.2%. CHDs were found in 19/29 fetuses with suspicion of some cardiac abnormality by obstetrician (65.5%. Conclusion. We observed a high rate of CHD in our population. We also found that there was higher incidence of complex cases.
Beukers, F.; Houtzager, B. A.; Paap, M C S; Middelburg, K J; Hadders-Algra, M; Bos, A.F.; Kok, J.H.
Background: Infertility treatment has an acknowledged psychological impact on women and their partners; however, information about the development of parental well-being after child birth is inconclusive. Preimplantation genetic screening (PGS) has been suggested to increase the efficacy of
Beukers, F.; Houtzager, B. A.; Paap, M. C. S.; Middelburg, K. J.; Hadders-Algra, M.; Bos, A. F.; Kok, J. H.; Cobben, Jan Maarten; van der Heide, Maaike; Koomen, Alice; Repping, Sjoerd; Silberbusch, Lobke; Twisk, Moniek; Mastenbroek, Sebastiaan; van der Veen, Fulco; Bos, Arend F.; Haadsma, Maaike; Hadders-Algra, Mijna; Heineman, Maas Jan; van Hoften, Jacorina; Jongbloed-Pereboom, Marjolein; Keating, Paul; Seggers, Jorien
Background: Infertility treatment has an acknowledged psychological impact on women and their partners; however, information about the development of parental well-being after child birth is inconclusive. Preimplantation genetic screening (PGS) has been suggested to increase the efficacy of
Beukers, F.; Houtzager, B.A.; Paap, Muirne; Middelburg, K.; Hadders-Algra, M.; Bos, A.F.; Kok, J.H.
Background Infertility treatment has an acknowledged psychological impact on women and their partners; however, information about the development of parental well-being after child birth is inconclusive. Preimplantation genetic screening (PGS) has been suggested to increase the efficacy of
Seggers, Jorien; Haadsma, Maaike L.; Bastide-van Gemert, Sacha la; Heineman, Maas Jan; Kok, Joke H.; Middelburg, Karin J.; Roseboom, Tessa J.; Schendelaar, Pamela; van den Heuvel, Edwin R.; Hadders-Algra, Mijna
Recent studies suggest that in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are associated with suboptimal cardiometabolic outcome in offspring. It is unknown whether preimplantation genetic screening (PGS), which involves embryo biopsy, affects blood pressure (BP),
Seggers, Jorien; Haadsma, Maaike L.; la Bastide-van Gemert, Sacha; Heineman, Maas Jan; Kok, Joke H.; Middelburg, Karin J.; Roseboom, Tessa J.; Schendelaar, Pamela; Van den Heuvel, Edwin R.; Hadders-Algra, Mijna
BACKGROUND: Recent studies suggest that in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are associated with suboptimal cardiometabolic outcome in offspring. It is unknown whether preimplantation genetic screening (PGS), which involves embryo biopsy, affects blood pressure
Full Text Available A common limitation for the identification of novel activities from functional (meta genomic screens is the low number of active clones detected relative to the number of clones screened. Here we demonstrate that constructing libraries with strains known to produce bioactives can greatly enhance the screening efficiency, by increasing the “hit-rate” and unmasking multiple activities from the same bacterial source.
Hastedt, Martin; Krumbiegel, Franziska; Gapert, René; Tsokos, Michael; Hartwig, Sven
Alcohol consumption during pregnancy is a widespread problem and can cause severe fetal damage. As the diagnosis of fetal alcohol syndrome is difficult, the implementation of a reliable marker for alcohol consumption during pregnancy into meconium drug screening programs would be invaluable. A previously published gas chromatography mass spectrometry method for the detection of fatty acid ethyl esters (FAEEs) as alcohol markers in meconium was optimized and newly validated for a sample size of 50 mg. This method was applied to 122 cases from a drug-using population. The meconium samples were also tested for common drugs of abuse. In 73 % of the cases, one or more drugs were found. Twenty percent of the samples tested positive for FAEEs at levels indicating significant alcohol exposure. Consequently, alcohol was found to be the third most frequently abused substance within the study group. This re-validated method provides an increase in testing sensitivity, is reliable and easily applicable as part of a drug screening program. It can be used as a non-invasive tool to detect high alcohol consumption in the last trimester of pregnancy. The introduction of FAEEs testing in meconium screening was found to be of particular use in a drug-using population.
Trottier, R.W.; Hodgin, F.C.; Imara, M.; Phoenix, D.; Lybrook, S. (Morehouse Coll., Atlanta, GA (United States). School of Medicine); Crandall, L.A.; Moseley, R.E.; Armotrading, D. (Florida Univ., Gainesville, FL (United States). Coll. of Medicine)
Genetic medical services provided by the Georgia Division of Public Health in two northern and two central districts are compared to services provided in a district in which a tertiary care facility is located. Genetics outreach public health nurses play key roles in Georgia's system of Children's Health Services Genetics Program, including significant roles as counselors and information sources on special needs social services and support organizations. Unique features of individual health districts, (e.g., the changing face of some rural communities in ethnocultural diversity and socioeconomic character), present new challenges to current and future genetics services delivery. Preparedness as to educational needs of both health professionals and the lay population is of foremost concern in light of the ever expanding knowledge and technology in medical genetics. Perspectives on genetics and an overview of services offered by a local private sector counselor are included for comparison to state supported services. The nature of the interactions which transpire between private and public genetic services resources in Georgia will be described. A special focus of this research includes issues associated with sickle cell disease newborn screening service delivery process in Georgia, with particular attention paid to patient follow-up and transition to primary care. Of particular interest to this focus is the problem of loss to follow-up in the current system. Critical factors in education and counseling of sickle cell patients and the expectations of expanding roles of primary care physicians are discussed. The Florida approach to the delivery of genetic services contrasts to the Georgia model by placing more emphasis on a consultant-specialist team approach.
López, Jaime Octavio; Saldarriaga, Wilmar; Fundación Valle de Lili
Diagnóstico Prenatal/ propósitos del diagnóstico prenatal/ Tamizaje a partir del Control Prenatal/ Pacientes de bajo riesgo/ Tamizaje bioquímico/ Pacientes de alto riesgo/ Pruebas invasivas y no invasivas
... Twitter Pinterest Email Print About Preconception Care and Prenatal Care What is preconception care? Preconception care is the ... improve the health of your child. What is prenatal care? Prenatal care is the health care a woman ...
Mazzoni, Sara E; Carter, Ebony B
Patients participating in group prenatal care gather together with women of similar gestational ages and 2 providers who cofacilitate an educational session after a brief medical assessment. The model was first described in the 1990s by a midwife for low-risk patients and is now practiced by midwives and physicians for both low-risk patients and some high-risk patients, such as those with diabetes. The majority of literature on group prenatal care uses CenteringPregnancy, the most popular model. The first randomized controlled trial of CenteringPregnancy showed that it reduced the risk of preterm birth in low-risk women. However, recent meta-analyses have shown similar rates of preterm birth, low birthweight, and neonatal intensive care unit admission between women participating in group prenatal care and individual prenatal care. There may be subgroups, such as African Americans, who benefit from this type of prenatal care with significantly lower rates of preterm birth. Group prenatal care seems to result in increased patient satisfaction and knowledge and use of postpartum family planning as well as improved weight gain parameters. The literature is inconclusive regarding breast-feeding, stress, depression, and positive health behaviors, although it is theorized that group prenatal care positively affects these outcomes. It is unclear whether group prenatal care results in cost savings, although it may in large-volume practices if each group consists of approximately 8-10 women. Group prenatal care requires a significant paradigm shift. It can be difficult to implement and sustain. More randomized trials are needed to ascertain the true benefits of the model, best practices for implementation, and subgroups who may benefit most from this innovative way to provide prenatal care. In short, group prenatal care is an innovative and promising model with comparable pregnancy outcomes to individual prenatal care in the general population and improved outcomes in some
Individual prenatal care is intended to prevent poor perinatal outcomes and provide education to women throughout pregnancy, childbirth, and the postpartum period through a series of one-on-one encounters between a woman and her obstetrician or other obstetric care provider. Concerns regarding increasing health care costs, health care provider availability, dissatisfaction with wait times, and the minimal opportunity for education and support associated with the individual care model have given rise to interest in alternative models of prenatal care. One alternative model, group prenatal care, may be beneficial or preferred for some practice settings and patient populations, although individual prenatal care remains standard practice. Group prenatal care models are designed to improve patient education and include opportunities for social support while maintaining the risk screening and physical assessment of individual prenatal care. Bringing patients with similar needs together for health care encounters increases the time available for the educational component of the encounter, improves efficiency, and reduces repetition. Evidence suggests patients have better prenatal knowledge, feel more ready for labor and delivery, are more satisfied with care in prenatal care groups, and initiate breastfeeding more often. There is no evidence that suggests that group prenatal care causes harm. Individual and group care models warrant additional study with a goal of demonstrating differences in outcomes and identifying populations that benefit most from specific care models.
Individual prenatal care is intended to prevent poor perinatal outcomes and provide education to women throughout pregnancy, childbirth, and the postpartum period through a series of one-on-one encounters between a woman and her obstetrician or other obstetric care provider. Concerns regarding increasing health care costs, health care provider availability, dissatisfaction with wait times, and the minimal opportunity for education and support associated with the individual care model have given rise to interest in alternative models of prenatal care. One alternative model, group prenatal care, may be beneficial or preferred for some practice settings and patient populations, although individual prenatal care remains standard practice. Group prenatal care models are designed to improve patient education and include opportunities for social support while maintaining the risk screening and physical assessment of individual prenatal care. Bringing patients with similar needs together for health care encounters increases the time available for the educational component of the encounter, improves efficiency, and reduces repetition. Evidence suggests patients have better prenatal knowledge, feel more ready for labor and delivery, are more satisfied with care in prenatal care groups, and initiate breastfeeding more often. There is no evidence that suggests that group prenatal care causes harm. Individual and group care models warrant additional study with a goal of demonstrating differences in outcomes and identifying populations that benefit most from specific care models.
Full Text Available Recent developments in molecular genetics improved our knowledge on fetal genome and physiology. Novel scientific innovations in prenatal diagnosis have accelerated in the last decade changing our vision immensely. Data obtained from fetal genomic studies brought new insights to fetal medicine and by the advances in fetal DNA and RNA sequencing technology novel treatment strategies has evolved. Non-invasive prenatal diagnosis found ground in genetics and the results are widely studied in scientific arena. When Lo and colleges proved fetal genetic material can be extracted from maternal plasma and fetal DNA can be isolated from maternal serum, the gate to many exciting discoveries was open. Microarray technology and advances in sequencing helped fetal diagnosis as well as other areas of medicine. Today it is a very crucial prerequisite for physicians practicing prenatal diagnosis to have a profound knowledge in genetics. Prevailing practical use and application of fetal genomic tests in maternal and fetal medicine mandates obstetricians to update their knowledge in genetics. The purpose of this review is to assist physicians to understand and update their knowledge in fetal genetic testing from maternal blood, individualized prenatal counseling and advancements on the subject by sharing our experiences as İstanbul University Fetal Nucleic Acid Research Group.
Ginsburg, Elizabeth S; Baker, Valerie L; Racowsky, Catherine; Wantman, Ethan; Goldfarb, James; Stern, Judy E
To comprehensively report Society for Assisted Reproductive Technology (SART) member program usage of preimplantation genetic testing (PGT), preimplantation genetic diagnosis (PGD) for diagnosis of specific conditions, and preimplantation genetic screening for aneuploidy (PGS). Retrospective study. United States SART cohort data. Women undergoing a PGT cycle in which at least one embryo underwent biopsy. PGT. PGT use, indications, and delivery rates. Of 190,260 fresh, nondonor assisted reproductive technology (ART) cycles reported to SART CORS in 2007-2008, 8,337 included PGT. Of 6,971 cycles with a defined indication, 1,382 cycles were for genetic diagnosis, 3,645 for aneuploidy screening (PGS), 527 for translocation, and 1,417 for elective sex election. Although the total number of fresh, autologous cycles increased by 3.6% from 2007 to 2008, the percentage of cycles with PGT decreased by 5.8% (4,293 in 2007 and 4,044 in 2008). As a percentage of fresh, nondonor ART cycles, use dropped from 4.6% (4,293/93,433) in 2007 to 4.2% (4,044/96,827) in 2008. The primary indication for PGT was PGS: cycles performed for this indication decreased (-8.0%). PGD use for single-gene defects (+3.2%), elective sex selection (+5.3%), and translocation analysis (+0.5%) increased. PGT usage varied significantly by geographical region. PGT usage in the United States decreased between 2007 and 2008 owing to a decrease in PGS. Use of elective sex selection increased. High transfer cancellation rates correlated with reduced live-birth rates for some PGT indications. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Cornel, M.C.; van El, C.G.; Dondorp, W.J.
New screening possibilities become available at a high rate, both useful and unsound possibilities. All screening programmes do harm, and only few have more advantages than disadvantages at reasonable cost. Horizon scanning is needed to identify those few possibilities with more pros than cons.
Engell, Anna Elise; Carlsson, Elin Rebecka; Jørgensen, Finn Stener
OBJECTIVES: The biochemical serum markers free β-human chorionic gonadotropin (hCGβ) and pregnancy associated plasma protein A (PAPP-A), used in screening for trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13) during the first trimester, can be measured on different laboratory instruments e.......g. Kryptor (Brahms) and Cobas (Roche). We compared the performance of these two analytical instruments when used for first trimester combined testing. DESIGN AND METHODS: Serum samples from 944 singleton pregnant women attending for first trimester combined testing were routinely assayed for hCGβ and PAPP...
Eijzenga, W; Bleiker, E M A; Hahn, D E E; Kluijt, I; Sidharta, G N; Gundy, C; Aaronson, N K
Up to three-quarters of individuals who undergo cancer genetic counseling and testing report psychosocial problems specifically related to that setting. The objectives of this study were to develop and evaluate the screening properties of a questionnaire designed to assess specific psychosocial problems related to cancer genetic counseling. We adopted the European Organisation for Research and Treatment of Cancer Quality of Life Group guidelines to develop the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, a 26-item questionnaire organized into six problem domains: genetics, practical issues, family, living with cancer, emotions, and children. The Distress Thermometer and a question per domain on the perceived need for extra psychosocial services were included as well. We administered the questionnaire and the Hospital Anxiety and Depression Scale to 127 counselees at the time of genetic counseling and 3 weeks after DNA test disclosure. As a gold standard to evaluate the screening properties of the questionnaire, participants underwent a semi-structured interview with an experienced social worker who assessed the presence and severity of problems per domain. A cutoff score representing responses of 'quite a bit' or 'very much' to one or more items within a given problem domain yielded moderate to high sensitivity across domains. A cutoff of 4 on the Distress Thermometer yielded high sensitivity. The questions regarding the perceived need for extra psychosocial services yielded high specificity and negative predictive values. The Psychosocial Aspects of Hereditary Cancer questionnaire in combination with the Distress Thermometer can be used as a first-line screener for psychosocial problems within the cancer genetic counseling setting. Copyright © 2014 John Wiley & Sons, Ltd.
Full Text Available Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI screens can provide insights into the biological role(s of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.
Mitchell, M X
In the years following World War II, and increasingly during the 1960s and 1970s, professional scientific societies developed internal sub-committees to address the social implications of their scientific expertise (Moore, Disrupting Science: Social Movements, American Scientists, and the Politics of the Military, 1945-1975. Princeton: Princeton University Press, 2008). This article explores the early years of one such committee, the American Society of Human Genetics' "Social Issues Committee," founded in 1967. Although the committee's name might suggest it was founded to increase the ASHG's public and policy engagement, exploration of the committee's early years reveals a more complicated reality. Affronted by legislators' recent unwillingness to seek the expert advice of human geneticists before adopting widespread neonatal screening programs for phenylketonuria (PKU), and feeling pressed to establish their relevance in an increasingly resource-scarce funding environment, committee members sought to increase the discipline's expert authority. Painfully aware of controversy over abortion rights and haunted by the taint of the discipline's eugenic past, however, the committee proceeded with great caution. Seeking to harness interest in and assert professional control over emerging techniques of genetic diagnosis, the committee strove to protect the society's image by relegating ethical and policy questions about their use to the individual consciences of member scientists. It was not until 1973, after the committee's modest success in organizing support for a retrospective public health study of PKU screening and following the legalization of abortion on demand, that the committee decided to take a more publicly engaged stance.
Simopoulos, A P
Screening programs for genetic diseases and characteristics have multiplied in the last 50 years. 'Genetic Screening: Programs, Principles, and Research' is the report of the Committee for the Study of Inborn Errors of Metabolism (SIEM Committee) commissioned by the Division of Medical Sciences of the National Research Council at the National Academy of Sciences in Washington, DC, published in 1975. The report is considered a classic in the field worldwide, therefore it was thought appropriate 30 years later to present the Committee's modus operandi and bring the Committee's recommendations to the attention of those involved in genetics, including organizational, educational, legal, and research aspects of genetic screening. The Committee's report anticipated many of the legal, ethical, economic, social, medical, and policy aspects of genetic screening. The recommendations are current, and future committees should be familiar with them. In 1975 the Committee stated: 'As new screening tests are devised, they should be carefully reviewed. If the experimental rate of discovery of new genetic characteristics means an accelerating rate of appearance of new screening tests, now is the time to develop the medical and social apparatus to accommodate what later on may otherwise turn out to be unmanageable growth.' What a prophetic statement that was. If the Committee's recommendations had been implemented on time, there would be today a federal agency in existence, responsive and responsible to carry out the programs and support research on various aspects of genetic screening, including implementation of a federal law that protects consumers from discrimination by their employers and the insurance industry on the basis of genetic information. Copyright 2008 S. Karger AG, Basel.
Scicali, R; Di Pino, A; Platania, R; Purrazzo, G; Ferrara, V; Giannone, A; Urbano, F; Filippello, A; Rapisarda, V; Farruggia, E; Piro, S; Rabuazzo, A M; Purrello, F
Familial hypercholesterolemia (FH) is underdiagnosed and public cholesterol screening may be useful to find new subjects. In this study, we aim to investigate the prevalence of FH patients in a hospital screening program and evaluate their atherosclerotic burden using intima-media thickness (IMT). We screened 1575 lipid profiles and included for genetic analysis adults with a low-density lipoprotein (LDL) cholesterol >190 mg/dL and triglycerides 160 mg/dL and triglycerides 8 it was 100%. Mean IMT was higher in FH patients compared to non FH (0.73 [0.61-0.83] vs 0.71 [0.60-0.75] mm, p 190 mg/dL and corneal arcus (p < 0.01 and p < 0.001, respectively). A hospital screening was useful to detect FH subjects with increased atherosclerosis. Also, next-generation sequencing was able to detect new FH mutations. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Scholtens, Ingrid; Laurensse, Emile; Molenaar, Bonnie; Zaaijer, Stephanie; Gaballo, Heidi; Boleij, Peter; Bak, Arno; Kok, Esther
Nowadays most animal feed products imported into Europe have a GMO (genetically modified organism) label. This means that they contain European Union (EU)-authorized GMOs. For enforcement of these labeling requirements, it is necessary, with the rising number of EU-authorized GMOs, to perform an increasing number of analyses. In addition to this, it is necessary to test products for the potential presence of EU-unauthorized GMOs. Analysis for EU-authorized and -unauthorized GMOs in animal feed has thus become laborious and expensive. Initial screening steps may reduce the number of GMO identification methods that need to be applied, but with the increasing diversity also screening with GMO elements has become more complex. For the present study, the application of an informative detailed 24-element screening and subsequent identification strategy was applied in 50 animal feed samples. Almost all feed samples were labeled as containing GMO-derived materials. The main goal of the study was therefore to investigate if a detailed screening strategy would reduce the number of subsequent identification analyses. An additional goal was to test the samples in this way for the potential presence of EU-unauthorized GMOs. Finally, to test the robustness of the approach, eight of the samples were tested in a concise interlaboratory study. No significant differences were found between the results of the two laboratories.
Egan, Crystelle; Marakovitz, Susan; O’Rourke, Julia; Osiecki, Lisa; Illmann, Cornelia; Barton, Lauren; McLaughlin, Elizabeth; Proujansky, Rachel; Royal, Justin; Cowley, Heather; Rangel-Lugo, Martha; Pauls, David; Scharf, Jeremiah M.; Mathews, Carol A.
Genome-wide association studies (GWAS) and other emerging technologies offer great promise for the identification of genetic risk factors for complex psychiatric disorders, yet such studies are constrained by the need for large sample sizes. Web-based collection offers a relatively untapped resource for increasing participant recruitment. Therefore, we developed and implemented a novel web-based screening and phenotyping protocol for genetic studies of Tourette Syndrome (TS), a childhood-onset neuropsychiatric disorder characterized by motor and vocal tics. Participants were recruited over a 13 month period through the membership of the Tourette Syndrome Association (TSA) (n=28,878). Of the TSA members contacted, 4.3% (1,242) initiated the questionnaire, and 79.5% (987) of these were enrollment eligible. 63.9% (631) of enrolled participants completed the study by submitting phenotypic data and blood specimens. Age was the only variable that predicted study completion; children and young adults were significantly less likely to be study completers than adults 26 and older. Compared to a clinic-based study conducted over the same time period, the web-based method yielded a 60% larger sample. Web-based participants were older and more often female; otherwise, the sample characteristics did not differ significantly. TS diagnoses based on the web-screen demonstrated 100% accuracy compared to those derived from in-depth clinical interviews. Our results suggest that a web-based approach is effective for increasing the sample size for genetic studies of a relatively rare disorder and that our web-based screen is valid for diagnosing TS. Findings from this study should aid in the development of web-based protocols for other disorders. PMID:23090870
Zhang, J; Wang, Y N; Wang, J S; Wu, L; Wei, N; Fu, L; Gao, Z; Chen, J H; Pei, R J; Wang, Z
To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH). Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations. The DNA mutations of the four families included missense mutation c.T172C (p.S58P) and non- frameshift deletions c.1083_1094del (p.361_365del), missense mutation c.C1349T (p.T450M) and frameshift mutation c.1090_1091delCT (p.T364fsX93) in PRF1 gene, missense mutation c.G2588A (p.G863D) in UNC13D gene and hemizygous mutation c.32T>G (p.I11S) in SH2D1A gene. The patients and their family members presented decreased NK cell activities. Individuals who carried mutations of PRF1 gene and SH2D1A gene showed low expression of perforin (PRF1) and signaling lymphocytic activation molecule associated protein (SAP). And the patient with UNC13D gene mutation and his family member with identical mutation showed significant reducing cytotoxic degranulation function (expression of CD107a). Pedigree genetic screening and rapid detection of immunological parameters might play an important role in the diagnosis of primary HLH, and both of them had good consistency. As an efficient detection means, the rapid immunological detection indicators would provide reliable basis for the early diagnosis of the primary HLH.
Lackova, Eliska; Cunderlik, Anton; Ticha, Lubica; Gabor, Maria
The enlargement of suprarenal gland is related to preterm birth and the birth weight. The ultrasound measurement of fetal adrenal gland volume may identify women at risk for impending preterm birth. The aim of our study was to investigate the newborns in the region of western Slovakia followed up due to suprarenal gland enlargement. To set the ratio of prenatally diagnosed suprarenal gland enlargment, postnatal managment and treatment and interventions. The newborns with congenital adrenal hyperplasia were excluded. We have analyzed 6 years of medical records of all cases from the western Slovakia region of suprarenal gland enlargement encountered to 1st Pediatric Department, Children's University Hospital Bratislava Republic in the time period of January 2010 to Janurary 2016. The diagnosis of suprarenal gland enlargement was set by ultrasound examination performed on the 4th postnatal day as an overall screening test. Newborns with positive laboratory screening on congenital adrenal hyperplasia (CAH) were excluded from our study. We analyzed the origin of surarenal gland enlargement, gestation week on the due date, the birth weight and other comorbidities and genetic pathologies in newborns with the enlarged suprarenal glands. There were 6 newborns followed up due to suprarenal gland enlargement. All of the patients had diagnosed the adrenal haemorrhage. Adrenal lesions like adrenal cysts or neuroblastomas were not confirmed. All of the adrenal enlargements were benign with no need of other medical or surgical intervention. None of the newborn patients had other genetic abnormalities, mineral or hormonal imbalances, problems with arterial pressure or haemodynamic instability. All of the patients underwent at least 5 prenatal ultrasound tests and at least 2 postnatal ultrasound measurements. The avarage birth weight was 3030 grams (2700 grams - to 3750 grams). The avarage birth lenght was 50 cm (47 centimeter to 53 cm).The average gestation week (gw) on due date
Full Text Available modified crops which brought up a controversy on the safety usage of genetically modified organisms (GMOs. It has been implemented globally that all GMO products and its derived ingredients should have regulations on the usage and labelling. Thus, it is necessary to develop methods that allow rapid screening of GMO products to comply with the regulations. This study employed a reliable and flexible multiplex polymerase chain reaction (PCR method for the rapid detection of transgenic elements in genetically modified soy and maize along with the soybean LECTIN gene and maize ZEIN gene respectively. The selected four common transgenic elements were 35S promoter (35S; Agrobacterium tumefaciens nopaline synthase terminator (NOS; 5-enolypyruvylshikimate-3-phosphate synthase (epsps gene; and Cry1Ab delta-endotoxin (cry1Ab gene. Optimization of the multiplex PCR methods were carried out by using 1% Roundup ReadyTM Soybean (RRS as the certified reference material for soybean that produced fourplex PCR method detecting 35S promoter, NOS terminator, epsps gene and soybean LECTIN gene and by using 1% MON810 as the certified reference material for maize that produced triplex PCR method detecting 35S promoter, cry1Ab gene and maize ZEIN gene prior to screening of the GMO traits in various food products and animal feeds. 1/9 (11.1% of the animal feed contained maize and 1/15 (6.7% of the soybean food products showed positive results for the detection of GMO transgenic gene. None of the maize food products showed positive results for GMO transgenic gene. In total, approximately 4% of the food products and animal feed were positive as GMO. This indicated GMOs have not widely entered the food chain. However, it is necessary to have an appropriate screening method due to GMOs’ unknown potential risk to humans and to animals. This rapid screening method will provide leverage in terms of being economically wise, time saving and reliable.
Hendrickx, Gretl; Boudin, Eveline; Steenackers, Ellen
A role for WNT4 and WNT5B in bone metabolism was indicated by genome-wide association studies (GWAS) and a Wnt4 knockout mouse model. The aim of this study was therefore to replicate and further investigate the causality between genetic variation in WNT4 and WNT5B and deviating bone mineral density...... (BMD) values. A WNT4 and WNT5B mutation screening was performed in patients with craniotubular hyperostosis using Sanger sequencing. Here, no putative causal mutations were detected. Moreover, a high and low BMD cohort was selected from the Odense Androgen Study population for re-sequencing. In WNT4 we...
Frankum, J.; Moudrý, P.; Brough, R.; Hodný, Zdeněk; Ashworth, A.; Bartek, Jiří; Lord, C.J.
Roč. 6, č. 13 (2015), s. 10746-10758 ISSN 1949-2553 R&D Projects: GA ČR GA13-17555S EU Projects: European Commission HEALTH-F2-2010-259893 Grant - others:Lundbeck Foundation(DK) R93-A8990; Danish Council for Independent Research(DK) DFF-1331-00262 Institutional support: RVO:68378050 Keywords : DNA damage response * ubiquitin-proteasome system * RNA interference screens * PARP inhibitors * CBLC Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.008, year: 2015
Rodríguez, Sally Ann; Roter, Debra L; Castillo-Salgado, Carlos; Hooker, Gillian W; Erby, Lori H
Literacy deficits and underutilization of medical services have been linked to health disparities among minorities, and this appears especially relevant for the Latino population. Given the increasing importance of genetics, assessment of genetic health literacy may direct future efforts to better serve this vulnerable population. The current study was designed to contribute to this area by translating and validating a Spanish-language genetic health literacy measure. This was a cross-sectional study involving an interviewer-administered questionnaire. Eligible individuals were Latinos between the ages of 18 and 75 residing in Maryland, who self-reported Spanish as their primary language, recruited through convenience sampling. The genetic health literacy measure components were adapted from existing English-language measures [Erby, Roter, Larson, & Cho's (2008) Rapid Estimate of Adult Literacy in Genetics (REAL-G) and Hooker et al.'s (2014) Genetic Literacy and Comprehension]. An existing Spanish-language general health literacy measure was used to establish preliminary concurrent validity [Lee, Bender, Ruiz, & Cho's (2006) SAHLSA]. 116 individuals completed the assessment. The Spanish-language REAL-G (REAL-G-Sp) was found to correlate well with the SAHLSA (Pearson's r = .77, p validity with an existing health literacy measure in the Latino population residing in Maryland. Significant proportions of this population are predicted to have limitations in genetic health literacy, even when information is provided in Spanish.
Bailey, Beth A; Sokol, Robert J
Pregnancy alcohol consumption has been linked to poor birth outcomes and long-term developmental problems. Despite this, a significant number of women drink during pregnancy. Although most prenatal care providers are asking women about alcohol use, validated screening tools are infrequently employed. Research has demonstrated that currently available screening methods and intervention techniques are effective in identifying and reducing pregnancy drinking. Implementing universal screening and appropriate intervention for pregnancy alcohol use should be a priority for prenatal care providers, as these efforts could substantially improve pregnancy, birth, and longer term developmental outcomes for those affected.
Tay-Sachs disease (TSD) is a severe progressive neurologic disease that causes death in early childhood. Carrier screening, should be offered before pregnancy to individuals and couples at high-risk, including those of Ashkenazi Jewish, French-Canadian, or Cajun descent and those with a family history consistent with TSD. If both partners are determined to be carriers of TSD, genetic counseling and prenatal diagnosis should be offered.
Sidebottom, Abbey C; Hellerstedt, Wendy L; Harrison, Patricia A; Jones-Webb, Rhonda J
We examined associations of depressive symptoms and social support with late and inadequate prenatal care in a low-income urban population. The sample was prenatal care patients at five community health centers. Measures of depressive symptoms, social support, and covariates were collected at prenatal care entry. Prenatal care entry and adequacy came from birth certificates. We examined outcomes of late prenatal care and less than adequate care in multivariable models. Among 2341 study participants, 16% had elevated depressive symptoms, 70% had moderate/poor social support, 21% had no/low partner support, 37% had late prenatal care, and 29% had less than adequate prenatal care. Women with both no/low partner support and elevated depressive symptoms were at highest risk of late care (AOR 1.85, CI 1.31, 2.60, p care (AOR 0.74, CI 0.54, 1.10, p = 0.051). Women with moderate/high depressive symptoms were less likely to experience less than adequate care compared to women with low symptoms (AOR 0.73, CI 0.56, 0.96, p = 0.022). Social support and partner support were negatively associated with indices of prenatal care use. Partner support was identified as protective for women with depressive symptoms with regard to late care. Study findings support public health initiatives focused on promoting models of care that address preconception and reproductive life planning. Practice-based implications include possible screening for social support and depression in preconception contexts.
Mary E. Norton
Full Text Available Little is known about women’s comparative attitudes towards prenatal testing for different categories of genetic disorders. We interviewed women who delivered healthy infants within the past year and assessed attitudes towards prenatal screening and diagnostic testing, as well as pregnancy termination, for Down syndrome (DS, fragile X (FraX, cystic fibrosis (CF, spinal muscular atrophy (SMA, phenylketonuria (PKU and congenital heart defects (CHD. Ninety-five women aged 21 to 48 years participated, of whom 60% were Caucasian, 23% Asian, 10% Latina and 7% African American; 82% were college graduates. Ninety-five to ninety-eight percent indicated that they would have screening for each condition, and the majority would have amniocentesis (64% for PKU to 72% for SMA. Inclinations regarding pregnancy termination varied by condition: Whereas only 10% reported they would probably or definitely terminate a pregnancy for CHD, 41% indicated they would do so for DS and 62% for SMA. Most women in this cohort reported that they would undergo screening for all six conditions presented, the majority without the intent to terminate an affected pregnancy. These women were least inclined to terminate treatable disorders (PKU, CHD versus those associated with intellectual disability (DS, FraX and were most likely to terminate for SMA, typically lethal in childhood.
Hiraoka, Miki; Takahashi, Hiroshi; Orimo, Hideo; Hiraoka, Miina; Ogata, Tsutomu; Azuma, Noriyuki
Purpose To evaluate the possibility of genetic involvement in retinopathy of prematurity (ROP). Although ROP is most often associated with low birthweight and low gestational age, these factors do not necessarily predict the severity of ROP. The possible involvement of other factors, including genetic variants, has been considered. Familial exudative vitreoretinopathy (FEVR) is a hereditary vitreoretinal disorder with clinical manifestations similar to those of ROP. Three genes involving the ...
Genetic interaction studies are a powerful approach to identify functional interactions between genes. This approach can reveal networks of regulatory hubs and connect uncharacterized genes to well-studied pathways. However, this approach has previously been limited to simple gene inactivation studies. Here, we present an orthogonal CRISPR/Cas-mediated genetic interaction approach that allows the systematic activation of one gene while simultaneously knocking out a second gene in the same cell.
Medina, Paul Mark B.; Swick, Lance L.; Andersen, Ryan; Blalock, Zachary; Brenman, Jay E.
Vertebrate and invertebrate dendrites are information-processing compartments that can be found on both central and peripheral neurons. Elucidating the molecular underpinnings of information processing in the nervous system ultimately requires an understanding of the genetic pathways that regulate dendrite formation and maintenance. Despite the importance of dendrite development, few forward genetic approaches have been used to analyze the latest stages of dendrite development, including the ...
Rudra, S; Chakrabarty, P; Hossain, M A; Ripon, M J; Rudra, M; Mirza, T T
Thalassemia is one of the most common genetic diseases in the world. It is a major health problem, brings much morbidity, early mortality and a great deal of misery for a family both financially and emotionally. The patients suffering from beta thalassemia major do not survive for more than 5 years without blood transfusion. Blood transfusion is usually administered every two to five weeks to maintain the pre-transfusion hemoglobin level of 9-10 gm/dL. This study carried out in the department of Transfusion Medicine of Mymensingh Medical College Hospital from January 2014 to June 2014. A total of 200 parents were interviewed. There was a slight preponderance of females which accounted for 57.5% of the parents. Ninety seven (45.5%) had an income less than Rs. 5000 per month. Nearly 50% were illiterate with only 24.5% with a higher education. Consanguinity was positive in 72.5% of the parents with extended family history of thalassemia positive in 40.8%. Only 29.5% were immunized against Hepatitis B. Around 27.5% did not know whether they should be immunized. Fifty five percent of parents knew children should receive Dysferol. Twelve percent were aware of consanguinity to be a risk factor for thalassaemia with only 5% having undergone antenatal diagnosis. Parental knowledge about thalassemia and its preventive measures is inadequate; this requires intervention in the form of public health education programs concentrating on high risk/targeted population.
Hall, Alison; Bostanci, A; Wright, C F
Cell-free fetal DNA and RNA circulating in maternal blood can be used for the early non-invasive prenatal diagnosis (NIPD) of an increasing number of genetic conditions, both for pregnancy management and to aid reproductive decision-making. Here we present a brief review of the scientific and clinical status of the technology, and an overview of key ethical, legal and social issues raised by the analysis of cell-free fetal DNA for NIPD. We suggest that the less invasive nature of the technology brings some distinctive issues into focus, such as the possibility of broader uptake of prenatal diagnosis and access to the technology directly by the consumer via the internet, which have not been emphasised in previous work in this area. We also revisit significant issues that are familiar from previous debates about prenatal testing. Since the technology seems to transect existing distinctions between screening and diagnostic tests, there are important implications for the form and process involved in obtaining informed consent or choice. This analysis forms part of the work undertaken by a multidisciplinary group of experts which made recommendations about the implementation of this technology within the UK National Health Service. Copyright 2010 S. Karger AG, Basel.
Shailaja Gada Saxena
Full Text Available Context: There is a high incidence of numerical chromosomal aberration in couples with repeated in vitro fertilization (IVF failure, advanced maternal age, repeated unexplained abortions, severe male factor infertility and unexplained infertility. Pre-implantation genetic screening (PGS, a variant of pre-implantation genetic diagnosis, screens numerical chromosomal aberrations in couples with normal karyotype, experiencing poor reproductive outcome. The present study includes the results of the initial pilot study on 9 couples who underwent 10 PGS cycles. Aim: The aim of the present study was to evaluate the beneficial effects of PGS in couples with poor reproductive outcome. Settings and Design: Data of initial 9 couples who underwent 10 PGS for various indications was evaluated. Subjects and Methods: Blastomere biopsy was performed on cleavage stage embryos and subjected to two round fluorescence in situ hybridization (FISH testing for chromosomes 13, 18, 21, X and Y as a two-step procedure. Results: Six of the 9 couples (10 PGS cycles conceived, including a twin pregnancy in a couple with male factor infertility, singleton pregnancies in a couple with secondary infertility, in three couples with adverse obstetric outcome in earlier pregnancies and in one couple with repeated IVF failure. Conclusion: In the absence of availability of array-comparative genomic hybridization in diagnostic clinical scenario for PGS and promising results with FISH based PGS as evident from the current pilot study, it is imperative to offer the best available services in the present scenario for better pregnancy outcome for patients.
Abbott, Kenneth L; Nyre, Erik T; Abrahante, Juan; Ho, Yen-Yi; Isaksson Vogel, Rachel; Starr, Timothy K
Identification of cancer driver gene mutations is crucial for advancing cancer therapeutics. Due to the overwhelming number of passenger mutations in the human tumor genome, it is difficult to pinpoint causative driver genes. Using transposon mutagenesis in mice many laboratories have conducted forward genetic screens and identified thousands of candidate driver genes that are highly relevant to human cancer. Unfortunately, this information is difficult to access and utilize because it is scattered across multiple publications using different mouse genome builds and strength metrics. To improve access to these findings and facilitate meta-analyses, we developed the Candidate Cancer Gene Database (CCGD, http://ccgd-starrlab.oit.umn.edu/). The CCGD is a manually curated database containing a unified description of all identified candidate driver genes and the genomic location of transposon common insertion sites (CISs) from all currently published transposon-based screens. To demonstrate relevance to human cancer, we performed a modified gene set enrichment analysis using KEGG pathways and show that human cancer pathways are highly enriched in the database. We also used hierarchical clustering to identify pathways enriched in blood cancers compared to solid cancers. The CCGD is a novel resource available to scientists interested in the identification of genetic drivers of cancer. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
Kimberling, William J; Hildebrand, Michael S; Shearer, A Eliot; Jensen, Maren L; Halder, Jennifer A; Trzupek, Karmen; Cohn, Edward S; Weleber, Richard G; Stone, Edwin M; Smith, Richard J H
Usher syndrome is a major cause of genetic deafness and blindness. The hearing loss is usually congenital and the retinitis pigmentosa is progressive and first noticed in early childhood to the middle teenage years. Its frequency may be underestimated. Newly developed molecular technologies can detect the underlying gene mutation of this disorder early in life providing estimation of its prevalence in at risk pediatric populations and laying a foundation for its incorporation as an adjunct to newborn hearing screening programs. A total of 133 children from two deaf and hard of hearing pediatric populations were genotyped first for GJB2/6 and, if negative, then for Usher syndrome. Children were scored as positive if the test revealed > or =1 pathogenic mutations in any Usher gene. Fifteen children carried pathogenic mutations in one of the Usher genes; the number of deaf and hard of hearing children carrying Usher syndrome mutations was 15/133 (11.3%). The population prevalence was estimated to be 1/6000. Usher syndrome is more prevalent than has been reported before the genome project era. Early diagnosis of Usher syndrome has important positive implications for childhood safety, educational planning, genetic counseling, and treatment. The results demonstrate that DNA testing for Usher syndrome is feasible and may be a useful addition to newborn hearing screening programs.
Bellcross, Cecelia; Hermstad, April; Tallo, Christine; Stanislaw, Christine
Despite increased awareness of hereditary breast and ovarian cancer among clinicians and the public, many BRCA1/2 mutation carriers remain unaware of their risk status. The Breast Cancer Genetics Referral Screening Tool (B-RST™) was created and validated to easily identify individuals at increased risk for hereditary breast and ovarian cancer for referral to cancer genetics services. The purpose of this study was to revise B-RST™ to maximize sensitivity against BRCA1/2 mutation status. We analyzed pedigrees of 277 individuals who had undergone BRCA1/2 testing to determine modifications to the B-RST™ 2.0 algorithm that would maximize sensitivity for mutations, while maintaining simplicity. We used McNemar's chi-square test to compare validation measures between the revised version (3.0) and the 2.0 version. Algorithmic changes made to B-RST™ 2.0 increased the sensitivity against BRCA1/2 mutation analysis from 71.1 to 94.0% (P 3.0 demonstrates high sensitivity for BRCA1/2 mutations, yet remains a simple and quick screening tool for at-risk individuals.
Dey, Arup; Wall, Daniel
Upon physical contact with sibling cells, myxobacteria transiently fuse their outer membranes (OMs) and exchange OM proteins and lipids. From previous work, TraA and TraB were identified to be essential factors for OM exchange (OME) in donor and recipient cells. To define the genetic complexity of OME, we carried out a comprehensive forward genetic screen. The screen was based on the observation that Myxococcus xanthus nonmotile cells, by a Tra-dependent mechanism, block swarm expansion of motile cells when mixed. Thus, mutants defective in OME or a downstream responsive pathway were readily identified as escape flares from mixed inocula seeded on agar. This screen was surprisingly powerful, as we found >50 mutants defective in OME. Importantly, all of the mutations mapped to the traAB operon, suggesting that there may be few, if any, proteins besides TraA and TraB directly required for OME. We also found a second and phenotypically different class of mutants that exhibited wild-type OME but were defective in a responsive pathway. This pathway is postulated to control inner membrane homeostasis by covalently attaching amino acids to phospholipids. The identified proteins are homologous to the Staphylococcus aureus MprF protein, which is involved in membrane adaptation and antibiotic resistance. Interestingly, we also found that a small number of nonmotile cells were sufficient to block the swarming behavior of a large gliding-proficient population. This result suggests that an OME-derived signal could be amplified from a few nonmotile producers to act on many responder cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Avaliação da aplicação do protocolo de triagem pré-natal para toxoplasmose em Belo Horizonte, Minas Gerais, Brasil: estudo transversal em puérperas de duas maternidades Evaluation of prenatal screening for toxoplasmosis in Belo Horizonte, Minas Gerais State, Brazil: a cross-sectional study of postpartum women in two maternity hospitals
Ericka Viana Machado Carellos
Full Text Available Foi realizado estudo transversal, em duas maternidades públicas de Belo Horizonte, Minas Gerais, Brasil, com entrevista de 420 puérperas, de agosto de 2004 a maio de 2005, para avaliar a aplicação do protocolo de triagem pré-natal para toxoplasmose implantado, e as orientações oferecidas às gestantes suscetíveis. A cobertura do pré-natal foi de 98%, e da primeira triagem sorológica de 97%. O início do pré-natal e a realização da primeira sorologia ocorreram em média com 16 semanas. Foram identificadas 163 gestantes suscetíveis à toxoplasmose: 44% não repetiram a sorologia, e 42% alegaram não ter recebido orientações para prevenção da toxoplasmose. O início precoce do pré-natal e um maior número de consultas foram associados à repetição da sorologia e ao recebimento de orientações. As informações oferecidas foram: evitar contato com gatos (95%, não ingerir ou manipular carne crua (70% e lavar cuidadosamente as hortaliças (53%. Concluiu-se que a adesão inadequada ao protocolo de triagem pré-natal de toxoplasmose encontrada no estudo pode gerar gastos financeiros sem melhoria na qualidade do cuidado perinatal.This cross-sectional study of 420 women in two public maternity hospitals from August 2004 to May 2005 evaluated the application of a prenatal toxoplasmosis serological screening protocol in Belo Horizonte, Minas Gerais State, Brazil, and the information provided to susceptible pregnant women. Ninety-eight percent of women received prenatal care and 97% underwent the initial serological screening test, at an average of 16 weeks gestational age. The initial testing identified 163 women as susceptible to toxoplasmosis: 44% of these did not undergo repeat serological testing, and 42% of them did not remember having received information on the prevention of toxoplasmosis infection. Early prenatal care and a high number of prenatal visits were associated with repeat serological testing and orientation regarding
Rogowski, W H; Grosse, S D; Meyer, E; John, J; Palmer, S
Public decision makers face demands to invest in applied research in order to accelerate the adoption of new genetic tests. However, such an investment is profitable only if the results gained from further investigations have a significant impact on health care practice. An upper limit for the value of additional information aimed at improving the basis for reimbursement decisions is given by the expected value of perfect information (EVPI). This study illustrates the significance of the concept of EVPI on the basis of a probabilistic cost-effectiveness model of screening for hereditary hemochromatosis among German men. In the present example, population-based screening can barely be recommended at threshold values of 50,000 or 100,000 Euro per life year gained and also the value of additional research which might cause this decision to be overturned is small: At the mentioned threshold values, the EVPI in the German public health care system was ca. 500,000 and 2,200,000 Euro, respectively. An analysis of EVPI by individual parameters or groups of parameters shows that additional research about adherence to preventive phlebotomy could potentially provide the highest benefit. The potential value of further research also depends on methodological assumptions regarding the decision maker's time horizon as well as on scenarios with an impact on the number of affected patients and the cost-effectiveness of screening.
Full Text Available
Prenatal diagnosis of β-thalassemia was accomplished for the first time in the 1970s by globin chain synthesis analysis on fetal blood obtained by placental aspiration at 18-22 weeks gestation. Since then, the molecular definition of the β- globin gene pathology, the development of procedures of DNA analysis, and the introduction of chorionic villous sampling have dramatically improved prenatal diagnosis of this disease and of related disorders. Much information is now available about the molecular mechanisms of the diseases and the molecular testing is widespread.
As prenatal diagnosis has to provide an accurate, safe and early result, an efficient screening of the population and a rapid molecular characterization of the couple at risk, are necessary prerequisites. In the last decades earlier and less invasive approaches for prenatal diagnosis were developed . A overview of the most promising procedure will be done.
Moreover, in order to reduce the choice of interrupting the pregnancy in case of affected fetus, Preimplantation or Preconceptional Genetic Diagnosis (PGD has been setting up for several diseases including thalassemias.
Effects and Costs of Breast Cancer screening in women with a familial or genetic predisposition
A.J. Rijnsburger (Rian)
textabstract"Women with a BRCA1 or BRCA2 mutation, who have a considerable increased risk of developing breast cancer, now face the choice of intensive screening, prophylactic surgery or chemoprevention. The efficacy of the various medical options and the durability of its effects are of major
Dörries, Hans-Henno; Remus, Ivonne; Grönewald, Astrid; Grönewald, Cordt; Berghof-Jäger, Kornelia
The number of commercially available genetically modified organisms (GMOs) and therefore the diversity of possible target sequences for molecular detection techniques are constantly increasing. As a result, GMO laboratories and the food production industry currently are forced to apply many different methods to reliably test raw material and complex processed food products. Screening methods have become more and more relevant to minimize the analytical effort and to make a preselection for further analysis (e.g., specific identification or quantification of the GMO). A multiplex real-time PCR kit was developed to detect the 35S promoter of the cauliflower mosaic virus, the terminator of the nopaline synthase gene of Agrobacterium tumefaciens, the 35S promoter from the figwort mosaic virus, and the bar gene of the soil bacterium Streptomyces hygroscopicus as the most widely used sequences in GMOs. The kit contains a second assay for the detection of plant-derived DNA to control the quality of the often processed and refined sample material. Additionally, the plant-specific assay comprises a homologous internal amplification control for inhibition control. The determined limits of detection for the five assays were 10 target copies/reaction. No amplification products were observed with DNAs of 26 bacterial species, 25 yeasts, 13 molds, and 41 not genetically modified plants. The specificity of the assays was further demonstrated to be 100% by the specific amplification of DNA derived from reference material from 22 genetically modified crops. The applicability of the kit in routine laboratory use was verified by testing of 50 spiked and unspiked food products. The herein described kit represents a simple and sensitive GMO screening method for the reliable detection of multiple GMO-specific target sequences in a multiplex real-time PCR reaction.
Bell, Richard L.; Hauser, Sheketha; Rodd, Zachary A.; Liang, Tiebing; Sari, Youssef; McClintick, Jeanette; Rahman, Shafiqur; Engleman, Eric A.
The purpose of this review is to present up-to-date pharmacological, genetic and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein we sought to place the P rat’s behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this paper discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general. PMID:27055615
Bowl, Michael R.; Simon, Michelle M.; Ingham, Neil J.
The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. O...
Harper, J C; Aittomäki, K; Borry, P; Cornel, M C; de Wert, G; Dondorp, W; Geraedts, J; Gianaroli, L; Ketterson, K; Liebaers, I; Lundin, K; Mertes, H; Morris, M; Pennings, G; Sermon, K; Spits, C; Soini, S; van Montfoort, A P A; Veiga, A; Vermeesch, J R; Viville, S; Macek, M
Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.
van Zonneveld, Maarten; Ramirez, Marleni; Williams, David E; Petz, Michael; Meckelmann, Sven; Avila, Teresa; Bejarano, Carlos; Ríos, Llermé; Peña, Karla; Jäger, Matthias; Libreros, Dimary; Amaya, Karen; Scheldeman, Xavier
For most crops, like Capsicum, their diversity remains under-researched for traits of interest for food, nutrition and other purposes. A small investment in screening this diversity for a wide range of traits is likely to reveal many traditional varieties with distinguished values. One objective of this study was to demonstrate, with Capsicum as model crop, the application of indicators of phenotypic and geographic diversity as effective criteria for selecting promising genebank accessions for multiple uses from crop centers of diversity. A second objective was to evaluate the expression of biochemical and agromorphological properties of the selected Capsicum accessions in different conditions. Four steps were involved: 1) Develop the necessary diversity by expanding genebank collections in Bolivia and Peru; 2) Establish representative subsets of ~100 accessions for biochemical screening of Capsicum fruits; 3) Select promising accessions for different uses after screening; and 4) Examine how these promising accessions express biochemical and agromorphological properties when grown in different environmental conditions. The Peruvian Capsicum collection now contains 712 accessions encompassing all five domesticated species (C. annuum, C. chinense, C. frutescens, C. baccatum, and C. pubescens). The collection in Bolivia now contains 487 accessions, representing all five domesticates plus four wild taxa (C. baccatum var. baccatum, C. caballeroi, C. cardenasii, and C. eximium). Following the biochemical screening, 44 Bolivian and 39 Peruvian accessions were selected as promising, representing wide variation in levels of antioxidant capacity, capsaicinoids, fat, flavonoids, polyphenols, quercetins, tocopherols, and color. In Peru, 23 promising accessions performed well in different environments, while each of the promising Bolivian accessions only performed well in a certain environment. Differences in Capsicum diversity and local contexts led to distinct outcomes in
Full Text Available BACKGROUND: Dimeric naphthoquinones (BiQ were originally synthesized as a new class of HIV integrase inhibitors but have shown integrase-independent cytotoxicity in acute lymphoblastic leukemia cell lines suggesting their use as potential anti-neoplastic agents. The mechanism of this cytotoxicity is unknown. In order to gain insight into the mode of action of binaphthoquinones we performed a systematic high-throughput screen in a yeast isogenic deletion mutant array for enhanced or suppressed growth in the presence of binaphthoquinones. METHODOLOGY/PRINCIPAL FINDINGS: Exposure of wild type yeast strains to various BiQs demonstrated inhibition of yeast growth with IC(50s in the microM range. Drug sensitivity and resistance screens were performed by exposing arrays of a haploid yeast deletion mutant library to BiQs at concentrations near their IC(50. Sensitivity screens identified yeast with deletions affecting mitochondrial function and cellular respiration as having increased sensitivity to BiQs. Corresponding to this, wild type yeast grown in the absence of a fermentable carbon source were particularly sensitive to BiQs, and treatment with BiQs was shown to disrupt the mitochondrial membrane potential and lead to the generation of reactive oxygen species (ROS. Furthermore, baseline ROS production in BiQ sensitive mutant strains was increased compared to wild type and could be further augmented by the presence of BiQ. Screens for resistance to BiQ action identified the mitochondrial external NAD(PH dehydrogenase, NDE1, as critical to BiQ toxicity and over-expression of this gene resulted in increased ROS production and increased sensitivity of wild type yeast to BiQ. CONCLUSIONS/SIGNIFICANCE: In yeast, binaphthoquinone cytotoxicity is likely mediated through NAD(PH:quonine oxidoreductases leading to ROS production and dysfunctional mitochondria. Further studies are required to validate this mechanism in mammalian cells.
Marie A Chaix; Gregor Andelfinger; Paul Khairy
Congenital heart disease(CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient followup. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.
Chaix, Marie A; Andelfinger, Gregor; Khairy, Paul
Congenital heart disease (CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient follow-up. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel. PMID:26981213
Full Text Available Increasing numbers of human diseases are being linked to genetic variants, but our understanding of the mechanistic links leading from DNA sequence to disease phenotype is limited. The majority of disease-causing nucleotide variants fall within the non-protein-coding portion of the genome, making it likely that they act by altering gene regulatory sequences. We hypothesised that SNPs within the binding sites of the transcriptional repressor REST alter the degree of repression of target genes. Given that changes in the effective concentration of REST contribute to several pathologies-various cancers, Huntington's disease, cardiac hypertrophy, vascular smooth muscle proliferation-these SNPs should alter disease-susceptibility in carriers. We devised a strategy to identify SNPs that affect the recruitment of REST to target genes through the alteration of its DNA recognition element, the RE1. A multi-step screen combining genetic, genomic, and experimental filters yielded 56 polymorphic RE1 sequences with robust and statistically significant differences of affinity between alleles. These SNPs have a considerable effect on the the functional recruitment of REST to DNA in a range of in vitro, reporter gene, and in vivo analyses. Furthermore, we observe allele-specific biases in deeply sequenced chromatin immunoprecipitation data, consistent with predicted differenes in RE1 affinity. Amongst the targets of polymorphic RE1 elements are important disease genes including NPPA, PTPRT, and CDH4. Thus, considerable genetic variation exists in the DNA motifs that connect gene regulatory networks. Recently available ChIP-seq data allow the annotation of human genetic polymorphisms with regulatory information to generate prior hypotheses about their disease-causing mechanism.
Johnson, Rory; Richter, Nadine; Bogu, Gireesh K.; Bhinge, Akshay; Teng, Siaw Wei; Choo, Siew Hua; Andrieux, Lise O.; de Benedictis, Cinzia; Jauch, Ralf; Stanton, Lawrence W.
Increasing numbers of human diseases are being linked to genetic variants, but our understanding of the mechanistic links leading from DNA sequence to disease phenotype is limited. The majority of disease-causing nucleotide variants fall within the non-protein-coding portion of the genome, making it likely that they act by altering gene regulatory sequences. We hypothesised that SNPs within the binding sites of the transcriptional repressor REST alter the degree of repression of target genes. Given that changes in the effective concentration of REST contribute to several pathologies—various cancers, Huntington's disease, cardiac hypertrophy, vascular smooth muscle proliferation—these SNPs should alter disease-susceptibility in carriers. We devised a strategy to identify SNPs that affect the recruitment of REST to target genes through the alteration of its DNA recognition element, the RE1. A multi-step screen combining genetic, genomic, and experimental filters yielded 56 polymorphic RE1 sequences with robust and statistically significant differences of affinity between alleles. These SNPs have a considerable effect on the the functional recruitment of REST to DNA in a range of in vitro, reporter gene, and in vivo analyses. Furthermore, we observe allele-specific biases in deeply sequenced chromatin immunoprecipitation data, consistent with predicted differenes in RE1 affinity. Amongst the targets of polymorphic RE1 elements are important disease genes including NPPA, PTPRT, and CDH4. Thus, considerable genetic variation exists in the DNA motifs that connect gene regulatory networks. Recently available ChIP–seq data allow the annotation of human genetic polymorphisms with regulatory information to generate prior hypotheses about their disease-causing mechanism. PMID:22496669
Fusco, Dahlene N; Brisac, Cynthia; John, Sinu P; Huang, Yi-Wen; Chin, Christopher R; Xie, Tiao; Zhao, Hong; Jilg, Nikolaus; Zhang, Leiliang; Chevaliez, Stephane; Wambua, Daniel; Lin, Wenyu; Peng, Lee; Chung, Raymond T; Brass, Abraham L
Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease. Interferon-α (IFNα) is an important component of anti-HCV therapy; it up-regulates transcription of IFN-stimulated genes, many of which have been investigated for their antiviral effects. However, all of the genes required for the antiviral function of IFNα (IFN effector genes [IEGs]) are not known. IEGs include not only IFN-stimulated genes, but other nontranscriptionally induced genes that are required for the antiviral effect of IFNα. In contrast to candidate approaches based on analyses of messenger RNA (mRNA) expression, identification of IEGs requires a broad functional approach. We performed an unbiased genome-wide small interfering RNA screen to identify IEGs that inhibit HCV. Huh7.5.1 hepatoma cells were transfected with small interfering RNAs incubated with IFNα and then infected with JFH1 HCV. Cells were stained using HCV core antibody, imaged, and analyzed to determine the percent infection. Candidate IEGs detected in the screen were validated and analyzed further. The screen identified 120 previously unreported IEGs. From these, we more fully evaluated the following: asparagine-linked glycosylation 10 homolog (yeast, α-1,2-glucosyltransferase); butyrylcholinesterase; dipeptidyl-peptidase 4 (CD26, adenosine deaminase complexing protein 2); glucokinase (hexokinase 4) regulator; guanylate cyclase 1, soluble, β 3; MYST histone acetyltransferase 1; protein phosphatase 3 (formerly 2B), catalytic subunit, β isoform; peroxisomal proliferator-activated receptor-γ-DBD-interacting protein 1; and solute carrier family 27 (fatty acid transporter), member 2; and demonstrated that they enabled IFNα-mediated suppression of HCV at multiple steps of its life cycle. Expression of these genes had more potent effects against flaviviridae because a subset was required for IFNα to suppress dengue virus but not influenza A virus. In addition, many of the host genes detected in this
M., Adamopoulou; E.M., Pallesen; A., Levann
engineered GlycoSkin tissue models can be used to study biological interactions involving glycan structure on lipids, or glycosaminoglycans. This engineering approach will allow us to investigate the functions of glycans in homeostasis and elucidate the role of glycans in normal epithelial formation....... We use genetic engineering with CRISPR/Cas9 combined with 3D organotypic skin models to examine how distinct glycans influence epithelial formation. We have performed knockout and knockin of more than 100 select genes in the genome of human immortalized human keratinocytes, enabling a systematic...... analysis of the impact of specific glycans in the formation and transformation of the human skin. The genetic engineered human skin models (GlycoSkin) was designed with and without all major biosynthetic pathways in mammalian glycan biosynthesis, including GalNAc-O-glycans, O-fucosylation, O...
Havndrup, Ole; Christiansen, Michael; Stoevring, Birgitte
AIMS: Fabry disease, an X-linked storage disorder caused by defective lysosomal enzyme alpha-galactosidase A activity, may resemble sarcomere-gene-associated hypertrophic cardiomyopathy (HCM). The 'cardiac variant' of Fabry disease which only affects the heart may be missed unless specifically te...... therapy, supports systematic testing for Fabry disease. Enzyme measurements are sufficient in men, but genetic testing is needed in women....
Rossing, Maria; Albrechtsen, Anders; Skytte, Anne-Bine
Pathogenic germline mutations in the folliculin (FLCN) tumor suppressor gene predispose to Birt-Hogg-Dubé (BHD) syndrome, a rare disease characterized by the development of cutaneous hamartomas (fibrofolliculomas), multiple lung cysts, spontaneous pneumothoraces and renal cell cancer. In this stu...... understanding of BHD syndrome and management of BHD patients.Journal of Human Genetics advance online publication, 13 October 2016; doi:10.1038/jhg.2016.118....
factories vary largely, including industrial production of valuable compounds for biofuels, polymer synthesis and food, cosmetic and pharmaceutical industry. The improvement of computational and biochemical tools has revolutionized the synthesis of novel modified microbial strains, opening up new......The importance of metabolic engineering has been growing over the last decades, establishing the use of genetically modified microbial strains for overproduction of metabolites at industrial scale as an innovative, convenient and biosustainable method. Nowadays, application areas of microbial...
Dengjel, Jörn; Høyer-Hansen, Maria; Nielsen, Maria
Autophagy is one of the major intracellular catabolic pathways, but little is known about the composition of autophagosomes. To study the associated proteins, we isolated autophagosomes from human breast cancer cells using two different biochemical methods and three stimulus types: amino acid dep...... regulators of autophagy, including subunits of the retromer complex. The combined spatiotemporal proteomic and genetic data sets presented here provide a basis for further characterization of autophagosome biogenesis and cargo selection....
Champagne , and Pierre Drapeau. 25th international symposium on ALS/MND (5-7 December 2014) Patten SA, Vaccaro A, Drapeau P, Kabashi E, Parker JA...transgenic mice produced with TDP- 43 genomic fragments. Brain 134, 2610-2626 (2011). 6 Kabashi, E., Champagne , N., Brustein, E. & Drapeau, P. In the...swim of things: recent insights to neurogenetic disorders from zebrafish. Trends Genet 26, 373-381 (2010). 7 Kabashi, E., Brustein, E., Champagne , N
red. Chlo= Chlorprothixene hydrochloride; Amo= Amoxapine; Mians = Mianserine hydrochloride; Pizo= Pizotifen malate; Pimet= Pimethixene maleate; Cloz...lobar degeneration in transgenic mice produced with TDP-43 genomic fragments. Brain. 32. Li Y, Ray P, Rao EJ, Shi C, Guo W, et al. (2010) A Drosophila...2008) Sirtuin Inhibition Protects from the Polyalanine Muscular Dystrophy Protein PABPN1. Hum Mol Genet. 36. Wang J, Farr GW, Hall DH, Li F, Furtak
Sills, E Scott; Anderson, Robert E; McCaffrey, Mary; Li, Xiang; Arrach, Nabil; Wood, Samuel H
Preimplantation genetic screening (PGS) is a component of IVF entailing selection of an embryo for transfer on the basis of chromosomal normalcy. If PGS were integrated with single embryo transfer (SET) in a surrogacy setting, this approach could improve pregnancy rates, minimize miscarriage risk, and limit multiple gestations. Even without PGS, pregnancy rates for IVF surrogacy cases are generally satisfactory, especially when treatment utilizes embryos derived from young oocytes and transferred to a healthy surrogate. However, there could be a more general role for PGS in surrogacy, since background aneuploidy in embryos remains a major factor driving implantation failure and miscarriage for all infertility patients. At present, the proportion of IVF cases involving GS is limited, while the number of IVF patients requesting PGS appears to be increasing. In this report, the relevance of PGS for surrogacy in the rapidly changing field of assisted fertility medicine is discussed. © 2015 Wiley Periodicals, Inc.
Full Text Available Accumulation of toxic proteins in neurons has been linked with the onset of neurodegenerative diseases, which in many cases are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and the resolubilization of unfolded proteins, thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance remains largely unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes. Ubiquitous actin5C-Gal4-mediated RNAi knockdown revealed that ∼50% of the chaperones are essential in Drosophila. Knocking down these genes in eyes revealed that ∼30% of the essential chaperones are crucial for eye development. Using neuron-specific knockdown, immunocytochemistry, and robust behavioral assays, we identified a new set of chaperones that play critical roles in the regulation of Drosophila NMJ structural organization. Together, our data present the first classification and comprehensive analysis of Drosophila chaperones. Our screen identified a new set of chaperones that regulate eye and NMJ morphogenesis. The outcome of the screen reported here provides a useful resource for further elucidating the role of individual chaperones in Drosophila eye morphogenesis and synaptic development.
Full Text Available Chronic infections with Staphylococcus aureus such as septicemia, osteomyelitis, endocarditis, and biofilm infections are difficult to treat because of persisters. Despite many efforts in understanding bacterial persistence, the mechanisms of persister formation in S. aureus remain elusive. Here, we performed a genome-wide screen of a transposon mutant library to study the molecular mechanisms involved in persistence of community-acquired S. aureus. Screening of the library for mutants defective in persistence or tolerance to rifampicin revealed many genes involved in metabolic pathways that are important for antibiotic persistence. In particular, the identified mutants belonged to metabolic pathways involved in carbohydrate, amino acid, lipid, vitamin and purine biosynthesis. Five mutants played a role in purine biosynthesis and two mutants, purB, an adenylosuccinate lyase, and purM, a phosphoribosylaminoimidazole synthetase, were selected for further confirmation. Mutants purB and purM showed defective persistence compared to the parental strain USA300 in multiple stress conditions including various antibiotics, low pH, and heat stress. The defect in persistence was restored by complementation with the wildtype purB and purM gene in the respective mutants. These findings provide new insights into the mechanisms of persistence in S. aureus and provide novel therapeutic targets for developing more effective treatment for persistent infections due to S. aureus.
Debra A O'Leary
Full Text Available One therapeutic approach to Duchenne Muscular Dystrophy (DMD recently entering clinical trials aims to convert DMD phenotypes to that of a milder disease variant, Becker Muscular Dystrophy (BMD, by employing antisense oligonucleotides (AONs targeting splice sites, to induce exon skipping and restore partial dystrophin function. In order to search for small molecule and genetic modulators of AON-dependent and independent exon skipping, we screened approximately 10,000 known small molecule drugs, >17,000 cDNA clones, and >2,000 kinase- targeted siRNAs against a 5.6 kb luciferase minigene construct, encompassing exon 71 to exon 73 of human dystrophin. As a result, we identified several enhancers of exon skipping, acting on both the reporter construct as well as endogenous dystrophin in mdx cells. Multiple mechanisms of action were identified, including histone deacetylase inhibition, tubulin modulation and pre-mRNA processing. Among others, the nucleolar protein NOL8 and staufen RNA binding protein homolog 2 (Stau2 were found to induce endogenous exon skipping in mdx cells in an AON-dependent fashion. An unexpected but recurrent theme observed in our screening efforts was the apparent link between the inhibition of cell cycle progression and the induction of exon skipping.
Takabatake, Reona; Koiwa, Tomohiro; Kasahara, Masaki; Takashima, Kaori; Futo, Satoshi; Minegishi, Yasutaka; Akiyama, Hiroshi; Teshima, Reiko; Oguchi, Taichi; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi
To reduce the cost and time required to routinely perform the genetically modified organism (GMO) test, we developed a duplex quantitative real-time PCR method for a screening analysis simultaneously targeting an event-specific segment for GA21 and Cauliflower Mosaic Virus 35S promoter (P35S) segment [Oguchi et al., J. Food Hyg. Soc. Japan, 50, 117-125 (2009)]. To confirm the validity of the method, an interlaboratory collaborative study was conducted. In the collaborative study, conversion factors (Cfs), which are required to calculate the GMO amount (%), were first determined for two real-time PCR instruments, the ABI PRISM 7900HT and the ABI PRISM 7500. A blind test was then conducted. The limit of quantitation for both GA21 and P35S was estimated to be 0.5% or less. The trueness and precision were evaluated as the bias and reproducibility of the relative standard deviation (RSD(R)). The determined bias and RSD(R) were each less than 25%. We believe the developed method would be useful for the practical screening analysis of GM maize.
Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang
Digital PCR has developed rapidly since it was first reported in the 1990 s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products.
Fendler, W; Borowiec, M; Baranowska-Jazwiecka, A; Szadkowska, A; Skala-Zamorowska, E; Deja, G; Jarosz-Chobot, P; Techmanska, I; Bautembach-Minkowska, J; Mysliwiec, M; Zmyslowska, A; Pietrzak, I; Malecki, M T; Mlynarski, W
The aim of this study was to study dynamic changes in the prevalence of different types of diabetes in paediatric populations in Poland, with a specific focus on monogenic diabetes (MD). Using epidemiologic data (PolPeDiab Collaboration) and nationwide genetic test results (TEAM Programme), we compared the prevalence of type 1, type 2 and cystic fibrosis-related diabetes (CFRD) and MD. Genetically confirmed MD included MODY, neonatal diabetes and Wolfram and Alström syndromes. The study covered all children aged 0-18 years treated for diabetes between 2005 and 2011 in three regions, inhabited by 23.7% (1,989,988) of Polish children, with a low prevalence of childhood obesity (type 1 diabetes showed a continuous increase, from 96 to 138/100,000 children. The prevalence of type 2 diabetes and CFRD also increased, from 0.3 to 1.01/100,000 children and from 0.1 to 0.95/100,000 children, respectively. The prevalence of MD was stable at between 4.2 and 4.6/100,000 children, accounting for 3.1-4.2% of children with diabetes, with glucokinase (GCK)-MODY being the most frequent type, amounting to 83% of patients with MD. The percentage of positive test results decreased with the number of referrals, suggesting that children with the highest probability of MD were referred initially, followed by those with a less clear-cut phenotype. The prevalence of neonatal diabetes equalled 1 in 300,000 children. The prevalence of MD in a paediatric population with a low prevalence of obesity remains stable and is nearly fivefold higher than that of type 2 diabetes and CFRD, justifying a need for increased access to genetic diagnostic procedures in diabetic children.
Meeske, Alexander J; Rodrigues, Christopher D A; Brady, Jacqueline; Lim, Hoong Chuin; Bernhardt, Thomas G; Rudner, David Z
The differentiation of the bacterium Bacillus subtilis into a dormant spore is among the most well-characterized developmental pathways in biology. Classical genetic screens performed over the past half century identified scores of factors involved in every step of this morphological process. More recently, transcriptional profiling uncovered additional sporulation-induced genes required for successful spore development. Here, we used transposon-sequencing (Tn-seq) to assess whether there were any sporulation genes left to be discovered. Our screen identified 133 out of the 148 genes with known sporulation defects. Surprisingly, we discovered 24 additional genes that had not been previously implicated in spore formation. To investigate their functions, we used fluorescence microscopy to survey early, middle, and late stages of differentiation of null mutants from the B. subtilis ordered knockout collection. This analysis identified mutants that are delayed in the initiation of sporulation, defective in membrane remodeling, and impaired in spore maturation. Several mutants had novel sporulation phenotypes. We performed in-depth characterization of two new factors that participate in cell-cell signaling pathways during sporulation. One (SpoIIT) functions in the activation of σE in the mother cell; the other (SpoIIIL) is required for σG activity in the forespore. Our analysis also revealed that as many as 36 sporulation-induced genes with no previously reported mutant phenotypes are required for timely spore maturation. Finally, we discovered a large set of transposon insertions that trigger premature initiation of sporulation. Our results highlight the power of Tn-seq for the discovery of new genes and novel pathways in sporulation and, combined with the recently completed null mutant collection, open the door for similar screens in other, less well-characterized processes.
Brady, Jacqueline; Lim, Hoong Chuin; Bernhardt, Thomas G.; Rudner, David Z.
The differentiation of the bacterium Bacillus subtilis into a dormant spore is among the most well-characterized developmental pathways in biology. Classical genetic screens performed over the past half century identified scores of factors involved in every step of this morphological process. More recently, transcriptional profiling uncovered additional sporulation-induced genes required for successful spore development. Here, we used transposon-sequencing (Tn-seq) to assess whether there were any sporulation genes left to be discovered. Our screen identified 133 out of the 148 genes with known sporulation defects. Surprisingly, we discovered 24 additional genes that had not been previously implicated in spore formation. To investigate their functions, we used fluorescence microscopy to survey early, middle, and late stages of differentiation of null mutants from the B. subtilis ordered knockout collection. This analysis identified mutants that are delayed in the initiation of sporulation, defective in membrane remodeling, and impaired in spore maturation. Several mutants had novel sporulation phenotypes. We performed in-depth characterization of two new factors that participate in cell–cell signaling pathways during sporulation. One (SpoIIT) functions in the activation of σE in the mother cell; the other (SpoIIIL) is required for σG activity in the forespore. Our analysis also revealed that as many as 36 sporulation-induced genes with no previously reported mutant phenotypes are required for timely spore maturation. Finally, we discovered a large set of transposon insertions that trigger premature initiation of sporulation. Our results highlight the power of Tn-seq for the discovery of new genes and novel pathways in sporulation and, combined with the recently completed null mutant collection, open the door for similar screens in other, less well-characterized processes. PMID:26735940
Most land plants possess the capacity to protect themselves from UV light, and do so by producing pigments that absorb efficiently in the UV-A and UV-B regions of the spectrum while allowing transmission of nearly all photosynthetically useful wavelengths. These UV-absorbing pigments are mainly phenylpropanoids and flavonoids. This chapter summarizes current understanding of the mechanism of UV protection in higher land plants, evaluates the information available from lower land plants and their green-algal relatives, and then considers the possible evolutionary origins of this use of chemical filters for selectively screening UV light from solar radiation. It is proposed that photo control over the biosynthesis of UV-absorbing phenylpropanoids and flavonoids may have evolved in concert with the evolution of the high biosynthetic activity necessary for UV protection. The toxicity of phenylpropanoids and flavonoids has been postulated to have been a barrier to the evolution of an effective chemical UV screen, and that some means for sequestering these compounds and/or for controlling their synthesis probably evolved prior to, or in concert with, the evolution of high rates of biosynthesis. The original photoreceptor and signal transduction system is speculated to have been based on photo isomerization of a phenylpropanoid ester and a pre-existing product feedback mechanism for controlling phenylpropanoid biosynthesis. Understanding the original mechanism for photo control of the chemical UV screen of land plants could be valuable for understanding the adaptability of extant land plants to rising levels of solar UV-B radiation and may suggest genetic strategies for engineering improved UV tolerance in crop plants. (author)
Full Text Available Genetic and chemical biology screens of C. elegans have been of enormous benefit in providing fundamental insight into neural function and neuroactive drugs. Recently the exploitation of microfluidic devices has added greater power to this experimental approach providing more discrete and higher throughput phenotypic analysis of neural systems. Here we make a significant addition to this repertoire through the design of a semi-automated microfluidic device, NeuroChip, which has been optimised for selecting worms based on the electrophysiological features of the pharyngeal neural network. We demonstrate this device has the capability to sort mutant from wild-type worms based on high definition extracellular electrophysiological recordings. NeuroChip resolves discrete differences in excitatory, inhibitory and neuromodulatory components of the neural network from individual animals. Worms may be fed into the device consecutively from a reservoir and recovered unharmed. It combines microfluidics with integrated electrode recording for sequential trapping, restraining, recording, releasing and recovering of C. elegans. Thus mutant worms may be selected, recovered and propagated enabling mutagenesis screens based on an electrophysiological phenotype. Drugs may be rapidly applied during the recording thus permitting compound screening. For toxicology, this analysis can provide a precise description of sub-lethal effects on neural function. The chamber has been modified to accommodate L2 larval stages showing applicability for small size nematodes including parasitic species which otherwise are not tractable to this experimental approach. We also combine NeuroChip with optogenetics for targeted interrogation of the function of the neural circuit. NeuroChip thus adds a new tool for exploitation of C. elegans and has applications in neurogenetics, drug discovery and neurotoxicology.
Full Text Available Amyotrophic Lateral Sclerosis (ALS is a progressive neurodegenerative disorder characterized by selective death of motor neurons. In 5–10% of the familial cases, the disease is inherited because of mutations. One such mutation, P56S, was identified in human VAPB that behaves in a dominant negative manner, sequestering wild type protein into cytoplasmic inclusions. We have conducted a reverse genetic screen to identify interactors of Drosophila VAPB. We screened 2635 genes and identified 103 interactors, of which 45 were enhancers and 58 were suppressors of VAPB function. Interestingly, the screen identified known ALS loci – TBPH, alsin2 and SOD1. Also identified were genes involved in cellular energetics and homeostasis which were used to build a gene regulatory network of VAPB modifiers. One key modifier identified was Tor, whose knockdown reversed the large bouton phenotype associated with VAP(P58S expression in neurons. A similar reversal was seen by over-expressing Tuberous Sclerosis Complex (Tsc1,2 that negatively regulates TOR signaling as also by reduction of S6K activity. In comparison, the small bouton phenotype associated with VAP(wt expression was reversed with Tsc1 knock down as well as S6K-CA expression. Tor therefore interacts with both VAP(wt and VAP(P58S, but in a contrasting manner. Reversal of VAP(P58S bouton phenotypes in larvae fed with the TOR inhibitor Rapamycin suggests upregulation of TOR signaling in response to VAP(P58S expression. The VAPB network and further mechanistic understanding of interactions with key pathways, such as the TOR cassette, will pave the way for a better understanding of the mechanisms of onset and progression of motor neuron disease.
Deivasigamani, Senthilkumar; Verma, Hemant Kumar; Ueda, Ryu; Ratnaparkhi, Anuradha; Ratnaparkhi, Girish S
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by selective death of motor neurons. In 5-10% of the familial cases, the disease is inherited because of mutations. One such mutation, P56S, was identified in human VAPB that behaves in a dominant negative manner, sequestering wild type protein into cytoplasmic inclusions. We have conducted a reverse genetic screen to identify interactors of Drosophila VAPB. We screened 2635 genes and identified 103 interactors, of which 45 were enhancers and 58 were suppressors of VAPB function. Interestingly, the screen identified known ALS loci - TBPH, alsin2 and SOD1. Also identified were genes involved in cellular energetics and homeostasis which were used to build a gene regulatory network of VAPB modifiers. One key modifier identified was Tor, whose knockdown reversed the large bouton phenotype associated with VAP(P58S) expression in neurons. A similar reversal was seen by over-expressing Tuberous Sclerosis Complex (Tsc1,2) that negatively regulates TOR signaling as also by reduction of S6K activity. In comparison, the small bouton phenotype associated with VAP(wt) expression was reversed with Tsc1 knock down as well as S6K-CA expression. Tor therefore interacts with both VAP(wt) and VAP(P58S), but in a contrasting manner. Reversal of VAP(P58S) bouton phenotypes in larvae fed with the TOR inhibitor Rapamycin suggests upregulation of TOR signaling in response to VAP(P58S) expression. The VAPB network and further mechanistic understanding of interactions with key pathways, such as the TOR cassette, will pave the way for a better understanding of the mechanisms of onset and progression of motor neuron disease. © 2014. Published by The Company of Biologists Ltd.
Full Text Available Anchorage-independent proliferation is a hallmark of oncogenic transformation and is thought to be conducive to proliferation of cancer cells away from their site of origin. We have previously reported that primary Schwann cells expressing the SV40 Large T antigen (LT are not fully transformed in that they maintain a strict requirement for attachment, requiring a further genetic change, such as oncogenic Ras, to gain anchorage-independence. Using the LT-expressing cells, we performed a genetic screen for anchorage-independent proliferation and identified Sensory and Motor Neuron Derived Factor (SMDF, a transmembrane class III isoform of Neuregulin 1. In contrast to oncogenic Ras, SMDF induced enhanced proliferation in normal primary Schwann cells but did not trigger cellular senescence. In cooperation with LT, SMDF drove anchorage-independent proliferation, loss of contact inhibition and tumourigenicity. This transforming ability was shared with membrane-bound class III but not secreted class I isoforms of Neuregulin, indicating a distinct mechanism of action. Importantly, we show that despite being membrane-bound signalling molecules, class III neuregulins transform via a cell intrinsic mechanism, as a result of constitutive, elevated levels of ErbB signalling at high cell density and in anchorage-free conditions. This novel transforming mechanism may provide new targets for cancer therapy.
Covassin, L D; Siekmann, A F; Kacergis, M C; Laver, E; Moore, J C; Villefranc, J A; Weinstein, B M; Lawson, N D
In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development.
Full Text Available Seong Soo An,1,* Sun Ah Park,2,* Eva Bagyinszky,1 Sun Oh Bae,1 Yoon-Jeong Kim,2 Ji Young Im,2 Kyung Won Park,3 Kee Hyung Park,4 Eun-Joo Kim,5 Jee Hyang Jeong,6 Jong Hun Kim,7 Hyun Jeong Han,8 Seong Hye Choi,9 SangYun Kim10 1Department of Bionano Technology, Gachon University, Seongnam-si, 2Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 3Department of Neurology, Dong-A University College of Medicine and Institute of Convergence Bio-Health, Busan, 4Department of Neurology, Gachon University Gil Medical Center, Incheon, 5Department of Neurology, Pusan National University Hospital, Busan, 6Department of Neurology, Ewha Womans University Mokdong Hospital, Seoul, 7Department of Neurology, Ilsan Hospital, National Health Insurance Corporation, 8Department of Neurology, Myongii Hospital, Goyang, 9Department of Neurology, Inha University School of Medicine, Incheon, 10Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea *These authors contributed equally to this work Abstract: Early-onset Alzheimer’s disease (EOAD has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD. The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD
Molina Silvia M.G.
Full Text Available Aiming at contributing to technological improvements in plant fiber processing methods, this paper reports research work on the obtainment of more efficient pectinase-producing fungi strains. More specifically, this work reports the analysis of 18 strains of filamentous fungi, with the purpose of obtaining enzymes for textile fibers degumming. The strains were evaluated for production of pectinolytic enzymes under several growth conditions (culture medium and growth temperature. Production of pectinases was measured by an enzymatic index (EI in solid pectin medium. Among the tested strains, Penicillium chrysogenum IFO 4626 (Q 176 showed the best performance. Genetic improvement of this strain was carried out to increase its pectinase production, while keeping cellulase activity down to a negligible level, since cellulases are known to decrease the resistance of the fiber. Variability was induced through several cycles of mutation and selection by exposing conidea to ultra-violet light (UV. We selected 39 out of 390 isolated colonies. Resulting mutants produced nine times more pectin lyase (PL than the original strain in terms of PL specific activity, and five times more in terms of PL activity (i.e. mmoles liberated per minute of reaction per mL of medium. Periodically, mutant performance was evaluated in solid pectin medium. Genetic stability was maintained for four years after isolation.
... Pregnancy week by week During the second trimester, prenatal care includes routine lab tests and measurements of your ... too. By Mayo Clinic Staff The goal of prenatal care is to ensure that you and your baby ...
... Pregnancy week by week During the third trimester, prenatal care might include vaginal exams to check the baby's position. By Mayo Clinic Staff Prenatal care is an important part of a healthy pregnancy, ...
Wang, Hao; Liu, Ning; Xi, Lijun; Rong, Xiaoying; Ruan, Jisheng; Huang, Ying
Polyether ionophores are a unique class of polyketides with broad-spectrum activity and outstanding potency for the control of drug-resistant bacteria and parasites, and they are produced exclusively by actinomycetes. A special epoxidase gene encoding a critical tailoring enzyme involved in the biosynthesis of these compounds has been found in all five of the complete gene clusters of polyether ionophores published so far. To detect potential producer strains of these antibiotics, a pair of degenerate primers was designed according to the conserved regions of the five known polyether epoxidases. A total of 44 putative polyether epoxidase gene-positive strains were obtained by the PCR-based screening of 1,068 actinomycetes isolated from eight different habitats and 236 reference strains encompassing eight major families of Actinomycetales. The isolates spanned a wide taxonomic diversity based on 16S rRNA gene analysis, and actinomycetes isolated from acidic soils seemed to be a promising source of polyether ionophores. Four genera were detected to contain putative polyether epoxidases, including Micromonospora, which has not previously been reported to produce polyether ionophores. The designed primers also detected putative epoxidase genes from diverse known producer strains that produce polyether ionophores unrelated to the five published gene clusters. Moreover, phylogenetic and chemical analyses showed a strong correlation between the sequence of polyether epoxidases and the structure of encoded polyethers. Thirteen positive isolates were proven to be polyether ionophore producers as expected, and two new analogues were found. These results demonstrate the feasibility of using this epoxidase gene screening strategy to aid the rapid identification of known products and the discovery of unknown polyethers in actinomycetes.
Wang, Hao; Liu, Ning; Xi, Lijun; Rong, Xiaoying; Ruan, Jisheng; Huang, Ying
Polyether ionophores are a unique class of polyketides with broad-spectrum activity and outstanding potency for the control of drug-resistant bacteria and parasites, and they are produced exclusively by actinomycetes. A special epoxidase gene encoding a critical tailoring enzyme involved in the biosynthesis of these compounds has been found in all five of the complete gene clusters of polyether ionophores published so far. To detect potential producer strains of these antibiotics, a pair of degenerate primers was designed according to the conserved regions of the five known polyether epoxidases. A total of 44 putative polyether epoxidase gene-positive strains were obtained by the PCR-based screening of 1,068 actinomycetes isolated from eight different habitats and 236 reference strains encompassing eight major families of Actinomycetales. The isolates spanned a wide taxonomic diversity based on 16S rRNA gene analysis, and actinomycetes isolated from acidic soils seemed to be a promising source of polyether ionophores. Four genera were detected to contain putative polyether epoxidases, including Micromonospora, which has not previously been reported to produce polyether ionophores. The designed primers also detected putative epoxidase genes from diverse known producer strains that produce polyether ionophores unrelated to the five published gene clusters. Moreover, phylogenetic and chemical analyses showed a strong correlation between the sequence of polyether epoxidases and the structure of encoded polyethers. Thirteen positive isolates were proven to be polyether ionophore producers as expected, and two new analogues were found. These results demonstrate the feasibility of using this epoxidase gene screening strategy to aid the rapid identification of known products and the discovery of unknown polyethers in actinomycetes. PMID:21421776
Hu, Guo-Xin; Dai, Da-Peng; Wang, Hao; Huang, Xiang-Xin; Zhou, Xiao-Yang; Cai, Jie; Chen, Hao; Cai, Jian-Ping
To systematically investigate the genetic polymorphisms of the CYP3A4 gene in a Han Chinese population. The promoter and exons of CYP3A4 gene in 1114 unrelated, healthy Han Chinese subjects were amplified and genotyped by direct sequencing. In total, five previously reported alleles (*1G, *4, *5, *18B and *23) were detected, of which one allele (*23) was reported for the first time in Han Chinese population. Additionally, seven novel exonic variants were also identified and designated as new alleles CYP3A4*28-*34. This study provides the most comprehensive data of CYP3A4 polymorphisms in Han Chinese population and detects the largest number of novel CYP3A4 alleles in one ethnic group.
... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...
... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...
Middelburg, Karin J.; van der Heide, Maaike; Houtzager, Bregje; Pereboom, Marjolein; Fidler, Vaclav; Bos, Arend F.; Kok, Joke; Hadders-Algra, Mijna
Objective: To evaluate the effect of preimplantation genetic screening (PGS) on neurodevelopmental outcomes in children. Design: Prospective, assessor-blinded, follow-up study of children born to women randomly assigned to in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) with or
This paper explores the role of identity in relation to the ethics of prenatal testing for conditions that cause intellectual disabilities. Specifically, it considers the question of identity and the moral status of the fetus. It argues that both the arguments in favour and opposed to prenatal testing mistakenly presuppose that there is no moral status attached to the fetus. That status is grounded in an identity-constituting characteristic, such as 'intellectual disability', which is brought about by the purpose of genetic testing, and the meaning of which is culturally constructed. This paper examines the implications this has for the debate around both prenatal testing and termination in general and considers the nature of the ethical politics which follows from this position with regard to prenatal testing related to intellectual disability.
Full Text Available Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS cells to demonstrate: 1. molecular mechanisms shared by various types of environmental stressors, 2. the mechanisms by which the affected extracortical tissues indirectly impact the cortical development and function, and 3. interaction between prenatal environmental stress and the genetic predisposition of neuropsychiatric disorders. Finally, we discuss current challenges for achieving a comprehensive understanding of the role of environmentally disturbed molecular expressions in cortical maldevelopment, knowledge of which may eventually facilitate discovery of interventions for prenatal environment-linked neuropsychiatric disorders.
Chitty, Lyn S; Mason, Sarah; Barrett, Angela N; McKay, Fiona; Lench, Nicholas; Daley, Rebecca; Jenkins, Lucy A
Accurate prenatal diagnosis of genetic conditions can be challenging and usually requires invasive testing. Here, we demonstrate the potential of next-generation sequencing (NGS) for the analysis of cell-free DNA in maternal blood to transform prenatal diagnosis of monogenic disorders. Analysis of cell-free DNA using a PCR and restriction enzyme digest (PCR-RED) was compared with a novel NGS assay in pregnancies at risk of achondroplasia and thanatophoric dysplasia. PCR-RED was performed in 72 cases and was correct in 88.6%, inconclusive in 7% with one false negative. NGS was performed in 47 cases and was accurate in 96.2% with no inconclusives. Both approaches were used in 27 cases, with NGS giving the correct result in the two cases inconclusive with PCR-RED. NGS provides an accurate, flexible approach to non-invasive prenatal diagnosis of de novo and paternally inherited mutations. It is more sensitive than PCR-RED and is ideal when screening a gene with multiple potential pathogenic mutations. These findings highlight the value of NGS in the development of non-invasive prenatal diagnosis for other monogenic disorders. © 2015 John Wiley & Sons, Ltd.
Rochette, Claire; Baumstarck, Karine; Canoni-Zattara, Hélène; Abdullah, Ahmad Esmaeel; Figarella-Branger, Dominique; Pertuit, Morgane; Barlier, Anne; Castinetti, Frédéric; Pacak, Karel; Metellus, Philippe; Taïeb, David
Von Hippel-Lindau (VHL) syndrome is a hereditary cancer syndrome characterized by a high risk of developing benign and malignant tumors, including central nervous system hemangioblastomas (CNS HBs). For an early diagnosis of VHL, before the occurrence of cancers (especially renal cell carcinoma), it is of huge importance to initiate VHL genetic testing in at-risk patients. The aim of the study was to assess the psychological impact of VHL genetic testing in patients previously diagnosed with a CNS HB. From 1999 until 2015, 55 patients underwent surgery for CNS HBs. Eleven patients were already screened for VHL mutations and 3 patients deceased before the start of the study. From the remaining 42 patients, 24 were accepted to be enrolled in the study. Assessment of psychological impact of VHL genetic testing was performed by measuring anxiety levels, mood disorders, quality of life, and psychological consequences of genetic screening. Twenty-one of the enrolled 24 patients underwent VHL genetic testing and 12 patients came back for the communication of positive genetic results. The baseline psychological status did not differ between these 2 groups. Patients who attended the visit of communication of genetic results had similar anxiety levels compared to those who had not. Furthermore, they also experienced an improvement in the level of anxiety and two QoL dimension scores compared to their baseline status. In summary, there is no evidence of a negative psychosocial impact of VHL genetic testing in patients with a previous history of CNS HB. We, therefore, recommend the recall of patients who have not been previously screened.
Nguyen, Quang; McKinney, Jason; Johnson, Donald J; Roberts, Katherine A; Hardy, Winters R
In this proof-of-concept study, high-resolution melt curve (HRMC) analysis was investigated as a postquantification screening tool to discriminate human CSF1PO and THO1 genotypes amplified with mini-STR primers in the presence of SYBR Green or LCGreen Plus dyes. A total of 12 CSF1PO and 11 HUMTHO1 genotypes were analyzed on the LightScanner HR96 and LS-32 systems and were correctly differentiated based upon their respective melt profiles. Short STR amplicon melt curves were affected by repeat number, and single-source and mixed DNA samples were additionally differentiated by the formation of heteroduplexes. Melting curves were shown to be unique and reproducible from DNA quantities ranging from 20 to 0.4 ng and distinguished identical from nonidentical genotypes from DNA derived from different biological fluids and compromised samples. Thus, a method is described which can assess both the quantity and the possible probative value of samples without full genotyping. 2012 American Academy of Forensic Sciences. Published 2012. This article is a U.S. Government work and is in the public domain in the U.S.A.
Full Text Available Model organisms have played an important role in the elucidation of multiple genes and cellular processes that regulate aging. In this study we utilized the budding yeast, Saccharomyces cerevisiae, in a large-scale screen for genes that function in the regulation of chronological lifespan, which is defined by the number of days that non-dividing cells remain viable. A pooled collection of viable haploid gene deletion mutants, each tagged with unique identifying DNA "bar-code" sequences was chronologically aged in liquid culture. Viable mutants in the aging population were selected at several time points and then detected using a microarray DNA hybridization technique that quantifies abundance of the barcode tags. Multiple short- and long-lived mutants were identified using this approach. Among the confirmed short-lived mutants were those defective for autophagy, indicating a key requirement for the recycling of cellular organelles in longevity. Defects in autophagy also prevented lifespan extension induced by limitation of amino acids in the growth media. Among the confirmed long-lived mutants were those defective in the highly conserved de novo purine biosynthesis pathway (the ADE genes, which ultimately produces IMP and AMP. Blocking this pathway extended lifespan to the same degree as calorie (glucose restriction. A recently discovered cell-extrinsic mechanism of chronological aging involving acetic acid secretion and toxicity was suppressed in a long-lived ade4Delta mutant and exacerbated by a short-lived atg16Delta autophagy mutant. The identification of multiple novel effectors of yeast chronological lifespan will greatly aid in the elucidation of mechanisms that cells and organisms utilize in slowing down the aging process.
Rudo L Simeon
Full Text Available Genetic suppressor elements (GSEs are biomolecules derived from a gene or genome of interest that act as transdominant inhibitors of biological functions presumably by disruption of critical biological interfaces. We exploited a cell death reporter cell line for hepatitis C virus (HCV infection, n4mBid, to develop an iterative selection/enrichment strategy for the identification of anti-HCV GSEs. Using this approach, a library of fragments of an HCV genome was screened for sequences that suppress HCV infection. A 244 amino acid gene fragment, B1, was strongly enriched after 5 rounds of selection. B1 derives from a single-base frameshift of the enhanced green fluorescent protein (eGFP which was used as a filler during fragment cloning. B1 has a very high net positive charge of 43 at neutral pH and a high charge-to-mass (kDa ratio of 1.5. We show that B1 expression specifically inhibits HCV replication. In addition, five highly positively charged B1 fragments produced from progressive truncation at the C-terminus all retain the ability to inhibit HCV, suggesting that a high positive charge, rather than a particular motif in B1, likely accounts for B1's anti-HCV activity. Another supercharged protein, +36GFP, was also found to strongly inhibit HCV replication when added to cells at the time of infection. This study reports a new methodology for HCV inhibitor screening and points to the anti-HCV potential of positively charged proteins/peptides.
Ferrari, Raffaele; Ferrara, Michela; Alinani, Anwar; Sutton, Roger Brian; Famà, Francesco; Picco, Agnese; Rodriguez, Guido; Nobili, Flavio; Momeni, Parastoo
Cohorts from a defined geographical area enable ad hoc genotype-phenotype correlation studies providing novel and unique insight into disease. We analysed genetic risk factors associated with early and late onset Alzheimer's disease (EOAD and LOAD) in a population from Liguria (northern Italy), as part of an ongoing longitudinal study. We screened 37 AD, 8 mild cognitive impairment (MCI), 3 AD and CVD (cerebrovascular disease), 3 MCI and CVD, 8 frontotemporal dementia (FTD) and 2 progressive supranuclear palsy (PSP) patients, and 28 normal controls (NCs).We sequenced PSEN1, PSEN2 and APP (EOAD risk factors), as well as MAPT, GRN and TARDBP for all cases and NCs, and analysed the APOE, CLU, CR1 and PICALM genotypes as well as the MAPT and ACE haplotypes (LOAD risk factors) for the AD (n = 37) and AD + MCI (n = 45) cases and NCs (n = 28).We identified variants in PSEN1, PSEN2 and TARDBP across a range of phenotypes (AD, AD and CVD, FTD and PSP), suggesting that screening of all known candidate genes of Alzheimer's and non-Alzheimer's forms of dementias in all dementia cases might be warranted. The analysis of the LOAD risk factors revealed no association with AD or AD + MCI status after Bonferroni correction. Lack of association with APOE is supported by previous studies in the Italian population. Our data also evidenced: 1) a potentially protective haplotype at the PSEN2 locus; 2) a nominal association with the GWAS-risk allele A for rs3818361 in CR1 and; 3) a threefold prevalence of AD in the female population compared to men.Our results will need to be further assessed and confirmed in larger cohorts from this area.
Heijink, Anne Margriet; Blomen, Vincent A; Bisteau, Xavier; Degener, Fabian; Matsushita, Felipe Yu; Kaldis, Philipp; Foijer, Floris; van Vugt, Marcel A T M
The Wee1 cell cycle checkpoint kinase prevents premature mitotic entry by inhibiting cyclin-dependent kinases. Chemical inhibitors of Wee1 are currently being tested clinically as targeted anticancer drugs. Wee1 inhibition is thought to be preferentially cytotoxic in p53-defective cancer cells. However, TP53 mutant cancers do not respond consistently to Wee1 inhibitor treatment, indicating the existence of genetic determinants of Wee1 inhibitor sensitivity other than TP53 status. To optimally facilitate patient selection for Wee1 inhibition and uncover potential resistance mechanisms, identification of these currently unknown genes is necessary. The aim of this study was therefore to identify gene mutations that determine Wee1 inhibitor sensitivity. We performed a genome-wide unbiased functional genetic screen in TP53 mutant near-haploid KBM-7 cells using gene-trap insertional mutagenesis. Insertion site mapping of cells that survived long-term Wee1 inhibition revealed enrichment of G1/S regulatory genes, including SKP2, CUL1, and CDK2. Stable depletion of SKP2, CUL1, or CDK2 or chemical Cdk2 inhibition rescued the γ-H2AX induction and abrogation of G2 phase as induced by Wee1 inhibition in breast and ovarian cancer cell lines. Remarkably, live cell imaging showed that depletion of SKP2, CUL1, or CDK2 did not rescue the Wee1 inhibition-induced karyokinesis and cytokinesis defects. These data indicate that the activity of the DNA replication machinery, beyond TP53 mutation status, determines Wee1 inhibitor sensitivity, and could serve as a selection criterion for Wee1-inhibitor eligible patients. Conversely, loss of the identified S-phase genes could serve as a mechanism of acquired resistance, which goes along with development of severe genomic instability.
Studies in many species, including humans, have demonstrated that stress during gestation can have long-term developmental, neuroendocrine, and behavioural effects on the offspring. Because pregnant sows can be subjected to regular stressful situations, it is relevant to study whether prenatal
Full Text Available In recent years, prenatal diagnosis and elective pregnancy termination have affected the reported birth prevalence of trisomies. Trisomy 13, or Patau syndrome, represents the third autosomic trisomy in order of frequency, after trisomy 21 (Down syndrome and trisomy 18 (Edwards syndrome, with a prevalence at birth estimated as between 1:12000 and 1:29000. In this study, we are presenting the results of cytogenetic analysis and clinic assessment in fetus of a woman at 22 weeks gestation, who were referred to our genetic diagnostic laboratory with abnormal triple test result, omphalosel and hydrocephaly. We performed the cordocentesis and pedigree analysis. We found a karyotype (47,XY,+13 in fetus. Because individuals of the family didn’t want, we were not followed the pregnancy prognosis for the mother and the fetus. We were recommending to the prenatal diagnosis for their further pregnancies.
Huber, Ingrid; Block, Annette; Sebah, Daniela; Debode, Frédéric; Morisset, Dany; Grohmann, Lutz; Berben, Gilbert; Stebih, Dejan; Milavec, Mojca; Zel, Jana; Busch, Ulrich
Worldwide, qualitative methods based on PCR are most commonly used as screening tools for genetically modified material in food and feed. However, the increasing number and diversity of genetically modified organisms (GMO) require effective methods for simultaneously detecting several genetic elements marking the presence of transgenic events. Herein we describe the development and validation of a pentaplex, as well as complementary triplex and duplex real-time PCR assays, for the detection of the most common screening elements found in commercialized GMOs: P-35S, T-nos, ctp2-cp4-epsps, bar, and pat. The use of these screening assays allows the coverage of many GMO events globally approved for commercialization. Each multiplex real-time PCR assay shows high specificity and sensitivity with an absolute limit of detection below 20 copies for the targeted sequences. We demonstrate by intra- and interlaboratory tests that the assays are robust as well as cost- and time-effective for GMO screening if applied in routine GMO analysis.
Dondorp, Wybo; de Wert, Guido; Bombard, Yvonne
following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure...
Full Text Available Bacterial infection of plants often begins with colonization of the plant surface, followed by entry into the plant through wounds and natural openings (such as stomata, multiplication in the intercellular space (apoplast of the infected tissues, and dissemination of bacteria to other plants. Historically, most studies assess bacterial infection based on final outcomes of disease and/or pathogen growth using whole infected tissues; few studies have genetically distinguished the contribution of different host cell types in response to an infection. The phytotoxin coronatine (COR is produced by several pathovars of Pseudomonas syringae. COR-deficient mutants of P. s. tomato (Pst DC3000 are severely compromised in virulence, especially when inoculated onto the plant surface. We report here a genetic screen to identify Arabidopsis mutants that could rescue the virulence of COR-deficient mutant bacteria. Among the susceptible to coronatine-deficient Pst DC3000 (scord mutants were two that were defective in stomatal closure response, two that were defective in apoplast defense, and four that were defective in both stomatal and apoplast defense. Isolation of these three classes of mutants suggests that stomatal and apoplastic defenses are integrated in plants, but are genetically separable, and that COR is important for Pst DC3000 to overcome both stomatal guard cell- and apoplastic mesophyll cell-based defenses. Of the six mutants defective in bacterium-triggered stomatal closure, three are defective in salicylic acid (SA-induced stomatal closure, but exhibit normal stomatal closure in response to abscisic acid (ABA, and scord7 is compromised in both SA- and ABA-induced stomatal closure. We have cloned SCORD3, which is required for salicylic acid (SA biosynthesis, and SCORD5, which encodes an ATP-binding cassette (ABC protein, AtGCN20/AtABCF3, predicted to be involved in stress-associated protein translation control. Identification of SCORD5 begins to
Objective To establish a means for prenatal prediction of spinal muscular atrophy (SMA) through survival motor neuron (SMN) gene deletion analysis and genetic counseling in families with a child affected with SMA. Methods Genetic analysis for prenatal prediction of Werdnig-Hoffmann disease was performed in a at risk Chinese family by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) in SMN gene exons 7 and 8.Results The pregnancy was positive for the homozygous deletion of the SMN gene, thus the fetus was diagnosed as being affected and the pregnancy was terminated.Conclusion This approach is fast and reliable for DNA-based prenatal diagnosis of Werdnig-Hoffmann disease.
Luz, Rita; George, Astrid; Spitz, Elisabeth; Vieux, Rachel
The diagnosis of a fetal anomaly in perinatal medicine forces expectant parents and healthcare providers to face the difficult process of breaking bad news. This exploratory literature review was aimed at providing a medical and psychological view of the psychological experience in expectant parents and physicians in the context of prenatal diagnosis of a fetal anomaly. An exploratory search of PubMed and PsycINFO/PsycARTICLES databases performed by an interdisciplinary team composed of a physician and psychologists. Search terms were: prenatal diagnosis AND bad news; prenatal diagnosis AND psychological consequences; prenatal diagnosis AND psychological sequelae; prenatal diagnosis AND fetal abnormality. The processing of selected articles followed a standardised five-step procedure. A total of 860 articles were screened of which 32 were retained for analysis. Four main themes emerged from the explanatory content analysis: (1) parents' subjective experience; (2) physicians' subjective experience; (3) encounters between expectant parents and professionals; and (4) ethical challenges in breaking bad news in prenatal medicine. Expectant parents go through a complex and multidimensional experience when the diagnosis of a fetal anomaly is disclosed. Simultaneously, physicians consider breaking bad news as a very stressful event and are poorly prepared in this regard. A better knowledge of factors underlying psychological adjustment of the parental dyad and on the subjective experience of physicians delivering these diagnoses could enable better adaptation for both patients and professionals.
Mikropoulos, Christos; Selkirk, Christina G Hutten; Saya, Sibel
BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA...... and PSAV for identifying PrCa and high-grade disease in this cohort. METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA...... elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV...
Gason, Alexandra A; Aitken, MaryAnne; Delatycki, Martin B; Sheffield, Edith; Metcalfe, Sylvia A
Tay Sachs disease is a recessively inherited neurodegenerative disorder, for which carrier screening programs exist worldwide. Education for those offered a screening test is essential in facilitating informed decision-making. In Melbourne, Australia, we have designed, developed, and evaluated a computer-based instructional resource for use in the Tay Sachs disease carrier screening program for secondary school students attending Jewish schools. The resource entitled "Genetics in the Community: Tay Sachs disease" was designed on a platform of educational learning theory. The development of the resource included formative evaluation using qualitative data analysis supported by descriptive quantitative data. The final resource was evaluated within the screening program and compared with the standard oral presentation using a questionnaire. Knowledge outcomes were measured both before and after either of the educational formats. Data from the formative evaluation were used to refine the content and functionality of the final resource. The questionnaire evaluation of 302 students over two years showed the multimedia resource to be equally effective as an oral educational presentation in facilitating participants' knowledge construction. The resource offers a large number of potential benefits, which are not limited to the Tay Sachs disease carrier screening program setting, such as delivery of a consistent educational message, short delivery time, and minimum financial and resource commitment. This article outlines the value of considering educational theory and describes the process of multimedia development providing a framework that may be of value when designing genetics multimedia resources in general.
Griswold, Carol H.; Nasso, Jacqueline T.; Swider, Susan; Ellison, Brenda R.; Griswold, Daniel L.; Brooks, Marilyn
School absenteeism and poor compliance with prenatal appointments are concerns for pregnant teens. The Prenatal Care at School (PAS) program is a new model of prenatal care involving local health care providers and school personnel to reduce the need for students to leave school for prenatal care. The program combines prenatal care and education…
Screening in Diabetes : Candidate Gene Analysis for Diabetic Retinopathy PRINCIPAL INVESTIGATOR: Robert A. Vigersky, COL MC CONTRACTING ORGANIZATION... Diabetes Institute of the Walter Reed Health Care System Genetic Screening in Diabetes : Candidate Gene Analysis for Diabetic Retinopathy 5c. PROGRAM... diabetic neuropathy, and diabetic retinopathy . This was an observational study in which the investigators obtained DNA samples from the blood of
Buekens, P; Hernández, P; Infante, C
Available data on the coverage of prenatal care in Latin America were reviewed. In recent years, only Bolivia had a coverage of prenatal care of less than 50 per cent. More than 90 per cent of pregnant women received prenatal care in Chile, Cuba, the Dominican Republic, and Puerto Rico. Prenatal care increased between the 1970 and 1980 in the Dominican Republic, Ecuador, Guatemala, Honduras, Mexico, and Peru. The coverage of prenatal care decreased in Bolivia and Colombia. The mean number of visits increased in Cuba and Puerto Rico. The increase of prenatal care in Guatemala and Honduras is due to increased care by traditional birth attendants, compared to the role of health care institutions. We compared the more recent data on tetanus immunization of pregnant women to the more recent data on prenatal care. The rates of tetanus immunization are always lower than the rates of prenatal care attendance, except in Costa Rica. The rates of tetanus immunization was less than half as compared to the rates of prenatal care in Bolivia, Guatemala, and Peru. To improve the content of prenatal care should be an objective complementary to the increase of the number of attending women.
Ajibola, Ayodeji J; Netzloff, Michael; Samaraweera, Ranji; Omar, Said A
We report the clinical characteristics and the outcome of two cases of pontocerebellar hypoplasia (PCH) in one family. The objective of this report is to describe the mode of presentation, discuss the clinical course, and address the dilemma of prenatal diagnosis and the prospects for genetic diagnosis for PCH. The first case is a 4-year-old boy in whom the diagnosis was made in the neonatal period. Despite extensive prenatal follow-up during the mother's subsequent pregnancy, prenatal diagnosis could not be made and a second affected child was born. Both siblings have severe developmental delay. The cases raise an important ethical dilemma about the most appropriate intervention if the mother of a child affected with PCH becomes pregnant. PCH is considered to have an autosomal-recessive mode of inheritance and a recurrence risk of 25% in each pregnancy. Until recently when genetic mutations in PCH types 2, 4, and 6 began to be identified, the lack of well-recognized genetic testing precluded experts from making clear recommendations. The best advice to these parents was difficult or elusive. With two children currently affected, should the parents terminate or continue with the latest pregnancy? Extensive monitoring with serial prenatal ultrasound failed in the previous pregnancy and resulted in the birth of the second affected child. It is evident that serial ultrasound scan may not be helpful in making the diagnosis prenatally. Therefore, other diagnostic modalities such as magnetic resonance imaging may be necessary and should be considered. With the identification of genetic basis or mutations in PCH types 2, 4, and 6 and possible development of commercial genetic testing for these types of PCH, reproductive decision or genetic testing during pregnancy should be recommended to affected families to enable informed choices. Thieme Medical Publishers.
Niu, Chenqi; Xu, Yuancong; Zhang, Chao; Zhu, Pengyu; Huang, Kunlun; Luo, Yunbo; Xu, Wentao
As genetically modified (GM) technology develops and genetically modified organisms (GMOs) become more available, GMOs face increasing regulations and pressure to adhere to strict labeling guidelines. A singleplex detection method cannot perform the high-throughput analysis necessary for optimal GMO detection. Combining the advantages of multiplex detection and droplet digital polymerase chain reaction (ddPCR), a single universal primer-multiplex-ddPCR (SUP-M-ddPCR) strategy was proposed for accurate broad-spectrum screening and quantification. The SUP increases efficiency of the primers in PCR and plays an important role in establishing a high-throughput, multiplex detection method. Emerging ddPCR technology has been used for accurate quantification of nucleic acid molecules without a standard curve. Using maize as a reference point, four heterologous sequences ( 35S, NOS, NPTII, and PAT) were selected to evaluate the feasibility and applicability of this strategy. Surprisingly, these four genes cover more than 93% of the transgenic maize lines and serve as preliminary screening sequences. All screening probes were labeled with FAM fluorescence, which allows the signals from the samples with GMO content and those without to be easily differentiated. This fiveplex screening method is a new development in GMO screening. Utilizing an optimal amplification assay, the specificity, limit of detection (LOD), and limit of quantitation (LOQ) were validated. The LOD and LOQ of this GMO screening method were 0.1% and 0.01%, respectively, with a relative standard deviation (RSD) < 25%. This method could serve as an important tool for the detection of GM maize from different processed, commercially available products. Further, this screening method could be applied to other fields that require reliable and sensitive detection of DNA targets.
Thiébaut, Rodolphe; Leproust, Sandy; Chêne, Geneviève
BACKGROUND: Despite three decades of prenatal screening for congenital toxoplasmosis in some European countries, uncertainty remains about the effectiveness of prenatal treatment. METHODS: We did a systematic review of cohort studies based on universal screening for congenital toxoplasmosis. We did...... a meta-analysis using individual patients' data to assess the effect of timing and type of prenatal treatment on mother-to-child transmission of infection and clinical manifestations before age 1 year. Analyses were adjusted for gestational age at maternal seroconversion and other covariates. FINDINGS......: We included 26 cohorts in the review. In 1438 treated mothers identified by prenatal screening, we found weak evidence that treatment started within 3 weeks of seroconversion reduced mother-to-child transmission compared with treatment started after 8 or more weeks (adjusted odds ratio [OR] 0.48, 95...
Chini, Vasiliki; Stambouli, Danai; Nedelea, Florina Mihaela; Filipescu, George Alexandru; Mina, Diana; Kambouris, Marios; El-Shantil, Hatem
Prenatal diagnosis was requested for an undiagnosed eye disease showing X-linked inheritance in a family. No medical records existed for the affected family members. Mapping of the X chromosome and candidate gene mutation screening identified a c.C267A[p.F89L] mutation in NPD previously described as possibly causing Norrie disease. The detection of the c.C267A[p.F89L] variant in another unrelated family confirms the pathogenic nature of the mutation for the Norrie disease phenotype. Gene mapping, haplotype analysis, and candidate gene screening have been previously utilized in research applications but were applied here in a diagnostic setting due to the scarcity of available clinical information. The clinical diagnosis and mutation identification were critical for providing proper genetic counseling and prenatal diagnosis for this family.
Montag, Christian; Bleek, Benjamin; Breuer, Svenja; Prüss, Holger; Richardt, Kirsten; Cook, Susanne; Yaruss, J Scott; Reuter, Martin
The prevalence of stuttering is much higher in males compared to females. The biological underpinnings of this skewed sex-ratio is poorly understood, but it has often been speculated that sex hormones could play an important role. The present study investigated a potential link between prenatal testosterone and stuttering. Here, an indirect indicator of prenatal testosterone levels, the Digit Ratio (2D:4D) of the hand, was used. As numerous studies have shown, hands with more "male" characteristics (putatively representing greater prenatal testosterone levels) are characterized by a longer ring finger compared to the index finger (represented as a lower 2D:4D ratio) in the general population. We searched for differences in the 2D:4D ratios between 38 persons who stutter and 36 persons who do not stutter. In a second step, we investigated potential links between the 2D:4D ratio and the multifaceted symptomatology of stuttering, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES), in a larger sample of 44 adults who stutter. In the first step, no significant differences in the 2D:4D were observed between individuals who stutter and individuals who do not stutter. In the second step, 2D:4D correlated negatively with higher scores of the OASES (representing higher negative experiences due to stuttering), and this effect was more pronounced for female persons who stutter. The findings indicate for the first time that prenatal testosterone may influence individual differences in psychosocial impact of this speech disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.
Zhou, Qin-Wei; Zhang, Shuo-Ping; Lu, Chang-Fu; Gong, Fei; Tan, Yue-Qiu; Lu, Guang-Xiu; Lin, Ge
Background The use of assisted reproductive technology (ART) has been reported to increase the incidence of monozygotic twinning (MZT) compared with the incidence following natural conception. It has been hypothesized that splitting of the inner cell mass (ICM) through a small zona hole may result in MZT. In this study, using a cohort of patients undergoing preimplantation genetic diagnosis/screening (PGD/PGS), we compared the clinical and neonatal outcomes of human 8-shaped blastocysts hatching with ICM incarceration with partially or fully hatched blastocysts, and attempted to verify whether this phenomenon increases the incidence of MZT pregnancy or negatively impact newborns. Methods This retrospective study included 2059 patients undergoing PGD/PGS between March 1, 2013, and December 31, 2015. Clinical and neonatal outcomes were only collected from patients who received a single blastocyst transfer after PGD/PGS (n = 992). A 25- to 30-μm hole was made in the zona of day 3 embryos by laser. The blastocysts were biopsied and vitrified on day 6. The biopsied trophectoderm (TE) cells were analyzed using different genetic methods. One tested blastocyst was thawed and transferred to each patient in the subsequent frozen embryo transfer cycle. All the biopsied blastocysts were divided into three types: 8-shaped with ICM incarceration (type I), partially hatched without ICM incarceration (type II), and fully hatched (type III). ICM/TE grading, clinical and neonatal outcomes were compared between the groups. Results The percentage of grade A ICMs in type I blastocysts (22.2%) was comparable to that in type III blastocysts (20.1%) but higher than that in type II blastocysts (4.5%). The percentage of grade A TEs in type I blastocysts (4.2%) was comparable to that in type II (3.6%) but lower than that in type III (13.5%). There were no significant differences in clinical pregnancy, MZT pregnancy, miscarriage, live birth, MZT births, and neonatal outcomes between the
Genes Underlying Positive Influence Of Prenatal Environmental Enrichment And ... Prenatal environmental enrichment (EE) has been proven to positively affect but ... Conclusion: The negative-positive prenatal effect could contribute to altered ...
Gekas, Jean; Langlois, Sylvie; Ravitsky, Vardit; Audibert, François; van den Berg, David Gradus; Haidar, Hazar; Rousseau, François
Genomics-based non-invasive prenatal screening using cell-free DNA (cfDNA screening) was proposed to reduce the number of invasive procedures in current prenatal diagnosis for fetal aneuploidies. We review here the clinical and ethical issues of cfDNA screening. To date, it is not clear how cfDNA screening is going to impact the performances of clinical prenatal diagnosis and how it could be incorporated in real life. The direct marketing to users may have facilitated the early introduction of cfDNA screening into clinical practice despite limited evidence-based independent research data supporting this rapid shift. There is a need to address the most important ethical, legal, and social issues before its implementation in a mass setting. Its introduction might worsen current tendencies to neglect the reproductive autonomy of pregnant women.