Uniparental disomy in fetuses diagnosed with balanced Robertsonian translocations: risk estimate

Forty-two fetuses with non-homologous Robertsonian translocations were analyzed for uniparental disomy (UPD). One fetus with a de novo translocation t(13q;14q) had maternal isodisomy of chromosome 14. In a summary of the published data (including the present study), 315 cases were analyzed for UPD after prenatal diagnosis of balanced Robertsonian translocations, of these two fetuses had UPD, giving a risk estimate of 0.65% (CI 0.2–2.3). This risk justifies the recommendation of UPD analysis in fetuses diagnosed prenatally with Robertsonian translocations, with the emphasis on the chromosomes known to contain imprinted genes, such as 14 and 15. We also discuss the possibility of UPD in offspring of Robertsonian translocation carriers with normal karyotype. Based on the risk for UPD in fetuses with Robertsonian translocation we suggest to test these fetuses for UPD and to do so on amniocytes rather than chorionic villi when the risk for unbalanced karyotype is ∼1%, comparable to the risk for UPD. Copyright © 2002 John Wiley & Sons, Ltd.     

Identification of a case of maternal uniparental disomy of chromosome 10 associated with confined placental mosaicism

We report a case of maternal uniparental disomy of chromosome 10 discovered after chorionic villus sampling (CVS). Direct preparations revealed mosaic trisomy 10, while cultured CVS cells, as well as amniotic fluid cells, showed only a normal 46,XY complement. DNA analysis using microsatellite markers showed both chromosomes 10 to have been inherited from the mother. The pregnancy was complicated by polyhydramnios. A phenotypically normal male infant of appropriate size was delivered by Caesarean section at 41 weeks' gestation. Since only the direct preparations showed trisomy 10, this case illustrates the importance of CVS direct preparations in the detection of pregnancies at risk of uniparental disomy (UPD). Although the increased frequency of confined placental mosaicism (CPM) diagnosed when direct preparations are performed has been viewed negatively, identification of both CPM and UPD may have biological and clinical significance for a pregnancy. Even though only a single case of maternal disomy 10 is reported here, the apparently normal phenotype provides evidence that there are no major imprinted loci on chromosome 10 that affect in utero growth and development. However, other potential effects such as mental retardation will require long-term follow-up of this as well as additional cases.     

A second case of intrauterine growth retardation and primary hypospadias associated with a trisomy 22 placenta but with biparental inheritance of chromosome 22 in the fetus

We report a case of severe intrauterine growth retardation (IUGR) and hypospadias in association with trisomy 22 diagnosed following chorionic villus sampling (CVS). Subsequent analysis of amniotic fluid cultures showed a normal male karyotype, 46,XY. As a previous case had been reported with similar abnormalities, in association with maternal uniparental disomy (UPD) 22, molecular studies were also performed. Microsatellite marker studies showed biparental inheritance. Follow-up studies after delivery showed a normal cell line in lymphocytes with the trisomy appearing to be confined to the placenta. The present case concurs with other earlier reports that maternal UPD for chromosome 22 has no impact on the phenotype. The features seen in the fetus are most likely the result of placental dysfunction due to trisomy, tissue-specific mosaicism and/or the effects of local growth restriction. Copyright © 2002 John Wiley & Sons, Ltd.     

Discordant results between fetal karyotyping and non-invasive prenatal testing by maternal plasma sequencing in a case of uniparental disomy 21 due to trisomic rescue

Uniparental disomy (UPD) is an uncommon chromosome condition, but UPD involving chromosome 21 is rarely reported. We reported here a case who had first trimester screening test for Down syndrome, chorionic villus sampling for fetal karyotyping, quantitative fluorescence polymerase chain reaction (QF-PCR), as well as non-invasive prenatal testing (NIPT) by maternal plasma sequencing. There were discordant results between fetal karyotyping and NIPT due to UPD 21combined with confined placental mosaicism of trisomy 21. This demonstrated that it is possible to detect placental mosaicism by NIPT, but further studies are required to confirm its sensitivity. Therefore, all positive NIPT results must be confirmed by conventional invasive test and karyotyping. QF-PCR has the additional benefit in diagnosing UPD. © 2013 John Wiley & Sons, Ltd.     

Uniparental disomy: Origin,frequency, and clinical significance

Uniparental disomy (UPD) is defined as two copies of a whole chromosome derived from the same parent. There can be multiple mechanisms that lead to UPD; these are reviewed in the context of contemporary views on the mechanism leading to aneuploidy. Recent studies indicate that UPD is rare in an apparently healthy population and also rare in spontaneous abortion tissues. The most common type of UPD is a maternal heterodisomy (both maternal allele sets present). Isodisomy (a duplicated single set of alleles) or segmental loss of heterozygosity is sometimes encountered in SNP-based microarray referrals. Decisions regarding the most appropriate follow-up testing should consider the possibility of consanguinity (that will generally involve multiple regions), an imprinted gene disorder (chromosomes 6, 7, 11, 14, 15, 20), expression of an autosomal recessive disorder, and an occult aneuploid cell line that may be confined to the placenta. Upd(16)mat, per se, does not appear to be associated with an abnormal phenotype. UPD provides an insight into the history of early chromosome segregation error and understanding the rates and fate of these events are of key importance in the provision of fertility management and prenatal healthcare.     

The importance of investigating for uniparental disomy in prenatally identified balanced acrocentric rearrangements

We report the finding of paternal isodisomy for chromosome 14 in a fetus found to have a der(14;14)(q10;q10) by amniocentesis. The pregnancy was complicated by severe polyhydramnios and elevated amniotic fluid alpha-fetoprotein (AFP). The infant showed features consistent with paternal uniparental disomy (UPD) including postnatal growth retardation, poor respiratory function, feeding difficulties, and evidence of hypertrophic cardiomyopathy. The present case, in addition to other reported cases of UPD involving balanced acrocentric rearrangements, supports testing for UPD in prenatally detected Robertsonian translocations and isochromosomes. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of a homologous Robertsonian translocation involving chromosome 15

We report the prenatal diagnosis of a fetus with a de novo Robertsonian translocation: 45,XY,der(15;15)(q10;q10). Although Robertsonian translocations are common chromosomal rearrangements, those involving homologous chromosomes are infrequent. Since chromosome 15 is imprinted, uniparental disomy (UPD) is a concern when chromosomal rearrangements involving chromosome 15 are identified. In the present case, UPD studies showed normal biparental inheritance. In contrast to the fact that most homologous acrocentric rearrangements are isochromosomes, these results indicate postzygotic formation of a Robertsonian translocation between biparentally inherited chromosomes 15. Copyright © 2001 John Wiley & Sons, Ltd.     

Implications of 'low maternal serum alpha-fetoprotein levels: Are maternal age risk criteria obsolete?

An association has been reported between “low” maternal serum alpha-fetoprotein (MSAFP) and fetal chromosome abnormalities, notably Down syndrome. We suggest the predictive value be used for genetic counselling when a “low” MSAFP is found, and present an illustrative risk table. It can also be seen that normal MSAFP in a woman may lower her age-related risks below that previously defined as “high risk”. However, until good estimates of sensitivity and specificity are available from prospective, population based studies, patients should be told that any risk estimates are rough approximations. When good estimates are available, use of age risks alone may become obsolete.     

Maternal UPD 20 in an infant from a pregnancy with mosaic trisomy 20

Maternal uniparental disomy (UPD) 20 was found in a 35-month-old girl, the product of a pregnancy complicated by a prenatal diagnosis of mosaic trisomy 20. Phenotypic abnormalities included pre- and postnatal growth failure, microcephaly, minor dysmorphic features and psychomotor developmental delay. Chromosomal analysis on cord blood revealed only a normal 46,XX karyotype. Microsatellite analysis of 27 chromosome 20 loci confirmed maternal UPD for all 11 informative markers. Maternal heterodisomy was detected in two and maternal isodisomy in three loci. In the remaining six loci, a non-informative maternal UPD pattern was displayed, as mother and proband are homozygous for the same allele. To our knowledge this is the first reported case of maternal disomy 20 with normal karyotype ascertained by a mosaic trisomy 20 pregnancy. Copyright © 2001 John Wiley & Sons, Ltd.     

An audit of trisomy 16 in man

Sufficient information is now available from the literature to produce an audit of trisomy 16, in a theoretical cohort of 100 000 recognized pregnancies, from gametogenesis to term and onwards. Recent reports of premature separation of chromosome 16 bivalents during maternal meiosis I provide a novel mechanism for generation of this aneuploidy. Most, if not all, errors resulting in recognized mosaic and non-mosaic trisomy 16 pregnancies investigated using polymorphic DNA markers appear to originate at that stage. The incidence of this maternally derived trisomy 16 in the late first trimester is equivalent to 1500 cases in 100 000 recognized pregnancies, a figure which now corresponds very closely to the reinterpreted oogenesis data. Most trisomy 16 pregnancies are lost around 12 weeks' gestation, but of the order of 10 per cent (120–150 in this audit) undergo reduction to disomy, with 30 of these excluding aneuploidy from the fetal cell lineage (trisomic zygote rescue) and continuing into the second trimester. Maternal uniparental disomy (UPD) in one-third of this latter group is associated with loss later in pregnancy or severe intrauterine growth retardation, but can be compatible with a viable pregnancy. Adverse pregnancy outcomes are not restricted to those with UPD. Analysis of reports of confined placental mosaicism for chromosome 16 without associated UPD indicates that the presence of high levels of trisomic cells in the placenta alone consistently produces a more variable inhibition of fetal growth, which may also, in cases, be associated with late pregnancy loss.     

Inaccurate estimation of risk in second trimester serum screening for Down syndrome among women who have already had first trimester screening

Problems can arise in prenatal screening for Down syndrome when tests are performed in the first and second trimester and some women who have a negative first trimester test have a second trimester serum test. The second test result does not usually take account of the previous one being negative. Even if it does, it is often inaccurate. Using published data the extent of the error was examined. The age-specific risk of an affected pregnancy in such women will be lower than if no first trimester test had been performed. The distributions of the screening markers in affected and unaffected pregnancies will be different from those in unscreened women. If the appropriate age-specific risk and marker distributions are not used, error will arise. For example, a 35-year-old woman with nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotrophin (hCG) levels at the normal median would have a risk of 1 in 6500. If she then had the Triple Test with alpha-fetoprotein (AFP), unconjugated oestriol, and hCG levels of 0.7, 0.7 and 1.5 multiples of the median (MoM), respectively, her risk, ignoring the previous result, would be overestimated (1 in 95 compared with the correct estimate of 1 in 705). If the previous result was included, but the age-specific risk and second trimester marker distributions were not revised, her risk would be underestimated (1 in 820). If the correct age-specific risk and screening marker distributions were used, risk estimates would be accurate, but two tests would be less efficient than integrating all the screening information into a single test. The practice of offering second trimester serum screening to women who have already been screened is best avoided. Copyright © 2001 John Wiley & Sons, Ltd.     

Human maternal uniparental disomy for chromosome 16 and fetal development

Two severely growth-retarded fetuses found to have maternal uniparental disomy (UPD) for chromosome 16 and trisomy 16 placental mosaicism both had an unfavourable outcome. Antenatally, the first case was complicated by an unexplained raised maternal serum alpha-fetoprotein concentration, preterm premature rupture of the membranes, and growth retardation detectable at 21 weeks' gestation, whilst the other had an unexplained raised maternal serum human chorionic gonadotrophin level, a two-vessel cord on ultrasound, and cessation of growth at 25 weeks. At post-mortem, both babies had an imperforate anus. Fetal maternal UPD may explain the poor outcome that occurs in some cases of confined placental mosaicism for chromosome 16 and is also associated with specific fetal abnormalities.     

How much deforestation do protected areas avoid in tropical Andean landscapes?

For many decades, protected areas (PAs) have been considered by decision makers and conservation practitioners as one of the most common policies to promote biodiversity conservation. Diverse studies have assessed the impact of conservation policies at global and regional levels by comparing deforestation rates between PAs and unprotected areas. Most of these studies are based on conventional methods and could overestimate the avoided deforestation of PAs by omitting from their analyses the lack of randomness in the allocation of forest protection.We demonstrate that estimates of effectiveness can be substantially improved by controlling for biases along dimensions that are observable and testing the sensitivity of estimates of potential hidden biases. We used matching methods to evaluate the impact on deforestation of Ecuador's tropical Andean forest protected-area system between 1990 and 2008. We found that protection reduced deforestation in approximately 6% of the protected forests. These would have been deforested had they not been protected. Conventional approaches to estimate conservation impact, which fail to control for observable covariates correlated with both protection and deforestation, substantially overestimate avoided deforestation. Our conclusions are robust to potential hidden bias, as well as to changes in modeling assumptions. In addition, it is assumed that this research will help decision-making in the framework of international climate change mitigation policies, such as REDD+.     

The Social Costs of Climate Change: The IPCC Second Assessment Report and Beyond

Climate change is expected to have far-reaching impacts. Earlier studies have estimated an aggregated monetised damage equivalent to 1.5 to 2.0 % of World GDP (for 2 × CO₂). According to these estimates, the OECD would face losses equivalent to 1.0 to 1.5 % of GDP, and developing countries 2.0 to 9.0 %. While these figures are preliminary and highly uncertain, recent findings have not, as yet, changed the general picture. As is shown in this paper, estimates that are fully corrected for differences in purchasing power parity do not significantly differ from the initial figures. Newer studies increasingly emphasise adaptation, variability, extreme events, other (non-climate change) stress factors, and the need for integrated assessment of damages. Incorporating these factors has lead to increased differences in estimated impacts between different regions and sectors. Estimates of market impacts in developed countries tended to fall, while non-market impacts have become more important. Marginal damages are more interesting from a policy point of view. Earlier estimates range from about $5 to $125 per tonne of carbon, with most estimates at the lower end of this range. These figures are based on power functions in the level of climate change. The rate of change may be equally important, as are the speed of adaptation, restoration and value adjustment. Furthermore, future vulnerability to climate change will differ from current vulnerability: market impacts could fall (relatively) with economic growth while non-market impacts may rise. This revised version was published online in August 2006 with corrections to the Cover Date.     

Wisconsin Electric’s experience with fish impingement and entrainment studies

Since 1975, Wisconsin Electric has conducted impingement studies at seven steam electric, once-through cooling-equipped power plants, as well as at one closed-cycle cooling system-equipped plant. Entrainment studies were also conducted at all seven once-through cooling-equipped plants. All eight plants are located on the Great Lakes or on major tributaries to them. Two of the eight plants have since been retired, while portions of two remaining multi-unit plants have been retired.As part of the study reports ultimately filed with the state agencies overseeing the studies, companies were also required to provide information on: intake design, capacity, and operation; whether biocides were used at the plants to control biofouling; and what ice control measures were employed during the winter season. Companies were also asked to provide brief assessments of available intake design alternatives that could be reasonably expected to reduce entrainment or impingement, as well as order of magnitude cost estimates for retrofiting plants with feasible alternative technologies.The studies concluded that since the vast majority of fish impinged during the 1975–1976 period were alewife and rainbow smelt (the then most abundant species in Lakes Michigan and Superior) and since the historic commercial harvests of these two species greatly exceeded annual impingement estimates, the impact of these incremental losses to lake-wide populations was inconsequential. With respect to the entrainment results, the studies detected few fish eggs or larvae that were not alewife or smelt.As a consequence of these findings, the company did not believe that any structural modifications to the intakes were necessary, since any one of the feasible alternatives would have been very costly. The state agencies concurred with these findings.     

Mitigation,adaptation, and climate change: results from recent research on US timber markets

This paper reviews recent studies that have addressed how US timber markets may adapt to climate change, and how US forests could be used to mitigate potential climate change. The studies are discussed in light of the ecological and economic assumptions used to estimate adaptation. Estimates of both economic impacts and carbon sequestration costs depend heavily on the assumptions and methods used, although some general conclusions can be drawn. Studies of economic impacts suggest that average market effects in the United States may range from +$1.3 to +7.4 billion per year by the middle of the next century. Estimates of the cost of sequestering carbon have generally increased over the last 10 years, with a current range of <1–73 million metric t per year of additional sequestration from afforestation projects costing $5–66 per metric t. Estimates of the potential for alternative methods for carbon sequestration, such as product markets and recycling, are as large as afforestation estimates, with up to 50 million metric tons per year of additional storage considered possible. Cost estimates have not been developed for these alternative methods, however.     

Fetal phenotype of Prader–Willi syndrome due to maternal disomy for chromosome 15

Prader–Willi syndrome (PWS) results from either paternal deletion of 15q11–q13, or maternal uniparental disomy (UPD) of chromosome 15 or imprinting center mutation. Prenatal diagnosis of PWS is currently indicated for chromosomal parental translocation involving chromosome 15 and for decreased fetal movements during the third trimester of gestation. Here we present the prenatal diagnosis of PWS during the first trimester of gestation and autopsy findings. Chorionic villus sampling (CVS) was performed for advanced maternal age at 13 weeks' gestation. CVS showed mosaicism including cells with a normal karyotype and cells with trisomy 15. Amniocentesis showed cells with a normal karyotype. Molecular analysis demonstrated that the fetus had a typical PWS abnormal methylation profile and maternal disomy for chromosome 15. Fetal ultrasound examination showed slightly enlarged lateral ventricles and hypoplasic male external genitalia without intra-uterine growth retardation. The autopsy showed a eutrophic male fetus with facial dysmorphy, hypoplasic genitalia, abnormal position of both feet and posterior hypoplasia of the corpus callosum. This report points out that in a karyotypically normal fetus with ambiguous male external genitalia and cerebral anomalies, extensive cytogenetic and molecular biology studies are strongly recommended because of risk of PWS. Copyright © 2003 John Wiley & Sons, Ltd.     

Maternal uniparental heterodisomy for chromosome 2: detection through ‘atypical’ maternal AFP/hCG levels,with an update on a previous case

We report a case of maternal uniparental disomy 2, detected through routine screening of placental karyotypes following the finding of ‘atypical’ AFP/hCG levels in the second trimester, with intrauterine growth retardation (IUGR) but otherwise normal outcome at term. Although the child remained small, subsequent early physical and mental development has also been normal. Additionally, we report long-term follow-up of an earlier case, again with relatively normal physical and mental development. The significance of atypical AFP/hCG results and the predictive value of prenatal testing for UPD2 in trisomy 2 confined placental mosaicism (CPM) cases are discussed. Copyright © 2001 John Wiley & Sons, Ltd.     

基于互联网的自然灾害风险沟通平台研究

通过调查发现,国内自然灾害风险沟通平台尚不完善,普遍存在沟通主体分类不清、风险消息真假难辨、沟通方式单一等不足之处,本文针对这些问题开展研究。通过案例分析,明确将沟通主体分为政府、专家和公众三类;利用多指标综合评价法构建面向沟通过程的自然灾害风险消息评价体系;并集成多种网络通信技术建设一个基于互联网的自然灾害风险沟通示...     

Climate change and local level disaster risk reduction planning: need, opportunities and challenges

The field of climate change is full of uncertainties that are limiting strategic disaster risk reduction planning. In this paper, however, we argued that there is lot to do before we get our hands on reliable estimates of future climate change impacts. It includes bringing together different stakeholders in a framework suggested in this paper, developing case studies that reflect long-term local impacts of climate change, capacity building of local stakeholders that enables them to take decisions under uncertainty etc. We proposed a simple scheme that brings together climate, disaster and policy community together to start a dialogue in a run-up to understanding wider aspects of long-term risk reduction at local level. Strategic thinking, which has only been restricted to national and regional planning to date, needs to be inculcated in local level disaster risk reduction and policy personnel as well. There is a need to move from the attitude of considering local level players as ‘implementers’ to ‘innovators’ for which developing a network of self learning and evolving organizations are required at the local level.