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1.
van Dooren M Tibboel D Torfs C 《Birth defects research. Part A, Clinical and molecular teratology》2005,73(1):53-57
BACKGROUND: Two severe birth defects, congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) with or without tracheoesophageal fistula (TEF), have traditionally been analyzed separately in epidemiological studies. Lung hypoplasia (LH), part of the CDH spectrum, is not usually associated with EA/TEF, yet both are foregut malformations. METHODS: We conducted an epidemiological study of two combinations of the defects in the population of 3,318,966 live births and stillbirths monitored from 1983 to 1996 by the California Birth Defects Monitoring Program (CBDMP). RESULTS: A total of 433 cases had a Bochdalek type CDH/LH (0.13 per 1000 births), 893 had EA/TEF (0.27 per 1000 births), and 646 had LH (0.19 per 1000 births). Among them, 18 cases had CDH/LH with EA/TEF (0.005 per 1000 births), and 53 had EA/TEF and LH (0.02 per 1000 births); both prevalences are significantly higher than expected. Sixteen of 17 cases of CDH/LH with EA/TEF, and 34 of 40 cases of EA/TEF with LH were stillborn or died; 72% and 74%, respectively, had an autopsy. The male to female sex ratios were 1.43 and 1.13, respectively. In both groups, infants had similar proportions of additional severe defects, except for genitourinary and anal defects and syndromes/associations, which were more prevalent in the EA/TEF with LH group. We reviewed human studies and experimental animal models for factors reported to cause any combination of the defects. CONCLUSIONS: Several genetic and environmental factors could affect the significant co-occurrence of the defects. Future studies should include storage of patients' biological materials for DNA analysis, karyotyping, and environmental exposure evaluation. 相似文献
2.
Que J Choi M Ziel JW Klingensmith J Hogan BL 《Differentiation; research in biological diversity》2006,74(7):422-437
The development of the anterior foregut of the mammalian embryo involves changes in the behavior of both the epithelial endoderm and the adjacent mesoderm. Morphogenetic processes that occur include the extrusion of midline notochord cells from the epithelial definitive endoderm, the folding of the endoderm into a foregut tube, and the subsequent separation of the foregut tube into trachea and esophagus. Defects in foregut morphogenesis underlie the constellation of human birth defects known as esophageal atresia (EA) and tracheoesophageal fistula (TEF). Here, we review what is known about the cellular events in foregut morphogenesis and the gene mutations associated with EA and TEF in mice and humans. We present new evidence that about 70% of mouse embryos homozygous null for Nog, the gene encoding noggin, a bone morphogenetic protein (Bmp) antagonist, have EA/TEF as well as defects in lung branching. This phenotype appears to correlate with abnormal morphogenesis of the notochord and defects in its separation from the definitive endoderm. The abnormalities in foregut and lung morphogenesis of Nog null mutant can be rescued by reducing the gene dose of Bmp4 by 50%. This suggests that normal foregut morphogenesis requires that the level of Bmp4 activity is carefully controlled by means of antagonists such as noggin. Several mechanisms are suggested for how Bmps normally function, including by regulating the intercellular adhesion and behavior of notochord and foregut endoderm cells. Future research must determine how Noggin/Bmp antagonism fits into the network of other factors known to regulate tracheal and esophagus development, both in mouse or humans. 相似文献
3.
A comparison of incidence trends for esophageal atresia and tracheoesophageal fistula, and infectious disease 总被引:1,自引:0,他引:1
There has been a suggestion that esophageal atresia with tracheoesophageal fistula (EA/TEF) may be related to the occurrence of infectious disease in the population during the time of early gestation. There is therefore a need for further data on trends in incidence related to infectious diseases. Data on the occurrence of EA/TEF with and without additional congenital malformations may also be relevant. The British Columbia Health Surveillance Registry is population-based with excellent case ascertainment of birth defects, and data are available on the incidence of infectious diseases for B.C., allowing comparison of trends to be made. One hundred forty-nine cases of EA/TEF occurred among 534,834 consecutive livebirths during the period 1966-1980 for an incidence rate of 1/3,590. No significant (p less than 0.05) annual, seasonal or monthly incidence trends were observed. In addition, the occurrence of EA/TEF could not be correlated with the prior incidence of infectious hepatitis, rubella, salmonella, or rubeola. Fifty-five percent of individuals with EA/TEF had congenital malformations in other systems, most frequently cardiovascular, gastrointestinal, and genitourinary. Most individuals with additional congenital malformations had multiple system involvement. 相似文献
4.
Matthew F. Buas Lynn Onstad David M. Levine Harvey A. Risch Wong-Ho Chow Geoffrey Liu Rebecca C. Fitzgerald Leslie Bernstein Weimin Ye Nigel C. Bird Yvonne Romero Alan G. Casson Douglas A. Corley Nicholas J. Shaheen Anna H. Wu Marilie D. Gammon Brian J. Reid Laura J. Hardie Ulrike Peters David C. Whiteman Thomas L. Vaughan 《PloS one》2015,10(6)
5.
Shastry BS 《Microbial & comparative genomics》2000,5(2):61-69
Deafness is the most common sensory hereditary disorder. It is a genetically heterogeneous and multifactorial disease affecting approximately 1 infant in 2000. It can be acquired or congenital and can also be syndromic or nonsyndromic. There are approximately 70 genetic loci that have been described for nonsyndromic deafness in humans and 25 auditory-pigmentary diseases in mice. The past 2 years have witnessed remarkable progress in identifying the genes involved in both syndromic and nonsyndromic disorders in humans and mice. Many of these are expressed in the inner ear and are most likely involved in cochlear physiology and development. However, the phenotypic variability in patients carrying the same genetic change, and discrepancies between the phenotypes of mice and humans carrying the same gene defect, emphasize environmental factors and interacting genes in producing the clinical outcome. In the future, molecular understanding of the etiology of the disorder may lead to a cure or delay the onset of the disorder. 相似文献
6.
Matteo Bianchi Stina Dahlgren Jonathan Massey Elisabeth Dietschi Marcin Kierczak Martine Lund-Ziener Katarina Sundberg Stein Istre Thoresen Olle K?mpe G?ran Andersson William E. R. Ollier ?ke Hedhammar Tosso Leeb Kerstin Lindblad-Toh Lorna J. Kennedy Frode Lingaas Gerli Rosengren Pielberg 《PloS one》2015,10(8)
Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds—the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10-11). Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018–5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans. 相似文献
7.
Ethnic differences in key candidate genes for spontaneous preterm birth: TNF-alpha and its receptors
Menon R Velez DR Thorsen P Vogel I Jacobsson B Williams SM Fortunato SJ 《Human heredity》2006,62(2):107-118
OBJECTIVES: Spontaneous preterm birth (PTB) has a significant ethnic disparity with people of African descent having an almost 2-fold higher incidence than those of European descent in the United States. This disparity may be caused by differences in the distribution of genetic risk factors. The objective of this study is to examine genetic differences between African-Americans and European Americans for single nucleotide polymorphisms (SNPs) in candidate genes for PTB. METHODS: We examined patterns of variation in 19 SNPs in 3 candidate genes for preterm birth: TNF-alpha, TNF-receptor 1 and TNF-receptor 2. Allele, genotype and haplotype frequencies were compared between African-Americans (AA) and European-Americans (EA) in cases and controls separately. Both maternal and fetal genotypes were studied, as it is unclear whether one or both of these are important in the etiology of PTB. RESULTS: The vast majority of the SNPs differed significantly between ethnic groups, although there are only a few suggestive results comparing cases and controls within an ethnic group. For TNF-alpha, four of six SNPs; for TNF-R1, 5/6; and for TNF-R2, 6/7 showed significant differences between ethnic groups in either allele and/or genotype frequency. CONCLUSIONS: Our data demonstrate highly significant genetic differences between ethnic groups in genes that may play a role in the risk of PTB. 相似文献
8.
Solomon BD Pineda-Alvarez DE Hadley DW Keaton AA Agochukwu NB Raam MS Carlson-Donohoe HE Kamat A Chandrasekharappa SC 《Birth defects research. Part A, Clinical and molecular teratology》2011,91(9):862-865
BACKGROUND
Tracheo‐esophageal fistula (TEF) with/or without esophageal atresia (EA) is a common congenital malformation that is often accompanied by other anomalies. The causes of this condition are thought to be heterogeneous but are overall not well understood.CASE REPORT
We identified a patient with a TEF/EA, as well as cardiac and genitourinary anomalies, who was found to have a 0.7 Mb de novo deletion of chromosome 20q13.33. One gene within the deleted interval, GTPBP5, is of particular interest as a candidate gene.CONCLUSIONS
GTPBP5 bears further study as a cause of TEF/EA accompanied by other malformations. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc. 相似文献9.
Atherosclerosis is a complex disease involving genetic and environmental risk factors, acting on their own or in synergy. Within the general population, polymorphisms within genes in lipid metabolism, inflammation, and thrombogenesis are probably responsible for the wide range of susceptibility to myocardial infarction, a fatal consequence of atherosclerosis. Genetic linkage studies have been carried out in both humans and mouse models to identify these polymorphisms. Approximately 40 quantitative trait loci for atherosclerotic disease have been found in humans, and approximately 30 in mice. Recently, genome-wide association studies have been used to identify atherosclerosis-susceptibility polymorphisms. Although discovering new atherosclerosis genes through these approaches remains challenging, the pace at which these polymorphisms are being found is accelerating due to rapidly improving bioinformatics resources and biotechnologies. The outcome of these efforts will not only unveil the molecular basis of atherosclerosis but also facilitate the discovery of drug targets and individualized medication against the disease. 相似文献
10.
Prostate cancer is the most frequent malignancy in males and its etiology is strongly influenced by genetic factors. Nevertheless, no mutated genes which could be used for diagnosis have been identified in a major proportion of familial cases. Three genes with germline mutations have been identified after linkage analysis (ELAC2, RNASEL, MSR1), but these mutations are very rare and their penetrance is not well defined. The association of most genes with genetic variants is weak, and only BRCA2/familial breast cancer is of clinical relevance. As a consequence of the extreme genetic heterogeneity, diagnostic tools are not available and genetic counseling has to rely on risk estimates from pedigree data in which a single affected first degree relative indicates a relevant risk. 相似文献
11.
Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm 总被引:3,自引:0,他引:3
Que J Okubo T Goldenring JR Nam KT Kurotani R Morrisey EE Taranova O Pevny LH Hogan BL 《Development (Cambridge, England)》2007,134(13):2521-2531
Sox2 is expressed in developing foregut endoderm, with highest levels in the future esophagus and anterior stomach. By contrast, Nkx2.1 (Titf1) is expressed ventrally, in the future trachea. In humans, heterozygosity for SOX2 is associated with anopthalmia-esophageal-genital syndrome (OMIM 600992), a condition including esophageal atresia (EA) and tracheoesophageal fistula (TEF), in which the trachea and esophagus fail to separate. Mouse embryos heterozygous for the null allele, Sox2(EGFP), appear normal. However, further reductions in Sox2, using Sox2(LP) and Sox2(COND) hypomorphic alleles, result in multiple abnormalities. Approximately 60% of Sox2(EGFP/COND) embryos have EA with distal TEF in which Sox2 is undetectable by immunohistochemistry or western blot. The mutant esophagus morphologically resembles the trachea, with ectopic expression of Nkx2.1, a columnar, ciliated epithelium, and very few p63(+) basal cells. By contrast, the abnormal foregut of Nkx2.1-null embryos expresses elevated Sox2 and p63, suggesting reciprocal regulation of Sox2 and Nkx2.1 during early dorsal/ventral foregut patterning. Organ culture experiments further suggest that FGF signaling from the ventral mesenchyme regulates Sox2 expression in the endoderm. In the 40% Sox2(EGFP/COND) embryos in which Sox2 levels are approximately 18% of wild type there is no TEF. However, the esophagus is still abnormal, with luminal mucus-producing cells, fewer p63(+) cells, and ectopic expression of genes normally expressed in glandular stomach and intestine. In all hypomorphic embryos the forestomach has an abnormal phenotype, with reduced keratinization, ectopic mucus cells and columnar epithelium. These findings suggest that Sox2 plays a second role in establishing the boundary between the keratinized, squamous esophagus/forestomach and glandular hindstomach. 相似文献
12.
Gastric cancer (GC) is an important cause of morbidity and mortality worldwide. In addition to environmental factors, genetic factors also play an important role in GC etiology, as demonstrated by the fact that only a small proportion of individuals exposed to the known environmental risk factors develop GC. Molecular studies have provided evidence that GC arises not only from the combined effects of environmental factors and susceptible genetic variants but also from the accumulation of genetic and epigenetic alterations that play crucial roles in the process of cellular immortalization and tumorigenesis. This review is intended to focus on the recently described basic aspects that play key roles in the process of gastric carcinogenesis. Genetic variation in the genes DNMT3A, PSCA, VEGF, and XRCC1 has been reported to modify the risk of developing gastric carcinoma. Several genes have been newly associated with gastric carcinogenesis, both through oncogenic activation (MYC, SEMA5A, BCL2L12, RBP2 and BUBR1) and tumor suppressor gene inactivation mechanisms (KLF6, RELN, PTCH1A, CLDN11, and SFRP5). At the level of gastric carcinoma treatment, the HER-2 tyrosine kinase receptor has been demonstrated to be a molecular target of therapy. 相似文献
13.
Understanding of how interactions between genes and environment contribute to the development of arthritis is a central issue in understanding the etiology of rheumatoid arthritis (RA), as well as for eventual subsequent efforts to prevent the disease. In this paper, we review current published data on genes and environment in RA as well as in certain induced animal models of disease, mainly those in which adjuvants only or adjuvants plus organ-specific autoantigens are used to induce arthritis. We refer to some new data on environmental and genetic factors of importance for RA generated from a large case-control study in Sweden (1200 patients, 1200 matched controls). We found an increased risk of seropositive but not of seronegative RA in smokers, and there are indications that this effect may be due to a gene-environment interaction involving MHC class II genes. We also found an increased risk of RA in individuals heavily exposed to mineral oils. This was of particular interest because mineral oils are strong inducers of arthritis in certain rodent strains and because polymorphisms in human genetic regions syntenic with genes predisposing for oil-induced arthritis in rats have now been shown to associate with RA in humans. Taken together, our data support the notion that concepts and data on gene-environment interactions in arthritis can now be taken from induced animal models of arthritis to generate new etiological hypotheses for RA. 相似文献
14.
《Journal of lipid research》2017,58(5):853-865
Since its initial report in 2009, the intestinal enteroid culture system has been a powerful tool used to study stem cell biology and development in the gastrointestinal tract. However, a major question is whether enteroids retain intestinal function and physiology. There have been significant contributions describing ion transport physiology of human intestinal organoid cultures, as well as physiology of gastric organoids, but critical studies on dietary fat absorption and chylomicron synthesis in primary intestinal enteroids have not been undertaken. Here we report that primary murine enteroid cultures recapitulate in vivo intestinal lipoprotein synthesis and secretion, and reflect key aspects of the physiology of intact intestine in regard to dietary fat absorption. We also show that enteroids can be used to elucidate intestinal mechanisms behind CVD risk factors, including tissue-specific apolipoprotein functions. Using enteroids, we show that intestinal apoC-III overexpression results in the secretion of smaller, less dense chylomicron particles along with reduced triacylglycerol secretion from the intestine. This model significantly expands our ability to test how specific genes or genetic polymorphisms function in dietary fat absorption and the precise intestinal mechanisms that are critical in the etiology of metabolic disease. 相似文献
15.
The etiology of heritable diseases may be elucidated by localizing genes conferring susceptibility and by subsequent biological characterization of these genes. To localize genetic components for multifactorial traits, both hypothesis-driven candidate gene and hypothesis-free genome scan approaches have been applied. To date, only a handful of results have been reproduced in either a different cohort or model organisms. The integration of genetic approaches with high-throughput genomic techniques is very promising. Unfortunately, most genetic studies completely ignore strong nongenetic effects such as low education and poverty even though these factors are well-known to predict, for example, obesity. Thus, what are most needed in future research are statistical methods for discovering sets of susceptibility genes and environmental factors, as well as systematic verifications of the gene-environment-disease network. 相似文献
16.
While substance abuse disorders only occur in humans, mice and other model organisms can make valuable contributions to genetic studies of these disorders. In this review, we consider a few specific examples of how model organisms have been used in conjunction with studies in humans to study the role of genetic factors in substance use disorders. In some examples genes that were first discovered in mice were subsequently studied in humans. In other examples genes or specific polymorphisms in genes were first studied in humans and then modeled in mice. Using anatomically and temporally specific genetic, pharmacological and other environmental manipulations in conjunction with histological analyses, mechanistic insights that would be difficult to obtain in humans have been obtained in mice. We hope these examples illustrate how novel biological insights about the effect of genes on substance use disorders can be obtained when mouse and human genetic studies are successfully integrated. 相似文献
17.
Phylogeny,morphology and pathogenicity of Elsinoë ampelina,the causal agent of grapevine anthracnose in Brazil and Australia
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Ricardo Feliciano dos Santos Marcel Bellato Spósito Matthew Ronald Ayres Mark Roman Sosnowski 《Journal of Phytopathology》2018,166(3):187-198
Anthracnose caused by Elsinoë ampelina is one of the most important table grape diseases in humid regions in Brazil and Australia. The objective of this study was to characterize E. ampelina isolates from Brazil and Australia by means of phylogenetic analyses, morphological features and pathogenicity tests. Phylogenetic relationships among 35 isolates were determined based on a data set of internal transcribed spacer (ITS), histone H3 (HIS3) and elongation factor 1‐α (TEF) sequences. In phylogenetic tree analyses, using a combined ITS and TEF sequence alignment, all E. ampelina isolates were clustered together in a single well‐supported clade. In contrast to the absence of genetic variability within ITS and TEF sequences, HIS3 sequences showed 54 polymorphic sites. The haplotype network generated from HIS3 data set showed four distinct haplotypes. EA1 was the predominant haplotype including 29 isolates from both countries. High genetic variability was observed in two Brazilian isolates, haplotype EA4, which may have lost the intron region during species evolution. Colony colours differed between Brazilian and Australian isolates, but showed similar wrinkled colony texture, absence of spores, sparse‐to‐absent white aerial mycelium and slow growth (0.049–0.060 mm/day). Brazilian isolates produced conidia of 5.65 × 2.65 μm, larger than conidia from Australian isolates, which measured 5.14 × 2.30 μm. In pathogenicity tests, all nine Australian isolates inoculated were pathogenic on detached canes and potted vines of table grape. 相似文献
18.
The molecular requirements for neural tube closure are complex. This is illustrated by the occurrence of neural tube defects (NTDs) in many genetic mouse mutants, which implicate a variety of genes, pathways and cellular functions. NTDs are also prevalent birth defects in humans, affecting around 1 per 1,000 pregnancies worldwide. In humans the causation is thought to involve the interplay of fetal genes and the effect of environmental factors. Recent studies on the etiology of human NTDs, as well as analysis of mouse models, have raised the question of the possible involvement of epigenetic factors in determining susceptibility. A consideration of potential causative factors in human NTDs must now include both alterations in the regulation of gene expression, through mutation of promoter or regulatory elements and the additional analysis of epigenetic regulation. Alterations in the epigenetic status can be directly modified by various environmental insults or maternal dietary factors.Key words: neural tube defects, diet, folic acid, epigenome, epigenetic regulation, methylation, chromatin, histones, acetylation 相似文献
19.
Maryam Rezazadeh Hassan Hosseinzadeh Mohsen Moradi Behnaz Salek Esfahani Shahrzad Talebian Shaho Parvin Jalal Gharesouran 《Journal of cellular physiology》2019,234(10):16873-16884
Alzheimer’s disease (AD) is a heterogeneous disorder with multiple patterns of clinical manifestations. Recently, due to the advance of linkage studies, next-generation sequencing and genome-wide association studies, a large number of putative risk genes for AD have been identified using acquired genome mega data. The genetic association between three causal genes, including amyloid precursor protein, presenilin1, and presenilin2 in early-onset AD (EOAD), was discovered over the past few decades. These discoveries showed that there should be additional genetic risk factors for both EOAD and late-onset AD (LOAD) to help fully explain the leading molecular mechanisms in a single pathophysiological entity. This study reviews the clinical features and genetic etiology of LOAD and discusses a variety of AD-mediated genes that are involved in cholesterol and lipid metabolism, endocytosis, and immune response according to their mutations for more efficient selection of functional candidate genes for LOAD. New mechanisms and pathways have been identified as a result. 相似文献
20.
Genetic Background of Hirschsprung Disease: A Bridge Between Basic Science and Clinical Application
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Afsane Bahrami Marjan Joodi Mehrdad Moetamani‐Ahmadi Mina Maftouh Seyed Mahdi Hassanian Gordon A. Ferns Amir Avan 《Journal of cellular biochemistry》2018,119(1):28-33
Hirschsprung's disease (HSCR) is a congenital disorder, defined by partial or complete loss of the neuronal ganglion cells in the intestinal tract, which is caused by the failure of neural crest cells to migrate completely during intestinal development during fetal life. HSCR has a multifactorial etiology, and genetic factors play a key role in its pathogenesis; these include mutations within several gene loci. These have been identified by screening candidate genes, or by conducting genome wide association (GWAS) studies. However, only a small portion of them have been proposed as major genetic risk factors for the HSCR. In this review, we focus on those genes that have been identified as either low penetrant or high penetrant variants that determine the risk of Hirschsprung's disease. J. Cell. Biochem. 119: 28–33, 2018. © 2017 Wiley Periodicals, Inc. 相似文献