63 research outputs found
Особенности разработки палеозойских отложений Томской области
peer reviewedProton magnetic resonance spectroscopic data ((1)H-MR spectroscopy) of patients with 18q deletion syndrome have not yet been reported. (1)H-MR spectroscopy, performed in an affected 2-year-old girl with markedly delayed neuromotor development and typical supratentorial white-matter disease (WMD), showed an increase of choline and alpha-glutamate concentrations. Eight months later, simultaneously with clinical improvement, alpha-glutamate had normalised whereas choline remained slightly increased. Active demyelination or increased myelin turnover might contribute to the hitherto unexplained WMD of this rare disorder
Carrier Screening for Spinal Muscular Atrophy (SMA) in 107,611 Pregnant Women during the Period 2005–2009: A Prospective Population-Based Cohort Study
BACKGROUND: Spinal muscular atrophy (SMA) is the most common neuromuscular autosomal recessive disorder. The American College of Medical Genetics has recently recommended routine carrier screening for SMA because of the high carrier frequency (1 in 25-50) as well as the severity of that genetic disease. Large studies are needed to determine the feasibility, benefits, and costs of such a program. METHODS AND FINDINGS: This is a prospective population-based cohort study of 107,611 pregnant women from 25 counties in Taiwan conducted during the period January 2005 to June 2009. A three-stage screening program was used: (1) pregnant women were tested for SMA heterozygosity; (2) if the mother was determined to be heterozygous for SMA (carrier status), the paternal partner was then tested; (3) if both partners were SMA carriers, prenatal diagnostic testing was performed. During the study period, a total of 2,262 SMA carriers with one copy of the SMN1 gene were identified among the 107,611 pregnant women that were screened. The carrier rate was approximately 1 in 48 (2.10%). The negative predictive value of DHPLC coupled with MLPA was 99.87%. The combined method could detect approximately 94% of carriers because most of the cases resulted from a common single deletion event. In addition, 2,038 spouses were determined to be SMA carriers. Among those individuals, 47 couples were determined to be at high risk for having offspring with SMA. Prenatal diagnostic testing was performed in 43 pregnant women (91.49%) and SMA was diagnosed in 12 (27.91%) fetuses. The prevalence of SMA in our population was 1 in 8,968. CONCLUSION: The main benefit of SMA carrier screening is to reduce the burden associated with giving birth to an affected child. In this study, we determined the carrier frequency and genetic risk and provided carrier couples with genetic services, knowledge, and genetic counseling
Genetic and expression studies of SMN2 gene in Russian patients with spinal muscular atrophy type II and III
<p>Abstract</p> <p>Background</p> <p>Spinal muscular atrophy (SMA type I, II and III) is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (<it>SMN1</it>). <it>SMN2 </it>is a centromeric copy gene that has been characterized as a major modifier of SMA severity. SMA type I patients have one or two <it>SMN2 </it>copies while most SMA type II patients carry three <it>SMN2 </it>copies and SMA III patients have three or four <it>SMN2 </it>copies. The <it>SMN1 </it>gene produces a full-length transcript (FL-SMN) while <it>SMN2 </it>is only able to produce a small portion of the FL-SMN because of a splice mutation which results in the production of abnormal SMNΔ7 mRNA.</p> <p>Methods</p> <p>In this study we performed quantification of the <it>SMN2 </it>gene copy number in Russian patients affected by SMA type II and III (42 and 19 patients, respectively) by means of real-time PCR. Moreover, we present two families consisting of asymptomatic carriers of a homozygous absence of the <it>SMN1 </it>gene. We also developed a novel RT-qPCR-based assay to determine the FL-SMN/SMNΔ7 mRNA ratio as SMA biomarker.</p> <p>Results</p> <p>Comparison of the <it>SMN2 </it>copy number and clinical features revealed a significant correlation between mild clinical phenotype (SMA type III) and presence of four copies of the <it>SMN2 </it>gene. In both asymptomatic cases we found an increased number of <it>SMN2 </it>copies in the healthy carriers and a biallelic <it>SMN1 </it>absence. Furthermore, the novel assay revealed a difference between SMA patients and healthy controls.</p> <p>Conclusions</p> <p>We suggest that the <it>SMN2 </it>gene copy quantification in SMA patients could be used as a prognostic tool for discrimination between the SMA type II and SMA type III diagnoses, whereas the FL-SMN/SMNΔ7 mRNA ratio could be a useful biomarker for detecting changes during SMA pharmacotherapy.</p
Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72 400 specimens
Spinal muscular atrophy (SMA) is a leading inherited cause of infant death with a reported incidence of ∼1 in 10 000 live births and is second to cystic fibrosis as a common, life-shortening autosomal recessive disorder. The American College of Medical Genetics has recommended population carrier screening for SMA, regardless of race or ethnicity, to facilitate informed reproductive options, although other organizations have cited the need for additional large-scale studies before widespread implementation. We report our data from carrier testing (n=72 453) and prenatal diagnosis (n=121) for this condition. Our analysis of large-scale population carrier screening data (n=68 471) demonstrates the technical feasibility of high throughput testing and provides mutation carrier and allele frequencies at a level of accuracy afforded by large data sets. In our United States pan-ethnic population, the calculated a priori carrier frequency of SMA is 1/54 with a detection rate of 91.2%, and the pan-ethnic disease incidence is calculated to be 1/11 000. Carrier frequency and detection rates provided for six major ethnic groups in the United States range from 1/47 and 94.8% in the Caucasian population to 1/72 and 70.5% in the African American population, respectively. This collective experience can be utilized to facilitate accurate pre- and post-test counseling in the settings of carrier screening and prenatal diagnosis for SMA
Recommended from our members
Validation of a high resolution NGS method for detecting spinal muscular atrophy carriers among phase 3 participants in the 1000 Genomes Project
BACKGROUND: Spinal muscular atrophy (SMA) is the most common pan-ethnic cause of early childhood death due to mutations in a single gene, SMN1. Most chromosome 5 homologs have a functional gene and dysfunctional copy, SMN2, with a single synonymous base substitution that results in faulty RNA splicing. However, the copy number of SMN1 and SMN2 is highly variable, and one in 60 adults worldwide are SMA carriers. Although population-wide screening is recommended, current SMA carrier tests have not been incorporated into targeted gene panels. METHODS: Here we describe a novel computational protocol for determining SMA carrier status based solely on individual exome data. Our method utilizes a Bayesian hierarchical model to quantify an individual’s carrier probability given only his or her SMN1 and SMN2 reads at six loci of interest. RESULTS: We find complete concordance with results obtained with the current qPCR-based testing standard in known SMA carriers and affecteds. We applied our protocol to the phase 3 cohort of the 1,000 Genomes Project and found carrier frequencies in multiple populations consistent with the present literature. CONCLUSION: Our process is a convenient, robust alternative to qPCR, which can easily be integrated into the analysis of large multi-gene NGS carrier screens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0246-2) contains supplementary material, which is available to authorized users
Trans-Amazon dispersal potential for Crotalus durissus during Pleistocene climate events
Phylogeography and evolutionary history of the Crocidura olivieri complex (Mammalia, Soricomorpha): from a forest origin to broad ecological expansion across Africa
Long-Term Vegetation Change in Central Africa: The Need for an Integrated Management Framework for Forests and Savannas
peer reviewedTropical forests and savannas are the main biomes in sub-Saharan Africa, covering most of the continent. Collectively they offer important habitat for biodiversity and provide multiple ecosystem services. Considering their global importance and the multiple sustainability challenges they face in the era of the Anthropocene, this chapter undertakes a comprehensive analysis of the past, present, and future vegetation patterns in central African forests and savannas. Past changes in climate, vegetation, land use, and human activity have affected the distribution of forests and savannas across central Africa. Currently, forests form a continuous block across the wet and moist areas of central Africa, and are characterized by high tree cover (>90% tree cover). Savannas and woodlands have lower tree cover (<40% tree cover), are found in drier sites in the north and south of the region, and are maintained by frequent fires. Recent tree cover loss (2000–2015) has been more important for forests than for savannas, which, however, reportedly experienced woody encroachment. Future cropland expansion is expected to have a strong impact on savannas, while the extent of climatic impacts depends on the actual scenario. We finally identify some of the policy implications for restoring ecosystems, expanding protected areas, and designing sustainable ecosystem management approaches in the region
A remarkable relationship of the stable carbon isotopic compositions of wood and cellulose in tree-rings of the ropical speices Cariniana micrantha (Ducke) from Brazil
The stable isotopes of carbon were analysed in total wood and cellulose from the tree-rings of the tropical wood species Cariniana micrantha (Ducke). The aim was to examine the isotopic relationship between total wood and its cellulose over the last two and a half centuries. Although the correlation for the whole time period is very high (r = 0.96) it is remarkable that different sub-periods deviate strongly from this close relationship. Consequently, a good correlation from the subset of a longer isotopic record cannot necessarily prove its validity for the whole record. The study indicates that changes of the carbon isotopes of cellulose and of total wood show sometimes during short sub-periods different isotope patterns presumably caused by different environmental effects. Thorough calculations indicate that strong variations within the isotopic record especially changes of the isotopic level along a chronology lead to high correlations between δ13Cwood and δ13Ccel. Contrary thereto subsections with low isotopic variability lead to low correlations. The results imply that long term trends provide similar patterns. Therefore, if long term trends are of interest such as e.g. in climate reconstruction then total wood can be analysed in favour of cellulose, thus saving a tremendous amount of work. However, if short term aspects from a longer record are of interest, cellulose and total wood may sometimes provide different information. In addition it is hypothesized that during intervals of low isotopic variability the proportions of the various wood components may change relative to each other, leading for certain time intervals to different isotope patterns
- …