Environmentally induced epigenetic transgenerational inheritance of disease susceptibility.

Science.gov (United States)

Nilsson, Eric E; Skinner, Michael K

2015-01-01

Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure-specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed with regard to disease etiology. Copyright © 2015 Elsevier Inc. All rights reserved.

Inherent X-Linked Genetic Variability and Cellular Mosaicism Unique to Females Contribute to Sex-Related Differences in the Innate Immune Response

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Zoltan Spolarics

2017-11-01

Full Text Available Females have a longer lifespan and better general health than males. Considerable number of studies also demonstrated that, after trauma and sepsis, females present better outcomes as compared to males indicating sex-related differences in the innate immune response. The current notion is that differences in the immuno-modulatory effects of sex hormones are the underlying causative mechanism. However, the field remains controversial and the exclusive role of sex hormones has been challenged. Here, we propose that polymorphic X-linked immune competent genes, which are abundant in the population are important players in sex-based immuno-modulation and play a key role in causing sex-related outcome differences following trauma or sepsis. We describe the differences in X chromosome (ChrX regulation between males and females and its consequences in the context of common X-linked polymorphisms at the individual as well as population level. We also discuss the potential pathophysiological and immune-modulatory aspects of ChrX cellular mosaicism, which is unique to females and how this may contribute to sex-biased immune-modulation. The potential confounding effects of ChrX skewing of cell progenitors at the bone marrow is also presented together with aspects of acute trauma-induced de novo ChrX skewing at the periphery. In support of the hypothesis, novel observations indicating ChrX skewing in a female trauma cohort as well as case studies depicting the temporal relationship between trauma-induced cellular skewing and the clinical course are also described. Finally, we list and discuss a selected set of polymorphic X-linked genes, which are frequent in the population and have key regulatory or metabolic functions in the innate immune response and, therefore, are primary candidates for mediating sex-biased immune responses. We conclude that sex-related differences in a variety of disease processes including the innate inflammatory response to injury

Non-syndromic posterior lenticonus a cause of childhood cataract: evidence for X-linked inheritance.

Science.gov (United States)

Russell-Eggitt, I M

2000-12-01

When an X-linked pedigree of posterior lenticonus with cataract was identified further evidence for X-linked inheritance of this condition was sought. Forty-three cases of posterior lenticonus were identified from a database of 354 children with cataract. Two children with the X-linked syndromes of Lowe and Nance-Horan and 3 children with Fanconi syndrome have been excluded from further analysis. None of the children was deaf. None of the non-syndromic cases had microcornea. There were 38 cases of non-syndromic posterior lenticonus (approximately 11%). There were 15 children from 13 pedigrees and 23 apparently sporadic cases. Of the 106 cases on the database with unilateral cataract 15 had posterior lenticonus (approximately 14%). Eleven of 13 pedigrees were compatible with X-linked inheritance or autosomal dominant inheritance with variable expression. However, in 2 pedigrees there was father to son transmission. Posterior lenticonus is a common cause of unilateral infantile cataract, but is thought to be a rare cause of bilateral cataracts. This study suggests that posterior lenticonus is responsible for a significant proportion of childhood cataracts (approximately 14% of unilateral and approximately 9% of bilateral cases). Posterior lenticonus is generally thought to occur as a sporadic condition. This study demonstrates that there is a family history of early-onset cataract in a significant number of bilateral cases (approximately 58%).

Experimental Models of Inherited PrP Prion Diseases.

Science.gov (United States)

Watts, Joel C; Prusiner, Stanley B

2017-11-01

The inherited prion protein (PrP) prion disorders, which include familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia, constitute ∼10%-15% of all PrP prion disease cases in humans. Attempts to generate animal models of these disorders using transgenic mice expressing mutant PrP have produced variable results. Although many lines of mice develop spontaneous signs of neurological illness with accompanying prion disease-specific neuropathological changes, others do not. Furthermore, demonstrating the presence of protease-resistant PrP species and prion infectivity-two of the hallmarks of the PrP prion disorders-in the brains of spontaneously sick mice has proven particularly challenging. Here, we review the progress that has been made toward developing accurate mouse models of the inherited PrP prion disorders. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

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Indian Academy of Sciences (India)

from a normal mother, in B 11-1 inherits the disease from an affected hemizygous father. ... disease. to a sex linked genetic disorder especially a recessive one. The pattern of inheritance of a sex linked dominant disorder is shown in the pedigree depicted inFigure 2 .... There are about 45 X-linked loci identified with mental.

Inherited XX sex reversal originating from wild medaka populations.

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Shinomiya, A; Otake, H; Hamaguchi, S; Sakaizumi, M

2010-11-01

The teleost fish, medaka (Oryzias latipes), has an XX/XY sex-determining mechanism. A Y-linked DM domain gene, DMY, has been isolated by positional cloning as the sex-determining gene in this species. Previously, we conducted a field survey of genotypic sex and found that approximately 1% of wild medaka are sex-reversed (XX males and XY females). Here, we performed genetic analyses of nine spontaneous XX sex-reversed males to elucidate its genetic basis. In all cases, the F(1) progeny were all females, whereas XX males reappeared in the backcross (BC) progeny, suggesting that XX sex reversal is a recessive trait. Although the incidences of sex reversal in the BC progeny were mostly low, 40% were males derived from one XX male. We performed linkage analysis using 55 BC males and located a single major factor, sda-1 (sex-determining autosomal factor-1), controlling sex reversal in an autosomal linkage group. Thus, genes involved in the sex-determining pathway can be isolated from spontaneous mutants in wild populations.

Rare inherited kidney diseases: challenges, opportunities, and perspectives.

NARCIS (Netherlands)

Devuyst, O.; Knoers, N.V.A.M.; Remuzzi, G.; Schaefer, F.; Bindels, R.J.; et al.,

2014-01-01

At least 10% of adults and nearly all children who receive renal-replacement therapy have an inherited kidney disease. These patients rarely die when their disease progresses and can remain alive for many years because of advances in organ-replacement therapy. However, these disorders substantially

Anticipated stigma and blameless guilt: Mothers' evaluation of life with the sex-linked disorder, hypohidrotic ectodermal dysplasia (XHED)

OpenAIRE

Clarke, Angus

2016-01-01

Practical experience of a genetic disorder may influence how parents approach reproduction, if they know their child may be affected by an inherited condition. One important aspect of this practical experience is the stigmatisation which family members may experience or witness. We outline the concept of stigma and how it affects those in families with a condition that impacts upon physical appearance. We then consider the accounts given by females in families affected by the rare sex-linked ...

Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.

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Guerrero-Bosagna, Carlos; Covert, Trevor R; Haque, Md M; Settles, Matthew; Nilsson, Eric E; Anway, Matthew D; Skinner, Michael K

2012-12-01

The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Affected parent sex and severity of autosomal dominant polycystic kidney disease: a retrospective cohort study
.

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Nowak, Kristen L; Chonchol, Michel; You, Zhiying; Gupta, Malika; Gitomer, Berenice

2018-03-01

Parental inheritance may differentially affect autosomal dominant polycystic kidney disease (-ADPKD) severity via genetic imprinting or in utero epigenetic modifications; however, evidence is inconsistent. We conducted a longitudinal retrospective cohort study to assess the association between sex of the affected parent and time to hypertension diagnosis, end-stage renal disease (ESRD), and death in patients with the PKD1 genotype. 814 individuals who participated in research at the University of Colorado were studied. Kaplan-Meier survival analysis was performed. The predictor was parental sex, and outcomes were diagnosis of hypertension, progression to ESRD, and death. We also examined associations in four strata according to affected parent and participant sex, as previous studies have reported earlier onset of ESRD in males compared to females. The median follow-up for each outcome was as follows: hypertension, 30 (interquartile range (IQR): 18, 37); ESRD, 43 (IQR: 31, 52), death 39 (IQR: 25, 52) years of age. Among affected offspring in the entire cohort, there was no difference in hypertension diagnosis (p = 0.97) or progression to ESRD (p = 0.79) according to affected parent sex; however, participants with an affected mother were more likely to die than participants with an affected father (p father (p < 0.01) but not when the affected parent was the mother (p ≥ 0.11). Our results are largely in contrast to the hypothesis that severity of ADPKD is worse with maternal inheritance of disease.
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Diagnostic value of proton MR spectroscopy and diffusion-weighted MR imaging in childhood inherited neurometabolic brain diseases and review of the literature

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Cakmakci, Handan, E-mail: handan.cakmakci@deu.edu.t [Dokuz Eylul University Faculty of Medicine, Department of Radiology, Izmir (Turkey); Pekcevik, Yeliz [Dokuz Eylul University Faculty of Medicine, Department of Radiology, Izmir (Turkey); Yis, Uluc [Dokuz Eylul University Faculty of Medicine, Department of Pediatric Neurology, Izmir (Turkey); Unalp, Aycan [Behcet Uz Hospital, Department of Pediatric Neurology, Izmir (Turkey); Kurul, Semra [Dokuz Eylul University Faculty of Medicine, Department of Pediatric Neurology, Izmir (Turkey)

2010-06-15

The purpose of this study is to evaluate parenchymal diffusion properties and metabolite ratios in affected brain tissues of inherited neurometabolic brain diseases with an overview of the current literature about the diagnostic data of both techniques in childhood inherited metabolic brain diseases. The study group was consisting, 19 patients (15 males, 4 females; mean age, 54 months (4.5 years); age range, 1-171 months (14.25 years)) diagnosed with inherited neurometabolic brain disease. Single- and multivoxel proton MRS was carried out and NAA/Cr, Cho/Cr, mI/Cr, Glx/Cr ratios were calculated. Presence of lactate peak and abnormal different peaks were noted. ADC values were calculated from brain lesions. Results are compared with age and sex matched normal subjects. Elevated NAA/Cr ratio (Canavan disease), galactitol peak (galactosemia) at 3.7 ppm, branched chain amino acids (Maple syrup urine disease-MSUD) at 0.9 ppm were seen on different diseases. In Leigh disease and MSUD restricted diffusion was detected. Different diffusion properties were seen only in one Glutaric aciduria lesions. NAA/Cr ratios and calculated ADC values were significantly different from normal subjects (p < 0.05). DWI combined with MRS are complementary methods to routine cranial MRI for evaluating neurometabolic diseases which can give detailed information about neurochemistry of affected brain areas.

Diagnostic value of proton MR spectroscopy and diffusion-weighted MR imaging in childhood inherited neurometabolic brain diseases and review of the literature

International Nuclear Information System (INIS)

Cakmakci, Handan; Pekcevik, Yeliz; Yis, Uluc; Unalp, Aycan; Kurul, Semra

2010-01-01

The purpose of this study is to evaluate parenchymal diffusion properties and metabolite ratios in affected brain tissues of inherited neurometabolic brain diseases with an overview of the current literature about the diagnostic data of both techniques in childhood inherited metabolic brain diseases. The study group was consisting, 19 patients (15 males, 4 females; mean age, 54 months (4.5 years); age range, 1-171 months (14.25 years)) diagnosed with inherited neurometabolic brain disease. Single- and multivoxel proton MRS was carried out and NAA/Cr, Cho/Cr, mI/Cr, Glx/Cr ratios were calculated. Presence of lactate peak and abnormal different peaks were noted. ADC values were calculated from brain lesions. Results are compared with age and sex matched normal subjects. Elevated NAA/Cr ratio (Canavan disease), galactitol peak (galactosemia) at 3.7 ppm, branched chain amino acids (Maple syrup urine disease-MSUD) at 0.9 ppm were seen on different diseases. In Leigh disease and MSUD restricted diffusion was detected. Different diffusion properties were seen only in one Glutaric aciduria lesions. NAA/Cr ratios and calculated ADC values were significantly different from normal subjects (p < 0.05). DWI combined with MRS are complementary methods to routine cranial MRI for evaluating neurometabolic diseases which can give detailed information about neurochemistry of affected brain areas.

Sex determination using free fetal DNA in early pregnancy: With the approach to sex linked recessive disorders

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Amir Monfaredan

2017-03-01

Full Text Available Introduction: Prenatal diagnosis is testing for detection of diseases or conditions in a fetus or embryo before it is born. Most of prenatal diagnostic (PD techniques are invasive and done in late stages of pregnancy. Using fetal DNA in maternal blood for fetal sex determination in early pregnancy might help in management of X-linked genetic diseases. This study aimed to investigate the accuracy of sex determination using fetal DNA in maternal blood at 8-12 weeks of gestation. Methods: In this cross-sectional study, 30 pregnant women at 8-12 weeks of gestation were enrolled. The sex-determining region Y (SRY gene expression with the internal control (IC glyceraldehyde 3-phosphate dehydrogenase (GAPDH was investigated with quantitative real-time polymerase chain reaction (PCR using specific primers and probes. Results: Accuracy of sex determination with SRY gene expression in 8-12 weeks of pregnancy were 85%, 85%, 90% and 100% respectively. Conclusion: It seems that fetal sex determining using fetal DNA in maternal blood is a reliable method for early stage of pregnancy.

Genetic testing and counselling in inherited eye disease

DEFF Research Database (Denmark)

Brøndum-Nielsen, Karen; Jensen, Hanne; Timshel, Susanne

2013-01-01

Advances in genetics have made genetic testing in patients with inherited eye disease increasingly accessible, and the initiation of clinical intervention trials makes it increasingly clinically relevant. Based on a multidisciplinary collaboration between ophthalmologists and clinical geneticists...

Inherited Retinal Degenerative Disease Clinical Trial Network. Addendum

Science.gov (United States)

2010-10-01

Stargardt disease, and Usher syndrome represent the predominant forms of inherited orphan retinal degenerative diseases and are estimated to affect...working with Oxford Biomedica and a separate project with academic investigators on gene therapy for Usher lb syndrome (deaf-blindness due to a gene...s. The NEER Network will also develop standard protocols for data collection, mainta i n and expand patient databases, classified by genotype and

Hypoglycaemia related to inherited metabolic diseases in adults

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Douillard Claire

2012-05-01

Full Text Available Abstract In non-diabetic adult patients, hypoglycaemia may be related to drugs, critical illness, cortisol or glucagon insufficiency, non-islet cell tumour, insulinoma, or it may be surreptitious. Nevertheless, some hypoglycaemic episodes remain unexplained, and inborn errors of metabolism (IEM should be considered, particularly in cases of multisystemic involvement. In children, IEM are considered a differential diagnosis in cases of hypoglycaemia. In adulthood, IEM-related hypoglycaemia can persist in a previously diagnosed childhood disease. Hypoglycaemia may sometimes be a presenting sign of the IEM. Short stature, hepatomegaly, hypogonadism, dysmorphia or muscular symptoms are signs suggestive of IEM-related hypoglycaemia. In both adults and children, hypoglycaemia can be clinically classified according to its timing. Postprandial hypoglycaemia can be an indicator of either endogenous hyperinsulinism linked to non-insulinoma pancreatogenic hypoglycaemia syndrome (NIPHS, unknown incidence in adults or very rarely, inherited fructose intolerance. Glucokinase-activating mutations (one family are the only genetic disorder responsible for NIPH in adults that has been clearly identified so far. Exercise-induced hyperinsulinism is linked to an activating mutation of the monocarboxylate transporter 1 (one family. Fasting hypoglycaemia may be caused by IEM that were already diagnosed in childhood and persist into adulthood: glycogen storage disease (GSD type I, III, 0, VI and IX; glucose transporter 2 deficiency; fatty acid oxidation; ketogenesis disorders; and gluconeogenesis disorders. Fasting hypoglycaemia in adulthood can also be a rare presenting sign of an IEM, especially in GSD type III, fatty acid oxidation [medium-chain acyl-CoA dehydrogenase (MCAD, ketogenesis disorders (3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA lyase deficiency, and gluconeogenesis disorders (fructose-1,6-biphosphatase deficiency].

Inheritance-mode specific pathogenicity prioritization (ISPP) for human protein coding genes.

Science.gov (United States)

Hsu, Jacob Shujui; Kwan, Johnny S H; Pan, Zhicheng; Garcia-Barcelo, Maria-Mercè; Sham, Pak Chung; Li, Miaoxin

2016-10-15

Exome sequencing studies have facilitated the detection of causal genetic variants in yet-unsolved Mendelian diseases. However, the identification of disease causal genes among a list of candidates in an exome sequencing study is still not fully settled, and it is often difficult to prioritize candidate genes for follow-up studies. The inheritance mode provides crucial information for understanding Mendelian diseases, but none of the existing gene prioritization tools fully utilize this information. We examined the characteristics of Mendelian disease genes under different inheritance modes. The results suggest that Mendelian disease genes with autosomal dominant (AD) inheritance mode are more haploinsufficiency and de novo mutation sensitive, whereas those autosomal recessive (AR) genes have significantly more non-synonymous variants and regulatory transcript isoforms. In addition, the X-linked (XL) Mendelian disease genes have fewer non-synonymous and synonymous variants. As a result, we derived a new scoring system for prioritizing candidate genes for Mendelian diseases according to the inheritance mode. Our scoring system assigned to each annotated protein-coding gene (N = 18 859) three pathogenic scores according to the inheritance mode (AD, AR and XL). This inheritance mode-specific framework achieved higher accuracy (area under curve  = 0.84) in XL mode. The inheritance-mode specific pathogenicity prioritization (ISPP) outperformed other well-known methods including Haploinsufficiency, Recessive, Network centrality, Genic Intolerance, Gene Damage Index and Gene Constraint scores. This systematic study suggests that genes manifesting disease inheritance modes tend to have unique characteristics. ISPP is included in KGGSeq v1.0 (http://grass.cgs.hku.hk/limx/kggseq/), and source code is available from (https://github.com/jacobhsu35/ISPP.git). mxli@hku.hkSupplementary information: Supplementary data are available at Bioinformatics online. © The Author

Psychosocial impact of inherited and autoimmune blistering diseases

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Swaranjali V. Jain, B Med Sci (Hons MD

2018-03-01

Full Text Available Inherited and autoimmune blistering diseases are rare, chronic, and often severe disorders that have the potential to significantly affect patients’ quality of life. The effective management of these conditions requires consideration of the physical, emotional, and social aspects of the disease. Self-esteem is integral to patients’ ability to cope with their illness, participate in treatment, and function in society. This article discusses quality-of-life studies of patients with blistering diseases with a particular focus on self-esteem issues that patients may face.

Atypical mitochondrial inheritance patterns in eukaryotes.

Science.gov (United States)

Breton, Sophie; Stewart, Donald T

2015-10-01

Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

Establishment and evolution of the Australian Inherited Retinal Disease Register and DNA Bank.

Science.gov (United States)

De Roach, John N; McLaren, Terri L; Paterson, Rachel L; O'Brien, Emily C; Hoffmann, Ling; Mackey, David A; Hewitt, Alex W; Lamey, Tina M

2013-07-01

Inherited retinal disease represents a significant cause of blindness and visual morbidity worldwide. With the development of emerging molecular technologies, accessible and well-governed repositories of data characterising inherited retinal disease patients is becoming increasingly important. This manuscript introduces such a repository. Participants were recruited from the Retina Australia membership, through the Royal Australian and New Zealand College of Ophthalmologists, and by recruitment of suitable patients attending the Sir Charles Gairdner Hospital visual electrophysiology clinic. Four thousand one hundred ninety-three participants were recruited. All participants were members of families in which the proband was diagnosed with an inherited retinal disease (excluding age-related macular degeneration). Clinical and family information was collected by interview with the participant and by examination of medical records. In 2001, we began collecting DNA from Western Australian participants. In 2009 this activity was extended Australia-wide. Genetic analysis results were stored in the register as they were obtained. The main outcome measurement was the number of DNA samples (with associated phenotypic information) collected from Australian inherited retinal disease-affected families. DNA was obtained from 2873 participants. Retinitis pigmentosa, Stargardt disease and Usher syndrome participants comprised 61.0%, 9.9% and 6.4% of the register, respectively. This resource is a valuable tool for investigating the aetiology of inherited retinal diseases. As new molecular technologies are translated into clinical applications, this well-governed repository of clinical and genetic information will become increasingly relevant for tasks such as identifying candidates for gene-specific clinical trials. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

Understanding of and attitudes to genetic testing for inherited retinal disease: a patient perspective.

Science.gov (United States)

Willis, T A; Potrata, B; Ahmed, M; Hewison, J; Gale, R; Downey, L; McKibbin, M

2013-09-01

The views of people with inherited retinal disease are important to help develop health policy and plan services. This study aimed to record levels of understanding of and attitudes to genetic testing for inherited retinal disease, and views on the availability of testing. Telephone questionnaires comprising quantitative and qualitative items were completed with adults with inherited retinal disease. Participants were recruited via postal invitation (response rate 48%), approach at clinic or newsletters of relevant charitable organisations. Questionnaires were completed with 200 participants. Responses indicated that participants' perceived understanding of genetic testing for inherited retinal disease was variable. The majority (90%) considered testing to be good/very good and would be likely to undergo genetic testing (90%) if offered. Most supported the provision of diagnostic (97%) and predictive (92%) testing, but support was less strong for testing as part of reproductive planning. Most (87%) agreed with the statement that testing should be offered only after the individual has received genetic counselling from a professional. Subgroup analyses revealed differences associated with participant age, gender, education level and ethnicity (p<0.02). Participants reported a range of perceived benefits (eg, family planning, access to treatment) and risks (eg, impact upon family relationships, emotional consequences). Adults with inherited retinal disease strongly support the provision of publicly funded genetic testing. Support was stronger for diagnostic and predictive testing than for testing as part of reproductive planning.

Primer in Genetics and Genomics, Article 4-Inheritance Patterns.

Science.gov (United States)

Aiello, Lisa B; Chiatti, Beth Desaretz

2017-07-01

Since the completion of the Human Genome Project, much has been uncovered about inheritance of various illnesses and disorders. There are two main types of inheritance: Mendelian and non-Mendelian. Mendelian inheritance includes autosomal dominant, autosomal recessive, X-linked, and Y-linked inheritance. Non-Mendelian inheritance includes mitochondrial and multifactorial inheritance. Nurses must understand the types of inheritance in order to identify red flags that may indicate the possibility of a hereditary disorder in a patient or family.

Data Mining and Pattern Recognition Models for Identifying Inherited Diseases: Challenges and Implications

OpenAIRE

Iddamalgoda, Lahiru; Das, Partha S.; Aponso, Achala; Sundararajan, Vijayaraghava S.; Suravajhala, Prashanth; Valadi, Jayaraman K.

2016-01-01

Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how the genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately prioritizing the single nucleotide polymorphisms (SNP) associated with the disease. In this commentary, we review the state-of-art data mining and pattern recognition models for identifying inherited ...

Epigenetic modification and inheritance in sexual reversal of fish.

Science.gov (United States)

Shao, Changwei; Li, Qiye; Chen, Songlin; Zhang, Pei; Lian, Jinmin; Hu, Qiaomu; Sun, Bing; Jin, Lijun; Liu, Shanshan; Wang, Zongji; Zhao, Hongmei; Jin, Zonghui; Liang, Zhuo; Li, Yangzhen; Zheng, Qiumei; Zhang, Yong; Wang, Jun; Zhang, Guojie

2014-04-01

Environmental sex determination (ESD) occurs in divergent, phylogenetically unrelated taxa, and in some species, co-occurs with genetic sex determination (GSD) mechanisms. Although epigenetic regulation in response to environmental effects has long been proposed to be associated with ESD, a systemic analysis on epigenetic regulation of ESD is still lacking. Using half-smooth tongue sole (Cynoglossus semilaevis) as a model-a marine fish that has both ZW chromosomal GSD and temperature-dependent ESD-we investigated the role of DNA methylation in transition from GSD to ESD. Comparative analysis of the gonadal DNA methylomes of pseudomale, female, and normal male fish revealed that genes in the sex determination pathways are the major targets of substantial methylation modification during sexual reversal. Methylation modification in pseudomales is globally inherited in their ZW offspring, which can naturally develop into pseudomales without temperature incubation. Transcriptome analysis revealed that dosage compensation occurs in a restricted, methylated cytosine enriched Z chromosomal region in pseudomale testes, achieving equal expression level in normal male testes. In contrast, female-specific W chromosomal genes are suppressed in pseudomales by methylation regulation. We conclude that epigenetic regulation plays multiple crucial roles in sexual reversal of tongue sole fish. We also offer the first clues on the mechanisms behind gene dosage balancing in an organism that undergoes sexual reversal. Finally, we suggest a causal link between the bias sex chromosome assortment in the offspring of a pseudomale family and the transgenerational epigenetic inheritance of sexual reversal in tongue sole fish.

Genetic evaluation of Addison's disease in the Portuguese Water Dog.

Science.gov (United States)

Oberbauer, A M; Bell, J S; Belanger, J M; Famula, T R

2006-05-02

Addison's disease, also known as hypoadrenocorticism, has been reported in many individual dogs, although some breeds exhibit a greater incidence than the population as a whole. Addison's is presumed to be an autoimmune mediated hereditary defect but the mode of inheritance remains unclear. In particular, the heritability and mode of inheritance have not been defined for the Portuguese Water Dog although Addison's is known to be prevalent in the breed. The analyses present clear evidence that establishes Addison's disease as an inherited disorder in the Portuguese Water Dog with an estimate of heritability of 0.49 (+/- 0.16); there were no differences in risk for disease across sexes (p > 0.49). Further, the complex segregation analysis provides suggestive evidence that Addison's disease in the Portuguese Water Dog is inherited under the control of a single, autosomal recessive locus. The high heritability and mode of inheritance of Addison's disease in the Portuguese Water Dog should enable the detection of segregating markers in a genome-wide scan and the identification of a locus linked to Addison's. Though the confirmation of Addison's disease as an autosomal recessive disorder must wait until the gene is identified, breeders of these dogs may wish to keep the present findings in mind as they plan their breeding programs to select against producing affected dogs.

Genetic evaluation of Addison's disease in the Portuguese Water Dog

Directory of Open Access Journals (Sweden)

Belanger JM

2006-05-01

Full Text Available Abstract Background Addison's disease, also known as hypoadrenocorticism, has been reported in many individual dogs, although some breeds exhibit a greater incidence than the population as a whole. Addison's is presumed to be an autoimmune mediated hereditary defect but the mode of inheritance remains unclear. In particular, the heritability and mode of inheritance have not been defined for the Portuguese Water Dog although Addison's is known to be prevalent in the breed. Results The analyses present clear evidence that establishes Addison's disease as an inherited disorder in the Portuguese Water Dog with an estimate of heritability of 0.49 (± 0.16; there were no differences in risk for disease across sexes (p > 0.49. Further, the complex segregation analysis provides suggestive evidence that Addison's disease in the Portuguese Water Dog is inherited under the control of a single, autosomal recessive locus. Conclusion The high heritability and mode of inheritance of Addison's disease in the Portuguese Water Dog should enable the detection of segregating markers in a genome-wide scan and the identification of a locus linked to Addison's. Though the confirmation of Addison's disease as an autosomal recessive disorder must wait until the gene is identified, breeders of these dogs may wish to keep the present findings in mind as they plan their breeding programs to select against producing affected dogs.

Non-genomic transgenerational inheritance of disease risk.

Science.gov (United States)

Gluckman, Peter D; Hanson, Mark A; Beedle, Alan S

2007-02-01

That there is a heritable or familial component of susceptibility to chronic non-communicable diseases such as type 2 diabetes, obesity and cardiovascular disease is well established, but there is increasing evidence that some elements of such heritability are transmitted non-genomically and that the processes whereby environmental influences act during early development to shape disease risk in later life can have effects beyond a single generation. Such heritability may operate through epigenetic mechanisms involving regulation of either imprinted or non-imprinted genes but also through broader mechanisms related to parental physiology or behaviour. We review evidence and potential mechanisms for non-genomic transgenerational inheritance of 'lifestyle' disease and propose that the 'developmental origins of disease' phenomenon is a maladaptive consequence of an ancestral mechanism of developmental plasticity that may have had adaptive value in the evolution of generalist species such as Homo sapiens. Copyright 2007 Wiley Periodicals, Inc.

Malformations among 289,365 Births Attributed to Mutations with Autosomal Dominant and Recessive and X-Linked Inheritance.

Science.gov (United States)

Toufaily, M Hassan; Westgate, Marie-Noel; Nasri, Hanah; Holmes, Lewis B

2018-01-01

The number of malformations attributed to mutations with autosomal or X-linked patterns of inheritance has increased steadily since the cataloging began in the 1960s. These diagnoses have been based primarily on the pattern of phenotypic features among close relatives. A malformations surveillance program conducted in consecutive pregnancies can identify both known and "new" hereditary disorders. The Active Malformations Surveillance Program was carried out among 289,365 births over 41 years (1972-2012) at Brigham and Women's Hospital in Boston. The findings recorded by examining pediatricians and all consultants were reviewed by study clinicians to establish the most likely diagnoses. The findings in laboratory testing in the newborn period were reviewed, as well. One hundred ninety-six (0.06%) infants among 289,365 births had a malformation or malformation syndrome that was attributed to Mendelian inheritance. A total of 133 (68%) of the hereditary malformations were attributed to autosomal dominant inheritance, with 94 (71%) attributed to apparent spontaneous mutations. Forty-six (23%) were attributed to mutations with autosomal recessive inheritance, 17 associated with consanguinity. Seventeen (9%) were attributed to X-linked inheritance. Fifteen novel familial phenotypes were identified. The family histories showed that most (53 to 71%) of the affected infants were born, as a surprise, to healthy, unaffected parents. It is important for clinicians to discuss with surprised healthy parents how they can have an infant with an hereditary condition. Future studies, using DNA samples from consecutive populations of infants with malformations and whole genome sequencing, will identify many more mutations in loci associated with mendelizing phenotypes. Birth Defects Research 110:92-97, 2018.© 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

X-Linked Lymphoproliferative Disease (XLP)

Science.gov (United States)

... Primary Immune Deficiency Diseases (PIDDs) Primary Immune Deficiency Diseases (PIDDs) Types of PIDDs Genetics & Inheritance Talking to Your Doctor XLP primarily affects boys, and is characterized by a life-long vulnerability to Epstein-Barr virus (EBV), a common type of herpes virus ...

Simultaneous Occurence of an Autosomal Dominant Inherited MSX1 Mutation and an X-linked Recessive Inherited EDA Mutation in One Chinese Family with Non-syndromic Oligodontia.

Science.gov (United States)

Zhang, Xiao Xia; Wong, Sing Wai; Han, Dong; Feng, Hai Lan

2015-01-01

To describe the simultaneous occurence of an autosomal dominant inherited MSX1 mutation and an X-linked recessive inherited EDA mutation in one Chinese family with nonsyndromic oligodontia. Clinical data of characteristics of tooth agenesis were collected. MSX1 and EDA gene mutations were detected in a Chinese family of non-syndromic oligodontia. Mild hypodontia in the parents and severe oligodontia in the son was recorded. A novel missense heterozygous mutation c.517C>A (p.Arg173Ser) was detected in the MSX1 gene in the boy and the father. A homozygous missense mutation c.1001G>A (p.Arg334His) was detected in the EDA gene in the boy and the same mutant occurred heterozygously in the mother. Simultaneous occurence of two different gene mutations with different inheritence patterns, which both caused oligodontia, which occurred in one subject and in one family, was reported.

Adaptive optics imaging of inherited retinal diseases.

Science.gov (United States)

Georgiou, Michalis; Kalitzeos, Angelos; Patterson, Emily J; Dubra, Alfredo; Carroll, Joseph; Michaelides, Michel

2017-11-15

Adaptive optics (AO) ophthalmoscopy allows for non-invasive retinal phenotyping on a microscopic scale, thereby helping to improve our understanding of retinal diseases. An increasing number of natural history studies and ongoing/planned interventional clinical trials exploit AO ophthalmoscopy both for participant selection, stratification and monitoring treatment safety and efficacy. In this review, we briefly discuss the evolution of AO ophthalmoscopy, recent developments and its application to a broad range of inherited retinal diseases, including Stargardt disease, retinitis pigmentosa and achromatopsia. Finally, we describe the impact of this in vivo microscopic imaging on our understanding of disease pathogenesis, clinical trial design and outcome metrics, while recognising the limitation of the small cohorts reported to date. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Environmentally induced epigenetic transgenerational inheritance of altered Sertoli cell transcriptome and epigenome: molecular etiology of male infertility.

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Carlos Guerrero-Bosagna

Full Text Available Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell that influences the onset of a specific disease (male infertility. A gestating female rat (F0 generation was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, enhanced spermatogenic cell apoptosis was observed. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific cellular pathways were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR modified. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell epigenome and transcriptome that correlates with adult onset disease (male infertility. The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility.

[Identification of the genetic sex chromosomes in the monogenic blowfly Chrysomya rufifacies (Calliphoridae, Diptera)].

Science.gov (United States)

Ullerich, F H

1975-01-01

Previous investigations have shown the sex determination in the monogenic blowfly Chrysomya rufifacies to be controlled by a cytologically not discernible homogametry-heterogamety mechanism in the female. Female-producing (thelygenic) females are assumed to be heterozygous for a dominant female sex realizer (F') with sex-predetermining properties, while male-producing (arrhenogenic) females as well as males are supposed to be homozygous for the recessive allele (f). In order to identify the genetic sex chromosomes of C. rufifacies among its five pairs of long euchromatic chromosomes (nos. 1-5) plus one pair of small heterochromatic ones (no. 6), all chromosomes were marked by reciprocal translocations induced by X-ray treatment of adult males. The inheritance of thirteen different heteroxygous translocations has been analyzed. All of the translocations (eleven) between two of the four longer chromosomes did not show sex-linked inheritance, thus demonstrating the autosomal character of the chromosomes nos 1, 2, 3 and 4. The same is true for the translocation T6 (2/6). Therefore the small heterochromatic chromosome no. 6, corresponding to the morphlogically differentiated six chromosomes within the amphogenic calliphorid species, remains without sex determining function in the monogenic fly. This could be confirmed by the analysis of monosomic (monosomy-6) and trisomic (trisomy-6) individuals, which resulted from meiotic non-disfunction in T6/+ translocation heterozygotes. Contrary to these translocations, the heteroxygous 5/2 translocation (T14) exhibited sex-linked inheritance: There was but a very low frequency (0,76 per cent) of recombinants resulting from crossing-over between F'/f and the translocation breakage point in theylgenic F1 T14/+females. The sex-linked inheritance of T14 was confirmed by the progeny of a thelygenic F1 T14/+ female crossed to a homozygous T14/T14 translocation male.Among the offspring of that F1 T14/+ female, which had received the

[Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

Science.gov (United States)

Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

2017-02-10

Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

[Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart disease.

DEFF Research Database (Denmark)

Holst, Anders Gaarsdal; Tfelt-Hansen, 1jacob; Olesen, Morten S

2010-01-01

Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart disease, which can lead to life-threatening ventricular arrhythmias in patients with a structurally normal heart. The age of onset is usually between two and 12 years and the initial symptom is frequently syncope...

One and a half million medical papers reveal a link between author gender and attention to gender and sex analysis

DEFF Research Database (Denmark)

Nielsen, Mathias Wullum; Andersen, Jens Peter; Schiebinger, Londa

2017-01-01

Gender and sex analysis is increasingly recognized as a key factor in creating better medical research and health care. Using a sample of more than 1.5 million medical research papers, our study examined the potential link between women’s participation in medical science and attention to gender......-related and sex-related factors in disease-specific research. Adjusting for variations across countries, disease topics and medical research areas, we compared the participation of women authors in studies that do and do not involve gender and sex analysis. Overall, our results show a robust positive correlation...... between women’s authorship and the likelihood of a study including gender and sex analysis. These findings corroborate discussions of how women’s participation in medical science links to research outcomes, and show the mutual benefits of promoting both the scientific advancement of women...

Evaluation of Inheritance Pattern in Mentally Retarded Children

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F Behnaz

2011-07-01

Full Text Available Introduction: Mental retardation is one of the most important problems of general health. The purpose of this study was to evaluate inheritance pattern of mentally retarded patients in Yazd city. Methods: In a descriptive cross- sectional study, all medical records and pedigrees of 320 mentally retarded children whose parents had referred for genetic consultation to the Welfare center of Yazd city were reviewed. Results: Of the total, 62.8% of the parents had consanguineous marriage. Mean inbreeding coefficient of offsprings was 0.0713 in third degree related parents versus 0.0156 in non-related parents. Mental retardation was seen in 43.4% of first– degree relatives of children (6.6% of parents and 36.8% of siblings, respectively. Frequency of mental retardation did not differ significantly in both sexes. Pedigree showed inheritance pattern in 43.4% of patients (autosomal recessive, autosomal dominant and x-linked inheritance pattern were seen in 33.75%, 6.9% and 2.8%, respectively, while 37% of patients had no definite inheritance pattern. Abnormal karyotype were seen in 19.4% of patients, 28 of whom(8.75% of all patients had Down syndrome. The prevalence of autosomal recessive inheritance in patients with consanguineous marriages and non family marriages was 62.8 % and 10%, respectively (P=0. 002. Conclusion: Since multiple cases of mental retardation were seen in families and rate of consanguineous marriage was more in parents of mentally retarded children, genetic counseling in consanguinity marriages and families of mentally retarded children can prevent incidence of mental retardation in these families.

Data Mining and Pattern Recognition Models for Identifying Inherited Diseases: Challenges and Implications.

Science.gov (United States)

Iddamalgoda, Lahiru; Das, Partha S; Aponso, Achala; Sundararajan, Vijayaraghava S; Suravajhala, Prashanth; Valadi, Jayaraman K

2016-01-01

Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how the genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately prioritizing the single nucleotide polymorphisms (SNP) associated with the disease. In this commentary, we review the state-of-art data mining and pattern recognition models for identifying inherited diseases and deliberate the need of binary classification- and scoring-based prioritization methods in determining causal variants. While we discuss the pros and cons associated with these methods known, we argue that the gene prioritization methods and the protein interaction (PPI) methods in conjunction with the K nearest neighbors' could be used in accurately categorizing the genetic factors in disease causation.

Data mining and Pattern Recognizing Models for Identifying Inherited Diseases: Challenges and Implications

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Lahiru Iddamalgoda

2016-08-01

Full Text Available Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately determining the responsible genetic factors for prioritizing the single nucleotide polymorphisms (SNP associated with the disease. In this commentary, we review the state-of-art data mining and pattern recognition models for identifying inherited diseases and deliberate the need of binary classification and scoring based prioritization methods for determining causal variants. While we discuss the pros and cons associated with these methods known, we argue that the gene prioritization methods and the protein interaction (PPI methods in conjunction with the K nearest neighbors’ could be used in accurately categorizing the genetic factors in disease causation

Autosomal dominant inheritance Caffey-Silverman disease hyperostosis corticalis infantum

International Nuclear Information System (INIS)

Rogoyski, A.; Jakubowska, K.; Tronowska, T.D.

1984-01-01

A case of Caffey-Silverman disease is described in an infant aged 4.5 months. The case was erroneously diagnosed in the initial stage of the disease as osteitis. The correct diagnosis was established after radiological examination of the skeleton. The pathological lesions involved the mandible, both clavicles, all ribs, left shoulder blade, both radial bones and left ulna. Follow-up radiological examination after 12 months demonstrated nearly complete disappearance of the previously observed skeletal changes. At the age of 18 months the condition of the child was good and its development was normal. Radiological changes indicating past Caffey-Silverman disease were disclosed in the mother and maternal grandmother of the child. This indicates an autosomal dominant type of inheritance of the disease. (Author)

Inherited metabolic liver diseases in infants and children: an overview

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Ivo Barić

2013-10-01

Full Text Available Inborn errors of metabolism, which affect the liver are a large, continuously increasing group of diseases. Their clinical onset can occur at any age, from intrauterine period presenting as liver failure already at birth to late adulthood. Inherited metabolic disorders must be considered in differential diagnosis of every unexplained liver disease. Specific diagnostic work-up for either their confirmation or exclusion should start immediately since any postponing can result in delayed diagnosis and death or irreversible disability. This can be particularly painful while many inherited metabolic liver diseases are relatively easily treatable if diagnosed on time, for instance galactosemia or hereditary fructose intolerance by simple dietary means. Any unexplained liver disease, even one looking initially benign, should be considered as a potential liver failure and therefore should deserve proper attention. Diagnosis in neonates is additionally complicated because of the factors which can mask liver disease, such as physiological neonatal jaundice, normally relatively enlarged liver and increased transaminases at that age. In everyday practice, in order to reveal the etiology, it is useful to classify and distinguish some clinical patterns which, together with a few routine, widely available laboratory tests (aminotransferases, prothrombine time, albumin, gammaGT, total and conjugated bilirubin, ammonia, alkaline phosphatase and glucose make the search for the cause much easier. These patterns are isolated hyperbilirubinemia, syndrome of cholestasis in early infancy, hepatocellular jaundice, Reye syndrome, portal cirrhosis and isolated hepatomegaly. Despite the fact that some diseases can present with more than one pattern (for instance, alpha-1-antitrypsin deficiency as infantile cholestasis, but also as hepatocellular jaundice, and that in some disesases one pattern can evolve into another (for instance, Wilson disease from hepatocellular

Different perspectives on the sex-attachment link: towards an emotion-motivational account.

Science.gov (United States)

Dewitte, Marieke

2012-01-01

Although the link between sex and attachment was made decades ago (Hazan & Shaver, 1987), theories on sexual and attachment functioning have been developed in relative isolation. Recent efforts to integrate both literatures have been complicated by the fact that the sex-attachment link has been approached from very different perspectives, including biological, evolutionary, developmental, cognitive, and social psychology approaches. Also, at the empirical level, research on sex and attachment lacks overarching synthesis. This article gives an overview of the most important theoretical ideas and empirical insights on sex and attachment. It starts with describing general models that approach the sex-attachment link from an evolutionary and neurobiological perspective. Then, it summarizes theoretical and empirical ideas of attachment theory and describes how attachment style differences are manifested in intimate and sexual relationships. Research so far has been limited to studying the predicted link between sex and attachment in terms of broad descriptives, and it would benefit the literature to specify the processes and pathways that mediate the sex-attachment link. After a short discussion of the functional similarities between the sexual and the attachment systems, the article describes some specific--dynamical--models that focus on the emotional and cognitive-motivational processes through which attachment schemas influence sexual experiences. Such an emotion-motivational perspective on sex and attachment can help to organize theoretical ideas and empirical findings and eventually promote an integrative view on how attachment dynamics can interact with sexual experiences.

The ethical framework for performing research with rare inherited neurometabolic disease patients.

Science.gov (United States)

Giannuzzi, Viviana; Devlieger, Hugo; Margari, Lucia; Odlind, Viveca Lena; Ragab, Lamis; Bellettato, Cinzia Maria; D'Avanzo, Francesca; Lampe, Christina; Cassis, Linda; Cortès-Saladelafont, Elisenda; Cazorla, Ángels Garcia; Barić, Ivo; Cvitanović-Šojat, Ljerka; Fumić, Ksenija; Dali, Christine I; Bartoloni, Franco; Bonifazi, Fedele; Scarpa, Maurizio; Ceci, Adriana

2017-03-01

The need for performing clinical trials to develop well-studied and appropriate medicines for inherited neurometabolic disease patients faces ethical concerns mainly raising from four aspects: the diseases are rare; include young and very young patients; the neurological impairment may compromise the capability to provide 'consent'; and the genetic nature of the disease leads to further ethical implications. This work is intended to identify the ethical provisions applicable to clinical research involving these patients and to evaluate if these cover the ethical issues. Three searches have been performed on the European regulatory/legal framework, the literature and European Union-funded projects. The European legal framework offers a number of ethical provisions ruling the clinical research on paediatric, rare, inherited diseases with neurological symptoms. In the literature, relevant publications deal with informed consent, newborn genetic screenings, gene therapy and rights/interests of research participants. Additional information raised from European projects on sharing patients' data from different countries, the need to fill the gap of the regulatory framework and to improve information to stakeholders and patients/families. Several recommendations and guidelines on ethical aspects are applicable to the inherited neurometabolic disease research in Europe, even though they suffer from the lack of a common ethical approach. What is Known: • When planning and conducting clinical trials, sponsors and researchers know that clinical trials are to be performed according to well-established ethical rules, and patients should be aware about their rights. • In the cases of paediatric patients, vulnerable patients unable to provide consent, genetic diseases' further rules apply. What is New: • This work discusses which ethical rules apply to ensure protection of patient's rights if all the above-mentioned features coexist. • This work shows available data and

Inherited Disease Genetics Improves the Identification of Cancer-Associated Genes.

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Boyang Zhao

2016-06-01

Full Text Available The identification of biologically significant variants in cancer genomes is critical to therapeutic discovery, but it is limited by the statistical power needed to discern driver from passenger. Independent biological data can be used to filter cancer exomes and increase statistical power. Large genetic databases for inherited diseases are uniquely suited to this task because they contain specific amino acid alterations with known pathogenicity and molecular mechanisms. However, no rigorous method to overlay this information onto the cancer exome exists. Here, we present a computational methodology that overlays any variant database onto the somatic mutations in all cancer exomes. We validate the computation experimentally and identify novel associations in a re-analysis of 7362 cancer exomes. This analysis identified activating SOS1 mutations associated with Noonan syndrome as significantly altered in melanoma and the first kinase-activating mutations in ACVR1 associated with adult tumors. Beyond a filter, significant variants found in both rare cancers and rare inherited diseases increase the unmet medical need for therapeutics that target these variants and may bootstrap drug discovery efforts in orphan indications.

Contribution of inherited heart disease to sudden cardiac death in childhood

NARCIS (Netherlands)

Hofman, Nynke; Tan, Hanno L.; Clur, Sally-Ann; Alders, Mariel; van Langen, Irene M.; Wilde, Arthur A. M.

2007-01-01

BACKGROUND. In children aged 1 to 18 years, the causes of sudden cardiac death may remain unresolved when autopsy results are negative. Because inherited cardiac diseases are likely, cardiologic and genetic investigations of relatives may still yield the diagnosis in these cases. Moreover, these

Disease: H01971 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available Ochs HD ... TITLE ... Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance...teropathy and X-linked inheritance. This disease is caused by mutations in FOXP3, a critical regulator of T-...ked syndrome IPEX syndrome is a fatal disorder characterized by immune dysregulation, polyendocrinopathy, en

Clinical neurogenetics: behavioral management of inherited neurodegenerative disease.

Science.gov (United States)

Wexler, Eric

2013-11-01

Psychiatric symptoms often manifest years before overt neurologic signs in patients with inherited neurodegenerative disease. The most frequently cited example of this phenomenon is the early onset of personality changes in "presymptomatic" Huntington patients. In some cases the changes in mood and cognition are even more debilitating than their neurologic symptoms. The goal of this article is to provide the neurologist with a concise primer that can be applied in a busy clinic or private practice. Copyright © 2013 Elsevier Inc. All rights reserved.

The ethical framework for performing research with rare inherited neurometabolic disease patients

OpenAIRE

Giannuzzi, Viviana; Devlieger, Hugo; Margari, Lucia; Odlind, Viveca Lena; Ragab, Lamis; Bellettato, Cinzia Maria; D?Avanzo, Francesca; Lampe, Christina; Cassis, Linda; Cort?s-Saladelafont, Elisenda; Cazorla, ?ngels Garcia; Bari?, Ivo; Cvitanovi?-?ojat, Ljerka; Fumi?, Ksenija; Dali, Christine I

2017-01-01

The need for performing clinical trials to develop well-studied and appropriate medicines for inherited neurometabolic disease patients faces ethical concerns mainly raising from four aspects: the diseases are rare; include young and very young patients; the neurological impairment may compromise the capability to provide ?consent?; and the genetic nature of the disease leads to further ethical implications. This work is intended to identify the ethical provisions applicable to clinical resea...

Maternal inheritance and mitochondrial DNA variants in familial Parkinson's disease

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Pfeiffer Ronald F

2010-04-01

Full Text Available Abstract Background Mitochondrial function is impaired in Parkinson's disease (PD and may contribute to the pathogenesis of PD, but the causes of mitochondrial impairment in PD are unknown. Mitochondrial dysfunction is recapitulated in cell lines expressing mitochondrial DNA (mtDNA from PD patients, implicating mtDNA variants or mutations, though the role of mtDNA variants or mutations in PD risk remains unclear. We investigated the potential contribution of mtDNA variants or mutations to the risk of PD. Methods We examined the possibility of a maternal inheritance bias as well as the association between mitochondrial haplogroups and maternal inheritance and disease risk in a case-control study of 168 multiplex PD families in which the proband and one parent were diagnosed with PD. 2-tailed Fisher Exact Tests and McNemar's tests were used to compare allele frequencies, and a t-test to compare ages of onset. Results The frequency of affected mothers of the proband with PD (83/167, 49.4% was not significantly different from the frequency of affected females of the proband generation (115/259, 44.4% (Odds Ratio 1.22; 95%CI 0.83 - 1.81. After correcting for multiple tests, there were no significant differences in the frequencies of mitochondrial haplogroups or of the 10398G complex I gene polymorphism in PD patients compared to controls, and no significant associations with age of onset of PD. Mitochondrial haplogroup and 10398G polymorphism frequencies were similar in probands having an affected father as compared to probands having an affected mother. Conclusions These data fail to demonstrate a bias towards maternal inheritance in familial PD. Consistent with this, we find no association of common haplogroup-defining mtDNA variants or for the 10398G variant with the risk of PD. However, these data do not exclude a role for mtDNA variants in other populations, and it remains possible that other inherited mitochondrial DNA variants, or somatic m

Validation of Ion TorrentTM Inherited Disease Panel with the PGMTM Sequencing Platform for Rapid and Comprehensive Mutation Detection

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Abeer E. Mustafa

2018-05-01

Full Text Available Quick and accurate molecular testing is necessary for the better management of many inherited diseases. Recent technological advances in various next generation sequencing (NGS platforms, such as target panel-based sequencing, has enabled comprehensive, quick, and precise interrogation of many genetic variations. As a result, these technologies have become a valuable tool for gene discovery and for clinical diagnostics. The AmpliSeq Inherited Disease Panel (IDP consists of 328 genes underlying more than 700 inherited diseases. Here, we aimed to assess the performance of the IDP as a sensitive and rapid comprehensive gene panel testing. A total of 88 patients with inherited diseases and causal mutations that were previously identified by Sanger sequencing were randomly selected for assessing the performance of the IDP. The IDP successfully detected 93.1% of the mutations in our validation cohort, achieving high overall gene coverage (98%. The sensitivity for detecting single nucleotide variants (SNVs and short Indels was 97.3% and 69.2%, respectively. IDP, when coupled with Ion Torrent Personal Genome Machine (PGM, delivers comprehensive and rapid sequencing for genes that are responsible for various inherited diseases. Our validation results suggest the suitability of this panel for use as a first-line screening test after applying the necessary clinical validation.

Validation and discovery of genotype-phenotype associations in chronic diseases using linked data.

Science.gov (United States)

Pathak, Jyotishman; Kiefer, Richard; Freimuth, Robert; Chute, Christopher

2012-01-01

This study investigates federated SPARQL queries over Linked Open Data (LOD) in the Semantic Web to validate existing, and potentially discover new genotype-phenotype associations from public datasets. In particular, we report our preliminary findings for identifying such associations for commonly occurring chronic diseases using the Online Mendelian Inheritance in Man (OMIM) and Database for SNPs (dbSNP) within the LOD knowledgebase and compare them with Gene Wiki for coverage and completeness. Our results indicate that Semantic Web technologies can play an important role for in-silico identification of novel disease-gene-SNP associations, although additional verification is required before such information can be applied and used effectively.

Non-traditional inheritance

International Nuclear Information System (INIS)

Hall, J.G.

1992-01-01

In the last few years, several non-traditional forms of inheritance have been recognized. These include mosaicism, cytoplasmic inheritance, uniparental disomy, imprinting, amplification/anticipation, and somatic recombination. Genomic imprinting (GI) is the dependence of the phenotype on the sex of the transmitting parent. GI in humans seems to involve growth, behaviour, and survival in utero. The detailed mechanism of genomic imprinting is not known, but it seems that some process is involved in turning a gene off; this probably involves two genes, one of which produces a product that turns a gene off, and the gene that is itself turned off. The process of imprinting (turning off) may be associated with methylation. Erasure of imprinting can occur, and seems to be associated with meiosis. 10 refs

Woman with x-linked recessive dystonia-parkinsonism: clue to the epidemiology of parkinsonism in Filipino women?

Science.gov (United States)

Domingo, Aloysius; Lee, Lillian V; Brüggemann, Norbert; Freimann, Karen; Kaiser, Frank J; Jamora, Roland D G; Rosales, Raymond L; Klein, Christine; Westenberger, Ana

2014-09-01

Despite recessive inheritance, X-linked dystonia-parkinsonism (Lubag disease) has also been described in women presenting with a late-onset isolated parkinsonian syndrome. Interestingly, unlike in other populations, there is a slight female predominance in the prevalence of parkinsonism in the Philippines. In a Filipino woman with suspected Parkinson disease, we confirmed the presence of all changes specific for X-linked dystonia-parkinsonism in genomic DNA. Subsequently, we analyzed complementary DNA and evaluated the methylation status of the androgen receptor gene. Owing to extremely skewed (98%:2%) X-chromosome inactivation, the patient expressed almost solely the mutated allele in a disease-specific change, rendering her molecularly comparable with a hemizygously affected man. Skewed X-chromosome inactivation is the likely cause of parkinsonism in this heterozygous mutation carrier. Because women carriers of the genetic changes specific for X-linked dystonia-parkinsonism are common in the Philippines, the epigenetic factor of nonrandom X-chromosome inactivation may contribute to the skewing of the sex prevalence of parkinsonism toward women in this country, warranting further investigation.

Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17

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Nitrini Ricardo

2001-01-01

Full Text Available OBJECTIVE: To compare the clinical features of a familial prion disease with those of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17. BACKGROUND: Prion diseases are not usually considered in the differential diagnosis of FTDP-17, since familial Creutzfeldt-Jakob disease (CJD, the most common inherited prion disease, often manifests as a rapidly progressive dementia. Conversely, FTDP-17 usually has an insidious onset in the fifth decade, with abnormal behavior and parkinsonian features. METHOD: We present the clinical features of 12 patients from a family with CJD associated with a point mutation at codon 183 of the prion protein gene. RESULTS: The mean age at onset was 44.0 ± 3.7; the duration of the symptoms until death ranged from two to nine years. Behavioral disturbances were the predominant presenting symptoms. Nine patients were first seen by psychiatrists. Eight patients manifested parkinsonian signs. CONCLUSION: These clinical features bear a considerable resemblance to those described in FTDP-17.

Guanine holes are prominent targets for mutation in cancer and inherited disease.

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Albino Bacolla

Full Text Available Single base substitutions constitute the most frequent type of human gene mutation and are a leading cause of cancer and inherited disease. These alterations occur non-randomly in DNA, being strongly influenced by the local nucleotide sequence context. However, the molecular mechanisms underlying such sequence context-dependent mutagenesis are not fully understood. Using bioinformatics, computational and molecular modeling analyses, we have determined the frequencies of mutation at G • C bp in the context of all 64 5'-NGNN-3' motifs that contain the mutation at the second position. Twenty-four datasets were employed, comprising >530,000 somatic single base substitutions from 21 cancer genomes, >77,000 germline single-base substitutions causing or associated with human inherited disease and 16.7 million benign germline single-nucleotide variants. In several cancer types, the number of mutated motifs correlated both with the free energies of base stacking and the energies required for abstracting an electron from the target guanines (ionization potentials. Similar correlations were also evident for the pathological missense and nonsense germline mutations, but only when the target guanines were located on the non-transcribed DNA strand. Likewise, pathogenic splicing mutations predominantly affected positions in which a purine was located on the non-transcribed DNA strand. Novel candidate driver mutations and tissue-specific mutational patterns were also identified in the cancer datasets. We conclude that electron transfer reactions within the DNA molecule contribute to sequence context-dependent mutagenesis, involving both somatic driver and passenger mutations in cancer, as well as germline alterations causing or associated with inherited disease.

Invited review: sex ratio and rheumatic disease.

Science.gov (United States)

Lockshin, M D

2001-11-01

Human illnesses affect men and women differently. In some cases (diseases of sex organs, diseases resulting from X or Y chromosome mutations), reasons for sex discrepancy are obvious, but in other cases no reason is apparent. Explanations for sex discrepancy of illness occur at different biological levels: molecular (e.g., imprinting, X-inactivation), cellular (sex-specific receptor activity), organ (endocrine influences), whole organism (size, age), and environmental-behavioral, including intrauterine influences. Autoimmunity represents a prototypical class of illness that has high female-to-male (F/M) ratios. Although the F/M ratios in autoimmune diseases are usually attributed to the influence of estrogenic hormones, evidence demonstrates that the attributed ratios are imprecise and that definitions and classifications of autoimmune diseases vary, rendering at least part of the counting imprecise. In addition, many studies on sex discrepancy of human disease fail to distinguish between disease incidence and disease severity. In April 2001, the Institute of Medicine of the National Academy of Sciences published Exploring the Biological Contributions to Human Health: Does Sex Matter? (Wizemann T and Pardue M-L, editors). This minireview summarizes the section of that report that concerns autoimmune and infectious disease. Some thyroid, rheumatic, and hepatic autoimmune diseases have high F/M ratios, whereas others have low. Those that have high ratios occur primarily in young adulthood. Gonadal hormones, if they play a role, likely do so through a threshold or permissive mechanism. Examples of sex differences that could be caused by environmental exposure, X inactivation, imprinting, X or Y chromosome genetic modulators, and intrauterine influences are presented as alternate, theoretical, and largely unexplored explanations for sex differences of incidence. The epidemiology of autoimmune diseases (young, female) suggests that an explanation for sex discrepancy of

Induction of inherited sterility and sex ratio distribution due to exposure to substerilising doses of gamma radiation in cotton bollworm Earias vittella fabricius

International Nuclear Information System (INIS)

Tamhankar, A.J.; Shantharam, K.

2005-01-01

Substerilising doses of gamma radiation induced inherited sterility and sex ratio distortion in the cotton bollworm Earias vittella fabricius. Adults irradiated with 75 Gy and self-crossed, provided sterile F 1 adults, suitable for direct use in sterile insect technique (SIT). In case of 50 Gy, the F 1 adults, when backcrossed, produced F 2 progeny with sex ratio in favour of females (1: >3). With 25 Gy, a sex ratio distortion was recorded in F 1 (1 male: 2.25 females) and self-crossing of F 1 resulted in progeny with a sex ratio of 3:1. Backcrossing of the F 1 female produced F 2 progeny with a sex ratio of 1:5. These results have implications in improving cost/benefit ratio of SIT for this species. (author)

[Approach of gene medical treatment in neurological diseases with the neurologist's. "Approach of support to the patients with inherited and incurable neurological diseases"].

Science.gov (United States)

Hazama, Takanori; Sawada, Jin-ichi; Toda, Tatsushi

2009-11-01

Advancements in medical genetics have increased access to genetic diagnosis in clinical neurology and accompanying genetic counseling. However, its use has not yet spread and the frequency of general biochemistry inspection in medical treatment and by patients remains low. Many problems remain for doctors, though sociocultural and other various causes exist. Thus, a network of care specialists for inherited and incurable neurological diseases has been established, consisting of multi-occupational categories in medical treatment, health, and welfare such as clinical inheritance specialists, psychiatrists, public health nurses, and medical social workers, to meet the rise in availability of such methods. Businesses in areas such as training, consultation, and field research have arisen. An educational campaign for neurologists who have taken a central role in treatment of inherited and incurable neurological diseases, and related information have been disseminated to those working in fields related to regional welfare of neurological medicine, and patients are now supported totally by team and regional counseling. These new developments in support systems for inherited and incurable neurological diseases, have steadily achieved the respective goals. We aim to promote its evolution to a more advanced network to promote the independence of individual patients in the future.

Retinal Diseases

Science.gov (United States)

... Linked Retinoschisis (XLRS) X-Linked Retinitis Pigmentosa (XLRP) Usher Syndrome Other Retinal Diseases Glossary News & Research News & Research ... central portion of the retina called the macula. Usher Syndrome Usher syndrome is an inherited condition characterized by ...

Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry.

Science.gov (United States)

Han, Lianshu; Han, Feng; Ye, Jun; Qiu, Wenjuan; Zhang, Huiwen; Gao, Xiaolan; Wang, Yu; Ji, Wenjun; Gu, Xuefan

2015-03-01

Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients. Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests. Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years. In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants. © 2014 Wiley Periodicals, Inc.

The hidden Niemann-Pick type C patient : Clinical niches for a rare inherited metabolic disease

NARCIS (Netherlands)

Hendriksz, Christian J.; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J.; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Kluenemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Bergh, Florian Then; Topcu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A.

2017-01-01

Background: Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to

A Dutch family with autosomal recessively inherited lower motor neuron predominant motor neuron disease due to optineurin mutations

NARCIS (Netherlands)

Beeldman, Emma; van der Kooi, Anneke J.; de Visser, Marianne; van Maarle, Merel C.; van Ruissen, Fred; Baas, Frank

2015-01-01

Approximately 10% of motor neuron disease (MND) patients report a familial predisposition for MND. Autosomal recessively inherited MND is less common and is most often caused by mutations in the superoxide dismutase 1 (SOD1) gene. In 2010, autosomal recessively inherited mutations in the optineurin

Conservation of Sex-Linked Markers among Conspecific Populations of a Viviparous Skink, Niveoscincus ocellatus, Exhibiting Genetic and Temperature-Dependent Sex Determination

Science.gov (United States)

Burridge, Christopher P; Ezaz, Tariq; Wapstra, Erik

2018-01-01

Abstract Sex determination systems are exceptionally diverse and have undergone multiple and independent evolutionary transitions among species, particularly reptiles. However, the mechanisms underlying these transitions have not been established. Here, we tested for differences in sex-linked markers in the only known reptile that is polymorphic for sex determination system, the spotted snow skink, Niveoscincus ocellatus, to quantify the genomic differences that have accompanied this transition. In a highland population, sex is determined genetically, whereas in a lowland population, offspring sex ratio is influenced by temperature. We found a similar number of sex-linked loci in each population, including shared loci, with genotypes consistent with male heterogamety (XY). However, population-specific linkage disequilibrium suggests greater differentiation of sex chromosomes in the highland population. Our results suggest that transitions between sex determination systems can be facilitated by subtle genetic differences. PMID:29659810

Genetics Home Reference: Fabry disease

Science.gov (United States)

... Stroke: Fabry's Disease Information Page National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet Educational Resources (8 links) Children Living With Inherited Metabolic Diseases (CLIMB) (UK): Fabry ...

Data mining and Pattern Recognizing Models for Identifying Inherited Diseases: Challenges and Implications

OpenAIRE

Lahiru Iddamalgoda; Partha Sarathi Das; Partha Sarathi Das; Achala Aponso; Vijayaraghava Seshadri Sundararajan; Prashanth Suravajhala; Prashanth Suravajhala; Prashanth Suravajhala; Jayaraman K Valadi

2016-01-01

Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately determining the responsible genetic factors for prioritizing the single nucleotide polymorphisms (SNP) associated with the disease. In this commentary, we review the state-of-art data mining and pattern r...

Sex-linked hypophosphatemia in adults: Prevalence of radiologic features

International Nuclear Information System (INIS)

Hardy, D.C.; Reid, I.R.; Whyte, M.P.; Murphy, W.A.

1987-01-01

The authors performed a retrospective radiologic review of 38 adults (23 women, 15 men; aged 17-77 years) with clinically proved sex-linked hypophosphatemia to determine the prevalence of certain radiologic features, to compare the findings in men (hemizygotes) with findings in women (heterozygotes), and to elucidate the natural history of the disease by comparing a younger group (n = 12; mean age, 18) with an older group (n = 26; mean age, 43). They found age-related diminished skeletal mass on visual and CT studies and increased numbers of bone reinforcement lines (osteopenia) and Looser zones (osteomalacia). Osteoarthritis developed in many joints (88% of the older group), including the knees (87%) ankles (78%), feet (71%), sacroiliac joints (48%), and wrists (43%). Chondrocalcinosis was uncommon. Enthesopathy was absent in the younger group but present in every member of the older group, and was often accompanied by extra ossicles (48% hands; 37% feet). Phalangeal sclerosis (9%) and spinous process bridging (4%) wre uncommon. Except for traction spurs in the older group (60%), the thoracolumbar spine was unremarkable. There was no lumbar spinal stenosis detected by either radiogrammetric or CT measurement. Curvatures of the lower extremity long bones were common in both age groups. In keeping with the mode of genetic transmission, men were more severely affected than women. The authors noted three other skeletal alterations not previously described: (1) flaring of the iliac wgins (33% of the younger group, 75% of the older group), (2) trapezoidal distal femoral condyles (67% vs. 68%), and (3) thick, flat tali (100% vs. 89%). Our study of a large population of adult subjects with sex-linked hypophosphatemia reveals a variety of progressive skeletal features

Isolation of a sex-linked DNA sequence in cranes.

Science.gov (United States)

Duan, W; Fuerst, P A

2001-01-01

A female-specific DNA fragment (CSL-W; crane sex-linked DNA on W chromosome) was cloned from female whooping cranes (Grus americana). From the nucleotide sequence of CSL-W, a set of polymerase chain reaction (PCR) primers was identified which amplify a 227-230 bp female-specific fragment from all existing crane species and some other noncrane species. A duplicated versions of the DNA segment, which is found to have a larger size (231-235 bp) than CSL-W in both sexes, was also identified, and was designated CSL-NW (crane sex-linked DNA on non-W chromosome). The nucleotide similarity between the sequences of CSL-W and CSL-NW from whooping cranes was 86.3%. The CSL primers do not amplify any sequence from mammalian DNA, limiting the potential for contamination from human sources. Using the CSL primers in combination with a quick DNA extraction method allows the noninvasive identification of crane gender in less than 10 h. A test of the methodology was carried out on fully developed body feathers from 18 captive cranes and resulted in 100% successful identification.

Inherited Retinal Degenerative Clinical Trial Network. Addendum

Science.gov (United States)

2013-10-01

inherited orphan retinal degenerative diseases and dry age-related macular degeneration (AMD) through the conduct of clinical trials and other...design and conduct of effective and efficient clinical trials for inherited orphan retinal degenerative diseases and dry AMD; • Limited number and...linica l trial in the NEER network for autosomal dominant retinitis pigmentosa, and the ProgSTAR studies for Stargardt disease ) . As new interventions b

Severe recurrent achalasia cardia responding to treatment of severe autoimmune acquired haemophilia

OpenAIRE

Al-Jafar, H; Laffan, M; Al-Sabah, S; Elmorsi, M; Habeeb, M; Alnajar, F

2012-01-01

Acquired haemophilia A and severe acquired achalasia are both very rare conditions with unknown aetiology. Haemophilia A is a haemorrhagic disease induced by deficiency or malfunction of coagulation factor VIII. Congenital haemophilia is an inherited disease transmitted by the mother through X-linked inheritance and primarily affects males. However, acquired haemophilia A is a serious, sudden-onset, autoimmune disease that affects either sex. In addition, achalasia is a disease of the oesopha...

Leigh's Disease

Science.gov (United States)

... X-linked form of Leigh’s disease, a high-fat, low-carbohydrate diet may be recommended. View Full Treatment Information Definition Leigh's disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ...

Primary Immune Deficiency Disease Genetics & Inheritance

Science.gov (United States)

... types of inherited mutations can cause PIDDs. Autosomal Dominant Credit: National Library of Medicine In this example, ... Hill, Ph.D. History Dr. Joseph J. Kinyoun: Father of the NIH Kinyoun: NIH Podcast – July 2012 ...

Polymorphic male color morphs visualized with steroids in monomorphic females: a tool for designing analysis of sex-limited trait inheritance.

Science.gov (United States)

Olsson, Mats; Healey, Mo; Wilson, Mark; Tobler, Michael

2012-02-15

In diploid animals, males and females share most of the genome (except sex-specific elements, such as sex chromosome genes), yet despite sharing the underlying genes that hard-wire traits, males and females may differ in their phenotypes when traits are controlled by proximate mechanisms, such as hormones. In color polymorphic species where coloration is only expressed in one sex, the design of studies of the inheritance of color and coevolved morph-specific traits (e.g. territorial vs sneaker strategies, skewed energetic investment in territorial defense vs sperm production, etc.) is compromised as the expression of morph-coding genes is only visualized in one sex. Here, we circumvented this problem by first characterizing oxidative stress traits in both sexes and then using testosterone implants in females to expose their otherwise 'silent' coloration. Males of our model species are highly territorial and exhibit morph-specific levels of aggression, whereas females are non-territorial and display very low levels of aggression. Interestingly, reactive oxygen species levels were found to be morph specific regardless of sex, despite considerable differences in lifestyle. Males and females did differ remarkably, however, in superoxide levels depending on whether they sported a colored throat bib or not, a trait also used in male sexual signaling. Females with throat bibs had significantly lower levels of superoxide than females without a bib, which was not the case for males.

Genetic engineering and therapy for inherited and acquired cardiomyopathies.

Science.gov (United States)

Day, Sharlene; Davis, Jennifer; Westfall, Margaret; Metzger, Joseph

2006-10-01

The cardiac myofilaments consist of a highly ordered assembly of proteins that collectively generate force in a calcium-dependent manner. Defects in myofilament function and its regulation have been implicated in various forms of acquired and inherited human heart disease. For example, during cardiac ischemia, cardiac myocyte contractile performance is dramatically downregulated due in part to a reduced sensitivity of the myofilaments to calcium under acidic pH conditions. Over the last several years, the thin filament regulatory protein, troponin I, has been identified as an important mediator of this response. Mutations in troponin I and other sarcomere genes are also linked to several distinct inherited cardiomyopathic phenotypes, including hypertrophic, dilated, and restrictive cardiomyopathies. With the cardiac sarcomere emerging as a central player for such a diverse array of human heart diseases, genetic-based strategies that target the myofilament will likely have broad therapeutic potential. The development of safe vector systems for efficient gene delivery will be a critical hurdle to overcome before these types of therapies can be successfully applied. Nonetheless, studies focusing on the principles of acute genetic engineering of the sarcomere hold value as they lay the essential foundation on which to build potential gene-based therapies for heart disease.

CONFIRMATION OF X-LINKED INHERITANCE AND PROVISIONAL MAPPING OF THE KERATOSIS FOLLICULARIS SPINULOSA DECALVANS GENE ON XP IN A LARGE DUTCH FAMILY

NARCIS (Netherlands)

Oosterwijk, JC; NELEN, M; VANZANDVOORT, PM; VANOSCH, LDM; ORANJE, AP; WITTEBOLPOST, D; VANOOST, BA

In a large Dutch family with keratosis follicularis spinulosa decalvans (KFSD, MIM 308800), DNA linkage analysis was performed in order to locate the gene. Pedigree analysis and lod score calculation confirmed X-linked inheritance and revealed significant linkage to DNA markers on Xp. A maximum lod

Peripheral neuropathy in complex inherited diseases: an approach to diagnosis.

Science.gov (United States)

Rossor, Alexander M; Carr, Aisling S; Devine, Helen; Chandrashekar, Hoskote; Pelayo-Negro, Ana Lara; Pareyson, Davide; Shy, Michael E; Scherer, Steven S; Reilly, Mary M

2017-10-01

Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy, for example, spasticity, the type of neuropathy and the other neurological and non-neurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories: (1) ataxia, (2) spasticity and (3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy, for example, cardiomyopathy and neuropathy. We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain-Barré syndrome, as many will have a metabolic aetiology and be potentially treatable. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Co-morbidity of migraine and Ménière's disease -- is allergy the link?

NARCIS (Netherlands)

Sen, Purushotham; Georgalas, Christos; Papesch, Michael

2005-01-01

This study determined the prevalence of migraine and allergy in patients with Ménière's disease (MD) compared with age- and sex-matched controls. We tested the hypothesis that if migraine and MD is linked by allergy, then allergy should be more prevalent in patients with MD and migraine compared

PATTERN OF INHERITANCE OF IDIOPATHIC HYPERCALCIURIA IN TWO FAMILIES

Directory of Open Access Journals (Sweden)

A. Nickavar

2006-09-01

Full Text Available Idiopathic hypercalciuria is a leading cause of frequency-dysuria syndrome in childhood. Different modes of inheritance have been suggested in this disease. This article presents the occurrence of idiopathic hypercalciuria in all children of two families. In the first family, a 5.5 year old girl with a history of renal stones and dysuria due to hypercalciuria, had two involved brothers and one sister. In the second family, hypercalciuria and medullary nephrocalcinosis were detected in two siblings who were admitted for polyuria and dysuria. Idiopathic type of hypercalciuria was diagnosed in these two families by normal laboratory exams and exclusion of other causes of normocalcemic hypercalciuria. According to the involvement of all offsprings (both sexes in these two families, it is suggested that idiopathic hypercalciuria is an autosomal dominant disease with complete penetration.

Anticipated stigma and blameless guilt: Mothers' evaluation of life with the sex-linked disorder, hypohidrotic ectodermal dysplasia (XHED).

Science.gov (United States)

Clarke, Angus

2016-06-01

Practical experience of a genetic disorder may influence how parents approach reproduction, if they know their child may be affected by an inherited condition. One important aspect of this practical experience is the stigmatisation which family members may experience or witness. We outline the concept of stigma and how it affects those in families with a condition that impacts upon physical appearance. We then consider the accounts given by females in families affected by the rare sex-linked disorder, X-linked hypohidrotic ectodermal dysplasia (XHED), which principally affects males but can be passed through female carriers to affect their sons. The stigmatisation of affected males is as important in the accounts given by their womenfolk as the physical effects of the condition; this impacts on their talk about transmission of the disorder to the next generation. Perspectives may also change over time. The mothers of affected sons differ from their daughters, who do not yet have children, and from their mothers, who may express more strongly their sense of guilt at having transmitted the condition, despite there being no question of moral culpability. We conclude with suggestions about other contexts where the possibility of stigma may influence reproductive decisions. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

Disease: H01186 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available a disorder associated with an inherited selenocysteine (Sec) incorporation defect, caused by mutations in SECI...eiodinase type 2 (DIO2) enzymatic activity not linked to the DIO2 locus. Inherited metabolic disease SECISBP...C, Boran G, Schomburg L, Weiss RE, Refetoff S ... TITLE ... Mutations in SECISBP2 result in abnormal thyroid h

Transgenerational inheritance of heart disorders caused by paternal bisphenol A exposure

International Nuclear Information System (INIS)

Lombó, Marta; Fernández-Díez, Cristina; González-Rojo, Silvia; Navarro, Claudia; Robles, Vanesa; Herráez, María Paz

2015-01-01

Bisphenol A (BPA) is an endocrine disruptor used in manufacturing of plastic devices, resulting in an ubiquitous presence in the environment linked to human infertility, obesity or cardiovascular diseases. Both transcriptome and epigenome modifications lie behind these disorders that might be inherited transgenerationally when affecting germline. To assess potential effects of paternal exposure on offspring development, adult zebrafish males were exposed to BPA during spermatogenesis and mated with non-treated females. Results showed an increase in the rate of heart failures of progeny up to the F2, as well as downregulation of 5 genes involved in cardiac development in F1 embryos. Moreover, BPA causes a decrease in F0 and F1 sperm remnant mRNAs related to early development. Results reveal a paternal inheritance of changes in the insulin signaling pathway due to downregulation of insulin receptor β mRNAs, suggesting a link between BPA male exposure and disruption of cardiogenesis in forthcoming generations. - Highlights: • We examine the effects of adult male exposure to BPA on the progeny (F1 and F2). • Paternal exposure promotes similar cardiac malformations to those caused by direct exposure. • BPA applied during spermatogenesis decrease the insra and insrb transcripts in spermatozoa. • Sperm insrb transcript controls embryonic expression being the downregulation inherited by F1. • Paternal BPA exposure impairs heart development in F1 and F2 disrupting insulin signaling pathway. - Paternal bisphenol A exposure impairs cardiac development throughout generations.

Genetic Testing for Inherited Heart Disease

Science.gov (United States)

... pedigree. A pedigree ( Figure 2 ) is a family tree that shows who has and who does not have the condition of interest. It is drawn to organize information about the medical history of family members, to illustrate who is affected, to identify the pattern of inheritance, and to identify who ...

Analysis of case-parent trios for imprinting effect using a loglinear model with adjustment for sex-of-parent-specific transmission ratio distortion

DEFF Research Database (Denmark)

Huang, Lam Opal; Infante-Rivard, Claire; Labbe, Aurélie

2017-01-01

Transmission ratio distortion (TRD) is a phenomenon where parental transmission of disease allele to the child does not follow the Mendelian inheritance ratio. TRD occurs in a sex-of-parent-specific or non-sex-of-parent-specific manner. An offset computed from the transmission probability of the ...

Alport syndrome: impact of digenic inheritance in patients management.

Science.gov (United States)

Fallerini, C; Baldassarri, M; Trevisson, E; Morbidoni, V; La Manna, A; Lazzarin, R; Pasini, A; Barbano, G; Pinciaroli, A R; Garosi, G; Frullanti, E; Pinto, A M; Mencarelli, M A; Mari, F; Renieri, A; Ariani, F

2017-07-01

Alport syndrome (ATS) is a genetically heterogeneous nephropathy with considerable phenotypic variability and different transmission patterns, including monogenic (X-linked/autosomal) and digenic inheritance (DI). Here we present a new series of families with DI and we discuss the consequences for genetic counseling and risk assessment. Out of five families harboring variants in more than one COL4 gene detected by next generation sequencing (NGS), minigene-splicing assay allowed us to identify four as true digenic. Two families showed COL4A3/A4 mutations in cis, mimicking an autosomal dominant inheritance with a more severe phenotype and one showed COL4A3/A4 mutations in trans, mimicking an autosomal recessive inheritance with a less severe phenotype. In a fourth family, a de novo mutation (COL4A5) combined with an inherited mutation (COL4A3) triggered a more severe phenotype. A fifth family, predicted digenic on the basis of silico tools, rather showed monogenic X-linked inheritance due to a hypomorphic mutation, in accordance with a milder phenotype. In conclusion, this study highlights the impact of DI in ATS and explains the associated atypical presentations. More complex inheritance should be therefore considered when reviewing prognosis and recurrence risks. On the other side, these findings emphasize the importance to accompany NGS with splicing assays in order to avoid erroneous identification of at risk members. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sex differences in cognitive impairment and Alzheimer's disease.

Science.gov (United States)

Li, Rena; Singh, Meharvan

2014-08-01

Studies have shown differences in specific cognitive ability domains and risk of Alzheimer's disease between the men and women at later age. However it is important to know that sex differences in cognitive function during adulthood may have their basis in both organizational effects, i.e., occurring as early as during the neuronal development period, as well as in activational effects, where the influence of the sex steroids influence brain function in adulthood. Further, the rate of cognitive decline with aging is also different between the sexes. Understanding the biology of sex differences in cognitive function will not only provide insight into Alzheimer's disease prevention, but also is integral to the development of personalized, gender-specific medicine. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of sex differences in cognitive function from young to old, and examines the effects of sex hormone treatments on Alzheimer's disease in men and women. Copyright © 2014 Elsevier Inc. All rights reserved.

Maternal telomere length inheritance in the king penguin.

Science.gov (United States)

Reichert, S; Rojas, E R; Zahn, S; Robin, J-P; Criscuolo, F; Massemin, S

2015-01-01

Telomeres are emerging as a biomarker for ageing and survival, and are likely important in shaping life-history trade-offs. In particular, telomere length with which one starts in life has been linked to lifelong survival, suggesting that early telomere dynamics are somehow related to life-history trajectories. This result highlights the importance of determining the extent to which telomere length is inherited, as a crucial factor determining early life telomere length. Given the scarcity of species for which telomere length inheritance has been studied, it is pressing to assess the generality of telomere length inheritance patterns. Further, information on how this pattern changes over the course of growth in individuals living under natural conditions should provide some insight on the extent to which environmental constraints also shape telomere dynamics. To fill this gap partly, we followed telomere inheritance in a population of king penguins (Aptenodytes patagonicus). We tested for paternal and maternal influence on chick initial telomere length (10 days old after hatching), and how these relationships changed with chick age (at 70, 200 and 300 days old). Based on a correlative approach, offspring telomere length was positively associated with maternal telomere length early in life (at 10 days old). However, this relationship was not significant at older ages. These data suggest that telomere length in birds is maternally inherited. Nonetheless, the influence of environmental conditions during growth remained an important factor shaping telomere length, as the maternal link disappeared with chicks' age.

Pursuing the quest for better understanding the taxonomic distribution of the system of doubly uniparental inheritance of mtDNA

Directory of Open Access Journals (Sweden)

Arthur Gusman

2016-12-01

Full Text Available There is only one exception to strict maternal inheritance of mitochondrial DNA (mtDNA in the animal kingdom: a system named doubly uniparental inheritance (DUI, which is found in several bivalve species. Why and how such a radically different system of mitochondrial transmission evolved in bivalve remains obscure. Obtaining a more complete taxonomic distribution of DUI in the Bivalvia may help to better understand its origin and function. In this study we provide evidence for the presence of sex-linked heteroplasmy (thus the possible presence of DUI in two bivalve species, i.e., the nuculanoid Yoldia hyperborea(Gould, 1841and the veneroid Scrobicularia plana(Da Costa,1778, increasing the number of families in which DUI has been found by two. An update on the taxonomic distribution of DUI in the Bivalvia is also presented.

Sex Reversal and Comparative Data Undermine the W Chromosome and Support Z-linked DMRT1 as the Regulator of Gonadal Sex Differentiation in Birds.

Science.gov (United States)

Hirst, Claire E; Major, Andrew T; Ayers, Katie L; Brown, Rosie J; Mariette, Mylene; Sackton, Timothy B; Smith, Craig A

2017-09-01

The exact genetic mechanism regulating avian gonadal sex differentiation has not been completely resolved. The most likely scenario involves a dosage mechanism, whereby the Z-linked DMRT1 gene triggers testis development. However, the possibility still exists that the female-specific W chromosome may harbor an ovarian determining factor. In this study, we provide evidence that the universal gene regulating gonadal sex differentiation in birds is Z-linked DMRT1 and not a W-linked (ovarian) factor. Three candidate W-linked ovarian determinants are HINTW, female-expressed transcript 1 (FET1), and female-associated factor (FAF). To test the association of these genes with ovarian differentiation in the chicken, we examined their expression following experimentally induced female-to-male sex reversal using the aromatase inhibitor fadrozole (FAD). Administration of FAD on day 3 of embryogenesis induced a significant loss of aromatase enzyme activity in female gonads and masculinization. However, expression levels of HINTW, FAF, and FET1 were unaltered after experimental masculinization. Furthermore, comparative analysis showed that FAF and FET1 expression could not be detected in zebra finch gonads. Additionally, an antibody raised against the predicted HINTW protein failed to detect it endogenously. These data do not support a universal role for these genes or for the W sex chromosome in ovarian development in birds. We found that DMRT1 (but not the recently identified Z-linked HEMGN gene) is male upregulated in embryonic zebra finch and emu gonads, as in the chicken. As chicken, zebra finch, and emu exemplify the major evolutionary clades of birds, we propose that Z-linked DMRT1, and not the W sex chromosome, regulates gonadal sex differentiation in birds. Copyright © 2017 Endocrine Society.

Maternal condition but not corticosterone is linked to offspring sex ratio in a passerine bird.

Directory of Open Access Journals (Sweden)

Lindsay J Henderson

Full Text Available There is evidence of offspring sex ratio adjustment in a range of species, but the potential mechanisms remain largely unknown. Elevated maternal corticosterone (CORT is associated with factors that can favour brood sex ratio adjustment, such as reduced maternal condition, food availability and partner attractiveness. Therefore, the steroid hormone has been suggested to play a key role in sex ratio manipulation. However, despite correlative and causal evidence CORT is linked to sex ratio manipulation in some avian species, the timing of adjustment varies between studies. Consequently, whether CORT is consistently involved in sex-ratio adjustment, and how the hormone acts as a mechanism for this adjustment remains unclear. Here we measured maternal baseline CORT and body condition in free-living blue tits (Cyanistes caeruleus over three years and related these factors to brood sex ratio and nestling quality. In addition, a non-invasive technique was employed to experimentally elevate maternal CORT during egg laying, and its effects upon sex ratio and nestling quality were measured. We found that maternal CORT was not correlated with brood sex ratio, but mothers with elevated CORT fledged lighter offspring. Also, experimental elevation of maternal CORT did not influence brood sex ratio or nestling quality. In one year, mothers in superior body condition produced male biased broods, and maternal condition was positively correlated with both nestling mass and growth rate in all years. Unlike previous studies maternal condition was not correlated with maternal CORT. This study provides evidence that maternal condition is linked to brood sex ratio manipulation in blue tits. However, maternal baseline CORT may not be the mechanistic link between the maternal condition and sex ratio adjustment. Overall, this study serves to highlight the complexity of sex ratio adjustment in birds and the difficulties associated with identifying sex biasing mechanisms.

Network-based analysis of genotype-phenotype correlations between different inheritance modes.

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Hao, Dapeng; Li, Chuanxing; Zhang, Shaojun; Lu, Jianping; Jiang, Yongshuai; Wang, Shiyuan; Zhou, Meng

2014-11-15

Recent studies on human disease have revealed that aberrant interaction between proteins probably underlies a substantial number of human genetic diseases. This suggests a need to investigate disease inheritance mode using interaction, and based on which to refresh our conceptual understanding of a series of properties regarding inheritance mode of human disease. We observed a strong correlation between the number of protein interactions and the likelihood of a gene causing any dominant diseases or multiple dominant diseases, whereas no correlation was observed between protein interaction and the likelihood of a gene causing recessive diseases. We found that dominant diseases are more likely to be associated with disruption of important interactions. These suggest inheritance mode should be understood using protein interaction. We therefore reviewed the previous studies and refined an interaction model of inheritance mode, and then confirmed that this model is largely reasonable using new evidences. With these findings, we found that the inheritance mode of human genetic diseases can be predicted using protein interaction. By integrating the systems biology perspectives with the classical disease genetics paradigm, our study provides some new insights into genotype-phenotype correlations. haodapeng@ems.hrbmu.edu.cn or biofomeng@hotmail.com Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Allele-specific marker generation and linkage mapping on the Xiphophorus sex chromosomes.

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Woolcock, B; Kazianis, S; Lucito, R; Walter, R B; Kallman, K D; Morizot, D C; Vielkind, J R

2006-01-01

There is great interest in the sex chromosomes of Xiphophorus fishes because both WY/YY and XX/XY sex-determining mechanisms function in these species, with at least one taxon possessing all three types of sex chromosomes, and because in certain interspecific hybrids melanoma arises as a consequence of inheritance of the sex-linked macromelanophore determining locus (MDL). Representational difference analysis (RDA) has been used to clone two sequences from the sex-determining region of X. maculatus, including a cholinergic receptor, nicotinic, delta polypeptide (CHRND) orthologue. Allele-specific assays for these sequences, as well as for the sex-linked XMRK1 and XMRK2 genes, were developed to distinguish W, X, and Y chromosomes derived from a X. maculatus (XX/XY) strain and a X. helleri (WY/YY) strain. Linkage mapping localized these markers to linkage group (LG) 24. No recombinants were observed between XMRK2 and MDL, confirming a role for XMRK2 in macromelanophore development. Although the master sex-determining (SD) locus certainly resides on Xiphophorus LG 24, autosomal loci are probably involved in sex determination as well, as indicated by the abnormal sex ratios in the backcross hybrids that contrast theoretical predictions based on LG 24 genotyping. Marker development and allelic discrimination on the Xiphophorus sex chromosomes should prove highly useful for studies that utilize this genus as an animal model.

CHARCOT-MARIE-TOOTH DISEASE

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Lea Leonardis

2003-09-01

Full Text Available Background. Charcot-Marie-Tooth (CMT disease is a common inherited disorder of the peripheral nervous system. In our paper, different types of CMT are described with their typical clinical pictures, electrophysiological signs and molecular genetic studies. CMT is classified as demyelinative and axonal type and distal motor neuronopathy.Conclusions. CMT can be of autosomal dominant, recessive and X-linked inheritance. The most frequent form of CMT is the result of the dominantly inherited duplication of chromosome 17p11.2 and is marked as CMT1A. The same group involves also rare patients with point mutation in the peripheral myelin protein-22 gene. CMT1B is associated with point mutations in protein zero gene. CMT1C is linked to chromosome 16p13.1–12.3. Patients with point mutations in early growth response 2 gene (EGR2 are included in group CMT1D. The disease can be also inhereted X-linked (CMTX with the mutations in connexin-32 gene. In autosomal recessive inherited demyelinating polyneuropathies (CMT4, mutations are found in the myotubularin-related protein-2 (CMT4B, N-myc downstream-regulated gene 1 (CMT4D, EGR2 (CMT4E, and in the periaksin (CMT4F genes. In axonal inherited neuropathy, mutations are found in KIF1beta (CMT2A and in light neurofilament (CMT2E genes, other forms map to different chromosomal loci (CMT2B, CMT2D, CMT2F. Some suggestions for the diagnostic procedures of patients with CMT are given.

Influence of gender constancy and social power on sex-linked modeling.

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Bussey, K; Bandura, A

1984-12-01

Competing predictions derived from cognitive-developmental theory and social learning theory concerning sex-linked modeling were tested. In cognitive-developmental theory, gender constancy is considered a necessary prerequisite for the emulation of same-sex models, whereas according to social learning theory, sex-role development is promoted through a vast system of social influences with modeling serving as a major conveyor of sex role information. In accord with social learning theory, even children at a lower level of gender conception emulated same-sex models in preference to opposite-sex ones. Level of gender constancy was associated with higher emulation of both male and female models rather than operating as a selective determinant of modeling. This finding corroborates modeling as a basic mechanism in the sex-typing process. In a second experiment we explored the limits of same-sex modeling by pitting social power against the force of collective modeling of different patterns of behavior by male and female models. Social power over activities and rewarding resources produced cross-sex modeling in boys, but not in girls. This unexpected pattern of cross-sex modeling is explained by the differential sex-typing pressures that exist for boys and girls and socialization experiences that heighten the attractiveness of social power for boys.

Disease stage, but not sex, predicts depression and psychological distress in Huntington's disease

DEFF Research Database (Denmark)

Dale, Maria; Maltby, John; Shimozaki, Steve

2016-01-01

OBJECTIVE: Depression and anxiety significantly affect morbidity in Huntington's disease. Mice. models of Huntington's disease have identified sex differences in mood-like behaviours that vary across disease lifespan, but this interaction has not previously been explored in humans with Huntington......'s disease. However, among certain medical populations, evidence of sex differences in mood across various disease stages has been found, reflecting trends among the general population that women tend to experience anxiety and depression 1.5 to 2 times more than men. The current study examined whether...... disease stage and sex, either separately or as an interaction term, predicted anxiety and depression in Huntington's disease. METHODS: A cross-sectional study of REGISTRY data involving 453 Huntington's disease participants from 12 European countries was undertaken using the Hospital Anxiety...

Transcriptional profiling of human liver identifies sex-biased genes associated with polygenic dyslipidemia and coronary artery disease.

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Yijing Zhang

Full Text Available Sex-differences in human liver gene expression were characterized on a genome-wide scale using a large liver sample collection, allowing for detection of small expression differences with high statistical power. 1,249 sex-biased genes were identified, 70% showing higher expression in females. Chromosomal bias was apparent, with female-biased genes enriched on chrX and male-biased genes enriched on chrY and chr19, where 11 male-biased zinc-finger KRAB-repressor domain genes are distributed in six clusters. Top biological functions and diseases significantly enriched in sex-biased genes include transcription, chromatin organization and modification, sexual reproduction, lipid metabolism and cardiovascular disease. Notably, sex-biased genes are enriched at loci associated with polygenic dyslipidemia and coronary artery disease in genome-wide association studies. Moreover, of the 8 sex-biased genes at these loci, 4 have been directly linked to monogenic disorders of lipid metabolism and show an expression profile in females (elevated expression of ABCA1, APOA5 and LDLR; reduced expression of LIPC that is consistent with the lower female risk of coronary artery disease. Female-biased expression was also observed for CYP7A1, which is activated by drugs used to treat hypercholesterolemia. Several sex-biased drug-metabolizing enzyme genes were identified, including members of the CYP, UGT, GPX and ALDH families. Half of 879 mouse orthologs, including many genes of lipid metabolism and homeostasis, show growth hormone-regulated sex-biased expression in mouse liver, suggesting growth hormone might play a similar regulatory role in human liver. Finally, the evolutionary rate of protein coding regions for human-mouse orthologs, revealed by dN/dS ratio, is significantly higher for genes showing the same sex-bias in both species than for non-sex-biased genes. These findings establish that human hepatic sex differences are widespread and affect diverse cell

Popularity among Same-Sex and Cross-Sex Peers: A Process-Oriented Examination of Links to Aggressive Behaviors and Depressive Affect

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Troop-Gordon, Wendy; Ranney, John D.

2014-01-01

Popularity has been linked to heightened aggression and fewer depressive symptoms. The current study extends this literature by examining the unique contributions of same-sex and cross-sex popularity to children's development, as well as potential mediating processes. Third- and 4th-graders (212 boys, 250 girls) provided data at 3 time points over…

Update on gene therapy of inherited immune deficiencies.

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Engel, Barbara C; Kohn, Donald B; Podsakoff, Greg M

2003-10-01

Gene therapy has been under development as a way to correct inborn errors for many years. Recently, patients with two forms of inherited severe combined immunodeficiency (SCID), adenosine deaminase and X-linked, treated by three different clinical investigative teams, have shown significant immune reconstitution leading to protective immunity. These advances irrefutably prove the concept that hematopoietic progenitor cell gene therapy can ameliorate these diseases. However, due to proviral insertional oncogenesis, two individuals in one of the X-SCID studies developed T-cell leukemia more than two years after the gene transfer. Depending upon the results of long-term follow-up, the successes together with the side effects highlight the relative merits of this therapeutic approach.

Compensated for Life: Sex Work and Disease Risk

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Arunachalam, Raj; Shah, Manisha

2013-01-01

Sex workers draw a premium for engaging in unprotected sex. We theoretically motivate a test of whether this premium represents a compensating differential for disease, thereby mitigating sex workers' propensity to use condoms. Using transaction-level data and biological STI markers from sex workers in Ecuador, we exploit within-worker variation…

Inherited leukoencephalopathies with clinical onset in middle and old age.

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Nannucci, Serena; Donnini, Ida; Pantoni, Leonardo

2014-12-15

The currently widespread use of neuroimaging has led neurologists to often face the problem of the differential diagnosis of white matter diseases. There are various forms of leukoencephalopathies (vascular, inflammatory and immunomediated, infectious, metabolic, neoplastic) and sometimes white matter lesions are expression of a genetic disease. While many inherited leukoencephalopathies fall in the child neurologist's interest, others may have a delayed or even a typical onset in the middle or old age. This field is rapidly growing and, in the last few years, many new inherited white matter diseases have been described and genetically defined. A non-delayed recognition of middle and old age inherited leukoencephalopathies appears important to avoid unnecessary tests and therapies in the patient and to possibly anticipate the diagnosis in relatives. The aim of this review is to provide a guide to direct the diagnostic process when facing a patient with a suspicion of an inherited form of leukoencephalopathy and with clinical onset in middle or old age. Based on a MEDLINE search from 1990 to 2013, we identified 24 middle and old age onset inherited leukoencephalopathies and reviewed in this relation the most recent findings focusing on their differential diagnosis. We provide summary tables to use as a check list of clinical and neuroimaging findings that are most commonly associated with these forms of leukoencephalopathies. When present, we reported specific characteristics of single diseases. Several genetic diseases may be suspected in patients with middle or old age and white matter abnormalities. In only few instances, pathognomonic clinical or associated neuroimaging features help identifying a specific disease. Therefore, a comprehensive knowledge of the characteristics of these inherited white matter diseases appears important to improve the diagnostic work-up, optimize the choice of genetic tests, increase the number of diagnosed patients, and stimulate

Inheritance and identification of SCAR marker linked to bacterial wilt ...

African Journals Online (AJOL)

In the present work, the combinations (F1) were crossed between highly resistant and susceptible to bacterial wilt eggplant parents and its F2, BC1 segregation population plants were inoculated with race1 of Ralstonia solanacearum in greenhouse. In this paper, we reported that the inheritance of bacterial wilt resistance in ...

Inheritance of sterility in Dysdercus koenigii F. (Hemiptera: Pyrrhocoridae)

International Nuclear Information System (INIS)

Harwalkar, M.R.; Rahalkar, G.W.

1979-01-01

It has been suggested that for the control of Lepidopterous populations, release of fully competitive partially sterile males would be more advantageous than the release of completely sterile males. This suggestion is based on the fact, elucidated in many studies, that partially sterilized males mated to normal females produce totally sterile or partially sterile progeny. In Hemiptera too, F 1 progeny of partially sterile males has been shown to inherit sterility. Individual impact of sterility inherited by either sex of the F 1 progeny on population growth has been studied in an hemipteran insect Dysdercus koenigii. A dose of 7 krad induces near-complete sterility in males. When males irradiated with substerilizing doses of 1,2 and 3 krad were crossed with normal females, F 1 progeny of both sexes was partially sterile : the female being more sterile than the males. When the F 1 progeny was intercrossed, there was enhanced reduction in progeny production. (auth.)

Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

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Waldman, A.D.; Cordery, R.J.; Godbolt, A.; Rossor, M.N. [University College London, Dementia Research Group, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom); Imperial College of Science, Technology and Medicine, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, London (United Kingdom); MacManus, D.G. [University College London, NMR Research Unit, Department of Clinical Neurology, Institute of Neurology, London (United Kingdom); Collinge, J. [University College London, MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom)

2006-06-15

Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Waldman, A.D.; Cordery, R.J.; Godbolt, A.; Rossor, M.N.; MacManus, D.G.; Collinge, J.

2006-01-01

Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

Identifying new sex-linked genes through BAC sequencing in the dioecious plant Silene latifolia

Czech Academy of Sciences Publication Activity Database

Blavet, Nicolas; Blavet, Hana; Muyle, A.; Käfer, J.; Cegan, R.; Deschamps, C.; Zemp, N.; Mousset, S.; Aubourg, S.; Bergero, R.; Charlesworth, D.; Hobza, Roman; Widmer, A.; Marais, G.A.B.

2015-01-01

Roč. 16, JUL 25 (2015), s. 546 ISSN 1471-2164 R&D Projects: GA ČR GAP501/12/2220 Institutional support: RVO:61389030 Keywords : Sex chromosomes * Sex-linked genes * Plant Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.867, year: 2015

Sex Differences in Psychiatric Disease: A Focus on the Glutamate System

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Megan M. Wickens

2018-06-01

Full Text Available Alterations in glutamate, the primary excitatory neurotransmitter in the brain, are implicated in several psychiatric diseases. Many of these psychiatric diseases display epidemiological sex differences, with either males or females exhibiting different symptoms or disease prevalence. However, little work has considered the interaction of disrupted glutamatergic transmission and sex on disease states. This review describes the clinical and preclinical evidence for these sex differences with a focus on two conditions that are more prevalent in women: Alzheimer's disease and major depressive disorder, and three conditions that are more prevalent in men: schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder. These studies reveal sex differences at multiple levels in the glutamate system including metabolic markers, receptor levels, genetic interactions, and therapeutic responses to glutamatergic drugs. Our survey of the current literature revealed a considerable need for more evaluations of sex differences in future studies examining the role of the glutamate system in psychiatric disease. Gaining a more thorough understanding of how sex differences in the glutamate system contribute to psychiatric disease could provide novel avenues for the development of sex-specific pharmacotherapies.

Dominant inheritance of cerebral gigantism.

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Zonana, J; Sotos, J F; Romshe, C A; Fisher, D A; Elders, M J; Rimoin, D L

1977-08-01

Cerebral gigantism is a syndrome consisting of characteristic dysmorphic features, accelerated growth in early childhood, and variable degrees of mental retardation. Its etiology and pathogenesis have not been defined. Three families are presented with multiple affected members. The vertical transmission of the trait and equal expression in both sexes in these families indicates a genetic etiology with a dominant pattern of inheritance, probably autosomal. As in previously reported cases, extensive endocrine evaluation failed to define the pathogenesis of the accelerated growth present in this disorder.

Identification of Inherited Retinal Disease-Associated Genetic Variants in 11 Candidate Genes.

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Astuti, Galuh D N; van den Born, L Ingeborgh; Khan, M Imran; Hamel, Christian P; Bocquet, Béatrice; Manes, Gaël; Quinodoz, Mathieu; Ali, Manir; Toomes, Carmel; McKibbin, Martin; El-Asrag, Mohammed E; Haer-Wigman, Lonneke; Inglehearn, Chris F; Black, Graeme C M; Hoyng, Carel B; Cremers, Frans P M; Roosing, Susanne

2018-01-10

Inherited retinal diseases (IRDs) display an enormous genetic heterogeneity. Whole exome sequencing (WES) recently identified genes that were mutated in a small proportion of IRD cases. Consequently, finding a second case or family carrying pathogenic variants in the same candidate gene often is challenging. In this study, we searched for novel candidate IRD gene-associated variants in isolated IRD families, assessed their causality, and searched for novel genotype-phenotype correlations. Whole exome sequencing was performed in 11 probands affected with IRDs. Homozygosity mapping data was available for five cases. Variants with minor allele frequencies ≤ 0.5% in public databases were selected as candidate disease-causing variants. These variants were ranked based on their: (a) presence in a gene that was previously implicated in IRD; (b) minor allele frequency in the Exome Aggregation Consortium database (ExAC); (c) in silico pathogenicity assessment using the combined annotation dependent depletion (CADD) score; and (d) interaction of the corresponding protein with known IRD-associated proteins. Twelve unique variants were found in 11 different genes in 11 IRD probands. Novel autosomal recessive and dominant inheritance patterns were found for variants in Small Nuclear Ribonucleoprotein U5 Subunit 200 ( SNRNP200 ) and Zinc Finger Protein 513 ( ZNF513 ), respectively. Using our pathogenicity assessment, a variant in DEAH-Box Helicase 32 ( DHX32 ) was the top ranked novel candidate gene to be associated with IRDs, followed by eight medium and lower ranked candidate genes. The identification of candidate disease-associated sequence variants in 11 single families underscores the notion that the previously identified IRD-associated genes collectively carry > 90% of the defects implicated in IRDs. To identify multiple patients or families with variants in the same gene and thereby provide extra proof for pathogenicity, worldwide data sharing is needed.

SUMA Technology and Newborn Screening Tests for Inherited Metabolic Diseases in Cuba

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Ernesto Carlos González Reyes PhD

2016-07-01

Full Text Available The ultramicroanalytic system (SUMA, created in the 1980s, is a complete system of reagents and instrumentation to perform ultramicroassays combining the sensitivity of the micro-enzyme-linked immunosorbent assay (ELISA tests with the use of ultramicrovolumes. This technology permitted establishing large-scale newborn screening programs (NSPs for metabolic and endocrine disorders in Cuba. This article summarizes the main results of the implementation during the 30 years of SUMA technology in NSP for 5 inherited metabolic diseases, using ultramicroassays developed at the Department of Newborn Screening at the Immunoassay Center. Since 1986, SUMA technology has been used in the Cuban NSP for congenital hypothyroidism, initially studying thyroid hormone in cord serum samples. In 2000, a decentralized program for the detection of hyperphenylalaninemias using heel dried blood samples was initiated. These successful experiences permitted including protocols for screening congenital adrenal hyperplasia, galactosemia, and biotinidase deficiency in 2005. A program for the newborn screening of CH using the thyroid-stimulating hormone Neonatal ultramicro-ELISA was fully implemented in 2010. Nowadays, the NSP is supported by a network of 175 SUMA laboratories. After 30 years, more than 3.8 million Cuban newborns have been screened, and 1002 affected children have been detected. Moreover, SUMA technology has been presented in Latin America for over 2 decades and has contributed to screen around 17 million newborns. These results prove that developing countries can develop appropriate diagnostic technologies for making health care accessible to all.

De novo and rare inherited copy-number variations in the hemiplegic form of cerebral palsy.

Science.gov (United States)

Zarrei, Mehdi; Fehlings, Darcy L; Mawjee, Karizma; Switzer, Lauren; Thiruvahindrapuram, Bhooma; Walker, Susan; Merico, Daniele; Casallo, Guillermo; Uddin, Mohammed; MacDonald, Jeffrey R; Gazzellone, Matthew J; Higginbotham, Edward J; Campbell, Craig; deVeber, Gabrielle; Frid, Pam; Gorter, Jan Willem; Hunt, Carolyn; Kawamura, Anne; Kim, Marie; McCormick, Anna; Mesterman, Ronit; Samdup, Dawa; Marshall, Christian R; Stavropoulos, Dimitri J; Wintle, Richard F; Scherer, Stephen W

2018-02-01

PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to CP. We also sequenced exomes of "CNV-positive" trios.ResultsWe detected de novo CNVs and/or sex chromosome abnormalities in 7/97 (7.2%) of probands, impacting important developmental genes such as GRIK2, LAMA1, DMD, PTPRM, and DIP2C. In 18/97 individuals (18.6%), rare inherited CNVs were found, affecting loci associated with known genomic disorders (17p12, 22q11.21) or involving genes linked to neurodevelopmental disorders.ConclusionWe found an increased rate of de novo CNVs in the hemiplegic CP subtype (7.2%) compared to controls (1%). This result is similar to that for an unselected CP group. Combined with rare inherited CNVs, the genomic data impacts the understanding of the potential etiology of hemiplegic CP in 23/97 (23.7%) of participants.

The Molecular Revolution in Cutaneous Biology: Era of Molecular Diagnostics for Inherited Skin Diseases.

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McGrath, John A

2017-05-01

The discovery of pathogenic mutations in inherited skin diseases represents one of the major landmarks of late 20th century molecular genetics. Mutation data can provide accurate diagnoses, improve genetic counseling, help define disease mechanisms, establish disease models, and provide a basis for translational research and testing of novel therapeutics. The process of detecting disease mutations, however, has not always been straightforward. Traditional approaches using genetic linkage or candidate gene analysis have often been limited, costly, and slow to yield new insights, but the advent of next-generation sequencing (NGS) technologies has altered the landscape of current gene discovery and mutation detection approaches. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Panel-Based Clinical Genetic Testing in 85 Children with Inherited Retinal Disease.

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Taylor, Rachel L; Parry, Neil R A; Barton, Stephanie J; Campbell, Christopher; Delaney, Claire M; Ellingford, Jamie M; Hall, Georgina; Hardcastle, Claire; Morarji, Jiten; Nichol, Elisabeth J; Williams, Lindsi C; Douzgou, Sofia; Clayton-Smith, Jill; Ramsden, Simon C; Sharma, Vinod; Biswas, Susmito; Lloyd, I Chris; Ashworth, Jane L; Black, Graeme C; Sergouniotis, Panagiotis I

2017-07-01

To assess the clinical usefulness of genetic testing in a pediatric population with inherited retinal disease (IRD). Single-center retrospective case series. Eighty-five unrelated children with a diagnosis of isolated or syndromic IRD who were referred for clinical genetic testing between January 2014 and July 2016. Participants underwent a detailed ophthalmic examination, accompanied by electrodiagnostic testing (EDT) and dysmorphologic assessment where appropriate. Ocular and extraocular features were recorded using Human Phenotype Ontology terms. Subsequently, multigene panel testing (105 or 177 IRD-associated genes) was performed in an accredited diagnostic laboratory, followed by clinical variant interpretation. Diagnostic yield and clinical usefulness of genetic testing. Overall, 78.8% of patients (n = 67) received a probable molecular diagnosis; 7.5% (n = 5) of these had autosomal dominant disease, 25.4% (n = 17) had X-linked disease, and 67.2% (n = 45) had autosomal recessive disease. In a further 5.9% of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had a spectrum of clinical features consistent with ABCA4 retinopathy. Most participants (84.7%; n = 72) had undergone EDT and 81.9% (n = 59) of these patients received a probable molecular diagnosis. The genes most frequently mutated in the present cohort were CACNA1F and ABCA4, accounting for 14.9% (n = 10) and 11.9% (n = 8) of diagnoses respectively. Notably, in many cases, genetic testing helped to distinguish stationary from progressive IRD subtypes and to establish a precise diagnosis in a timely fashion. Multigene panel testing pointed to a molecular diagnosis in 84.7% of children with IRD. The diagnostic yield in the study population was significantly higher compared with that in previously reported unselected IRD cohorts. Approaches similar to the one described herein are expected to become a standard component of care in pediatric ophthalmology

FAMILY ANAMNESIS OF CHILDREN WITH MUTATION OF THE INHERITED HEMOCHROMATOSIS

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S.I. Polyakova

2010-01-01

Full Text Available The inherited burdened is studied on diseases, associated with an overload iron in 41 children with frequent mutations of the inherited hemochromatosis (IG of a 1 type (C282y, H63d, S65c. Control group was made by 27 children with undiscovered frequent mutations of NG. Frequencies of iron-associated diseases are compared for 560 members of families which have children with mutations of IG and 390 members of families which have children without IG mutations. Some features of medical-genealogical anamnesis, which can be conditioned of siderosis, are exposed, and indirectly specify in the presence of mutations in the gene of HFE. So, the high frequency of oncologic diseases, diabetes mellitus, hepatocirrhosis and deaths of relatives under the age of 50 years are the foundation for research of exchange of iron and holding of molecular-genetic research of the inherited hemochromatosis. Key words: inherited hemochromatosis, heredity, children. (Pediatric Pharmacology. – 2010; 7(3:52-56

A novel method for objective vision testing in canine models of inherited retinal disease.

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Gearhart, Patricia M; Gearhart, Chris C; Petersen-Jones, Simon M

2008-08-01

The use of canine models of retinal disease in the development of therapeutic strategies for inherited retinal disorders is a growing area of research. To evaluate accurately the success of potential vision-enhancing treatments, reliable methods for objectively assessing visual function in canine models is necessary. A simple vision-testing device was constructed that consisted of a junction box with four exit tunnels. Dogs were placed in the junction box and given one vision-based choice for exit. The first-choice tunnel and time to exit were recorded and analyzed. Two canine models of retinal disease with distinct molecular defects, a null mutation in the gene encoding the alpha subunit of rod cyclic GMP phosphodiesterase (PDE6A), and a null mutation in the gene encoding a retinal pigment epithelium-specific protein (RPE65) were tested and compared to those in unaffected dogs. With the use of bright light versus dim red light, the test differentiated between unaffected dogs and dogs affected with either mutation with a high degree of certainty. The white-light intensity series showed a significantly different performance between the unaffected and affected dogs. A significant difference in performance was detected between the dogs with each mutation. The results indicate that this novel canine vision-testing method is an accurate and sensitive means of distinguishing between unaffected dogs and dogs affected with two different forms of inherited retinal disease and should be useful as a means of assessing response to therapy in future studies.

Molecular Method for Sex Identification of Half-Smooth Tongue Sole (Cynoglossus semilaevis Using a Novel Sex-Linked Microsatellite Marker

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Xiaolin Liao

2014-07-01

Full Text Available Half-smooth tongue sole (Cynoglossus semilaevis is one of the most important flatfish species for aquaculture in China. To produce a monosex population, we attempted to develop a marker-assisted sex control technique in this sexually size dimorphic fish. In this study, we identified a co-dominant sex-linked marker (i.e., CyseSLM by screening genomic microsatellites and further developed a novel molecular method for sex identification in the tongue sole. CyseSLM has a sequence similarity of 73%–75% with stickleback, medaka, Fugu and Tetraodon. At this locus, two alleles (i.e., A244 and A234 were amplified from 119 tongue sole individuals with primer pairs CyseSLM-F1 and CyseSLM-R. Allele A244 was present in all individuals, while allele A234 (female-associated allele, FAA was mostly present in females with exceptions in four male individuals. Compared with the sequence of A244, A234 has a 10-bp deletion and 28 SNPs. A specific primer (CyseSLM-F2 was then designed based on the A234 sequence, which amplified a 204 bp fragment in all females and four males with primer CyseSLM-R. A time-efficient multiplex PCR program was developed using primers CyseSLM-F2, CyseSLM-R and the newly designed primer CyseSLM-F3. The multiplex PCR products with co-dominant pattern could be detected by agarose gel electrophoresis, which accurately identified the genetic sex of the tongue sole. Therefore, we have developed a rapid and reliable method for sex identification in tongue sole with a newly identified sex-linked microsatellite marker.

Application of real-time PCR of sex-independent insertion-deletion polymorphisms to determine fetal sex using cell-free fetal DNA from maternal plasma.

Science.gov (United States)

Ho, Sherry Sze Yee; Barrett, Angela; Thadani, Henna; Asibal, Cecille Laureano; Koay, Evelyn Siew-Chuan; Choolani, Mahesh

2015-07-01

Prenatal diagnosis of sex-linked disorders requires invasive procedures, carrying a risk of miscarriage of up to 1%. Cell-free fetal DNA (cffDNA) present in cell-free DNA (cfDNA) from maternal plasma offers a non-invasive source of fetal genetic material for analysis. Detection of Y-chromosome sequences in cfDNA indicates presence of a male fetus; in the absence of a Y-chromosome signal a female fetus is inferred. We aimed to validate the clinical utility of insertion-deletion polymorphisms (INDELs) to confirm presence of a female fetus using cffDNA. Quantitative real-time PCR (qPCR) for the Y-chromosome-specific sequence, SRY, was performed on cfDNA from 82 samples at 6-39 gestational weeks. In samples without detectable SRY, qPCRs for eight INDELs were performed on maternal genomic DNA and cfDNA. Detection of paternally inherited fetal alleles in cfDNA negative for SRY confirmed a female fetus. Fetal sex was correctly determined in 77/82 (93.9%) cfDNA samples. SRY was detected in all 39 samples from male-bearing pregnancies, and none of the 43 female-bearing pregnancies (sensitivity and specificity of SRY qPCR is therefore 100%; 95% CI 91%-100%). Paternally inherited fetal alleles were detected in 38/43 samples with no SRY signal, confirming the presence of a female fetus (INDEL assay sensitivity is therefore 88.4%; 95% CI 74.1%-95.6%). Since paternally inherited fetal INDELs were not used in women bearing male fetuses, the specificity of INDELs cannot be calculated. Five cfDNA samples were negative for both SRY and INDELS. We have validated a non-invasive prenatal test to confirm fetal sex as early as 6 gestational weeks using cffDNA from maternal plasma.

Clinical Characteristics and Current Therapies for Inherited Retinal Degenerations

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Sahel, José-Alain; Marazova, Katia; Audo, Isabelle

2015-01-01

Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307–316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod–cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone–rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances. PMID:25324231

Machado-Joseph disease in pedigrees of Azorean descent is linked to chromosome 14.

Science.gov (United States)

St George-Hyslop, P; Rogaeva, E; Huterer, J; Tsuda, T; Santos, J; Haines, J L; Schlumpf, K; Rogaev, E I; Liang, Y; McLachlan, D R

1994-07-01

A locus for Machado-Joseph disease (MJD) has recently been mapped to a 30-cM region of chromosome 14q in five pedigrees of Japanese descent. MJD is a clinically pleomorphic neurodegenerative disease that was originally described in subjects of Azorean descent. In light of the nonallelic heterogeneity in other inherited spinocerebellar ataxias, we were interested to determine if the MJD phenotype in Japanese and Azorean pedigrees arose from mutations at the same locus. We provide evidence that MJD in five pedigrees of Azorean descent is also linked to chromosome 14q in an 18-cM region between the markers D14S67 and AACT (multipoint lod score +7.00 near D14S81). We also report molecular evidence for homozygosity at the MJD locus in an MJD-affected subject with severe, early-onset symptoms. These observations confirm the initial report of linkage of MJD to chromosome 14; suggest that MJD in Japanese and Azorean subjects may represent allelic or identical mutations at the same locus; and provide one possible explanation (MJD gene dosage) for the observed phenotypic heterogeneity in this disease.

Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

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Daniel R. Bayzigitov

2016-01-01

Full Text Available Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes.

Fully automated pipeline for detection of sex linked genes using RNA-Seq data.

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Michalovova, Monika; Kubat, Zdenek; Hobza, Roman; Vyskot, Boris; Kejnovsky, Eduard

2015-03-11

Sex chromosomes present a genomic region which to some extent, differs between the genders of a single species. Reliable high-throughput methods for detection of sex chromosomes specific markers are needed, especially in species where genome information is limited. Next generation sequencing (NGS) opens the door for identification of unique sequences or searching for nucleotide polymorphisms between datasets. A combination of classical genetic segregation analysis along with RNA-Seq data can present an ideal tool to map and identify sex chromosome-specific expressed markers. To address this challenge, we established genetic cross of dioecious plant Rumex acetosa and generated RNA-Seq data from both parental generation and male and female offspring. We present a pipeline for detection of sex linked genes based on nucleotide polymorphism analysis. In our approach, tracking of nucleotide polymorphisms is carried out using a cross of preferably distant populations. For this reason, only 4 datasets are needed - reads from high-throughput sequencing platforms for parent generation (mother and father) and F1 generation (male and female progeny). Our pipeline uses custom scripts together with external assembly, mapping and variant calling software. Given the resource-intensive nature of the computation, servers with high capacity are a requirement. Therefore, in order to keep this pipeline easily accessible and reproducible, we implemented it in Galaxy - an open, web-based platform for data-intensive biomedical research. Our tools are present in the Galaxy Tool Shed, from which they can be installed to any local Galaxy instance. As an output of the pipeline, user gets a FASTA file with candidate transcriptionally active sex-linked genes, sorted by their relevance. At the same time, a BAM file with identified genes and alignment of reads is also provided. Thus, polymorphisms following segregation pattern can be easily visualized, which significantly enhances primer design

Case series of Stargardt's disease: Our experience

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Syed Abdul Wadud

2016-08-01

Full Text Available Stargardt disease is the most common form of juvenile macular degeneration. Clinically, it is characterized by pisciform flecks at lhe level of the retinal pigment epithelium and a bull's-eye maculopathy. Inheritance is usually autosomal recessive, although dominantly inherited case have been described. Both sexes are affected equally. We reported here three cases of Stargardt's macular dystrophy, who are siblings and daughters of non consanguineous parents. In case-1,2 and 3 we found the typical presentation with almost same findings.

Meiotic drive influences the outcome of sexually antagonistic selection at a linked locus.

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Patten, M M

2014-11-01

Most meiotic drivers, such as the t-haplotype in Mus and the segregation distorter (SD) in Drosophila, act in a sex-specific manner, gaining a transmission advantage through one sex although suffering only the fitness costs associated with the driver in the other. Their inheritance is thus more likely through one of the two sexes, a property they share with sexually antagonistic alleles. Previous theory has shown that pairs of linked loci segregating for sexually antagonistic alleles are more likely to remain polymorphic and that linkage disequilibrium accrues between them. I probe this similarity between drive and sexual antagonism and examine the evolution of chromosomes experiencing these selection pressures simultaneously. Reminiscent of previous theory, I find that: the opportunity for polymorphism increases for a sexually antagonistic locus that is physically linked to a driving locus; the opportunity for polymorphism at a driving locus also increases when linked to a sexually antagonistic locus; and stable linkage disequilibrium accompanies any polymorphic equilibrium. Additionally, I find that drive at a linked locus favours the fixation of sexually antagonistic alleles that benefit the sex in which drive occurs. Further, I show that under certain conditions reduced recombination between these two loci is selectively favoured. These theoretical results provide clear, testable predictions about the nature of sexually antagonistic variation on driving chromosomes and have implications for the evolution of genomic architecture. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Inherited myopathies and muscular dystrophies

NARCIS (Netherlands)

Cardamone, Michael; Darras, Basil T.; Ryan, Monique M.

The inherited myopathies and muscular dystrophies are a diverse group of muscle diseases presenting with common complaints and physical signs: weakness, motor delay, and respiratory and bulbar dysfunction. The myopathies are caused by genetic defects in the contractile apparatus of muscle, and

The Moroccan Genetic Disease Database (MGDD): a database for DNA variations related to inherited disorders and disease susceptibility.

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Charoute, Hicham; Nahili, Halima; Abidi, Omar; Gabi, Khalid; Rouba, Hassan; Fakiri, Malika; Barakat, Abdelhamid

2014-03-01

National and ethnic mutation databases provide comprehensive information about genetic variations reported in a population or an ethnic group. In this paper, we present the Moroccan Genetic Disease Database (MGDD), a catalogue of genetic data related to diseases identified in the Moroccan population. We used the PubMed, Web of Science and Google Scholar databases to identify available articles published until April 2013. The Database is designed and implemented on a three-tier model using Mysql relational database and the PHP programming language. To date, the database contains 425 mutations and 208 polymorphisms found in 301 genes and 259 diseases. Most Mendelian diseases in the Moroccan population follow autosomal recessive mode of inheritance (74.17%) and affect endocrine, nutritional and metabolic physiology. The MGDD database provides reference information for researchers, clinicians and health professionals through a user-friendly Web interface. Its content should be useful to improve researches in human molecular genetics, disease diagnoses and design of association studies. MGDD can be publicly accessed at http://mgdd.pasteur.ma.

Sex differences in prenatal epigenetic programming of stress pathways.

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Bale, Tracy L

2011-07-01

Maternal stress experience is associated with neurodevelopmental disorders including schizophrenia and autism. Recent studies have examined mechanisms by which changes in the maternal milieu may be transmitted to the developing embryo and potentially translated into programming of the epigenome. Animal models of prenatal stress have identified important sex- and temporal-specific effects on offspring stress responsivity. As dysregulation of stress pathways is a common feature in most neuropsychiatric diseases, molecular and epigenetic analyses at the maternal-embryo interface, especially in the placenta, may provide unique insight into identifying much-needed predictive biomarkers. In addition, as most neurodevelopmental disorders present with a sex bias, examination of sex differences in the inheritance of phenotypic outcomes may pinpoint gene targets and specific windows of vulnerability in neurodevelopment, which have been disrupted. This review discusses the association and possible contributing mechanisms of prenatal stress in programming offspring stress pathway dysregulation and the importance of sex.

Why do people buy dogs with potential welfare problems related to extreme conformation and inherited disease? A representative study of Danish owners of four small dog breeds

OpenAIRE

Sand?e, P.; Kondrup, S. V.; Bennett, P. C.; Forkman, B.; Meyer, I; Proschowsky, H. F.; Serpell, J. A.; Lund, T. B.

2017-01-01

number of dog breeds suffer from welfare problems due to extreme phenotypes and high levels of inherited diseases but the popularity of such breeds is not declining. Using a survey of owners of two popular breeds with extreme physical features (French Bulldog and Chihuahua), one with a high load of inherited diseases not directly related to conformation (Cavalier King Charles Spaniel), and one representing the same size range but without extreme conformation and with the same level of disease...

Linking Temperamental Shyness and Social Anxiety in Childhood and Adolescence: Moderating Influences of Sex and Age.

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Tsui, Tiffany Y L; Lahat, Ayelet; Schmidt, Louis A

2017-10-01

Although childhood shyness has been linked to social anxiety problems, the factors playing a role in this association have gone largely unexplored. Here we examined the potential moderating roles of sex and age on this relation in a sample of 119 (75 girls) children (10-12 years) and adolescents (14-16 years). As predicted, shyness was positively associated with social anxiety symptoms. Sex, but not age, served as a moderating factor in linking shyness and social anxiety. Specifically, shyness was more strongly associated with social anxiety symptoms among girls than boys. These results suggest the importance of considering sex differences when examining the relation between shyness and social anxiety in childhood and adolescence.

Inheritance Law between Common and Civil Law - As exemplified by life-long support contracts

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Jadranka Đorđević-Crnobrnja

2016-02-01

Full Text Available The dualism between common law and civil law in Serbia has been examined in theoretical and factographical ethnological and legal literature, yet this problem in the sphere of inheritance law has been considered mostly within the context of inequality between the sexes in matters of inheritance. As a result, the question of the connection between life-long support contracts and inheritance remains unexplored, despite the fact that through the analysis of inheritance practices based on this kind of contract the influence of socio-cultural mechanisms on the institution of inheritance can be clearly observed. These insights, together with the fact that a dualism and parallelism of civil and common have existed in Serbia for more than a century, have inspired an analysis of life-long support contracts in order to problematize the relation between common law and civil law in practice.

Palmo-Plantar hyperkeratosis, intellectual disability, and spastic paraplegia in two maternal half brothers: further evidence for an X-linked inheritance.

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Isidor, Bertrand; Lefebvre, Tiphaine; Barbarot, Sébastien; Perrier, Julie; Mercier, Sandra; Péréon, Yann; Le Caignec, Cédric; David, Albert

2013-06-01

In 1983, Fitzsimmons et al. reported four brothers with an unrecognized disorder characterized by intellectual disability, spastic paraplegia, and palmo-plantar hyperkeratosis (OMIM 309500). In this report, we describe a family in which two males, maternal half-brothers, had learning disabilities. Both patients also showed spasticity in the lower limbs and palmo-plantar hyperkeratosis. The mother of the affected boys had learning difficulties but did not show any dermatological symptoms. This report confirms that the association of features reported by Fitzsimmons et al. is a distinct entity and further suggests an X-linked mode of inheritance. Copyright © 2013 Wiley Periodicals, Inc.

Inherited metabolic disorders in Thailand.

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Wasant, Pornswan; Svasti, Jisnuson; Srisomsap, Chantragan; Liammongkolkul, Somporn

2002-08-01

The study of inborn errors of metabolism (IEM) in Thailand is in its infancy. The majority are clinically diagnosed since there are only a handful of clinicians and scientists with expertise in inherited metabolic disorders, shortage of well-equipped laboratory facilities and lack of governmental financial support. Genetic metabolic disorders are usually not considered a priority due to prevalence of infectious diseases and congenital infections. From a retrospective study at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital; estimated pediatrics patients with suspected IEM were approximately 2-3 per cent of the total pediatric admissions of over 5,000 annually. After more than 10 years of research and accumulated clinical experiences, a genetic metabolic center is being established in collaboration with expert laboratories both in Bangkok (Chulabhorn Research Institute) and abroad (Japan and the United States). Numerous inherited metabolic disorders were identified--carbohydrate, amino acids, organic acids, mitochondrial fatty acid oxidation, peroxisomal, mucopolysaccharidoses etc. This report includes the establishment of genetic metabolic center in Thailand, research and pilot studies in newborn screening in Thailand and a multicenter study from 5 institutions (Children's National Center, King Chulalongkorn Memorial Hospital, Pramongkutklao Hospital, Ramathibodi and Siriraj Hospitals). Inherited metabolic disorders reported are fructose-1,6-bisphosphatase deficiency, phenylketonuria, homocystinuria, nonketotic hyperglycinemia, urea cycle defect (arginino succinate lyase deficiency, argininosuccinate synthetase deficiency), Menkes disease, propionic acidemia and mucopolysaccharidoses (Hurler, Hurler-Scheie).

APOE AND ALZHEIMER DISEASE: A MAJOR GENE WITH SEMI-DOMINANT INHERITANCE

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Genin, Emmanuelle; Hannequin, Didier; Wallon, David; Sleegers, Kristel; Hiltunen, Mikko; Combarros, Onofre; Bullido, Maria J; Engelborghs, Sebastiaan; De Deyn, Peter; Berr, Claudine; Pasquier, Florence; Dubois, Bruno; Tognoni, Gloria; Fiévet, Nathalie; Brouwers, Nathalie; Bettens, Karolien; Arosio, Beatrice; Coto, Eliecer; Zompo, Maria Del; Mateo, Ignacio; Epelbaum, Jacques; Frank-Garcia, Ana; Helisalmi, Seppo; Porcellini, Elisa; Pilotto, Alberto; Forti, Paola; Ferri, Raffaele; Scarpini, Elio; Siciliano, Gabriele; Solfrizzi, Vincenzo; Sorbi, Sandro; Spalletta, Gianfranco; Valdivieso, Fernando; Vepsäläinen, Saila; Alvarez, Victoria; Bosco, Paolo; Mancuso, Michelangelo; Panza, Francesco; Nacmias, Benedetta; Bossù, Paola; Hanon, Olivier; Piccardi, Paola; Annoni, Giorgio; Seripa, Davide; Galimberti, Daniela; Licastro, Federico; Soininen, Hilkka; Dartigues, Jean-François; Kamboh, M Ilyas; Van Broeckhoven, Christine; Lambert, Jean Charles; Amouyel, Philippe; Campion, Dominique

2011-01-01

Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios (ORs) alone are insufficient to assess these risks. We calculated AD lifetime risk in 7,351 cases and 10,132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68% and 35 % for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age- groups clearly demonstrates that APOE4 is a risk factor not only for late- onset but for early- onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease. PMID:21556001

Links between sex-typed time use in middle childhood and gender development in early adolescence.

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McHale, Susan M; Kim, Ji-Yeon; Whiteman, Shawn; Crouter, Ann C

2004-09-01

The authors studied sex-typing in the kinds (e.g., sports, handicrafts) and social contexts (same- vs. other-sex companions) of children's free time activities, and the links between sex-typed activities and gender development over 2 years. Participants were 200 White, working- and middle-class children (103 girls, 97 boys; mean age = 10.86 years). In annual home interviews, children rated their self-esteem, gender role attitudes and sex-typed personality qualities, academic interests, and school grades. During 7 nightly phone interviews each year, children reported on their activities. Boys were more sex-typed than girls in their peer activities, and children were least sex-typed in their activities with siblings. Sex-typed activities in middle childhood predicted individual differences in gender development in early adolescence. Copyright 2004 American Psychological Association

X inactivation in females with X-linked Charcot-Marie-Tooth disease.

LENUS (Irish Health Repository)

Murphy, Sinéad M

2012-07-01

X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common inherited neuropathy, caused by mutations in gap junction beta-1 (GJB1). Males have a uniformly moderately severe phenotype while females have a variable phenotype, suggested to be due to X inactivation. We aimed to assess X inactivation pattern in females with CMT1X and correlate this with phenotype using the CMT examination score to determine whether the X inactivation pattern accounted for the variable phenotype in females with CMT1X. We determined X inactivation pattern in 67 females with CMT1X and 24 controls using the androgen receptor assay. We were able to determine which X chromosome carried the GJB1 mutation in 30 females. There was no difference in X inactivation pattern between patients and controls. In addition, there was no correlation between X inactivation pattern in blood and phenotype. A possible explanation for these findings is that the X inactivation pattern in Schwann cells rather than in blood may explain the variable phenotype in females with CMT1X.

Inborn Errors of Metabolism with Hypoglycemia Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis : Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis

NARCIS (Netherlands)

Weinstein, David A.; Steuerwald, Ulrike; De Souza, Carolina F. M.; Derks, Terry G. J.

Although hyperinsulinism is the predominant inherited cause of hypoglycemia in the newborn period, inborn errors of metabolism are the primary etiologies after 1 month of age. Disorders of carbohydrate metabolism often present with hypoglycemia when fasting occurs. The presentation, diagnosis, and

Reliving emotional personal memories: affective biases linked to personality and sex-related differences.

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Denkova, Ekaterina; Dolcos, Sanda; Dolcos, Florin

2012-06-01

Although available evidence suggests that the emotional valence and recollective properties of autobiographical memories (AMs) may be influenced by personality- and sex-related differences, overall these relationships remain poorly understood. The present study investigated these issues by comparing the effect of general personality traits (extraversion and neuroticism) and specific traits linked to emotion regulation (ER) strategies (reappraisal and suppression) on the retrieval of emotional AMs and on the associated postretrieval emotional states, in men and women. First, extraversion predicted recollection of positive AMs in both men and women, whereas neuroticism predicted the proportion of negative AMs in men and the frequency of rehearsing negative AMs in women. Second, reappraisal predicted positive AMs in men, and suppression predicted negative AMs in women. Third, while reliving of positive memories had an overall indirect effect on postretrieval positive mood through extraversion, reliving of negative AMs had a direct effect on postretrieval negative mood, which was linked to inefficient engagement of suppression in women. Our findings suggest that personality traits associated with positive affect predict recollection of positive AMs and maintenance of a positive mood, whereas personality traits associated with negative affect, along with differential engagement of habitual ER strategies in men and women, predict sex-related differences in the recollection and experiencing of negative AMs. These findings provide insight into the factors that influence affective biases in reliving AMs, and into their possible link to sex-related differences in the susceptibility to affective disorders.

Sex modifies the APOE-related risk of developing Alzheimer disease.

Science.gov (United States)

Altmann, Andre; Tian, Lu; Henderson, Victor W; Greicius, Michael D

2014-04-01

The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer disease (AD). Case-control studies suggest the APOE4 link to AD is stronger in women. We examined the APOE4-by-sex interaction in conversion risk (from healthy aging to mild cognitive impairment (MCI)/AD or from MCI to AD) and cerebrospinal fluid (CSF) biomarker levels. Cox proportional hazards analysis was used to compute hazard ratios (HRs) for an APOE-by-sex interaction on conversion in controls (n = 5,496) and MCI patients (n = 2,588). The interaction was also tested in CSF biomarker levels of 980 subjects from the Alzheimer's Disease Neuroimaging Initiative. Among controls, male and female carriers were more likely to convert to MCI/AD, but the effect was stronger in women (HR = 1.81 for women; HR = 1.27 for men; interaction: p = 0.011). The interaction remained significant in a predefined subanalysis restricted to APOE3/3 and APOE3/4 genotypes. Among MCI patients, both male and female APOE4 carriers were more likely to convert to AD (HR = 2.16 for women; HR = 1.64 for men); the interaction was not significant (p = 0.14). In the subanalysis restricted to APOE3/3 and APOE3/4 genotypes, the interaction was significant (p = 0.02; HR = 2.17 for women; HR = 1.51 for men). The APOE4-by-sex interaction on biomarker levels was significant for MCI patients for total tau and the tau-to-Aβ ratio (p = 0.009 and p = 0.02, respectively; more AD-like in women). APOE4 confers greater AD risk in women. Biomarker results suggest that increased APOE-related risk in women may be associated with tau pathology. These findings have important clinical implications and suggest novel research approaches into AD pathogenesis. © 2014 American Neurological Association.

To inherit heritage or to inherit inheritance?

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Vladimir Krivošejev

2016-02-01

Full Text Available The Republic of Serbia is one of the few, if not the only country in the world that, at ratification and translation of the term „baština“– heritage which appears in two significant and related international conventions of UNESCO, used different terms: „baština“– „heritage“, with regard to the Convention Concerning the Protection of the World Cultural and Natural Heritage, and „nasledje“ –inheritance in the Convention for the Safeguarding of the Intangible Cultural Heritage. One of the reasons for the subsequent rejection of the term heritage could lay in the opinion that it was the case of (end of 20th and beginning of the 21st century political bureaucratic introduction of an old, forgotten word, which also contains the notion of gender incorrectness based on pointing out the inheritance through the male line, which could be in conflict with international law. The views expressed in this paper suggest the unsustainability of these claims, as well as greater suitability of the term „baština“– heritage. Namely, the ratification of the Convention Concerning the Protection of the World Cultural and Natural Heritage was done as early as in 1974, and since then the term „baština“– heritage was used, its new introduction into use on the basis of recent daily political aspirations cannot be the case. At the same time inheritance through the male line is encountered with the use of the Latin word „patrimonium“, which is the basis for the terms used in the official translation of the UNESCO-listed conventions in French and Spanish: „patrimoine“ and „patrimonio“ (and other Roman languages so that the use of the term „baština“ –heritage cannot be a violation of international legal norms. Finally, bearing in mind the fact that, in general, use of languages is impossible to achieve complete gender purism, it is necessary to emphasize that in contrast to the term „nasledje“ – inheritance, the

Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems.

Science.gov (United States)

Ye, Christine J; Regan, Sarah; Liu, Guo; Alemara, Sarah; Heng, Henry H

2018-01-01

In the past 15 years, impressive progress has been made to understand the molecular mechanism behind aneuploidy, largely due to the effort of using various -omics approaches to study model systems (e.g. yeast and mouse models) and patient samples, as well as the new realization that chromosome alteration-mediated genome instability plays the key role in cancer. As the molecular characterization of the causes and effects of aneuploidy progresses, the search for the general mechanism of how aneuploidy contributes to cancer becomes increasingly challenging: since aneuploidy can be linked to diverse molecular pathways (in regards to both cause and effect), the chances of it being cancerous is highly context-dependent, making it more difficult to study than individual molecular mechanisms. When so many genomic and environmental factors can be linked to aneuploidy, and most of them not commonly shared among patients, the practical value of characterizing additional genetic/epigenetic factors contributing to aneuploidy decreases. Based on the fact that cancer typically represents a complex adaptive system, where there is no linear relationship between lower-level agents (such as each individual gene mutation) and emergent properties (such as cancer phenotypes), we call for a new strategy based on the evolutionary mechanism of aneuploidy in cancer, rather than continuous analysis of various individual molecular mechanisms. To illustrate our viewpoint, we have briefly reviewed both the progress and challenges in this field, suggesting the incorporation of an evolutionary-based mechanism to unify diverse molecular mechanisms. To further clarify this rationale, we will discuss some key concepts of the genome theory of cancer evolution, including system inheritance, fuzzy inheritance, and cancer as a newly emergent cellular system. Illustrating how aneuploidy impacts system inheritance, fuzzy inheritance and the emergence of new systems is of great importance. Such synthesis

Sex and Management of Rheumatoid Arthritis.

Science.gov (United States)

Favalli, Ennio Giulio; Biggioggero, Martina; Crotti, Chiara; Becciolini, Andrea; Raimondo, Maria Gabriella; Meroni, Pier Luigi

2018-01-26

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease more common in women than men (3:1). Although sex-based differences may play a complex role in promoting an autoimmune dysfunction, to date the comprehensive knowledge of the link between sex and RA is still partially lacking. Furthermore, males and females have been demonstrated to differently deal with their chronic pathologies, modifying the perceived sex-based burden of disease. Gender medicine is a newly approach focusing on the impact of gender differences on human physiology, pathophysiology, and clinical features of diseases, analyzing the complex interrelation and integration of sex and psychological and cultural behavior. A better comprehension of possible factors influencing sexual dimorphism in RA susceptibility, pattern of presentation, disease activity, and outcome could contribute to a tailored approach, in order to limit the morbidity of the disease. RA disease activity seems to be higher in women, whereas the response rate to synthetic and biologic disease-modifying therapies appears to be better in males. Moreover, the common strategies for RA management may be affected by concomitant pregnancy or childbearing desire, with particular regard to treatments with potential teratogenic effects or impact on fertility. Finally, comorbidities, such as fibromyalgia, major depression, and osteoporosis, are more frequent in females, while the impact of sex on cardiovascular risk is still controversial. Moving from the role of sex in influencing RA pathogenesis, epidemiology, and disease characteristics, this review explores the evidence on how sex can have an impact on strategies for managing patients with RA.

The immigration delay disease: adermatoglyphia-inherited absence of epidermal ridges.

Science.gov (United States)

Burger, Bettina; Fuchs, Dana; Sprecher, Eli; Itin, Peter

2011-05-01

In the digital age, personal identification by fingerprints (epidermal ridges) has become more frequent and is often required for biometric passports. The more fingerprints are analyzed, the more variants in their formation are documented. Individuals completely missing fingerprints as an isolated finding are extremely rare. Only 4 kindreds have been described to date, with additional clinical features in most cases. We describe a female patient with missing epidermal ridges on the fingers, palms, toes, and soles as an isolated feature. Absent fingerprints, or adermatoglyphia, were inherited over 4 generations of her family in an autosomal dominant fashion. We present the clinical features of the index patient, and compare the case with previous reports in the literature. Because of problems in personal identification, this embryologic malformation caused the patient significant difficulties when traveling to other countries, which is why we name it the immigration delay disease. Copyright © 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Neural/Bayes network predictor for inheritable cardiac disease pathogenicity and phenotype.

Science.gov (United States)

Burghardt, Thomas P; Ajtai, Katalin

2018-04-11

The cardiac muscle sarcomere contains multiple proteins contributing to contraction energy transduction and its regulation during a heartbeat. Inheritable heart disease mutants affect most of them but none more frequently than the ventricular myosin motor and cardiac myosin binding protein c (mybpc3). These co-localizing proteins have mybpc3 playing a regulatory role to the energy transducing motor. Residue substitution and functional domain assignment of each mutation in the protein sequence decides, under the direction of a sensible disease model, phenotype and pathogenicity. The unknown model mechanism is decided here using a method combing neural and Bayes networks. Missense single nucleotide polymorphisms (SNPs) are clues for the disease mechanism summarized in an extensive database collecting mutant sequence location and residue substitution as independent variables that imply the dependent disease phenotype and pathogenicity characteristics in 4 dimensional data points (4ddps). The SNP database contains entries with the majority having one or both dependent data entries unfulfilled. A neural network relating causes (mutant residue location and substitution) and effects (phenotype and pathogenicity) is trained, validated, and optimized using fulfilled 4ddps. It then predicts unfulfilled 4ddps providing the implicit disease model. A discrete Bayes network interprets fulfilled and predicted 4ddps with conditional probabilities for phenotype and pathogenicity given mutation location and residue substitution thus relating the neural network implicit model to explicit features of the motor and mybpc3 sequence and structural domains. Neural/Bayes network forecasting automates disease mechanism modeling by leveraging the world wide human missense SNP database that is in place and expanding. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Private inherited microdeletion/microduplications: implications in clinical practice.

Science.gov (United States)

Mencarelli, Maria Antonietta; Katzaki, Eleni; Papa, Filomena Tiziana; Sampieri, Katia; Caselli, Rossella; Uliana, Vera; Pollazzon, Marzia; Canitano, Roberto; Mostardini, Rosa; Grosso, Salvatore; Longo, Ilaria; Ariani, Francesca; Meloni, Ilaria; Hayek, Josef; Balestri, Paolo; Mari, Francesca; Renieri, Alessandra

2008-01-01

The introduction of array-CGH analysis is allowing the identification of novel genomic disorders. However, this new high-resolution technique is also opening novel diagnostic challenges when inherited private CNVs of unclear clinical significance are found. Oligo array-CGH analysis of 84 patients with mild to severe mental retardation associated with multiple congenital anomalies revealed 10 private CNVs inherited from a healthy parent. Three were deletions (7q31, 14q21.1, Xq25) and seven duplications (12p11.22, 12q21.31, 13q31.1, 17q12, Xp22.31, Xq28) ranging between 0.1 and 3.8Mb. Six rearrangements were not polymorphic. Four overlapped polymorphic regions to the extent of 10-61%. In one case the size was different between the proband and the healthy relative. Three small rearrangements were gene deserts. The remaining seven had a mean gene content of five (ranging from 1 to 18). None of the rearranged genes is known to be imprinted. Three disease-genes were found in three different cases: KAL1 in dupXp22.31, STS in another dupXp22.31 and TCF2 in dup17q12. The patient carrying the last duplication presents sex reversal, Peters' anomaly and renal cysts and the duplication is located 4Mb away from the HSD17B1 gene, coding a key enzyme of testosterone biosynthesis. Considering the overlap with polymorphic regions, size-identity within the family, gene content, kind of rearrangement and size of rearrangement we suggest that at least in five cases the relationship to the phenotype has not to be excluded. We recommend to maintain caution when asserting that chromosomal abnormalities inherited from a healthy parent are benign. A more complex mechanism may in fact be involved, such as a concurrent variation in the other allele or in another chromosome that influences the phenotype.

Coalgebraic structure of genetic inheritance.

Science.gov (United States)

Tian, Jianjun; Li, Bai-Lian

2004-09-01

Although in the broadly defined genetic algebra, multiplication suggests a forward direction of from parents to progeny, when looking from the reverse direction, it also suggests to us a new algebraic structure-coalge- braic structure, which we call genetic coalgebras. It is not the dual coalgebraic structure and can be used in the construction of phylogenetic trees. Math- ematically, to construct phylogenetic trees means we need to solve equations x([n]) = a, or x([n]) = b. It is generally impossible to solve these equations inalgebras. However, we can solve them in coalgebras in the sense of tracing back for their ancestors. A thorough exploration of coalgebraic structure in genetics is apparently necessary. Here, we develop a theoretical framework of the coalgebraic structure of genetics. From biological viewpoint, we defined various fundamental concepts and examined their elementary properties that contain genetic significance. Mathematically, by genetic coalgebra, we mean any coalgebra that occurs in genetics. They are generally noncoassociative and without counit; and in the case of non-sex-linked inheritance, they are cocommutative. Each coalgebra with genetic realization has a baric property. We have also discussed the methods to construct new genetic coalgebras, including cocommutative duplication, the tensor product, linear combinations and the skew linear map, which allow us to describe complex genetic traits. We also put forward certain theorems that state the relationship between gametic coalgebra and gametic algebra. By Brower's theorem in topology, we prove the existence of equilibrium state for the in-evolution operator.

Sex difference in link between interleukin-6 and stress.

Science.gov (United States)

Jankord, Ryan; Turk, James R; Schadt, James C; Casati, Jennifer; Ganjam, Venkataseshu K; Price, Elmer M; Keisler, Duane H; Laughlin, M Harold

2007-08-01

Inflammation contributes to disease development, and the neuroimmunoendocrine interface is a potential site of action for inflammatory products like IL-6 to affect health. Although plasma IL-6 can stimulate the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis, the precise role, if any, for IL-6 in the HPA response to nonimmunological stressors is unclear. The purpose of this study was to test the hypothesis that IL-6 in the stalk median eminence (SME) can be directly involved in stimulating ACTH secretion in response to acute stress in female swine. This study was undertaken as a result of finding IL-6 localized to the external zone of the SME next to the hypophyseal portal vessels. Results indicate that content of IL-6 in the SME decreases in response to acute stress along with an increase in nuclear phosphorylated signal transducer and activator of transcription-3 (pSTAT-3) in pituitary corticotrophs and a simultaneous increase in plasma concentrations of IL-6 and ACTH. Furthermore, we show that females concomitantly display greater SME content of IL-6 and greater HPA responsiveness to stress, thereby suggesting that IL-6 release from the SME is an integral factor contributing to enhanced stress responsiveness in females. Our results provide evidence for a direct link between IL-6 and ACTH release and reveal a sex difference in this relationship.

Sex Difference in Link between IL-6 and Stress

Science.gov (United States)

Jankord, Ryan; Turk, James R.; Schadt, James C.; Casati, Jennifer; Ganjam, Venkataseshu K.; Price, Elmer M.; Keisler, Duane H.; Laughlin, M. Harold

2009-01-01

Inflammation contributes to disease development, and the neuro-immuno-endocrine interface is a potential site of action for inflammatory products like IL-6 to affect health. Although plasma IL-6 can stimulate the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis, the precise role, if any, for IL-6 in the HPA response to non-immunological stressors is unclear. The purpose of this study was to test the hypothesis that IL-6 in the stalk median eminence (SME) can be directly involved in stimulating ACTH secretion in response to acute stress in female swine. This study was undertaken as a result of finding IL-6 localized to the external zone of the stalk median eminence (SME) next to the hypophyseal portal vessels. Results indicate that content of IL-6 in the SME decreases in response to acute stress along with an increase in phosphorylation of STAT3 in the anterior pituitary and a simultaneous increase in plasma concentrations of IL-6 and ACTH. Furthermore, we show that females concomitantly display greater SME content of IL-6 and greater HPA responsiveness to stress, thereby suggesting that IL-6 release from the SME is an integral factor contributing to enhanced stress responsiveness in females. Our results provide evidence for a direct link between IL-6 and ACTH release and reveal a sex difference in this relationship. PMID:17510233

Identification of a sex-linked SNP marker in the salmon louse (Lepeophtheirus salmonis using RAD sequencing.

Directory of Open Access Journals (Sweden)

Stephen N Carmichael

Full Text Available The salmon louse (Lepeophtheirus salmonis (Krøyer, 1837 is a parasitic copepod that can, if untreated, cause considerable damage to Atlantic salmon (Salmo salar Linnaeus, 1758 and incurs significant costs to the Atlantic salmon mariculture industry. Salmon lice are gonochoristic and normally show sex ratios close to 1:1. While this observation suggests that sex determination in salmon lice is genetic, with only minor environmental influences, the mechanism of sex determination in the salmon louse is unknown. This paper describes the identification of a sex-linked Single Nucleotide Polymorphism (SNP marker, providing the first evidence for a genetic mechanism of sex determination in the salmon louse. Restriction site-associated DNA sequencing (RAD-seq was used to isolate SNP markers in a laboratory-maintained salmon louse strain. A total of 85 million raw Illumina 100 base paired-end reads produced 281,838 unique RAD-tags across 24 unrelated individuals. RAD marker Lsa101901 showed complete association with phenotypic sex for all individuals analysed, being heterozygous in females and homozygous in males. Using an allele-specific PCR assay for genotyping, this SNP association pattern was further confirmed for three unrelated salmon louse strains, displaying complete association with phenotypic sex in a total of 96 genotyped individuals. The marker Lsa101901 was located in the coding region of the prohibitin-2 gene, which showed a sex-dependent differential expression, with mRNA levels determined by RT-qPCR about 1.8-fold higher in adult female than adult male salmon lice. This study's observations of a novel sex-linked SNP marker are consistent with sex determination in the salmon louse being genetic and following a female heterozygous system. Marker Lsa101901 provides a tool to determine the genetic sex of salmon lice, and could be useful in the development of control strategies.

Familial epilepsy in Algeria: Clinical features and inheritance profiles.

Science.gov (United States)

Chentouf, Amina; Dahdouh, Aïcha; Guipponi, Michel; Oubaiche, Mohand Laïd; Chaouch, Malika; Hamamy, Hanan; Antonarakis, Stylianos E

2015-09-01

To document the clinical characteristics and inheritance pattern of epilepsy in multigeneration Algerian families. Affected members from extended families with familial epilepsy were assessed at the University Hospital of Oran in Algeria. Available medical records, neurological examination, electroencephalography and imaging data were reviewed. The epilepsy type was classified according to the criteria of the International League Against Epilepsy and modes of inheritance were deduced from pedigree analysis. The study population included 40 probands; 23 male (57.5%) and 17 female subjects (42.5%). The mean age of seizure onset was 9.5 ± 6.1 years. According to seizure onset, 16 patients (40%) had focal seizures and 20 (50%) had generalized seizures. Seizure control was achieved for two patients (5%) for 10 years, while 28 (70%) were seizure-free for 3 months. Eleven patients (27.5%) had prior febrile seizures, 12 were diagnosed with psychiatric disorders and four families had syndromic epilepsy. The consanguinity rate among parents of affected was 50% with phenotypic concordance observed in 25 families (62.5%). Pedigree analysis suggested autosomal dominant (AD) inheritance with or without reduced penetrance in 18 families (45%), probable autosomal recessive (AR) inheritance in 14 families (35%), and an X-linked recessive inheritance in one family. This study reveals large Algerian families with multigenerational inheritance of epilepsy. Molecular testing such as exome sequencing would clarify the genetic basis of epilepsy in some of our families. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Mutagenic Potential of Nitroguanidine in the Drosophila melanogaster Sex-Linked Recessive Lethal Test

Science.gov (United States)

1988-07-01

Security Classification) Mtutagenic potential of nitroguan idine in the Drosophila melano- gaster sex-linked recessive lethal test 12. PERSONAL AUTHOR(S...Frederick, MD 21701-5012 Commander Commandant US Army Environmental Hygine Academy of Health Sciences. US Army Agency ATTN: AHS-CDM ATTN: Librarian, HSDH

Novel mutation in TSPAN12 leads to autosomal recessive inheritance of congenital vitreoretinal disease with intra-familial phenotypic variability.

Science.gov (United States)

Gal, Moran; Levanon, Erez Y; Hujeirat, Yasir; Khayat, Morad; Pe'er, Jacob; Shalev, Stavit

2014-12-01

Developmental malformations of the vitreoretinal vasculature are a heterogeneous group of conditions with various modes of inheritance, and include familial exudative vitreoretinopathy (FEVR), persistent fetal vasculature (PFV), and Norrie disease. We investigated a large consanguineous kindred with multiple affected individuals exhibiting variable phenotypes of abnormal vitreoretinal vasculature, consistent with the three above-mentioned conditions and compatible with autosomal recessive inheritance. Exome sequencing identified a novel c.542G > T (p.C181F) apparently mutation in the TSPAN12 gene that segregated with the ocular disease in the family. The TSPAN12 gene was previously reported to cause dominant and recessive FEVR, but has not yet been associated with other vitreoretinal manifestations. The intra-familial clinical variability caused by a single mutation in the TSPAN12 gene underscores the complicated phenotype-genotype correlation of mutations in this gene, and suggests that there are additional genetic and environmental factors involved in the complex process of ocular vascularization during embryonic development. Our study supports considering PFV, FEVR, and Norrie disease a spectrum of disorders, with clinical and genetic overlap, caused by mutations in distinct genes acting in the Norrin/β-catenin signaling pathway. © 2014 Wiley Periodicals, Inc.

Climate-driven population divergence in sex-determining systems

NARCIS (Netherlands)

Pen, Ido; Uller, Tobias; Feldmeyer, Barbara; Harts, Anna; While, Geoffrey M.; Wapstra, Erik

2010-01-01

Sex determination is a fundamental biological process, yet its mechanisms are remarkably diverse(1,2). In vertebrates, sex can be determined by inherited genetic factors or by the temperature experienced during embryonic development(2,3). However, the evolutionary causes of this diversity remain

Menkes disease

DEFF Research Database (Denmark)

Tümer, Zeynep; Møller, Lisbeth B

2010-01-01

Menkes disease (MD) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar 'kinky' hair are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority...... of surplus copper from cells. Severely affected MD patients die usually before the third year of life. A cure for the disease does not exist, but very early copper-histidine treatment may correct some of the neurological symptoms....

Prevalence, phenotype and inheritance of benign neutropenia in Arabs

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Nagelkerke Nicollas

2009-03-01

Full Text Available Abstract Background Benign neutropenia, i.e., neutropenia not associated with an increased risk of infection, may result in serious medical consequences when a 'standard' definition of neutropenia (absolute neutrophil count (ANC 9cells/L is universally applied to all races. The aims of this study were to determine the prevalence of benign neutropenia among healthy Arabs and evaluate its mode of inheritance. Methods ANCs were studied prospectively amongst a healthy indigenous population (n = 1032 from the United Arab Emirates undergoing a nation-wide sickle-cell and thalassemia screening program. The mean neutrophil count and the prevalence of benign neutropenia were compared by age, sex and amongst various tribes. Results The mean neutrophil count (× 109cells/L was 3.3 (range 0.95–7.6. Benign neutropenia was present in 110 (10.7% subjects of whom 24 (2.3% individuals had moderate neutropenia (ANC 0.5 – 1.0 × 109 cells/L. In the 22 tribe-family groups, the prevalence of benign neutropenia varied between 0% and 38%. Benign neutropenia showed no difference in the frequency amongst the sexes (p = 0.23 and it was independent of age (Spearman's rho = 0.05, p = 0.13. The age-related mean neutrophil count was the lowest in Arabs when compared with other ethnic groups (Blacks, Europeans and Mexicans. The inheritance of benign neutropenia was consistent with an autosomal dominant pattern; however, the diversity of observed phenotypes suggested the presence of more than one genetic variant for this trait. Conclusion Arabs have a high prevalence of benign neutropenia that may be inherited as an autosomal dominant trait.

Mechanisms of rapid sympatric speciation by sex reversal and sexual selection in cichlid fish.

Science.gov (United States)

Lande, R; Seehausen, O; van Alphen, J J

2001-01-01

Mechanisms of speciation in cichlid fish were investigated by analyzing population genetic models of sexual selection on sex-determining genes associated with color polymorphisms. The models are based on a combination of laboratory experiments and field observations on the ecology, male and female mating behavior, and inheritance of sex-determination and color polymorphisms. The models explain why sex-reversal genes that change males into females tend to be X-linked and associated with novel colors, using the hypothesis of restricted recombination on the sex chromosomes, as suggested by previous theory on the evolution of recombination. The models reveal multiple pathways for rapid sympatric speciation through the origin of novel color morphs with strong assortative mating that incorporate both sex-reversal and suppressor genes. Despite the lack of geographic isolation or ecological differentiation, the new species coexists with the ancestral species either temporarily or indefinitely. These results may help to explain different patterns and rates of speciation among groups of cichlids, in particular the explosive diversification of rock-dwelling haplochromine cichlids.

Clinical and inheritance profiles of Kallmann syndrome in Jordan

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Shegem Nadima S

2004-10-01

Full Text Available Abstract Background Proper management of patients with Kallmann syndrome (KS allows them to attain a normal reproductive health. The purpose of this study is to demonstrate the presentation modalities, phenotypes and the modes of inheritance among 32 patients with Kallmann syndrome in Jordan. Recognition of the syndrome allows for prompt proper management and provision of genetic counselling. Subjects Over a period of five years (1999–2004, the clinical and inheritance profiles of 26 male and 6 female patients with Kallmann syndrome from 12 families were evaluated at the National Center for Diabetes, Endocrinology and Genetics in Jordan. Results The patients belonged to twelve Jordanian and Palestinian families and their age at presentation ranged from 4 – 46 years. Nine boys aged 4–14 years presented with cryptorchidism and microphallus, all other males presented with delayed puberty, hypogonadism and/or infertility. The main presentation among six female patients was primary amenorrhea. Intrafamilial variability in clinical phenotype was specifically evident for renal abnormalities and sensorineural hearing impairment. Familial KS was diagnosed in 27 patients belonging to five families with the X-linked mode of inheritance and two families with the autosomal recessive mode of inheritance. Conclusions (1 the majority of cases in this study represented the X-linked form of KS, which might point to a high prevalence of Kal 1 gene in the population. (2 Genetic counselling helps these families to reach a diagnosis at an early age and to decide about their reproductive options. (3 Children presenting with cryptorchidism and microphallus in our population should be investigated for KS.

The importance of studying sex differences in disease: The example of multiple sclerosis.

Science.gov (United States)

Golden, Lisa C; Voskuhl, Rhonda

2017-01-02

To date, scientific research has often focused on one sex, with assumptions that study of the other sex would yield similar results. However, many diseases affect males and females differently. The sex of a patient can affect the risk for both disease susceptibility and progression. Such differences can be brought to the laboratory bench to be investigated, potentially bringing new treatments back to the clinic. This method of research, known as a "bedside to bench to bedside" approach, has been applied to studying sex differences in multiple sclerosis (MS). Females have greater susceptibly to MS, while males have worse disease progression. These two characteristics of the disease are influenced by the immune system and the nervous system, respectively. Thus, sex differences in each system must be studied. Personalized medicine has been at the forefront of research recently, and studying sex differences in disease fits with this initiative. This review will discuss the known sex differences in MS and highlight how investigating them can lead to new insights and potential treatments for both men and women. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Osteosarcoma inheritance in two families of Scottish deerhounds.

Science.gov (United States)

Dillberger, John E; McAtee, Sara Ann

2017-01-01

Osteosarcoma is the most common neoplastic disease in Scottish Deerhounds. For Deerhounds, a 2007 population-based study concluded that a single dominant genetic factor largely governed disease risk. For Greyhounds, Rottweilers, and Irish Wolfhounds, a 2013 genome-wide association study found multiple genetic markers in each breed, with each marker only weakly associated with the disease. We obtained from two breeders the pedigrees, age (if alive) or age at death, and osteosarcoma status for two families of Scottish Deerhounds, designated Cohorts K and T. A dog was considered unaffected only if it was osteosarcoma-free and at least 8.5 years old. We analyzed the data in two ways, by assuming either a single recessive genetic factor or a single dominant genetic factor with high penetrance. Cohort K contained 54 evaluable dogs representing 12 litters. Cohort T contained 56 evaluable dogs representing eight litters. Osteosarcoma seemed clearly heritable in both cohorts; however, having a parent with osteosarcoma raised a pup's risk of developing osteosarcoma to 38% for Cohort K but 78% for Cohort T, suggesting the possibility of different genetic risk factors in each cohort. In Cohort K, osteosarcoma inheritance fit well with a single, recessive, autosomal risk factor, although we could not rule out the possibility of a single dominant risk factor with incomplete penetrance. In Cohort T, inheritance could be explained well by a single, dominant, autosomal risk factor but was inconsistent with recessive expression. Inheritance of osteosarcoma in two Scottish Deerhound families could be explained well by a single genetic risk factor residing on an autosome, consistent with a 2007 report. In one family, inheritance was consistent with dominant expression, as previously reported. In the other family, inheritance fit better with recessive expression, although the possibility of a dominant genetic factor influenced by one or more other genetic factors could not be ruled

Role of TGF-β signaling in inherited and acquired myopathies

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Burks Tyesha N

2011-05-01

Full Text Available Abstract The transforming growth factor-beta (TGF-β superfamily consists of a variety of cytokines expressed in many different cell types including skeletal muscle. Members of this superfamily that are of particular importance in skeletal muscle are TGF-β1, mitogen-activated protein kinases (MAPKs, and myostatin. These signaling molecules play important roles in skeletal muscle homeostasis and in a variety of inherited and acquired neuromuscular disorders. Expression of these molecules is linked to normal processes in skeletal muscle such as growth, differentiation, regeneration, and stress response. However, chronic elevation of TGF-β1, MAPKs, and myostatin is linked to various features of muscle pathology, including impaired regeneration and atrophy. In this review, we focus on the aberrant signaling of TGF-β in various disorders such as Marfan syndrome, muscular dystrophies, sarcopenia, and critical illness myopathy. We also discuss how the inhibition of several members of the TGF-β signaling pathway has been implicated in ameliorating disease phenotypes, opening up novel therapeutic avenues for a large group of neuromuscular disorders.

Computer model for predicting the effect of inherited sterility on population growth

International Nuclear Information System (INIS)

Carpenter, J.E.; Layton, R.C.

1993-01-01

A Fortran based computer program was developed to facilitate modelling different inherited sterility data sets under various paradigms. The model was designed to allow variable input for several different parameters, such as rate of increase per generation, release ratio and initial population levels, reproductive rates and sex ratios resulting from different matings, and the number of nights a female is active in mating and oviposition. The model and computer program should be valuable tools for recognizing areas in which information is lacking and for identifying the effect that different parameters can have on the efficacy of the inherited sterility method. (author). 8 refs, 4 figs

Paternal mtDNA and maleness are co-inherited but not causally linked in mytilid mussels.

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Ellen L Kenchington

Full Text Available BACKGROUND: In marine mussels of the genus Mytilus there are two mitochondrial genomes. One is transmitted through the female parent, which is the normal transmission route in animals, and the other is transmitted through the male parent which is an unusual phenomenon. In males the germ cell line is dominated by the paternal mitochondrial genome and the somatic cell line by the maternal. Research to date has not allowed a clear answer to the question of whether inheritance of the paternal genome is causally related to maleness. METHODOLOGY/PRINCIPAL FINDINGS: Here we present results from hybrid crosses, from triploid mussels and from observations of sperm mitochondria in fertilized eggs which clearly show that maleness and presence of the paternal mitochondrial genome can be decoupled. These same results show that the female mussel has exclusive control of whether her progeny will inherit the mitochondrial genome of the male parent. CONCLUSIONS/SIGNIFICANCE: These findings are important in our efforts to understand the mechanistic basis of this unusual mode of mitochondrial DNA inheritance that is common among bivalves.

Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan.

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Maleeha Maria

Full Text Available Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD.We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA, retinitis pigmentosa (RP, congenital stationary night blindness (CSNB, or cone dystrophy (CD. We employed genome-wide single nucleotide polymorphism (SNP array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.

[Gene Therapy for Inherited RETINAL AND OPTIC NERVE Disorders: Current Knowledge].

Science.gov (United States)

Ďuďáková, Ľ; Kousal, B; Kolářová, H; Hlavatá, L; Lišková, P

The aim of this review is to provide a comprehensive summary of current gene therapy clinical trials for monogenic and optic nerve disorders.The number of genes for which gene-based therapies are being developed is growing. At the time of writing this review gene-based clinical trials have been registered for Leber congenital amaurosis 2 (LCA2), retinitis pigmentosa 38, Usher syndrome 1B, Stargardt disease, choroideremia, achromatopsia, Leber hereditary optic neuropathy (LHON) and X-linked retinoschisis. Apart from RPE65 gene therapy for LCA2 and MT-ND4 for LHON which has reached phase III, all other trials are in investigation phase I and II, i.e. testing the efficacy and safety.Because of the relatively easy accessibility of the retina and its ease of visualization which allows monitoring of efficacy, gene-based therapies for inherited retinal disorders represent a very promising treatment option. With the development of novel therapeutic approaches, the importance of establishing not only clinical but also molecular genetic diagnosis is obvious.Key words: gene therapy, monogenic retinal diseases, optic nerve atrophy, mitochondrial disease.

Ancient origin and maternal inheritance of blue cuckoo eggs.

Science.gov (United States)

Fossøy, Frode; Sorenson, Michael D; Liang, Wei; Ekrem, Torbjørn; Moksnes, Arne; Møller, Anders P; Rutila, Jarkko; Røskaft, Eivin; Takasu, Fugo; Yang, Canchao; Stokke, Bård G

2016-01-12

Maternal inheritance via the female-specific W chromosome was long ago proposed as a potential solution to the evolutionary enigma of co-existing host-specific races (or 'gentes') in avian brood parasites. Here we report the first unambiguous evidence for maternal inheritance of egg colouration in the brood-parasitic common cuckoo Cuculus canorus. Females laying blue eggs belong to an ancient (∼2.6 Myr) maternal lineage, as evidenced by both mitochondrial and W-linked DNA, but are indistinguishable at nuclear DNA from other common cuckoos. Hence, cuckoo host races with blue eggs are distinguished only by maternally inherited components of the genome, which maintain host-specific adaptation despite interbreeding among males and females reared by different hosts. A mitochondrial phylogeny suggests that blue eggs originated in Asia and then expanded westwards as female cuckoos laying blue eggs interbred with the existing European population, introducing an adaptive trait that expanded the range of potential hosts.

Online Mendelian Inheritance in Man (OMIM).

Science.gov (United States)

Hamosh, A; Scott, A F; Amberger, J; Valle, D; McKusick, V A

2000-01-01

Online Mendelian Inheritance In Man (OMIM) is a public database of bibliographic information about human genes and genetic disorders. Begun by Dr. Victor McKusick as the authoritative reference Mendelian Inheritance in Man, it is now distributed electronically by the National Center for Biotechnology Information (NCBI). Material in OMIM is derived from the biomedical literature and is written by Dr. McKusick and his colleagues at Johns Hopkins University and elsewhere. Each OMIM entry has a full text summary of a genetic phenotype and/or gene and has copious links to other genetic resources such as DNA and protein sequence, PubMed references, mutation databases, approved gene nomenclature, and more. In addition, NCBI's neighboring feature allows users to identify related articles from PubMed selected on the basis of key words in the OMIM entry. Through its many features, OMIM is increasingly becoming a major gateway for clinicians, students, and basic researchers to the ever-growing literature and resources of human genetics. Copyright 2000 Wiley-Liss, Inc.

Genes and inheritance.

Science.gov (United States)

Middelton, L A; Peters, K F

2001-10-01

The information gained from the Human Genome Project and related genetic research will undoubtedly create significant changes in healthcare practice. It is becoming increasingly clear that nurses in all areas of clinical practice will require a fundamental understanding of basic genetics. This article provides the oncology nurse with an overview of basic genetic concepts, including inheritance patterns of single gene conditions, pedigree construction, chromosome aberrations, and the multifactorial basis underlying the common diseases of adulthood. Normal gene structure and function are introduced and the biochemistry of genetic errors is described.

MAPPIN: a method for annotating, predicting pathogenicity and mode of inheritance for nonsynonymous variants.

Science.gov (United States)

Gosalia, Nehal; Economides, Aris N; Dewey, Frederick E; Balasubramanian, Suganthi

2017-10-13

Nonsynonymous single nucleotide variants (nsSNVs) constitute about 50% of known disease-causing mutations and understanding their functional impact is an area of active research. Existing algorithms predict pathogenicity of nsSNVs; however, they are unable to differentiate heterozygous, dominant disease-causing variants from heterozygous carrier variants that lead to disease only in the homozygous state. Here, we present MAPPIN (Method for Annotating, Predicting Pathogenicity, and mode of Inheritance for Nonsynonymous variants), a prediction method which utilizes a random forest algorithm to distinguish between nsSNVs with dominant, recessive, and benign effects. We apply MAPPIN to a set of Mendelian disease-causing mutations and accurately predict pathogenicity for all mutations. Furthermore, MAPPIN predicts mode of inheritance correctly for 70.3% of nsSNVs. MAPPIN also correctly predicts pathogenicity for 87.3% of mutations from the Deciphering Developmental Disorders Study with a 78.5% accuracy for mode of inheritance. When tested on a larger collection of mutations from the Human Gene Mutation Database, MAPPIN is able to significantly discriminate between mutations in known dominant and recessive genes. Finally, we demonstrate that MAPPIN outperforms CADD and Eigen in predicting disease inheritance modes for all validation datasets. To our knowledge, MAPPIN is the first nsSNV pathogenicity prediction algorithm that provides mode of inheritance predictions, adding another layer of information for variant prioritization. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Selfish element maintains sex in natural populations of a parasitoid wasp.

NARCIS (Netherlands)

Stouthamer, R.; Tilborg, van M.; Jong, de J.H.; Nunney, L.; Luck, R.F.

2001-01-01

Genomic conflicts between heritable elements with different modes of inheritance are important in the maintenance of sex and in the evolution of sex ratio. Generally, we expect sexual populations to exhibit a 1:1 sex ratio. However, because of their biology, parasitoid wasps often exhibit a

Genetics Home Reference: X-linked lymphoproliferative disease

Science.gov (United States)

... my area? Other Names for This Condition Duncan disease Epstein-Barr virus-induced lymphoproliferative disease in males familial fatal ... the proapoptotic SAP function in X-linked lymphoproliferative disease aggravates Epstein-Barr virus (EBV) induced mononucleosis and promotes lymphoma development. ...

Genetics Home Reference: X-linked creatine deficiency

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... Health Conditions X-linked creatine deficiency X-linked creatine deficiency Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description X-linked creatine deficiency is an inherited disorder that primarily affects ...

Genetics Home Reference: X-linked sideroblastic anemia

Science.gov (United States)

... Conditions X-linked sideroblastic anemia X-linked sideroblastic anemia Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description X-linked sideroblastic anemia is an inherited disorder that prevents developing red ...

Sex-linkage of two enzyme loci in Oncorhyncus mykiss (rainbow trout)

Science.gov (United States)

Allendorf, F W; Gellman, W A; Thorgaard, G H

1994-05-01

We report the first sex-linked loci in Oncorhynchus mykiss (rainbow trout). Previous cytological and breeding experiments have demonstrated an XX/XY sex determining system in this and other salmonid species. Joint segregation data from fathers indicated an average of 8.1 per cent recombination between HEX-2 and the sex determining locus (SEX). The average recombination between HEX-2 and sSOD-1 in fathers was 26.8 per cent. No evidence of non-random segregation of HEX-2 and sSOD-1 was found in mothers; this difference in recombination rates between males and females is concordant with previous studies with rainbow trout and other salmonid species. These results also suggest the possibility that proper chromosomal pairing and segregation in salmonid males does not require a crossover event. Unlike the extreme XX/XY heteromorphy in mammals, functional alleles for HEX-2 and sSOD-1 occur on both the X and Y chromosomes. Significant non-random associations (i.e. gametic disequilibrium) occur between genotypes at HEX-2 and SEX in the hatchery population used for the inheritance study. This gametic disequilibrium has resulted in large changes in allele frequency at HEX-2 from one generation to the next and an excess of heterozygotes in comparison to expected binomial (i.e. Hardy-Weinberg) proportions.

Sex differences in chronic stress responses and Alzheimer's disease.

Science.gov (United States)

Yan, Yan; Dominguez, Sky; Fisher, Daniel W; Dong, Hongxin

2018-02-01

Clinical studies indicate that Alzheimer's disease (AD) disproportionately affects women in both disease prevalence and severity, but the mechanisms underlying this sex divergence are unknown. Though some have suggested this difference in risk is a reflection of known differences in longevity between men and women, mounting clinical and preclinical evidence supports women also having intrinsic susceptibilities towards the disease. While a number of potential risk factors have been hypothesized to affect these differences in risks, none have been definitively verified. In this review, we discuss a novel hypothesis whereby women's susceptibility to chronic stress also mediates increased risk for AD. As stress is a risk factor for AD, and women are twice as likely to develop mood disorders where stress is a major etiology, it is possible that sex dimorphisms in stress responses contribute to the increase in women with AD. In line with this, sex divergence in biochemical responses to stress have been noted along the hypothalamic-pituitary-adrenal (HPA) axis and among known molecular effectors of AD, with crosstalk between these processes also being likely. In addition, activation of the cortical corticotrophin-releasing factor receptor 1 (CRF1) signaling pathway leads to distinct female-biased increases in molecules associated with AD pathogenesis. Therefore, the different biochemical responses to stress between women and men may represent an intrinsic, sex-dependent risk factor for AD.

Channelopathies - Emerging Trends in The Management of Inherited Arrhythmias

Directory of Open Access Journals (Sweden)

Priya Chockalingam, MBBS, MRCPCH, PhD

2015-01-01

Full Text Available In spite of their relative rarity, inheritable arrhythmias have come to the forefront as a group of potentially fatal but preventable cause of sudden cardiac death in children and (young adults. Comprehensive management of inherited arrhythmias includes diagnosing and treating the proband and identifying and protecting affected family members. This has been made possible by the vast advances in the field of molecular biology enabling better understanding of the genetic underpinnings of some of these disease groups, namely congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome. The ensuing knowledge of the genotype-phenotype correlations enables us to risk-stratify, prognosticate and treat based on the genetic test results. The various diagnostic modalities currently available to us, including clinical tools and genetic technologies, have to be applied judiciously in order to promptly identify those affected and to spare the emotional burden of a potentially lethal disease in the unaffected individuals. The therapeutic armamentarium of inherited arrhythmias includes pharmacological agents, device therapies and surgical interventions. A treatment strategy keeping in mind the risk profile of the patients, the local availability of drugs and the expertise of the treating personnel is proving effective. While opportunities for research are numerous in this expanding field of medicine, there is also tremendous scope for incorporating the emerging trends in managing patients and families with inherited arrhythmias in the Indian subcontinent.

Considering sex and gender in Alzheimer disease and other dementias.

Science.gov (United States)

Podcasy, Jessica L; Epperson, C Neill

2016-12-01

Suffering related to dementia is multifaceted because cognitive and physical functioning slowly deteriorates. Advanced age and sex, two of the most prominent risk factors for dementia, are not modifiable. Lifestyle factors such as smoking, excessive alcohol use, and poor diet modulate susceptibility to dementia in both males and females. The degree to which the resulting health conditions (eg, obesity, type 2 diabetes, and cardiovascular disease) impact dementia risk varies by sex. Depending on the subtype of dementia, the ratio of male to female prevalence differs. For example, females are at greater risk of developing Alzheimer disease dementia, whereas males are at greater risk of developing vascular dementia. This review examines sex and gender differences in the development of dementia with the goal of highlighting factors that require further investigation. Considering sex as a biological variable in dementia research promises to advance our understanding of the pathophysiology and treatment of these conditions.

Prominent Optic Disc Featured in Inherited Retinopathy.

Science.gov (United States)

Todorova, M G; Bojinova, R I; Valmaggia, C; Schorderet, D F

2017-04-01

Background We investigated the relationship between prominent optic disc (POD) and inherited retinal dystrophy (IRD). Patients and Methods A cross-sectional consecutive study was performed in 10 children and 11 adults of 7 non-related families. We performed clinical phenotyping, including a detailed examination, fundus autofluorescence, and colour fundus and OCT imaging. Genetic testing was subsequently performed for all family members presenting retinal pathology. Results In 4 members of a 3-generation family, hyperfluorescent deposits on the surface of POD were related to a p.(L224M) heterozygous mutation in BEST1 . In the second family, one member presented deposits located on the surface on hyperaemic OD and a compound p.(R141H);(A195V) mutation in BEST1 . In the third family, POD was observed in father and child with early onset cone-rod dystrophy and a novel autosomal recessive p.(W31*) homozygous mutation in ABCA4 . In the fourth family, POD with "mulberry-like" deposits and attenuated vessels were observed in a 7-year old girl, with a mutation in USH1A , and with early onset rod-cone dystrophy, associated with hearing loss. In the fifth family, blurry OD with tortuous vessels was observed in 4 consanguineous female carriers and a hemizygous boy with a p.(R200H) mutation in the X-linked retinoschisis RS1 . In the sixth family, a mother and her son were both affected with POD and attenuated peripapillary vessels, and presented with a p.(Y836C) heterozygous mutation in TOPORS , thus confirming autosomal dominant RP. In the seventh family, in 3 family members with POD, compound p.(L541P;A1038 V);(G1961E) mutations in ABCA4 confirmed the diagnosis of Stargardt disease. Conclusions A variety of OD findings are found in a genetically heterogeneous group of IRDs. In the presence of POD, an inherited progressive photoreceptor disease should be ruled out. Georg Thieme Verlag KG Stuttgart · New York.

Linking human diseases to animal models using ontology-based phenotype annotation.

Directory of Open Access Journals (Sweden)

Nicole L Washington

2009-11-01

Full Text Available Scientists and clinicians who study genetic alterations and disease have traditionally described phenotypes in natural language. The considerable variation in these free-text descriptions has posed a hindrance to the important task of identifying candidate genes and models for human diseases and indicates the need for a computationally tractable method to mine data resources for mutant phenotypes. In this study, we tested the hypothesis that ontological annotation of disease phenotypes will facilitate the discovery of new genotype-phenotype relationships within and across species. To describe phenotypes using ontologies, we used an Entity-Quality (EQ methodology, wherein the affected entity (E and how it is affected (Q are recorded using terms from a variety of ontologies. Using this EQ method, we annotated the phenotypes of 11 gene-linked human diseases described in Online Mendelian Inheritance in Man (OMIM. These human annotations were loaded into our Ontology-Based Database (OBD along with other ontology-based phenotype descriptions of mutants from various model organism databases. Phenotypes recorded with this EQ method can be computationally compared based on the hierarchy of terms in the ontologies and the frequency of annotation. We utilized four similarity metrics to compare phenotypes and developed an ontology of homologous and analogous anatomical structures to compare phenotypes between species. Using these tools, we demonstrate that we can identify, through the similarity of the recorded phenotypes, other alleles of the same gene, other members of a signaling pathway, and orthologous genes and pathway members across species. We conclude that EQ-based annotation of phenotypes, in conjunction with a cross-species ontology, and a variety of similarity metrics can identify biologically meaningful similarities between genes by comparing phenotypes alone. This annotation and search method provides a novel and efficient means to identify

Modification of radiation-induced sex-linked recessive lethal mutation frequency by tocopherol

International Nuclear Information System (INIS)

Beckman, C.; Roy, R.M.; Sproule, A.

1982-01-01

The present study evaluates the effect of supplementing culture medium with α-tocopherol acetate on the yield of sex-linked recessive lethal mutants induced by X-irradiation in mature sperm of Drosophila. Although tocopherol treatment of males had no impact on the yield of mutations, a drastic reduction in mutation frequency was observed when irradiated males were mated to females raised and subsequently maintained on tocopherol-enriched diet. (orig./MG)

Genetics Home Reference: periventricular heterotopia

Science.gov (United States)

... of the two sex chromosomes . The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ...

Sexual dimorphism of miRNA expression: a new perspective in understanding the sex bias of autoimmune diseases

Directory of Open Access Journals (Sweden)

Dai R

2014-03-01

Full Text Available Rujuan Dai, S Ansar Ahmed Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA Abstract: Autoimmune diseases encompass a diverse group of diseases which emanate from a dysregulated immune system that launches a damaging attack on its own tissues. Autoimmune attacks on self tissues can occur in any organ or body system. A notable feature of autoimmune disease is that a majority of these disorders occur predominantly in females. The precise basis of sex bias in autoimmune diseases is complex and potentially involves sex chromosomes, sex hormones, and sex-specific gene regulation in response to internal and external stimuli. Epigenetic regulation of genes, especially by microRNAs (miRNAs, is now attracting significant attention. miRNAs are small, non-protein-coding RNAs that are predicted to regulate a majority of human genes, including those involved in immune regulation. Therefore, it is not surprising that dysregulated miRNAs are evident in many diseases, including autoimmune diseases. Because there are marked sex differences in the incidence of autoimmune diseases, this review focuses on the role of sex factors on miRNA expression in the context of autoimmune diseases, an aspect not addressed thus far. Here, we initially review miRNA biogenesis and miRNA regulation of immunity and autoimmunity. We then summarize the recent findings of sexual dimorphism of miRNA expression in diverse tissues, which imply a critical role of miRNA in sex differentiation and in sex-specific regulation of tissue development and/or function. We also discuss the important contribution of the X chromosome and sex hormones to the sexual dimorphism of miRNA expression. Understanding sexually dimorphic miRNA expression in sex-biased autoimmune diseases not only offers us new insight into the mechanism of sex bias of the disease but will also aid us in developing new sex

Application of Molecular Genetics to the Investigation of Inherited Bleeding Disorders

DEFF Research Database (Denmark)

Lethagen, Stefan Rune; Dunø, Morten; Nielsen, Lars Bo

2013-01-01

Hemophilia is an inherited bleeding disorder primarily caused by deficiency of coagulation factor (F)VIII (hemophilia A) or FIX (hemophilia B). Both conditions are X-linked. More than 2100 different F8 mutations have been described, the most common being a 500 kb inversion involving exon 1 to exo...... quality control systems in place, and participate in established external quality assessment programs....... the causative mutation is unknown. More rare bleeding disorders are generally recessively inherited, and are often caused by mutations that are specific for individual families, and mutations are scattered throughout the genes. Laboratories performing molecular genetic analyses must have validated internal...

Fitness and inheritance of metaflumizone resistance in Plutella xylostella.

Science.gov (United States)

Shen, Jun; Li, Dongyang; Zhang, Shuzhen; Zhu, Xun; Wan, Hu; Li, Jianhong

2017-06-01

The diamondback moth, Plutella xylostella (L.) has developed resistance to many types of insecticides in the field. To study inheritance and fitness cost of metaflumizone resistance, a susceptible strain of diamondback moth was continuously selected with metaflumizone during 37 generations under laboratory conditions. The resistance to metaflumizone was at a high level (resistance ratios from 250.37 to 1450.47-fold). We investigated a metaflumizone resistance strain (G 27 ) and a susceptible strain of P. xylostella, using the age-stage, two-sex life table approach. Compared to the susceptible strain, egg duration, the developmental time of the first and second instar larvae, pupae duration, adult preoviposition period (APOP), total preoviposition period (TPOP), egg hatchability, the survival rate of second instar larva and the mean generation time (T) were significantly differences in the resistant strain. The resistant strain had a relative fitness of 0.78. The inheritance of metaflumizone resistance was also studied by crossing the metaflumizone resistant and susceptible populations. Results revealed an autosomal and incompletely recessive mode of inheritance for metaflumizone resistance in the resistant population of P. xylostella. The present study provided useful information for planning potential management strategies to delay development of metaflumizone resistance in P. xylostella. Copyright © 2017 Elsevier Inc. All rights reserved.

Considering sex and gender in Alzheimer disease and other dementias

Science.gov (United States)

Podcasy, Jessica L.; Epperson, C. Neill

2016-01-01

Suffering related to dementia is multifaceted because cognitive and physical functioning slowly deteriorates. Advanced age and sex, two of the most prominent risk factors for dementia, are not modifiable. Lifestyle factors such as smoking, excessive alcohol use, and poor diet modulate susceptibility to dementia in both males and females. The degree to which the resulting health conditions (eg, obesity, type 2 diabetes, and cardiovascular disease) impact dementia risk varies by sex. Depending on the subtype of dementia, the ratio of male to female prevalence differs. For example, females are at greater risk of developing Alzheimer disease dementia, whereas males are at greater risk of developing vascular dementia. This review examines sex and gender differences in the development of dementia with the goal of highlighting factors that require further investigation. Considering sex as a biological variable in dementia research promises to advance our understanding of the pathophysiology and treatment of these conditions. PMID:28179815

Autophagy as an Emerging Common Pathomechanism in Inherited Peripheral Neuropathies

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Mansour Haidar

2017-05-01

Full Text Available The inherited peripheral neuropathies (IPNs comprise a growing list of genetically heterogeneous diseases. With mutations in more than 80 genes being reported to cause IPNs, a wide spectrum of functional consequences is expected to follow this genotypic diversity. Hence, the search for a common pathomechanism among the different phenotypes has become the holy grail of functional research into IPNs. During the last decade, studies on several affected genes have shown a direct and/or indirect correlation with autophagy. Autophagy, a cellular homeostatic process, is required for the removal of cell aggregates, long-lived proteins and dead organelles from the cell in double-membraned vesicles destined for the lysosomes. As an evolutionarily highly conserved process, autophagy is essential for the survival and proper functioning of the cell. Recently, neuronal cells have been shown to be particularly vulnerable to disruption of the autophagic pathway. Furthermore, autophagy has been shown to be affected in various common neurodegenerative diseases of both the central and the peripheral nervous system including Alzheimer’s, Parkinson’s, and Huntington’s diseases. In this review we provide an overview of the genes involved in hereditary neuropathies which are linked to autophagy and we propose the disruption of the autophagic flux as an emerging common pathomechanism. We also shed light on the different steps of the autophagy pathway linked to these genes. Finally, we review the concept of autophagy being a therapeutic target in IPNs, and the possibilities and challenges of this pathway-specific targeting.

Legal Inheritance in the Republic of Kosovo

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Dr.Sc. Hamdi Podvorica

2011-06-01

Full Text Available Legal inheritance is one of the most important institutions of inheritance law which regulates the process of legal transition of property of the decedent to one or several heirs. The establish-ment of the legal framework has brought about new reforms to the Inheritance Law. This has enabled the enrichment and functio-ning of the law. A particularly important step was taken towards regulation of legal procedures regarding to how courts, other or-gans and other persons should act regarding inheritance issues. Concretization of the legal authorizations of bodies authorized to enforce the procedure of processing hereditary property has estab-lished the legal basis for realization of the iso jure principle, accor-ding to which, at the moment of death of the person, the heirs gain the right of inheritance and the hereditary property is never left without a titleholder. This is a great advantage that we have noted in undertaking this analysis of the norms in this work, because leaving hereditary property for a longer period of time without a titleholder would render the property vulnerable to des-truction, theft and extermination. The goal of this paper is to avoid focusing only on finding the positive sides of the normative regulation of the legal inheritance process, but also in finding practical deficiencies that are weighing down at the moment on this important process in Kosovo, and in proposing measures for overcoming them. The dark side of the legal inheritance process is linked to the inefficiency of courts and the still fragile legal system in Kosovo. By implementing empirical methods, we have come to the con-clusion that the low number of judges in proportion with the huge number of cases has become a key liability for practical implemen-tation of the principle of initiating the legal procedure ex officio. The failure in enforcing this principle and initiating the procedu-res for processing of hereditary property by courts, even though they

A Regulatory RNA Inducing Transgenerationally Inherited Phenotypes

DEFF Research Database (Denmark)

Jensen, Lea Møller

. The variation in Arabidopsis enables different regulatory networks and mechanisms to shape the phenotypic characteristics. The thesis describes the identification of regulatory RNA encoded by an enzyme encoding gene. The RNA regulates by inducing transgenerationally inherited phenotypes. The function of the RNA...... is dependent on the genetic background illustrating that polymorphisms are found in either interactors or target genes of the RNA. Furthermore, the RNA provides a mechanistic link between accumulation of glucosinolate and onset of flowering....

Constraints of behavioural inheritance

NARCIS (Netherlands)

Roubtsova, E.E.; Roubtsov, S.A.; Oquendo, F.; Warboys, B.; Morrison, R.

2004-01-01

We present an approach to component inheritance and reuse which closes the gap between architectural design and process-oriented approaches. To apply inheritance checks in design and verification of a system, one should consider an inheritance relation as a property of the system and specify it as

Ethics of Inheritance

OpenAIRE

Guibet Lafaye , Caroline

2008-01-01

International audience; Both in the U.S. and in France, inheritance is probably the main factor of wealth concentration among the richest part of the population, and of its intergenerational reproduction. In so far as wealth is an opportunity, a reform of inheritance tax could be a mean to ensure a fairer distribution of opportunities in the society. Many reforms of inheritance systems have been conceived at least since Bentham. The identification and the analysis of ethical properties of ref...

Sex-Linked Mating Strategies Diverge with a Manipulation of Genital Salience.

Science.gov (United States)

Fetterman, Adam K; Kruger, Nicole N; Robinson, Michael D

2015-02-01

Trivers (1972) proposed that evolutionary factors should favor divergent mating strategies for males versus females. Such differences may be less pronounced among human beings than other animals and social norms and sex roles are also pertinent influences. The present experiment ( N = 133 college undergraduates, 74 female) sought to bypass some of these other influences. Participants were randomly assigned to a condition designed to increase attention to the genital region (a downward pointing arrow) or not (an upward pointing arrow). They then reported on their interest in short-term (e.g., a one-night stand) and long-term (e.g., a potential marital partner) mating opportunities. A theory-consistent three-way interaction occurred such that the genital salience manipulation primed a shorter-term reproductive strategy among men and a longer-term reproductive strategy among women. The results provide unique support for evolution-linked ideas about sex differences in the form of a role for bodily attention.

Severe mental deficiency, proportionate dwarfism, and delayed sexual maturation. A distinct inherited syndrome.

Science.gov (United States)

Cantú, J M; Sánchez-Corona, J; García-Cruz, D; Fragoso, R

1980-01-01

Two 46,XY brothers were found to have a previously undescribed syndrome characterized by severe mental deficiency, proportionate dwarfism, and delayed sexual development. A recessive mode of inheritance, either autosomal or X-linked, is assumed.

Compiler generation based on grammar inheritance

NARCIS (Netherlands)

Aksit, Mehmet; Mostert, Rene; Haverkort, Boudewijn R.H.M.

1990-01-01

The concept of grammar inheritance is introduced. Grammar inheritance is a structural organization of grammar rules by which a grammar inherits rules from ancestor grammars or may have its own rules inherited by descendant grammars. Grammar inheritance supports reusability and extensibility of

Light and inherited retinal degeneration

OpenAIRE

Paskowitz, D M; LaVail, M M; Duncan, J L

2006-01-01

Light deprivation has long been considered a potential treatment for patients with inherited retinal degenerative diseases, but no therapeutic benefit has been demonstrated to date. In the few clinical studies that have addressed this issue, the underlying mutations were unknown. Our rapidly expanding knowledge of the genes and mechanisms involved in retinal degeneration have made it possible to reconsider the potential value of light restriction in specific genetic contexts. This review summ...

Preliminary Evidence for an Automatic Link between Sex and Power among Men Who Molest Children

Science.gov (United States)

Kamphuis, Jan H.; De Ruiter, Corine; Janssen, Bas; Spiering, Mark

2005-01-01

Understanding critical motivational processes of sexual offenders may ultimately provide important clues to more effective treatments. Implicit, automatic cognitive processes have received minimal attention; however, a lexical decision experiment revealed automatic links between the concepts of power and sex among participants who self-reported…

SWJ:39-42 Inheritance of Pod Colour in Cowpea INHERITANCE

African Journals Online (AJOL)

Dr. Ahmed

Mustapha & Singh (2008) SWJ:39-42. Inheritance of Pod Colour in Cowpea. INHERITANCE OF POD COLOUR IN. COWPEA (Vigna unguiculata (L.) WALP). * MUSTAPHA, Y1. & SINGH, B. B2. 1 Department of Biological Sciences. Bayero University, Kano Nigeria. 2 Department of Genetics and Plant breeding,. G.B. Pant ...

Endocrine Dysfunctions in Patients with Inherited Metabolic Diseases.

Science.gov (United States)

Erdöl, Şahin; Sağlam, Halil

2016-09-01

Inherited metabolic diseases (IMDs) can affect many organ systems, including the endocrine system. There are limited data regarding endocrine dysfunctions related to IMDs in adults, however, no data exist in pediatric patients with IMDs. The aim of this study was to investigate endocrine dysfunctions in patients with IMDs by assessing their demographic, clinical, and laboratory data. Data were obtained retrospectively from the medical reports of patients with IMDs who were followed by the division of pediatric metabolism and nutrition between June 2011 and November 2013. In total, 260 patients [139 males (53%) and 121 females (47%)] with an IMD diagnosis were included in the study. The mean age of the patients was 5.94 (range; 0.08 to 49) years and 95.8% (249 of 260 patients) were in the pediatric age group. Growth status was evaluated in 258 patients and of them, 27 (10.5%) had growth failure, all cases of which were attributed to non-endocrine reasons. There was a significant correlation between growth failure and serum albumin levels below 3.5 g/dL (p=0.002). Only three of 260 (1.1%) patients had endocrine dysfunction. Of these, one with lecithin-cholesterol acyltransferase deficiency and another with Kearns-Sayre syndrome had diabetes, and one with glycerol kinase deficiency had glucocorticoid deficiency. Endocrine dysfunction in patients with IMDs is relatively rare. For this reason, there is no need to conduct routine endocrine evaluations in most patients with IMDs unless a careful and detailed history and a physical examination point to an endocrine dysfunction.

JS-X syndrome: A multiple congenital malformation with vocal cord paralysis, ear deformity, hearing loss, shoulder musculature underdevelopment, and X-linked recessive inheritance.

Science.gov (United States)

Hoeve, Hans L J; Brooks, Alice S; Smit, Liesbeth S

2015-07-01

We report on a family with a not earlier described multiple congenital malformation. Several male family members suffer from laryngeal obstruction caused by bilateral vocal cord paralysis, outer and middle ear deformity with conductive and sensorineural hearing loss, facial dysmorphisms, and underdeveloped shoulder musculature. The affected female members only have middle ear deformity and hearing loss. The pedigree is suggestive of an X-linked recessive inheritance pattern. SNP-array revealed a deletion and duplication on Xq28 in the affected family members. A possible aetiology is a neurocristopathy with most symptoms expressed in structures derived from branchial arches. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Revisiting telegony : Offspring inherit an acquired characteristic of their mother's previous mate

NARCIS (Netherlands)

Crean, Angela J.; Kopps, Anna M.; Bonduriansky, Russell

2014-01-01

Newly discovered non-genetic mechanisms break the link between genes and inheritance, thereby also raising the possibility that previous mating partners could influence traits in offspring sired by subsequent males that mate with the same female (‘telegony’). In the fly Telostylinus angusticollis,

A human model for multigenic inheritance : Phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus

NARCIS (Netherlands)

Bolk, S; Pelet, A; Hofstra, RMW; Angrist, M; Salomon, R; Croaker, D; Buys, CHCM; Lyonnet, S; Chakravarti, A

2000-01-01

Reduced penetrance in genetic disorders may be either dependent or independent of the genetic background of gene carriers. Hirschsprung disease (HSCR) demonstrates a complex pattern of inheritance with approximate to 50% of familial cases being heterozygous for mutations in the receptor tyrosine

Sex-linked pheromone receptor genes of the European corn borer, Ostrinia nubilalis, are in tandem arrays.

Directory of Open Access Journals (Sweden)

Yuji Yasukochi

Full Text Available BACKGROUND: Tuning of the olfactory system of male moths to conspecific female sex pheromones is crucial for correct species recognition; however, little is known about the genetic changes that drive speciation in this system. Moths of the genus Ostrinia are good models to elucidate this question, since significant differences in pheromone blends are observed within and among species. Odorant receptors (ORs play a critical role in recognition of female sex pheromones; eight types of OR genes expressed in male antennae were previously reported in Ostrinia moths. METHODOLOGY/PRINCIPAL FINDINGS: We screened an O. nubilalis bacterial artificial chromosome (BAC library by PCR, and constructed three contigs from isolated clones containing the reported OR genes. Fluorescence in situ hybridization (FISH analysis using these clones as probes demonstrated that the largest contig, which contained eight OR genes, was located on the Z chromosome; two others harboring two and one OR genes were found on two autosomes. Sequence determination of BAC clones revealed the Z-linked OR genes were closely related and tandemly arrayed; moreover, four of them shared 181-bp direct repeats spanning exon 7 and intron 7. CONCLUSIONS/SIGNIFICANCE: This is the first report of tandemly arrayed sex pheromone receptor genes in Lepidoptera. The localization of an OR gene cluster on the Z chromosome agrees with previous findings for a Z-linked locus responsible for O. nubilalis male behavioral response to sex pheromone. The 181-bp direct repeats might enhance gene duplications by unequal crossovers. An autosomal locus responsible for male response to sex pheromone in Heliothis virescens and H. subflexa was recently reported to contain at least four OR genes. Taken together, these findings support the hypothesis that generation of additional copies of OR genes can increase the potential for male moths to acquire altered specificity for pheromone components, and accordingly

Electrocardiographic manifestations of inherited heart diseases – a sports cardiologist’s point ofview. Part 2. Ion channel diseases

Directory of Open Access Journals (Sweden)

Zbigniew Krenc

2015-09-01

Full Text Available Physical activity is associated with an increased risk of sudden death for individuals with an undiagnosed cardiovascular disease. Medical evaluations, including a resting electrocardiogram, conducted before and during physical training, enable the identification of still asymptomatic athletes with life-threatening heart diseases and help to protect them from sudden cardiac death. The incidence of sudden cardiac death is estimated at two cases for each 100,000 young athletes per year and it is 2–4 times higher when compared with non-athletes. The most common causes of sudden cardiac death in athletes younger than 35 are cardiomyopathies: hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Three to four per cent of young athletes who die suddenly have no evidence of a structural heart disease, and the cause of their cardiac arrest is primarily electrical heart diseases, such as inherited cardiac ion channel defects (channelopathies, including long and short QT syndromes, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia The clinical courses of all these channelopathies are highly varied. They can be asymptomatic. In certain cases, episodic syncope or aborted cardiac arrest can occur. Sudden cardiac death, especially during physical exercise, can be the first sign. The aim of this article was to provide some information helpful in the recognition of electrocardiographic changes in genetic ion channel diseases, especially in the context of the prevention of sudden cardiac events in young athletes.

Human inherited diseases with altered mechanisms for DNA repair and mutagenesis

Energy Technology Data Exchange (ETDEWEB)

Cleaver, J.E.

1977-01-01

A variety of human diseases involving clinical symptoms of increased cancer risk, and disorders of the central nervous system, and of hematopoietic, immunological, ocular, and cutaneous tissues and embryological development have defects in biochemical pathways for excision repair of damaged DNA. Excision repair has multiple branches by which damaged nucleotides, bases, and cross-links are excised and requires cofactors that control the access of repair enzymes to damage in DNA in chromatin. Diseases in which repair defects are a consistent feature of their biochemistry include xeroderma pigmentosum, ataxia telangiectasia and Fanconi's anemia.

Machado-Joseph Disease in Pedigrees of Azorean descent is Linked to Chromosome 14

OpenAIRE

George-Hyslop, P. St; Rogaeva, E.; Huterer, J.; Tsuda, T.; Santos, J.; Haines, J. L.; Schlumpf, K.; Rogaev, E. I.; Liang, Y.; McLachlan, D. R. Crapper; Kennedy, J.; Weissenbach, J.; Billingsley, G. D.; Cox, D. W.; Lang, A. E.

1994-01-01

A locus for Machado-Joseph disease (MJD) has recently been mapped to a 30-cM region of chromosome 14q in five pedigrees of Japanese descent. MJD is a clinically pleomorphic neurodegenerative disease that was originally described in subjects of Azorean descent. In light of the nonallelic heterogeneity in other inherited spinocere-bellar ataxias, we were interested to determine if the MJD phenotype in Japanese and Azorean pedigrees arose from mutations at the same locus. We provide evidence tha...

Epigenetic Transgenerational Actions of Vinclozolin on the Development of Disease and Cancer

Science.gov (United States)

Skinner, Michael K.; Anway, Matthew D.

2018-01-01

Exposure to an environmental endocrine disruptor (e.g., vinclozolin) during embryonic gonadal sex determination appears to alter the male germ line epigenome and subsequently promotes transgenerational adult onset disease. The epigenetic mechanism involves the induction of new imprinted-like genes/DNA sequences in the germ line that appear to transmit disease phenotypes. The disease phenotypes include testis abnormalities, prostate disease, kidney disease, immune abnormalities, and tumor development. This epigenetic transgenerational disease mechanism provides a unique perspective from which to view inheritable adult onset disease states, such as cancer, and ultimately offers new insights into novel diagnostic and therapeutic strategies. PMID:17956218

Stargardt disease: towards developing a model to predict phenotype

OpenAIRE

Heathfield, Laura; Lacerda, Miguel; Nossek, Christel; Roberts, Lisa; Ramesar, Rajkumar S

2013-01-01

Stargardt disease is an ABCA4-associated retinopathy, which generally follows an autosomal recessive inheritance pattern and is a frequent cause of macular degeneration in childhood. ABCA4 displays significant allelic heterogeneity whereby different mutations can cause retinal diseases with varying severity and age of onset. A genotype–phenotype model has been proposed linking ABCA4 mutations, purported ABCA4 functional protein activity and severity of disease, as measured by degree of visual...

OVAS: an open-source variant analysis suite with inheritance modelling.

Science.gov (United States)

Mozere, Monika; Tekman, Mehmet; Kari, Jameela; Bockenhauer, Detlef; Kleta, Robert; Stanescu, Horia

2018-02-08

The advent of modern high-throughput genetics continually broadens the gap between the rising volume of sequencing data, and the tools required to process them. The need to pinpoint a small subset of functionally important variants has now shifted towards identifying the critical differences between normal variants and disease-causing ones. The ever-increasing reliance on cloud-based services for sequence analysis and the non-transparent methods they utilize has prompted the need for more in-situ services that can provide a safer and more accessible environment to process patient data, especially in circumstances where continuous internet usage is limited. To address these issues, we herein propose our standalone Open-source Variant Analysis Sequencing (OVAS) pipeline; consisting of three key stages of processing that pertain to the separate modes of annotation, filtering, and interpretation. Core annotation performs variant-mapping to gene-isoforms at the exon/intron level, append functional data pertaining the type of variant mutation, and determine hetero/homozygosity. An extensive inheritance-modelling module in conjunction with 11 other filtering components can be used in sequence ranging from single quality control to multi-file penetrance model specifics such as X-linked recessive or mosaicism. Depending on the type of interpretation required, additional annotation is performed to identify organ specificity through gene expression and protein domains. In the course of this paper we analysed an autosomal recessive case study. OVAS made effective use of the filtering modules to recapitulate the results of the study by identifying the prescribed compound-heterozygous disease pattern from exome-capture sequence input samples. OVAS is an offline open-source modular-driven analysis environment designed to annotate and extract useful variants from Variant Call Format (VCF) files, and process them under an inheritance context through a top-down filtering schema of

Sex and gender differences in chronic kidney disease: progression to end-stage renal disease and haemodialysis.

Science.gov (United States)

Cobo, Gabriela; Hecking, Manfred; Port, Friedrich K; Exner, Isabella; Lindholm, Bengt; Stenvinkel, Peter; Carrero, Juan Jesús

2016-07-01

Sex and gender differences are of fundamental importance in most diseases, including chronic kidney disease (CKD). Men and women with CKD differ with regard to the underlying pathophysiology of the disease and its complications, present different symptoms and signs, respond differently to therapy and tolerate/cope with the disease differently. Yet an approach using gender in the prevention and treatment of CKD, implementation of clinical practice guidelines and in research has been largely neglected. The present review highlights some sex- and gender-specific evidence in the field of CKD, starting with a critical appraisal of the lack of inclusion of women in randomized clinical trials in nephrology, and thereafter revisits sex/gender differences in kidney pathophysiology, kidney disease progression, outcomes and management of haemodialysis care. In each case we critically consider whether apparent discrepancies are likely to be explained by biological or psycho-socioeconomic factors. In some cases (a few), these findings have resulted in the discovery of disease pathways and/or therapeutic opportunities for improvement. In most cases, they have been reported as merely anecdotal findings. The aim of the present review is to expose some of the stimulating hypotheses arising from these observations as a preamble for stricter approaches using gender for the prevention and treatment of CKD and its complications. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Inheritance versus parameterization

DEFF Research Database (Denmark)

Ernst, Erik

2013-01-01

This position paper argues that inheritance and parameterization differ in their fundamental structure, even though they may emulate each other in many ways. Based on this, we claim that certain mechanisms, e.g., final classes, are in conflict with the nature of inheritance, and hence causes...

Using lod-score differences to determine mode of inheritance: a simple, robust method even in the presence of heterogeneity and reduced penetrance.

Science.gov (United States)

Greenberg, D A; Berger, B

1994-10-01

Determining the mode of inheritance is often difficult under the best of circumstances, but when segregation analysis is used, the problems of ambiguous ascertainment procedures, reduced penetrance, heterogeneity, and misdiagnosis make mode-of-inheritance determinations even more unreliable. The mode of inheritance can also be determined using a linkage-based method (maximized maximum lod score or mod score) and association-based methods, which can overcome many of these problems. In this work, we determined how much information is necessary to reliably determine the mode of inheritance from linkage data when heterogeneity and reduced penetrance are present in the data set. We generated data sets under both dominant and recessive inheritance with reduced penetrance and with varying fractions of linked and unlinked families. We then analyzed those data sets, assuming reduced penetrance, both dominant and recessive inheritance, and no heterogeneity. We investigated the reliability of two methods for determining the mode of inheritance from the linkage data. The first method examined the difference (delta) between the maximum lod scores calculated under the two mode-of-inheritance assumptions. We found that if delta was > 1.5, then the higher of the two maximum lod scores reflected the correct mode of inheritance with high reliability and that a delta of 2.5 appeared to practically guarantee a correct mode-of-inheritance inference. Furthermore, this reliability appeared to be virtually independent of alpha, the fraction of linked families in the data set, although the reliability decreased slightly as alpha fell below .50.(ABSTRACT TRUNCATED AT 250 WORDS)

Diallel analysis for sex-linked and maternal effects.

Science.gov (United States)

Zhu, J; Weir, B S

1996-01-01

Genetic models including sex-linked and maternal effects as well as autosomal gene effects are described. Monte Carlo simulations were conducted to compare efficiencies of estimation by minimum norm quadratic unbiased estimation (MINQUE) and restricted maximum likelihood (REML) methods. MINQUE(1), which has 1 for all prior values, has a similar efficiency to MINQUE(θ), which requires prior estimates of parameter values. MINQUE(1) has the advantage over REML of unbiased estimation and convenient computation. An adjusted unbiased prediction (AUP) method is developed for predicting random genetic effects. AUP is desirable for its easy computation and unbiasedness of both mean and variance of predictors. The jackknife procedure is appropriate for estimating the sampling variances of estimated variances (or covariances) and of predicted genetic effects. A t-test based on jackknife variances is applicable for detecting significance of variation. Worked examples from mice and silkworm data are given in order to demonstrate variance and covariance estimation and genetic effect prediction.

Common variants in mendelian kidney disease genes and their association with renal function

NARCIS (Netherlands)

A. Parsa (Afshin); C. Fuchsberger (Christian); A. Köttgen (Anna); C.M. O'Seaghdha (Conall); C. Pattaro (Cristian); M. de Andrade (Mariza); D.I. Chasman (Daniel); A. Teumer (Alexander); K. Endlich (Karlhans); M. Olden (Matthias); M-H. Chen (Ming-Huei); A. Tin (Adrienne); Y-J. Kim (Yong-Jin); D. Taliun (Daniel); M. Li (Man); M.F. Feitosa (Mary Furlan); M. Gorski (Mathias); Q. Yang (Qiong); C. Hundertmark (Claudia); M.C. Foster (Michael); N. Glazer (Nicole); A.J. Isaacs (Aaron); M. Rao (Madhumathi); G.D. Smith; J.R. O´Connell; M.V. Struchalin (Maksim); T. Tanaka (Toshiko); G. Li (Guo); S.J. Hwang; E.J. Atkinson (Elizabeth); K. Lohman (Kurt); M. Cornelis (Marilyn); A. Johansson (Åsa); A. Tönjes (Anke); A. Dehghan (Abbas); V. Couraki (Vincent); E.G. Holliday (Elizabeth); R. Sorice; Z. Kutalik (Zoltán); T. Lehtimäki (Terho); T. Esko (Tõnu); H. Deshmukh (Harshal); S. Ulivi (Shelia); A.Y. Chu (Audrey); D. Murgia (Daniela); S. Trompet (Stella); M. Imboden (Medea); B. Kollerits (Barbara); G. Pistis (Giorgio); T.B. Harris (Tamara); L.J. Launer (Lenore); T. Aspelund (Thor); G. Eiriksdottir (Gudny); B.D. Mitchell (Braxton); E.A. Boerwinkle (Eric); H. Schmidt (Helena); E. Hofer (Edith); F.B. Hu (Frank); A. Demirkan (Ayşe); B.A. Oostra (Ben); S.T. Turner (Stephen); J. Ding (Jingzhong); J.S. Andrews (Jeanette); B.I. Freedman (Barry); F. Giulianini (Franco); W. Koenig (Wolfgang); T. Illig (Thomas); A. Döring (Angela); H.E. Wichmann (Heinz Erich); L. Zgaga (Lina); T. Zemunik (Tatijana); M. Boban (Mladen); C. Minelli (Cosetta); H.E. Wheeler (Heather); W. Igl (Wilmar); G. Zaboli (Ghazal); S.H. Wild (Sarah); A.F. Wright (Alan); H. Campbell (Harry); D. Ellinghaus (David); U. Nöthlings (Ute); G. Jacobs (Gunnar); R. Biffar (Reiner); F.D.J. Ernst (Florian); G. Homuth (Georg); H.K. Kroemer (Heyo); M. Nauck (Matthias); S. Stracke (Sylvia); U. Vol̈ker (Uwe); H. Völzke (Henry); P. Kovacs (Peter); M. Stumvoll (Michael); R. Mägi (Reedik); A. Hofman (Albert); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); Y.S. Aulchenko (Yurii); O. Polasek (Ozren); N. Hastie (Nick); V. Vitart (Veronique); C. Helmer (Catherine); J.J. Wang (Jie Jin); B. Stengel (Bernd); D. Ruggiero; S.M. Bergmann (Sven); M. Kähönen (Mika); J. Viikari (Jorma); T. Nikopensius (Tiit); M.A. Province (Mike); H.M. Colhoun (H.); A.S.F. Doney (Alex); A. Robino (Antonietta); B.K. Krämer (Bernhard); L. Portas (Laura); I. Ford (Ian); B.M. Buckley (Brendan M.); M. Adam (Martin); G.-A. Thun (Gian-Andri); B. Paulweber (Bernhard); M. Haun (Margot); C. Sala (Cinzia); P. Mitchell (Paul); M. Ciullo; P. Vollenweider (Peter); O. Raitakari (Olli); A. Metspalu (Andres); C.N.A. Palmer (Colin); P. Gasparini (Paolo); M. Pirastu (Mario); J.W. Jukema (Jan Wouter); N.M. Probst-Hensch (Nicole M.); F. Kronenberg (Florian); D. Toniolo (Daniela); V. Gudnason (Vilmundur); A.R. Shuldiner (Alan); J. Coresh (Josef); R. Schmidt (Reinhold); L. Ferrucci (Luigi); C.M. van Duijn (Cornelia); I.B. Borecki (Ingrid); S.L.R. Kardia (Sharon); Y. Liu (YongMei); G.C. Curhan (Gary); I. Rudan (Igor); U. Gyllensten (Ulf); J.F. Wilson (James); A. Franke (Andre); P.P. Pramstaller (Peter Paul); R. Rettig (Rainer); I. Prokopenko (Inga); J.C.M. Witteman (Jacqueline); C. Hayward (Caroline); P.M. Ridker (Paul); M. Bochud (Murielle); I.M. Heid (Iris); D.S. Siscovick (David); C.S. Fox (Caroline); W.H.L. Kao (Wen); C.A. Böger (Carsten)

2013-01-01

textabstractMany common genetic variants identified by genome-wide association studies for complex traitsmap to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with

Testosterone-dependent sex differences in red blood cell hemolysis in storage, stress, and disease.

Science.gov (United States)

Kanias, Tamir; Sinchar, Derek; Osei-Hwedieh, David; Baust, Jeffrey J; Jordan, Andrew; Zimring, James C; Waterman, Hayley R; de Wolski, Karen S; Acker, Jason P; Gladwin, Mark T

2016-10-01

Red blood cell (RBC) hemolysis represents an intrinsic mechanism for human vascular disease. Intravascular hemolysis releases hemoglobin and other metabolites that inhibit nitric oxide signaling and drive oxidative and inflammatory stress. Although these pathways are important in disease pathogenesis, genetic and population modifiers of hemolysis, including sex, have not been established. We studied sex differences in storage or stress-induced hemolysis in RBC units from the United States and Canada in 22 inbred mouse strains and in patients with sickle cell disease (SCD) using measures of hemolysis in 315 patients who had homozygous SS hemoglobin from the Walk-PHASST cohort. A mouse model also was used to evaluate posttransfusion recovery of stored RBCs, and gonadectomy was used to determine the mechanisms related to sex hormones. An analysis of predisposition to hemolysis based on sex revealed that male RBCs consistently exhibit increased susceptibility to hemolysis compared with females in response to routine cold storage, under osmotic or oxidative stress, after transfusion in mice, and in patients with SCD. The sex difference is intrinsic to the RBC and is not mediated by plasmatic factors or female sex hormones. Importantly, orchiectomy in mice improves RBC storage stability and posttransfusion recovery, whereas testosterone repletion therapy exacerbates hemolytic response to osmotic or oxidative stress. Our findings suggest that testosterone increases susceptibility to hemolysis across human diseases, suggesting that male sex may modulate clinical outcomes in blood storage and SCD and establishing a role for donor genetic variables in the viability of stored RBCs and in human hemolytic diseases. © 2016 AABB.

Sex differences in acupuncture effectiveness in animal models of Parkinson's disease: A systematic review

NARCIS (Netherlands)

Lee, S.H.; Noort, M.W.M.L. van den; Bosch, M.P.C.; Lim, S.

2016-01-01

Background: Many animal experimental studies have been performed to investigate the efficacy of acupuncture in Parkinson's disease (PD). Sex differences are a major issue in all diseases including PD. However, to our knowledge, there have been no reviews investigating sex differences on the

Using lod-score differences to determine mode of inheritance: A simple, robust method even in the presence of heterogeneity and reduced penetrance

Energy Technology Data Exchange (ETDEWEB)

Greenberg, D.A.; Berger, B. [Mount Sinai Medical Center, New York, NY (United States)

1994-10-01

Determining the mode of inheritance is often difficult under the best of circumstances, but when segregation analysis is used, the problems of ambiguous ascertainment procedures, reduced penetrance, heterogeneity, and misdiagnosis make mode-of-inheritance determinations even more unreliable. The mode of inheritance can also be determined using a linkage-based method and association-based methods, which can overcome many of these problems. In this work, we determined how much information is necessary to reliably determine the mode of inheritance from linkage data when heterogeneity and reduced penetrance are present in the data set. We generated data sets under both dominant and recessive inheritance with reduced penetrance and with varying fractions of linked and unlinked families. We then analyzed those data sets, assuming reduced penetrance, both dominant and recessive inheritance, and no heterogeneity. We investigated the reliability of two methods for determining the mode of inheritance from the linkage data. The first method examined the difference ({Delta}) between the maximum lod scores calculated under the two mode-of-inheritance assumptions. We found that if {Delta} was >1.5, then the higher of the two maximum lod scores reflected the correct mode of inheritance with high reliability and that a {Delta} of 2.5 appeared to practically guarantee a correct mode-of-inheritance inference. Furthermore, this reliability appeared to be virtually independent of {alpha}, the fraction of linked families in the data set. The second method we tested was based on choosing the higher of the two maximum lod scores calculated under the different mode-of-inheritance assumptions. This method became unreliable as {alpha} decreased. These results suggest that the mode of inheritance can be inferred from linkage data with high reliability, even in the presence of heterogeneity and reduced penetrance. 12 refs., 3 figs., 2 tabs.

New clinical molecular diagnostic methods for congenital and inherited heart disease

NARCIS (Netherlands)

Jongbloed, Jan Dh; Pósafalvi, Anna; Kerstjens-Frederikse, Wilhelmina S.; Sinke, Richard J.; van Tintelen, J. Peter

2011-01-01

For patients with congenital and inherited heart disorders, causative mutations are often not identified owing to limitations of current screening techniques. Identifying the mutation is of major importance for genetic counseling of patients and families, facilitating the diagnosis in people at risk

The link between the epidemics of obesity and allergic diseases

DEFF Research Database (Denmark)

Hersoug, Lars-Georg; Linneberg, A

2007-01-01

There is increasing epidemiological evidence that obesity increases the risk of asthma, atopic, and autoimmune diseases. We hypothesize that the increase in these diseases is caused, at least in part, by decreased immunological tolerance as a consequence of immunological changes induced by adipok......There is increasing epidemiological evidence that obesity increases the risk of asthma, atopic, and autoimmune diseases. We hypothesize that the increase in these diseases is caused, at least in part, by decreased immunological tolerance as a consequence of immunological changes induced......-lymphocytes (Tregs). Additionally, adiponectin, which decreases with increasing obesity, down-regulates the secretion of IL10 from macrophages and adipocytes. These changes in IL6, leptin, and IL10 decrease the regulatory effect of Tregs resulting in decreased immunological tolerance to antigens. In pregnant women......, these obesity-induced immunological changes might be transmitted to the fetus by epigenetic inheritance thereby increasing the risk of atopic disease. We propose that obesity results in immunological changes resulting in decreased immunological tolerance to antigens and skewing of the immune system towards a Th...

Dominant inheritance of retinal ganglion cell resistance to optic nerve crush in mice

Directory of Open Access Journals (Sweden)

Schlamp Cassandra L

2007-03-01

Full Text Available Abstract Background Several neurodegenerative diseases are influenced by complex genetics that affect an individual's susceptibility, disease severity, and rate of progression. One such disease is glaucoma, a chronic neurodegenerative condition of the eye that targets and stimulates apoptosis of CNS neurons called retinal ganglion cells. Since ganglion cell death is intrinsic, it is reasonable that the genes that control this process may contribute to the complex genetics that affect ganglion cell susceptibility to disease. To determine if genetic background influences susceptibility to optic nerve damage, leading to ganglion cell death, we performed optic nerve crush on 15 different inbred lines of mice and measured ganglion cell loss. Resistant and susceptible strains were used in a reciprocal breeding strategy to examine the inheritance pattern of the resistance phenotype. Because earlier studies had implicated Bax as a susceptibility allele for ganglion cell death in the chronic neurodegenerative disease glaucoma, we conducted allelic segregation analysis and mRNA quantification to assess this gene as a candidate for the cell death phenotype. Results Inbred lines showed varying levels of susceptibility to optic nerve crush. DBA/2J mice were most resistant and BALB/cByJ mice were most susceptible. F1 mice from these lines inherited the DBA/2J phenotype, while N2 backcross mice exhibited the BALB/cByJ phenotype. F2 mice exhibited an intermediate phenotype. A Wright Formula calculation suggested as few as 2 dominant loci were linked to the resistance phenotype, which was corroborated by a Punnett Square analysis of the distribution of the mean phenotype in each cross. The levels of latent Bax mRNA were the same in both lines, and Bax alleles did not segregate with phenotype in N2 and F2 mice. Conclusion Inbred mice show different levels of resistance to optic nerve crush. The resistance phenotype is heritable in a dominant fashion involving

[Mitochondria inheritance in yeast saccharomyces cerevisiae].

Science.gov (United States)

Fizikova, A Iu

2011-01-01

The review is devoted to the main mechanisms of mitochondria inheritance in yeast Saccharonmyces cerevisiae. The genetic mechanisms of functionally active mitochondria inheritance in eukaryotic cells is one of the most relevant in modem researches. A great number of genetic diseases are associated with mitochondria dysfunction. Plasticity of eukaryotic cell metabolism according to the environmental changes is ensured by adequate mitochondria functioning by means of ATP synthesis coordination, reactive oxygen species accumulation, apoptosis regulation and is an important factor of cell adaptation to stress. Mitochondria participation in important for cell vitality processes masters the presence of accurate mechanisms of mitochondria functions regulation according to environment fluctuations. The mechanisms of mitochondria division and distribution are highly conserved. Baker yeast S. cerevisiae is an ideal model object for mitochondria researches due to energetic metabolism lability, ability to switch over respiration to fermentation, and petite-positive phenotype. Correction of metabolism according to the environmental changes is necessary for cell vitality. The influence of respiratory, carbon, amino acid and phosphate metabolism on mitochondria functions was shown. As far as the mechanisms that stabilize functions of mitochondria and mtDNA are highly conserve, we can project yeast regularities on higher eukaryotes systems. This makes it possible to approximate understanding the etiology and pathogenesis of a great number of human diseases.

Genome-Wide Locations of Potential Epimutations Associated with Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Using a Sequential Machine Learning Prediction Approach

OpenAIRE

Haque, M. Muksitul; Holder, Lawrence B.; Skinner, Michael K.

2015-01-01

Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation involves germline transmitted epimutations. The primary epimutations identified involve altered differential DNA methylation regions (DMRs). Different environmental toxicants have been shown to promote exposure (i.e., toxicant) specific signatures of germline epimutations. Analysis of genomic features associated with these epimutations identified low-density CpG regions (

Screening for X-linked adrenoleukodystrophy among adult men with Addison's disease.

Science.gov (United States)

Horn, Morten A; Erichsen, Martina M; Wolff, Anette S B; Månsson, Jan-Eric; Husebye, Eystein S; Tallaksen, Chantal M E; Skjeldal, Ola H

2013-09-01

X-linked adrenoleukodystrophy is an important cause of Addison's disease in boys, but less is known about its contribution to Addison's disease in adult men. After surveying all known cases of X-linked adrenoleukodystrophy in Norway in a separate study, we aimed to look for any missed cases among the population of adult men with nonautoimmune Addison's disease. Among 153 adult men identified in a National Registry for Addison's Disease (75% of identified male cases of Addison's disease in Norway), those with negative indices for 21-hydroxylase autoantibodies were selected. Additionally, cases with low autoantibody indices (48-200) were selected. Sera from subjects included were analysed for levels of very long-chain fatty acids, which are diagnostic for X-linked adrenoleukodystrophy in men. Eighteen subjects had negative indices and 17 had low indices for 21-hydroxylase autoantibodies. None of those with low indices and only one of those with negative indices were found to have X-linked adrenoleukodystrophy; this subject had already been diagnosed because of the neurological symptoms. Cases of Addison's disease proved to be caused by X-linked adrenoleukodystrophy constitute 1·5% of all adult male cases in Norway; the proportion among nonautoimmune cases was 15%. We found X-linked adrenoleukodystrophy to be an uncommon cause of Addison's disease in adult men. However, this aetiological diagnosis has far-reaching consequences both for the patient and for his extended family. We therefore recommend that all adult men with nonautoimmune Addison's disease be analysed for levels of very long-chain fatty acids. © 2013 John Wiley & Sons Ltd.

Genetics Home Reference: alpha thalassemia X-linked intellectual disability syndrome

Science.gov (United States)

... Alpha thalassemia X-linked intellectual disability syndrome Alpha thalassemia X-linked intellectual disability syndrome Printable PDF Open ... to view the expand/collapse boxes. Description Alpha thalassemia X-linked intellectual disability syndrome is an inherited ...

[The establishment of research inherit mode of famous academic thoughts].

Science.gov (United States)

Zhou, Xue-ping; Wu, Mian-hua; Guo, Wei-feng

2011-12-01

To study and summarize the academic thoughts of famous Chinese medicine doctors is the main pathway of developing Chinese medicine theories. It is of important significance in enriching and developing the Chinese medicine theories by combining traditional and modern research methods, merging multiple disciples to study the research inherit mode of famous academic thoughts. The major study links include: (1) To refine scientific hypotheses from huge amount of clinical case records; (2) To find the literature sources; (3) To embody the practice significance of the innovative theories by clinical studies; (4) To reveal the scientific connotation of Chinese medicine theories by experimental studies. We hope to reach the goal of innovating and developing Chinese medicine theories on the basis of inheritance by integrating clinical case records, tracing the literature sources, clinical and experimental studies.

Inherited Retinal Degenerative Disease Registry

Science.gov (United States)

2017-09-13

Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

Molecular and Clinical Studies of X-linked Deafness Among Pakistani Families

Science.gov (United States)

Waryah, Ali M.; Ahmed, Zubair M.; Choo, Daniel I.; Sisk, Robert A.; Binder, Munir A.; Shahzad, Mohsin; Khan, Shaheen N.; Friedman, Thomas B.; Riazuddin, Sheikh; Riazuddin, Saima

2011-01-01

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132, PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild to profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling, and molecular epidemiology of hearing loss among Pakistanis. PMID:21633365

Molecular and clinical studies of X-linked deafness among Pakistani families.

Science.gov (United States)

Waryah, Ali M; Ahmed, Zubair M; Bhinder, Munir A; Binder, Munir A; Choo, Daniel I; Sisk, Robert A; Shahzad, Mohsin; Khan, Shaheen N; Friedman, Thomas B; Riazuddin, Sheikh; Riazuddin, Saima

2011-07-01

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132 and PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild-to-profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling and molecular epidemiology of hearing loss among Pakistanis.

Inherited coagulation factor VII and X deficiencies associated with severe bleeding diathesis: Molecular genetics and pathophysiology

NARCIS (Netherlands)

Borensztajn, K.; Spek, C. A.

2005-01-01

The rare inherited coagulation disorders are a fascinating group of diseases that have provided us with important insights into the structure and functions of their respective deficient proteins. Factor (F)VII deficiency is the commonest of these inherited disorders of coagulation, whereas FX

Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states

Directory of Open Access Journals (Sweden)

Cunningham TJ

2014-09-01

. Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.55, 2.80 compared to none was associated with a higher likelihood of COPD among women only. Conclusion: ACEs are related to COPD, especially among women. These findings underscore the need for further research that examines sex-specific differences and the possible mechanisms linking ACEs and COPD. This work adds to a growing body of research suggesting that ACEs may contribute to health problems later in life and suggesting a need for program and policy solutions. Keywords: chronic obstructive pulmonary disease, childhood, abuse, sex

Inheritable and sporadic non-autoimmune hyperthyroidism.

Science.gov (United States)

Ferraz, Carolina; Paschke, Ralf

2017-03-01

Hyperthyroidism is a clinical state that results from high thyroid hormone levels which has multiple etiologies, manifestations, and potential therapies. Excluding the autoimmune Graves disease, autonomic adenomas account for the most import cause of non-autoimmune hyperthyroidism. Activating germline mutations of the TSH receptor are rare etiologies for hyperthyroidism. They can be inherited in an autosomal dominant manner (familial or hereditary, FNAH), or may occur sporadically as a de novo condition, also called: persistent sporadic congenital non-autoimmune hyperthyroidism (PSNAH). These three conditions: autonomic adenoma, FNAH and PSNAH constitute the inheritable and sporadic non-autoimmune hyperthyroidism. Particularities in epidemiology, etiology, molecular and clinical aspects of these three entities will be discussed in this review in order to guide to an accurate diagnosis allowing among others genetic counseling and presymptomatic diagnosis for the affected families. The optimal treatment based on the right diagnosis will avoid consequences of a persistent or relapsing hyperthyroidism. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

Science.gov (United States)

Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; Azbaoui, Safaa El; Agader, Aomar; Hassani, Amal; Hafidi, Naima El; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent

2015-01-01

Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. PMID:25703555

Aluminium and Alzheimer's disease: the science that describes the link

National Research Council Canada - National Science Library

Exley, Christopher

2001-01-01

... that has been encircled is the gene for the amyloid precursor protein. (Thanks to Walter Lukiw for supplying this information.) Aluminium and Alzheimer's Disease: The Science that Describes the LinkAluminium and Alzheimer's Disease The Science that Describes the Link Edited by Christopher Exley Birchall Centre for Inorganic Chemistry and Materials Scienc...

Neurological manifestations in Fabry's disease

DEFF Research Database (Denmark)

Møller, Anette Torvin; Jensen, Troels Staehelin

2007-01-01

. Neurological symptoms, such as burning sensations (occasionally accompanied by acroparesthesia) and stroke, are among the first to appear, and occur in both male and female patients. A delay in establishing the diagnosis of Fabry's disease can cause unnecessary problems, especially now that enzyme replacement...... treatment is available to prevent irreversible organ damage. Females with Fabry's disease who present with pain have often been ignored and misdiagnosed because of the disorder's X-linked inheritance. This Review will stress the importance of recognizing neurological symptoms for the diagnosis of Fabry...

Does cross-generational epigenetic inheritance contribute to cultural continuity?

Science.gov (United States)

Pembrey, Marcus E

2018-04-01

Human studies of cross-generational epigenetic inheritance have to consider confounding by social patterning down the generations, often referred to as 'cultural inheritance'. This raises the question to what extent is 'cultural inheritance' itself epigenetically mediated rather than just learnt. Human studies of non-genetic inheritance have demonstrated that, beyond foetal life, experiences occurring in mid-childhood before puberty are the most likely to be associated with cross-generational responses in the next generation(s). It is proposed that cultural continuity is played out along the axis, or 'payoff', between responsiveness and stability. During the formative years of childhood a stable family and/or home permits small children to explore and thereby learn. To counter disruptions to this family home ideal, cultural institutions such as local schools, religious centres and market places emerged to provide ongoing stability, holding the received wisdom of the past in an accessible state. This cultural support allows the growing child to freely indulge their responsiveness. Some of these prepubertal experiences induce epigenetic responses that also transfer molecular signals to the gametes through which they contribute to the conception of future offspring. In parallel co-evolution with growing cultural support for increasing responsiveness, 'runaway' responsiveness is countered by the positive selection of genetic variants that dampen responsiveness. Testing these ideas within longitudinal multigenerational cohorts will need information on ancestors/parents' own communities and experiences (Exposome scans) linked to ongoing Phenome scans on grandchildren; coupled with epigenome analysis, metastable epialleles and DNA methylation age. Interactions with genetic variants affecting responsiveness should help inform the broad hypothesis.

A previously unidentified deletion in G protein-coupled receptor 143 causing X-linked congenital nystagmus in a Chinese family

Directory of Open Access Journals (Sweden)

Jing Liu

2016-01-01

Full Text Available Background: Congenital nystagmus (CN is characterized by conjugated, spontaneous, and involuntary ocular oscillations. It is an inherited disease and the most common inheritance pattern is X-linked CN. In this study, our aim is to identify the disease-causing mutation in a large sixth-generation Chinese family with X-linked CN. Methods: It has been reported that mutations in four-point-one, ezrin, radixin, moesin domain-containing 7 gene (FRMD7 and G protein-coupled receptor 143 gene (GPR143 account for the majority patients of X-linked nystagmus. We collected 8 ml blood samples from members of a large sixth-generation pedigree with X-linked CN and 100 normal controls. FRMD7 and GPR143 were scanned by polymerase chain reaction (PCR-based DNA sequencing assays, and multiplex PCR assays were applied to detect deletions. Results: We identified a previously unreported deletion covering 7 exons in GPR143 in a Chinese family. The heterozygous deletion from exon 3 to exon 9 of GPR143 was detected in all affected males in the family, while it was not detected in other unaffected relatives or 100 normal controls. Conclusions: This is the first report of molecular characterization in GPR143 gene in the CN family. Our results expand the spectrum of GPR143 mutations causing CN and further confirm the role of GPR143 in the pathogenesis of CN.

The RNAi Inheritance Machinery of Caenorhabditis elegans.

Science.gov (United States)

Spracklin, George; Fields, Brandon; Wan, Gang; Becker, Diveena; Wallig, Ashley; Shukla, Aditi; Kennedy, Scott

2017-07-01

Gene silencing mediated by dsRNA (RNAi) can persist for multiple generations in Caenorhabditis elegans (termed RNAi inheritance). Here we describe the results of a forward genetic screen in C. elegans that has identified six factors required for RNAi inheritance: GLH-1/VASA, PUP-1/CDE-1, MORC-1, SET-32, and two novel nematode-specific factors that we term here (heritable RNAi defective) HRDE-2 and HRDE-4 The new RNAi inheritance factors exhibit mortal germline (Mrt) phenotypes, which we show is likely caused by epigenetic deregulation in germ cells. We also show that HRDE-2 contributes to RNAi inheritance by facilitating the binding of small RNAs to the inheritance Argonaute (Ago) HRDE-1 Together, our results identify additional components of the RNAi inheritance machinery whose conservation provides insights into the molecular mechanism of RNAi inheritance, further our understanding of how the RNAi inheritance machinery promotes germline immortality, and show that HRDE-2 couples the inheritance Ago HRDE-1 with the small RNAs it needs to direct RNAi inheritance and germline immortality. Copyright © 2017 by the Genetics Society of America.

Safe Dynamic Multiple Inheritance

DEFF Research Database (Denmark)

Ernst, Erik

2002-01-01

Multiple inheritance and similar mechanisms are usually only supported at compile time in statically typed languages. Nevertheless, dynamic multiple inheritance would be very useful in the development of complex systems, because it allows the creation of many related classes without an explosion...... in the size and level of redundancy in the source code. In fact, dynamic multiple inheritance is already available. The language gbeta is statically typed and has supported run-time combination of classes and methods since 1997, by means of the combination operator '&'. However, with certain combinations...

Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period.

Science.gov (United States)

Pappa, Theodora; Alevizaki, Maria

2012-08-01

Cardio- and cerebro-vascular diseases are two leading causes of death and long-term disability in postmenopausal women. The acute fall of estrogen in menopause is associated with increased cardiovascular risk. The relative contribution of androgen to this risk is also being recognized. The use of more sensitive assays for estradiol measurement and the study of receptor and carrier protein gene polymorphisms have provided some new information on the clinical relevance of endogenous sex steroids. We provide an update on the role of endogenous sex steroids on cardio- and cerebro-vascular disease in the postmenopausal period. We performed a PubMed search using the terms 'endogenous estrogen', 'androgen', 'cardiovascular disease', 'cerebro-vascular disease', 'stroke', 'carotid artery disease', and 'subclinical atherosclerosis'. The majority of studies show a beneficial effect of endogenous estrogen on the vasculature; however, there are a few studies reporting the contrary. A significant body of literature has reported associations of endogenous estrogen and androgen with early markers of atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex steroids in heart disease and stroke are inconclusive. Most studies support a beneficial role of endogenous estrogens and, probably, an adverse effect of androgens in the vasculature in postmenopausal women. However, the described associations may not always be considered as causal. It is possible that circulating estrogen might represent a marker of general health status or alternatively reflect the sum of endogenous androgens aromatized in the periphery. Elucidating the role of sex steroids in cardio- and cerebro-vascular disease remains an interesting field of future research.

Prenatal exclusion of Norrie disease with flanking DNA markers.

Science.gov (United States)

Gal, A; Uhlhaas, S; Glaser, D; Grimm, T

1988-10-01

Three polymorphic DNA markers linked to the locus of Norrie disease were used for indirect genotype analysis in a ten-wk-old fetus at risk for the disease. When haplotypes of the family members and the estimated recombination frequency between Norrie gene and each of the DNA marker loci DXS7, DXS84, and DXS146 were taken into account, the risk that the fetus had inherited the mutation was about 1%.

Uptake of a women-only, sex-work-specific drop-in center and links with sexual and reproductive health care for sex workers.

Science.gov (United States)

Kim, Soyoun Rachel; Goldenberg, Shira M; Duff, Putu; Nguyen, Paul; Gibson, Kate; Shannon, Kate

2015-03-01

To longitudinally examine female sex workers' (FSWs') uptake of a women-only, sex-work-specific drop-in service and its impact on their access to sexual and reproductive health (SRH) services. For the present longitudinal analysis, data were drawn from the AESHA (An Evaluation of Sex Workers' Health Access) study, a community-based, open, prospective cohort of FSWs from Vancouver, BC, Canada. Data obtained between January 2010 and February 2013 were analyzed. Participants are followed up on a semi-annual basis. Multivariable logistic regression using generalized estimating equations was used to identify correlates of service uptake. Of 547 FSWs included in the present analysis, 330 (60.3%) utilized the services during the 3-year study period. Service use was independently associated with age (adjusted odds ratio [AOR] 1.04; 95% confidence interval [CI] 1.03-1.06), Aboriginal ancestry (AOR 2.18; 95% CI 1.61-2.95), injection drug use (AOR 1.67; 95% CI 1.29-2.17), exchange of sex for drugs (AOR 1.40; 95%CI 1.15-1.71), and accessing SRH services (AOR 1.65; 95% CI 1.35-2.02). A sex-work-specific drop-in space for marginalized FSWs had high uptake. Women-centered and low-threshold drop-in services can effectively link marginalized women with SRH services. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences

Directory of Open Access Journals (Sweden)

Mielke MM

2014-01-01

Full Text Available Michelle M Mielke,1,2 Prashanthi Vemuri,3 Walter A Rocca1,2 1Department of Health Sciences Research, 2Department of Neurology, 3Department of Radiology, Mayo Clinic, Rochester, MN, USA Abstract: With the aging of the population, the burden of Alzheimer's disease (AD is rapidly expanding. More than 5 million people in the US alone are affected with AD and this number is expected to triple by 2050. While men may have a higher risk of mild cognitive impairment (MCI, an intermediate stage between normal aging and dementia, women are disproportionally affected with AD. One explanation is that men may die of competing causes of death earlier in life, so that only the most resilient men may survive to older ages. However, many other factors should also be considered to explain the sex differences. In this review, we discuss the differences observed in men versus women in the incidence and prevalence of MCI and AD, in the structure and function of the brain, and in the sex-specific and gender-specific risk and protective factors for AD. In medical research, sex refers to biological differences such as chromosomal differences (eg, XX versus XY chromosomes, gonadal differences, or hormonal differences. In contrast, gender refers to psychosocial and cultural differences between men and women (eg, access to education and occupation. Both factors play an important role in the development and progression of diseases, including AD. Understanding both sex- and gender-specific risk and protective factors for AD is critical for developing individualized interventions for the prevention and treatment of AD. Keywords: Alzheimer’s disease, dementia, sex, gender, risk factors, dimorphic medicine

Sex differences in correlates of intermediate phenotypes and prevalent cardiovascular disease in the general population

Directory of Open Access Journals (Sweden)

Renate B. Schnabel

2015-04-01

Full Text Available Background-There are marked sex differences in cardiovascular disease [CVD] manifestation. It is largely unknown how the distribution of CVD risk factors or intermediate phenotypes explain sex-specific differences.Methods and Results-In 5000 individuals of the population-based Gutenberg Health Study, mean age 55±11 years, 51% males, we examined sex-specific associations of classical CVD risk factors with intima-media thickness, ankle-brachial index, flow-mediated dilation, peripheral arterial tonometry, echocardiographic and electrocardiographic variables. Intermediate cardiovascular phenotypes were related to prevalent CVD (coronary artery disease, heart failure, stroke, myocardial infarction, lower extremity artery disease [LEAD] N=561.We observed differential distributions of CVD risk factors with a higher risk factor burden in men. Manifest coronary artery disease, stroke, myocardial infarction and LEAD were more frequent in men; the proportion of heart failure was higher in women. Intermediate phenotypes showed clear sex differences with more beneficial values in women. Fairly linear changes towards less beneficial values with age were observed in both sexes. In multivariable-adjusted regression analyses age, systolic blood pressure and body mass index were consistently associated with intermediate phenotypes in both sexes with different ranking according to random forests, maximum model R² 0.43. Risk factor-adjusted associations with prevalent CVD showed some differences by sex. No interactions by menopausal status were observed. Conclusions-In a population-based cohort we observed sex differences in risk factors and a broad range of intermediate phenotypes of noninvasive cardiovascular structure and function. Their relation to prevalent CVD differed markedly. Our results indicate the need of future investigations to understand sex differences in CVD manifestation.

Inherited and Acquired Muscle Weakness: A Moving Target for Diagnostic Muscle Biopsy.

Science.gov (United States)

Stenzel, Werner; Schoser, Benedikt

2017-08-01

Inherited and acquired muscular weakness is caused by multiple conditions. While the inherited ones are mostly caused by mutations in genes coding for myopathic or neurogenic diseases, the acquired ones occur due to inflammatory, endocrine, or toxic etiologies. Precise diagnosis of a specific disease may be challenging and may require a multidisciplinary approach. What is the current place for a diagnostic biopsy of skeletal muscle? Diagnostic muscle biopsy lost in this context its first-tier place in the primary diagnostic workup for some diseases, but it is still mandatory for others. We here summarize conditions in which we believe a diagnostic sample is most relevant and mention those in which a biopsy may be secondary or can even be left out. We would like to stress that muscle biopsy nowadays has a new important place in description and definition of new diseases, for example, discovered by modern genetic approaches. Georg Thieme Verlag KG Stuttgart, New York.

Disbiome database: linking the microbiome to disease.

Science.gov (United States)

Janssens, Yorick; Nielandt, Joachim; Bronselaer, Antoon; Debunne, Nathan; Verbeke, Frederick; Wynendaele, Evelien; Van Immerseel, Filip; Vandewynckel, Yves-Paul; De Tré, Guy; De Spiegeleer, Bart

2018-06-04

Recent research has provided fascinating indications and evidence that the host health is linked to its microbial inhabitants. Due to the development of high-throughput sequencing technologies, more and more data covering microbial composition changes in different disease types are emerging. However, this information is dispersed over a wide variety of medical and biomedical disciplines. Disbiome is a database which collects and presents published microbiota-disease information in a standardized way. The diseases are classified using the MedDRA classification system and the micro-organisms are linked to their NCBI and SILVA taxonomy. Finally, each study included in the Disbiome database is assessed for its reporting quality using a standardized questionnaire. Disbiome is the first database giving a clear, concise and up-to-date overview of microbial composition differences in diseases, together with the relevant information of the studies published. The strength of this database lies within the combination of the presence of references to other databases, which enables both specific and diverse search strategies within the Disbiome database, and the human annotation which ensures a simple and structured presentation of the available data.

A novel mutation in the nerve-specific 5'UTR of the GJB1 gene causes X-linked Charcot-Marie-Tooth disease.

LENUS (Irish Health Repository)

Murphy, Sinéad M

2011-03-01

X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene which codes for connexin 32 (CX32). CX32 has three tissue-specific promoters, P1 which is specific for liver and pancreas, P1a specific for liver, oocytes and embryonic stem cells, and P2 which is nerve-specific. Over 300 mutations have been described in GJB1, spread throughout the coding region. We describe two families with X-linked inheritance and a phenotype consistent with CMT1X who did not have mutations in the GJB1 coding region. The non-coding region of GJB1 was sequenced and an upstream exon-splicing variant found at approximately - 373G>A which segregated with the disease in both families and was not present in controls. This substitution is located at the last base of the nerve-specific 5\\'UTR and thus may disrupt splicing of the nerve-specific transcript. Online consensus splice-site programs predict a reduced score for the mutant sequence vs. the normal sequence. It is likely that other mutations within the GJB1 non-coding regions account for the CMT1X families who do not have coding region mutations.

Sex-specific expression of the X-linked histone demethylase gene Jarid1c in brain.

Directory of Open Access Journals (Sweden)

Jun Xu

Full Text Available Jarid1c, an X-linked gene coding for a histone demethylase, plays an important role in brain development and function. Notably, JARID1C mutations cause mental retardation and increased aggression in humans. These phenotypes are consistent with the expression patterns we have identified in mouse brain where Jarid1c mRNA was detected in hippocampus, hypothalamus, and cerebellum. Jarid1c expression and associated active histone marks at its 5'end are high in P19 neurons, indicating that JARID1C demethylase plays an important role in differentiated neuronal cells. We found that XX mice expressed Jarid1c more highly than XY mice, independent of their gonadal types (testes versus ovaries. This increased expression in XX mice is consistent with Jarid1c escape from X inactivation and is not compensated by expression from the Y-linked paralogue Jarid1d, which is expressed at a very low level compared to the X paralogue in P19 cells. Our observations suggest that sex-specific expression of Jarid1c may contribute to sex differences in brain function.

Spectrum of sonographic changes in hereditary motor and sensory neuropathy with autosomal dominant and X-linked inheritance

Directory of Open Access Journals (Sweden)

E. S. Naumova

2016-01-01

Full Text Available Background. In the recent years interest towards nerve sonography has largely increased, specifically in terms of differentiating types of hereditary motor and sensory neuropathy (HMSN. The diagnostic possibilities of high-resolution ultrasound (HRUS compared to standard neurophysiological tools in the peripheral nerve disorders is still a matter of debate.Objectives. Analysis of quantitative and qualitative ultrasound changes of limb nerves in patients with HMSN type 1 and its comparison with anthropometric and nerve conduction study data.Materials and methods. 44 HMSN patients were analyzed: 16 men, mean age 35,9 ± 6,8 years; 16 (37 % with autosomal dominant type 1А, 11 (25 % – with 1В type and 17 (38 % with Х-linked inheritance. Control group included 44 subjects, 16 male; mean age 35,9 ± 6,8 years. HRUS parameters were analyzed bilaterally on the selected levels: cross-sectional area (CSA, visual cross sectional and longitudinal patterns of the median and ulnar nerves, C5, C6, C7 spinal nerves, tibial, peroneal and sciatic nerves. HRUS parameters were compared to standard anthropometric data, nerve conduction velocity and CMAP amplitude.Results. In all HMSN cases CSA was enlarged compared to healthy controls. Greater changes were found in patients with autosomal dominant inheritance. CSA enlargement in С5, С6, С7 spinal nerves was found in patients with HMSN 1A, С6, С7 – in HMSN 1В, С6 – in HMSN 1X, confirming the necessity to include those nerves in the sonographic protocol in patients with HMSN. Three qualitative cross sectional and longitudinal patterns of the investigated arm nerves were identified, distinct for each of the HMSN type. Absence of significant differences in CSA of the upper limb nerves among analyzed types of HMSN makes it unreliable as the differential parameter, opposite to the defined sonographic patterns. Methodological issues and absence of significant quantitative and qualitative data

Clinical epidemiology of Alzheimer's disease: assessing sex and gender differences.

Science.gov (United States)

Mielke, Michelle M; Vemuri, Prashanthi; Rocca, Walter A

2014-01-01

With the aging of the population, the burden of Alzheimer's disease (AD) is rapidly expanding. More than 5 million people in the US alone are affected with AD and this number is expected to triple by 2050. While men may have a higher risk of mild cognitive impairment (MCI), an intermediate stage between normal aging and dementia, women are disproportionally affected with AD. One explanation is that men may die of competing causes of death earlier in life, so that only the most resilient men may survive to older ages. However, many other factors should also be considered to explain the sex differences. In this review, we discuss the differences observed in men versus women in the incidence and prevalence of MCI and AD, in the structure and function of the brain, and in the sex-specific and gender-specific risk and protective factors for AD. In medical research, sex refers to biological differences such as chromosomal differences (eg, XX versus XY chromosomes), gonadal differences, or hormonal differences. In contrast, gender refers to psychosocial and cultural differences between men and women (eg, access to education and occupation). Both factors play an important role in the development and progression of diseases, including AD. Understanding both sex- and gender-specific risk and protective factors for AD is critical for developing individualized interventions for the prevention and treatment of AD.

Inheritance is Specialisation

DEFF Research Database (Denmark)

Torgersen, Mads

2002-01-01

How can we get a simpler but much more general subclass construct? This position paper takes a "specialisationist" approach to inheritance. Old SIMULA virtues are restored to prominence, but boiled with new unificational ingredients to obtain a substrate of specialisation. Ever since the advent...... of Smalltalk there has been a strong tension in the object-oriented community between two opposing views of the role of inheritance: as an incremental modification mechanism or as a vehicle for conceptual modelling. Madsen [5] and many others characterise the two approaches as the “American ” and “Scandinavian......” schools, respectively. Nowadays, such a geographical terminology hardly remains valid (if ever it was), but the tension remains: should we strive for maximal flexibility of inheritance, to improve the possibilities for later unanticipated reuse, or should we attend above all to the conceptual integrity...

Influence of sex on chronic obstructive pulmonary disease risk and treatment outcomes

Directory of Open Access Journals (Sweden)

Aryal S

2014-10-01

Full Text Available Shambhu Aryal,1 Enrique Diaz-Guzman,2 David M Mannino3 1Division of Pulmonary, Allergy and Critical Care Medicine, Duke University, Durham, NC, 2Division of Pulmonary, Allergy and Critical Care, University of Alabama, Birmingham, AL, 3Department of Preventive Medicine and Environmental Health, University of Kentucky, Lexington, KY, USA Abstract: Chronic obstructive pulmonary disease (COPD, one of the most common chronic diseases and a leading cause of death, has historically been considered a disease of men. However, there has been a rapid increase in the prevalence, morbidity, and mortality of COPD in women over the last two decades. This has largely been attributed to historical increases in tobacco consumption among women. But the influence of sex on COPD is complex and involves several other factors, including differential susceptibility to the effects of tobacco, anatomic, hormonal, and behavioral differences, and differential response to therapy. Interestingly, nonsmokers with COPD are more likely to be women. In addition, women with COPD are more likely to have a chronic bronchitis phenotype, suffer from less cardiovascular comorbidity, have more concomitant depression and osteoporosis, and have a better outcome with acute exacerbations. Women historically have had lower mortality with COPD, but this is changing as well. There are also differences in how men and women respond to different therapies. Despite the changing face of COPD, care providers continue to harbor a sex bias, leading to underdiagnosis and delayed diagnosis of COPD in women. In this review, we present the current knowledge on the influence of sex on COPD risk factors, epidemiology, diagnosis, comorbidities, treatment, and outcomes, and how this knowledge may be applied to improve clinical practices and advance research. Keywords: chronic obstructive lung disease, sex, smoking, comorbidity, sex bias

Self-Reported Symptoms of Parkinson's Disease by Sex and Disease Duration.

Science.gov (United States)

Shin, Ju Young; Pohlig, Ryan T; Habermann, Barbara

2017-11-01

Parkinson's disease (PD) is a neurodegenerative disease with a wide range of symptom presentations. The purpose of this research was to compare self-reported motor and non-motor symptoms of PD by sex and disease duration. This study was a cross-sectional descriptive survey in community-dwelling people with PD. A total of 141 participants (64.6% response rate; 59.6% men; M age = 69.7 years) were included. Males reported more rigidity, speech problems, sexual dysfunction, memory problems, and socializing problems than females. The number of motor symptoms in three groups divided by increments of 5 years was significantly increased. Postural instability, freezing, off periods, dyskinesia, speech problems, and hallucinations/psychosis were significantly increased as the disease duration increased. Thorough assessment of motor and non-motor symptoms could decrease the risk of inadequate symptom management. Provision of information regarding PD symptoms at each stage may help people with PD and their caregivers in planning their future care and life.

Link Between Celiac Disease and Inflammatory Bowel Disease.

Science.gov (United States)

Shah, Ayesha; Walker, Marjorie; Burger, Daniel; Martin, Neal; von Wulffen, Moritz; Koloski, Natasha; Jones, Mike; Talley, Nicholas J; Holtmann, Gerald J

2018-05-14

The aim of this analysis was to assess in patients with inflammatory bowel disease (IBD) the risk of celiac disease and in celiac disease patients the risk of IBD. Previous studies report a possible association between IBD and celiac disease; however, this link is controversial. Using the search terms "inflammatory bowel disease" and "celiac disease," we identified initially 1525 publications. In total 27 studies met inclusion criteria. Proportions and 95% confidence intervals (CIs) for the prevalence of IBD in celiac disease and vice versa were compared with published prevalence rates for the respective geographic regions. We included 41,482 adult IBD patients (20,357 with Crohn's disease; 19,791 with ulcerative colitis; and 459 patients with celiac disease). Overall, in IBD patients the prevalence of celiac disease was 1110/100,000 (95% CI, 1010-1210/100,000) as compared with a prevalence of 620/100,000 (95% CI, 610-630/100,000) in the respective populations (odds ratio, 2.23; 95% CI, 1.99-2.50). In contrast, in patients with celiac disease, 2130/100,000 had IBD (95% CI, 1590-2670/100,000) as compared with 260/100,000 (95% CI, 250/100,000-270/100,000) in the respective populations (odds ratio, 11.10; 95% CI, 8.55-14.40). This effect was not different for ulcerative colitis and Crohn's disease. Although there was no evidence for publication bias for celiac disease in IBD, the funnel plot suggested that the association between IBD in celiac disease might be influenced by publication bias. The data are consistent with the notion that celiac disease is a risk factor for IBD and to lesser degree patients with IBD have an increased risk of celiac disease.

Hereditary spastic paraplegia: More than an upper motor neuron disease.

Science.gov (United States)

Parodi, L; Fenu, S; Stevanin, G; Durr, A

2017-05-01

Hereditary spastic paraplegias (HSPs) are a group of rare inherited neurological diseases characterized by extreme heterogeneity in both their clinical manifestations and genetic backgrounds. Based on symptoms, HSPs can be divided into pure forms, presenting with pyramidal signs leading to lower-limb spasticity, and complex forms, when additional neurological or extraneurological symptoms are detected. The clinical diversity of HSPs partially reflects their underlying genetic backgrounds. To date, 76 loci and 58 corresponding genes [spastic paraplegia genes (SPGs)] have been linked to HSPs. The genetic diagnosis is further complicated by the fact that causative mutations of HSP can be inherited through all possible modes of transmission (autosomal-dominant and -recessive, X-linked, maternal), with some genes showing multiple inheritance patterns. The pathogenic mutations of SPGs primarily lead to progressive degeneration of the upper motor neurons (UMNs) comprising corticospinal tracts. However, it is possible to observe lower-limb muscle atrophy and fasciculations on clinical examination that are clear signs of lower motor neuron (LMN) involvement. The purpose of this review is to classify HSPs based on their degree of motor neuron involvement, distinguishing forms in which only UMNs are affected from those involving both UMN and LMN degeneration, and to describe their differential diagnosis from diseases such as amyotrophic lateral sclerosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Disease Compass- a navigation system for disease knowledge based on ontology and linked data techniques.

Science.gov (United States)

Kozaki, Kouji; Yamagata, Yuki; Mizoguchi, Riichiro; Imai, Takeshi; Ohe, Kazuhiko

2017-06-19

Medical ontologies are expected to contribute to the effective use of medical information resources that store considerable amount of data. In this study, we focused on disease ontology because the complicated mechanisms of diseases are related to concepts across various medical domains. The authors developed a River Flow Model (RFM) of diseases, which captures diseases as the causal chains of abnormal states. It represents causes of diseases, disease progression, and downstream consequences of diseases, which is compliant with the intuition of medical experts. In this paper, we discuss a fact repository for causal chains of disease based on the disease ontology. It could be a valuable knowledge base for advanced medical information systems. We developed the fact repository for causal chains of diseases based on our disease ontology and abnormality ontology. This section summarizes these two ontologies. It is developed as linked data so that information scientists can access it using SPARQL queries through an Resource Description Framework (RDF) model for causal chain of diseases. We designed the RDF model as an implementation of the RFM for the fact repository based on the ontological definitions of the RFM. 1554 diseases and 7080 abnormal states in six major clinical areas, which are extracted from the disease ontology, are published as linked data (RDF) with SPARQL endpoint (accessible API). Furthermore, the authors developed Disease Compass, a navigation system for disease knowledge. Disease Compass can browse the causal chains of a disease and obtain related information, including abnormal states, through two web services that provide general information from linked data, such as DBpedia, and 3D anatomical images. Disease Compass can provide a complete picture of disease-associated processes in such a way that fits with a clinician's understanding of diseases. Therefore, it supports user exploration of disease knowledge with access to pertinent information

Inherited prion disease A117V is not simply a proteinopathy but produces prions transmissible to transgenic mice expressing homologous prion protein.

Science.gov (United States)

Asante, Emmanuel A; Linehan, Jacqueline M; Smidak, Michelle; Tomlinson, Andrew; Grimshaw, Andrew; Jeelani, Asif; Jakubcova, Tatiana; Hamdan, Shyma; Powell, Caroline; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

2013-01-01

Prions are infectious agents causing fatal neurodegenerative diseases of humans and animals. In humans, these have sporadic, acquired and inherited aetiologies. The inherited prion diseases are caused by one of over 30 coding mutations in the human prion protein (PrP) gene (PRNP) and many of these generate infectious prions as evidenced by their experimental transmissibility by inoculation to laboratory animals. However, some, and in particular an extensively studied type of Gerstmann-Sträussler-Scheinker syndrome (GSS) caused by a PRNP A117V mutation, are thought not to generate infectious prions and instead constitute prion proteinopathies with a quite distinct pathogenetic mechanism. Multiple attempts to transmit A117V GSS have been unsuccessful and typical protease-resistant PrP (PrP(Sc)), pathognomonic of prion disease, is not detected in brain. Pathogenesis is instead attributed to production of an aberrant topological form of PrP, C-terminal transmembrane PrP ((Ctm)PrP). Barriers to transmission of prion strains from one species to another appear to relate to structural compatibility of PrP in host and inoculum and we have therefore produced transgenic mice expressing human 117V PrP. We found that brain tissue from GSS A117V patients did transmit disease to these mice and both the neuropathological features of prion disease and presence of PrP(Sc) was demonstrated in the brains of recipient transgenic mice. This PrP(Sc) rapidly degraded during laboratory analysis, suggesting that the difficulty in its detection in patients with GSS A117V could relate to post-mortem proteolysis. We conclude that GSS A117V is indeed a prion disease although the relative contributions of (Ctm)PrP and prion propagation in neurodegeneration and their pathogenetic interaction remains to be established.

Inherited prion disease A117V is not simply a proteinopathy but produces prions transmissible to transgenic mice expressing homologous prion protein.

Directory of Open Access Journals (Sweden)

Emmanuel A Asante

Full Text Available Prions are infectious agents causing fatal neurodegenerative diseases of humans and animals. In humans, these have sporadic, acquired and inherited aetiologies. The inherited prion diseases are caused by one of over 30 coding mutations in the human prion protein (PrP gene (PRNP and many of these generate infectious prions as evidenced by their experimental transmissibility by inoculation to laboratory animals. However, some, and in particular an extensively studied type of Gerstmann-Sträussler-Scheinker syndrome (GSS caused by a PRNP A117V mutation, are thought not to generate infectious prions and instead constitute prion proteinopathies with a quite distinct pathogenetic mechanism. Multiple attempts to transmit A117V GSS have been unsuccessful and typical protease-resistant PrP (PrP(Sc, pathognomonic of prion disease, is not detected in brain. Pathogenesis is instead attributed to production of an aberrant topological form of PrP, C-terminal transmembrane PrP ((CtmPrP. Barriers to transmission of prion strains from one species to another appear to relate to structural compatibility of PrP in host and inoculum and we have therefore produced transgenic mice expressing human 117V PrP. We found that brain tissue from GSS A117V patients did transmit disease to these mice and both the neuropathological features of prion disease and presence of PrP(Sc was demonstrated in the brains of recipient transgenic mice. This PrP(Sc rapidly degraded during laboratory analysis, suggesting that the difficulty in its detection in patients with GSS A117V could relate to post-mortem proteolysis. We conclude that GSS A117V is indeed a prion disease although the relative contributions of (CtmPrP and prion propagation in neurodegeneration and their pathogenetic interaction remains to be established.

Status hierarchy, attractiveness hierarchy and sex ratio : Three contextual factors explaining the status-aggression link among adolescents

NARCIS (Netherlands)

Zwaan, Michiel; Dijkstra, Jan; Veenstra, René

The moderating effects of three specific conditions (status hierarchy, attractiveness hierarchy and sex ratio) on the link between status (popularity) and physical and relational aggression were examined in a large sample of adolescent boys (N = 1,665) and girls (N = 1,637) (M age = 13.60). In line

Condomless Sex: Gay Men, Barebacking, and Harm Reduction

Science.gov (United States)

Shernoff, Michael

2006-01-01

Social science research as well as a rise in sexually transmitted diseases and new HIV infections among men who have sex with men point to increasing numbers of gay men engaging in unprotected anal intercourse without condoms, a practice called "barebacking." There is some evidence that barebacking is linked to the rise of crystal methamphetamine…

Sex hormone therapy and progression of cardiovascular disease in menopausal women

Science.gov (United States)

Alhurani, Rabe E.; Chahal, C. Anwar A.; Ahmed, Ahmed T.; Mohamed, Essa A.; Miller, Virginia M.

2017-01-01

One of the most controversial health decisions facing women is deciding upon the use of hormonal treatments for symptoms of menopause. This brief review focuses on the historical context of use of menopausal hormone treatments (MHT), summarizes results of major observational, primary and secondary prevention studies of MHT and cardiovascular (CV) outcomes, provides evidence for how sex steroids modulate CV function and identifies challenges for future research. As medicine enters an era of personalization of treatment options, additional research into sex differences in the aetiology of CV diseases will lead to better risk identification for CV disease in women and identify whether a woman might receive CV benefit from specific formulations and doses of MHT. PMID:27215679

Status Hierarchy, Attractiveness Hierarchy and Sex Ratio: Three Contextual Factors Explaining the Status-Aggression Link among Adolescents

Science.gov (United States)

Zwaan, Michiel; Dijkstra, Jan Kornelis; Veenstra, Rene

2013-01-01

The moderating effects of three specific conditions (status hierarchy, attractiveness hierarchy and sex ratio) on the link between status (popularity) and physical and relational aggression were examined in a large sample of adolescent boys ("N" = 1,665) and girls ("N" = 1,637) ("M" age = 13.60). In line with the…

Inheritance and heritability of resistance to citrus leprosis.

Science.gov (United States)

Bastianel, Marinês; de Oliveira, Antonio Carlos; Cristofani, Mariângela; Filho, Oliveiro Guerreiro; Freitas-Astúa, Juliana; Rodrigues, Vandeclei; Astúa-Monge, Gustavo; Machado, Marcos Antônio

2006-10-01

ABSTRACT The genetic inheritance of resistance to leprosis, the most important viral disease of citrus in Brazil, was characterized through the phenotypic assessment of 143 hybrids resulting from crosses between tangor 'Murcott' (Citrus sinensis x C. reticulata) and sweet orange 'Pêra' (C. sinensis), considered to be resistant and susceptible to the disease, respectively. All plants were grafted onto Rangpur lime (C. limonia) and inoculated with Citrus leprosis virus, cytoplasmic type through the infestation with viruliferous mites, Brevipalpus phoenicis. The experiments were arranged in a completely randomized block design with 10 replicates. Incidence and severity of the disease in leaves and stems as well as plant growth parameters (plant height and stem diameter) were recorded for 3 years after the infestation with the viruliferous mites. The average values of all variables were analyzed using principal component analysis, discriminant factorial analysis, estimation of the clonal repeatability coefficients, and frequency of the distributions of the average values for each measured variable. The principal component analysis resulted in the identification of at least two groups with resistance and susceptibility to leprosis, respectively. About 99% of all hybrids were correctly classified according to the discriminant factorial analysis. The broad-sense heritability coefficients for characteristics associated with incidence and severity of leprosis ranged from 0.88 to 0.96. The data suggest that the inheritance of resistance to leprosis may be controlled by only a few genes.

Sex differences in the fetal programming of hypertension.

Science.gov (United States)

Grigore, Daniela; Ojeda, Norma B; Alexander, Barbara T

2008-01-01

Numerous clinical and experimental studies support the hypothesis that the intrauterine environment is an important determinant of cardiovascular disease and hypertension. This review examined the mechanisms linking an adverse fetal environment and increased risk for chronic disease in adulthood with an emphasis on gender differences and the role of sex hormones in mediating sexual dimorphism in response to a suboptimal fetal environment. This review focuses on current findings from the PubMed database regarding animal models of fetal programming of hypertension, sex differences in phenotypic outcomes, and potential mechanisms in offspring of mothers exposed to an adverse insult during gestation. For the years 1988 to 2007, the database was searched using the following terms: fetal programming, intrauterine growth restriction, low birth weight, sex differences, estradiol, testosterone, high blood pressure, and hypertension. The mechanisms involved in the fetal programming of adult disease are multifactorial and include alterations in the regulatory systems affecting the long-tterm control of arterial pressure. Sex differences have been observed in animal models of fetal programming, and recent studies suggest that sex hormones may modulate activity of regulatory systems, leading to a lower incidence of hypertension and vascular dysfunction in females compared with males. Animal models of fetal programming provide critical support for the inverse relationship between birth weight and blood pressure. Experimental models demonstrate that sex differences are observed in the pathophysiologic response to an adverse fetal environment. A role for sex hormone involvement is strongly suggested,with modulation of the renin-angiotensin system as a possible mechanism.

[Application of next-generation semiconductor sequencing technologies in genetic diagnosis of inherited cardiomyopathies].

Science.gov (United States)

Zhao, Yue; Zhang, Hong; Xia, Xue-shan

2015-07-01

Inherited cardiomyopathy is the most common hereditary cardiac disease. It also causes a significant proportion of sudden cardiac deaths in young adults and athletes. So far, approximately one hundred genes have been reported to be involved in cardiomyopathies through different mechanisms. Therefore, the identification of the genetic basis and disease mechanisms of cardiomyopathies are important for establishing a clinical diagnosis and genetic testing. Next-generation semiconductor sequencing (NGSS) technology platform is a high-throughput sequencer capable of analyzing clinically derived genomes with high productivity, sensitivity and specificity. It was launched in 2010 by Life Technologies of USA, and it is based on a high density semiconductor chip, which was covered with tens of thousands of wells. NGSS has been successfully used in candidate gene mutation screening to identify hereditary disease. In this review, we summarize these genetic variations, challenge and application of NGSS in inherited cardiomyopathy, and its value in disease diagnosis, prevention and treatment.

Functional and structural nerve fiber findings in heterozygote patients with Fabry disease

DEFF Research Database (Denmark)

Torvin, Moller A.; Winther, Bach F.; Feldt-Rasmussen, U.

2009-01-01

recently disease manifestations in female carriers of Fabry disease have been questioned. To explore the frequency of symptoms and the functional and structural involvement of the nervous system in female patients we examined the presence of pain, manifestations of peripheral neuropathy and nerve density......Fabry disease is an X-linked inherited lysosomal disorder with dysfunction of the lysosomal enzyme alpha-galactosidase A causing accumulation of glycolipids in multiple organs including the nervous system. Pain and somatosensory disturbances are prominent manifestations of this disease. Until...

sex and Cannibalism

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 12. The Secret Sex Lives of Rotifers Sex - sex and Cannibalism. T Ramakrishna Rao. General Article Volume 5 Issue 12 December 2000 pp 41-47. Fulltext. Click here to view fulltext PDF. Permanent link:

An overview and update of ATP7A mutations leading to menkes disease and occipital horn syndrome

DEFF Research Database (Denmark)

Tümer, Zeynep

2013-01-01

Menkes disease (MD) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar "kinky" hair, are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority of...

Impact of consanguineous marriages and degrees of inbreeding on fertility, child mortality, secondary sex ratio, selection intensity, and genetic load: a cross-sectional study from Northern India.

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Fareed, Mohd; Kaisar Ahmad, Mir; Azeem Anwar, Malik; Afzal, Mohammad

2017-01-01

The aim of our study was to understand the relationship between consanguineous marriages and reproductive outcomes. A total of 999 families were recruited from five Muslim populations of Jammu region. Family pedigrees were drawn to access the family history and inbreeding status in terms of coefficient of inbreeding (F). Fertility, mortality, secondary sex ratio, selection intensity, and lethal equivalents were measured using standard methods. The significant differences for gross fertility was found to be higher among inbred groups as compared to the unrelated families (P consanguineous families of all populations in comparison with the non-consanguineous family groups. Moreover, the prenatal and postnatal child mortality rates (i.e., U5MR and U18MR) have presented a persuasive increase with an upsurge in the homozygosity level. The mortality rate was found to be maximum among families with the highest value of coefficient of inbreeding (F). The selection intensity (SI) also showed inflations among families with respect to their increasing inbreeding coefficients. The greater values of lethal equivalents per gamete (LEs/gamete) were observed for autosomal inheritance in comparison with sex-linked inheritance. Our conclusive assessment brings out the deleterious consequence of consanguineous marriages on reproductive outcomes.

Sex differences in the genetic architecture of lifespan in a seed beetle: extreme inbreeding extends male lifespan

DEFF Research Database (Denmark)

Bilde, T.; Maklakov, Alexei A.; Meisner, Katrine

2009-01-01

Background Sex differences in lifespan are ubiquitous throughout the animal kingdom but the causes underlying this phenomenon remain poorly understood. Several explanations based on asymmetrical inheritance patterns (sex chromosomes or mitochondrial DNA) have been proposed, but these ideas have...

DNA mutation motifs in the genes associated with inherited diseases.

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Michal Růžička

Full Text Available Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate. These sites are termed hotspots and exhibit a higher mutation frequency than expected by chance. In contrast, DNA sequences with lower mutation frequencies than expected by chance are termed coldspots. Mutation hotspots are usually derived from a mutation spectrum, which reflects particular population where an effect of a common ancestor plays a role. To detect coldspots/hotspots unaffected by population bias, we analysed the presence of germline mutations obtained from HGMD database in the 5-nucleotide segments repeatedly occurring in genes associated with common inherited disorders, in particular, the PAH, LDLR, CFTR, F8, and F9 genes. Statistically significant sequences (mutational motifs rarely associated with mutations (coldspots and frequently associated with mutations (hotspots exhibited characteristic sequence patterns, e.g. coldspots contained purine tract while hotspots showed alternating purine-pyrimidine bases, often with the presence of CpG dinucleotide. Using molecular dynamics simulations and free energy calculations, we analysed the global bending properties of two selected coldspots and two hotspots with a G/T mismatch. We observed that the coldspots were inherently more flexible than the hotspots. We assume that this property might be critical for effective mismatch repair as DNA with a mutation recognized by MutSα protein is noticeably bent.

Gene therapy for inherited retinal and optic nerve degenerations.

Science.gov (United States)

Moore, Nicholas A; Morral, Nuria; Ciulla, Thomas A; Bracha, Peter

2018-01-01

The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity. Areas covered: This review covers Leber's congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, Stargardt disease, Leber's hereditary optic neuropathy, Achromatopsia, and X-linked retinoschisis. Expert opinion: Despite great potential, gene therapy for IRD raises many questions, including the potential for less invasive intravitreal versus subretinal delivery, efficacy, safety, and longevity of response, as well as acceptance of novel study endpoints by regulatory bodies, patients, clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will require widespread genetic screening to identify and diagnose patients based on genotype instead of phenotype.

The evolutionary implications of epigenetic inheritance.

Science.gov (United States)

Jablonka, Eva

2017-10-06

The Modern Evolutionary Synthesis (MS) forged in the mid-twentieth century was built on a notion of heredity that excluded soft inheritance, the inheritance of the effects of developmental modifications. However, the discovery of molecular mechanisms that generate random and developmentally induced epigenetic variations is leading to a broadening of the notion of biological heredity that has consequences for ideas about evolution. After presenting some old challenges to the MS that were raised, among others, by Karl Popper, I discuss recent research on epigenetic inheritance, which provides experimental and theoretical support for these challenges. There is now good evidence that epigenetic inheritance is ubiquitous and is involved in adaptive evolution and macroevolution. I argue that the many evolutionary consequences of epigenetic inheritance open up new research areas and require the extension of the evolutionary synthesis beyond the current neo-Darwinian model.

Prenatal molecular diagnosis of inherited neuromuscular diseases: Duchenne/Becker muscular dystrophy, myotonic dystrophy type 1 and spinal muscular atrophy.

Science.gov (United States)

Esposito, Gabriella; Ruggiero, Raffaella; Savarese, Maria; Savarese, Giovanni; Tremolaterra, Maria Roberta; Salvatore, Francesco; Carsana, Antonella

2013-12-01

Neuromuscular disease is a broad term that encompasses many diseases that either directly, via an intrinsic muscle disorder, or indirectly, via a nerve disorder, impairs muscle function. Here we report the experience of our group in the counselling and molecular prenatal diagnosis of three inherited neuromuscular diseases, i.e., Duchenne/Becker muscular dystrophy (DMD/BMD), myotonic dystrophy type 1 (DM1), spinal muscular atrophy (SMA). We performed a total of 83 DMD/BMD, 15 DM1 and 54 SMA prenatal diagnoses using a combination of technologies for either direct or linkage diagnosis. We identified 16, 5 and 10 affected foetuses, respectively. The improvement of analytical procedures in recent years has increased the mutation detection rate and reduced the analytical time. Due to the complexity of the experimental procedures and the high, specific professional expertise required for both laboratory activities and the related counselling, these types of analyses should be preferentially performed in reference molecular diagnostic centres.

Human Sex Determination at the Edge of Ambiguity: INHERITED XY SEX REVERSAL DUE TO ENHANCED UBIQUITINATION AND PROTEASOMAL DEGRADATION OF A MASTER TRANSCRIPTION FACTOR.

Science.gov (United States)

Racca, Joseph D; Chen, Yen-Shan; Yang, Yanwu; Phillips, Nelson B; Weiss, Michael A

2016-10-14

A general problem is posed by analysis of transcriptional thresholds governing cell fate decisions in metazoan development. A model is provided by testis determination in therian mammals. Its key step, Sertoli cell differentiation in the embryonic gonadal ridge, is initiated by SRY, a Y-encoded architectural transcription factor. Mutations in human SRY cause gonadal dysgenesis leading to XY female development (Swyer syndrome). Here, we have characterized an inherited mutation compatible with either male or female somatic phenotypes as observed in an XY father and XY daughter, respectively. The mutation (a crevice-forming substitution at a conserved back surface of the SRY high mobility group box) markedly destabilizes the domain but preserves specific DNA affinity and induced DNA bend angle. On transient transfection of diverse human and rodent cell lines, the variant SRY exhibited accelerated proteasomal degradation (relative to wild type) associated with increased ubiquitination; in vitro susceptibility to ubiquitin-independent ("default") cleavage by the 20S core proteasome was unchanged. The variant's gene regulatory activity (as assessed in a cellular model of the rat embryonic XY gonadal ridge) was reduced by 2-fold relative to wild-type SRY at similar levels of mRNA expression. Chemical proteasome inhibition restored native-like SRY expression and transcriptional activity in association with restored occupancy of a sex-specific enhancer element in principal downstream gene Sox9, demonstrating that the variant SRY exhibits essentially native activity on a per molecule basis. Our findings define a novel mechanism of impaired organogenesis, accelerated ubiquitin-directed proteasomal degradation of a master transcription factor leading to a developmental decision poised at the edge of ambiguity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

RESONANCE

Indian Academy of Sciences (India)

Teaching and Learning 'Genetics with Drosophila. 3. Pattern of Inheritance of Autosome and Sex . Chromosome Linked Genes/Characters. Phenotypic characters or traits are determined by genes, and genes are physically located on different chromosomes. This is the basic tenet of the chromosomal theory of inheritance.

Vitamin D deficiency and low ionized calcium are linked with semen quality and sex steroid levels in infertile men

DEFF Research Database (Denmark)

Jensen, Martin Blomberg; Lawaetz, Jacob Gerner; Andersson, Anna-Maria

2016-01-01

STUDY QUESTION: Are low vitamin D levels linked with semen quality and sex steroids in infertile men? SUMMARY ANSWER: Infertile men with vitamin D deficiency had lower sperm motility, total numbers of motile sperm, Inhibin B, sex-hormone-binding-globulin (SHBG) and testosterone/estradiol ratio......, but higher levels of free sex steroids, than infertile men with normal vitamin D levels. WHAT IS KNOWN ALREADY: Low vitamin D levels have been associated with decreased sperm motility in healthy men, but a relationship between vitamin D and calcium with semen quality and especially sex steroids has not been...... infertile men, consecutively referred to our tertiary andrological centre for fertility workup, underwent a physical examination and had semen quality assessed based on two samples and blood analysed for serum testosterone, SHBG, estradiol, inhibin B, luteinizing hormone, follicle-stimulating hormone (FSH...

Depression And The Link With Cardiovascular Disease

Directory of Open Access Journals (Sweden)

Arup Kumar Dhar

2016-03-01

Full Text Available This review provides an outline of the association between major depressive disorder (MDD and coronary heart disease (CHD. Much is known about the two individual clinical conditions; however it is not until recently, that biological mechanisms have been uncovered that link both MDD and CHD. The activation of stress pathways have been implicated as a neurochemical mechanism that links MDD and CHD. Depression is known to be associated with poorer outcomes of CHD. Psychological factors such as major depression and stress are now known as risk factors for developing CHD which is as important and is independent of classic risk factors such as hypertension, diabetes mellitus and cigarette smoking. Both conditions have great socioeconomic importance given that depression and CHD are likely to be two of the three leading causes of global burden of disease. Better understanding of the common causal pathways will help us delineate more appropriate treatments.

Effects of thyroid hormones on cartilage sulphation in sex-linked dwarf chickens

Energy Technology Data Exchange (ETDEWEB)

Hoshino, S.; Wakita, M.; Kobayashi, Y. (Faculty of Bioresources, Mie University, Tsu (Japan)); Kakegawa, T.; Suzuki, M. (Institute of Endocrinology, Gunma University, Maebashi (Japan))

1989-01-01

The present investigation was undertaken to see if exogenous thyroid hormone could stimulate cartilage sulphation in vivo and in vitro in sex-linked dwarf chickens. L-thyroxine or L-3,5,3'-triiodothyronine injection for 7 consecutive days stimulated in vivo /sup 35/SO/sub 4//sup 2-/ incorporation into trachea cartilages of the dwarf chicken. Both thyroid hormones added to the incubation medium with or without 2,5% dwarf chicken serum also stimulated in vitro /sup 35/SO/sub 4//sup 2-/ incorporation into pelvic rudiment from 11-day chick embryos. These data demonstrate that thyroid hormones, like insulin-like growth factor I, might be responsible for the reduced growth rate of dwarf chickens. (author).

Endocrine manifestations related to inherited metabolic diseases in adults

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Vantyghem Marie-Christine

2012-01-01

Full Text Available Abstract Most inborn errors of metabolism (IEM are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.. IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects, and metal (hemochromatosis and storage disorders (cystinosis. Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes, whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure, congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last. This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses.

Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis.

Science.gov (United States)

Brengdahl, Martin; Kimber, Christopher M; Maguire-Baxter, Jack; Friberg, Urban

2018-03-01

Life span differs between the sexes in many species. Three hypotheses to explain this interesting pattern have been proposed, involving different drivers: sexual selection, asymmetrical inheritance of cytoplasmic genomes, and hemizygosity of the X(Z) chromosome (the unguarded X hypothesis). Of these, the unguarded X has received the least experimental attention. This hypothesis suggests that the heterogametic sex suffers a shortened life span because recessive deleterious alleles on its single X(Z) chromosome are expressed unconditionally. In Drosophila melanogaster, the X chromosome is unusually large (∼20% of the genome), providing a powerful model for evaluating theories involving the X. Here, we test the unguarded X hypothesis by forcing D. melanogaster females from a laboratory population to express recessive X-linked alleles to the same degree as males, using females exclusively made homozygous for the X chromosome. We find no evidence for reduced life span or egg-to-adult viability due to X homozygozity. In contrast, males and females homozygous for an autosome both suffer similar, significant reductions in those traits. The logic of the unguarded X hypothesis is indisputable, but our results suggest that the degree to which recessive deleterious X-linked alleles depress performance in the heterogametic sex appears too small to explain general sex differences in life span. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Accounting for eXentricities: analysis of the X chromosome in GWAS reveals X-linked genes implicated in autoimmune diseases.

Directory of Open Access Journals (Sweden)

Diana Chang

Full Text Available Many complex human diseases are highly sexually dimorphic, suggesting a potential contribution of the X chromosome to disease risk. However, the X chromosome has been neglected or incorrectly analyzed in most genome-wide association studies (GWAS. We present tailored analytical methods and software that facilitate X-wide association studies (XWAS, which we further applied to reanalyze data from 16 GWAS of different autoimmune and related diseases (AID. We associated several X-linked genes with disease risk, among which (1 ARHGEF6 is associated with Crohn's disease and replicated in a study of ulcerative colitis, another inflammatory bowel disease (IBD. Indeed, ARHGEF6 interacts with a gastric bacterium that has been implicated in IBD. (2 CENPI is associated with three different AID, which is compelling in light of known associations with AID of autosomal genes encoding centromere proteins, as well as established autosomal evidence of pleiotropy between autoimmune diseases. (3 We replicated a previous association of FOXP3, a transcription factor that regulates T-cell development and function, with vitiligo; and (4 we discovered that C1GALT1C1 exhibits sex-specific effect on disease risk in both IBDs. These and other X-linked genes that we associated with AID tend to be highly expressed in tissues related to immune response, participate in major immune pathways, and display differential gene expression between males and females. Combined, the results demonstrate the importance of the X chromosome in autoimmunity, reveal the potential of extensive XWAS, even based on existing data, and provide the tools and incentive to properly include the X chromosome in future studies.

Maintaining epigenetic inheritance during DNA replication in plants

Directory of Open Access Journals (Sweden)

Francisco eIglesias

2016-02-01

Full Text Available Biotic and abiotic stresses alter the pattern of gene expression in plants. Depending on the frequency and duration of stress events, the effects on the transcriptional state of genes are remembered temporally or transmitted to daughter cells and, in some instances, even to offspring (transgenerational epigenetic inheritance. This memory effect, which can be found even in the absence of the original stress, has an epigenetic basis, through molecular mechanisms that take place at the chromatin and DNA level but do not imply changes in the DNA sequence. Many epigenetic mechanisms have been described and involve covalent modifications on the DNA and histones, such as DNA methylation, histone acetylation and methylation, and RNAi dependent silencing mechanisms. Some of these chromatin modifications need to be stable through cell division in order to be truly epigenetic. During DNA replication, histones are recycled during the formation of the new nucleosomes and this process is tightly regulated. Perturbations to the DNA replication process and/or the recycling of histones lead to epigenetic changes. In this mini-review, we discuss recent evidence aimed at linking DNA replication process to epigenetic inheritance in plants.

Skewing of X-chromosome inactivation in three generations of carriers with X-linked chronic granulomatous disease within one family

NARCIS (Netherlands)

Köker, M. Y.; Sanal, O.; de Boer, M.; Tezcan, I.; Metin, A.; Tan, C.; Ersoy, F.; Roos, D.

2006-01-01

BACKGROUND: Chronic granulomatous disease (CGD) is an inherited disorder of the innate immune system characterized by impairment of intracellular microbicidal activity of phagocytes. Mutations in one of the four known NADPH-oxidase components preclude generation of superoxide and related

Economics, cultural transmission, and the dynamics of the sex ratio at birth in China.

Science.gov (United States)

Lipatov, Mikhail; Li, Shuzhuo; Feldman, Marcus W

2008-12-09

In rural China, the ratio of newborn boys to newborn girls [sex ratio at birth (SRB)] has been rising for several decades, to values significantly above its biological norm. This trend has a number of alarming societal consequences, and has attracted the attention of scholars and politicians. The root of the problem lies in a 2,500-year-old culture of son preference. This culture is intricately linked with the economic reality of each couple's life, so that there are financial and psychological repercussions to parents who have no sons. To bring greater clarity and understanding to this issue, we present a quantitative framework that describes the interaction between economics and cultural transmission. We start with an explicit mechanism by which economic incentives can change cultural beliefs of a given individual, and go on to include a mechanism of cultural inheritance from generation to generation. We then show how economic conditions can affect the dynamics of cultural change in an entire society, and may lead to a decrease in the country's sex ratio at birth.

Sex differences in the effect of aging on dry eye disease

Directory of Open Access Journals (Sweden)

Ahn JH

2017-08-01

Full Text Available Jong Ho Ahn,1 Yoon-Hyeong Choi,2 Hae Jung Paik,1 Mee Kum Kim,3 Won Ryang Wee,3 Dong Hyun Kim1 1Department of Ophthalmology, Gachon University Gil Medical Center, 2Department of Preventive Medicine, Gachon University College of Medicine, Incheon, 3Department of Ophthalmology, Seoul National University College of Medicine, Seoul, South Korea Purpose: Aging is a major risk factor in dry eye disease (DED, and understanding sexual differences is very important in biomedical research. However, there is little information about sex differences in the effect of aging on DED. We investigated sex differences in the effect of aging and other risk factors for DED.Methods: This study included data of 16,824 adults from the Korea National Health and Nutrition Examination Survey (2010–2012, which is a population-based cross-sectional survey. DED was defined as the presence of frequent ocular dryness or a previous diagnosis by an ophthalmologist. Basic sociodemographic factors and previously known risk factors for DED were included in the analyses. Linear regression modeling and multivariate logistic regression modeling were used to compare the sex differences in the effect of risk factors for DED; we additionally performed tests for interactions between sex and other risk factors for DED in logistic regression models.Results: In our linear regression models, the prevalence of DED symptoms in men increased with age (R=0.311, P=0.012; however, there was no association between aging and DED in women (P>0.05. Multivariate logistic regression analyses showed that aging in men was not associated with DED (DED symptoms/diagnosis: odds ratio [OR] =1.01/1.04, each P>0.05, while aging in women was protectively associated with DED (DED symptoms/diagnosis: OR =0.94/0.91, P=0.011/0.003. Previous ocular surgery was significantly associated with DED in both men and women (men/women: OR =2.45/1.77 [DED symptoms] and 3.17/2.05 [DED diagnosis], each P<0.001. Tests for

The mechanisms underlying sexual differentiation of behavior and physiology in mammals and birds: relative contributions of sex steroids and sex chromosomes

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Fumihiko eMaekawa

2014-08-01

Full Text Available From a classical viewpoint, sex-specific behavior and physiological functions as well as the brain structures of mammals such as rats and mice, have been thought to be influenced by perinatal sex steroids secreted by the gonads. Sex steroids have also been thought to affect the differentiation of the sex-typical behavior of a few members of the avian order Galliformes, including the Japanese quail and chickens, during their development in ovo. However, recent mammalian studies that focused on the artificial shuffling or knockout of the sex-determining gene, Sry, have revealed that sex chromosomal effects may be associated with particular types of sex-linked differences such as aggression levels, social interaction, and autoimmune diseases, independently of sex steroid-mediated effects. In addition, studies on naturally occurring, rare phenomena such as gynandromorphic birds and experimentally constructed chimeras in which the composition of sex chromosomes in the brain differs from that in the other parts of the body, indicated that sex chromosomes play certain direct roles in the sex-specific differentiation of the gonads and the brain. In this article, we review the relative contributions of sex steroids and sex chromosomes in the determination of brain functions related to sexual behavior and reproductive physiology in mammals and birds.

Sex-linked strategies of human reproductive behavior.

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Jaffe, K; Urribarri, D; Chacon, G C; Diaz, G; Torres, A; Herzog, G

1993-01-01

We present data on fertility characteristics in the Venezuelan population for each sex separately, allowing a detailed comparative analysis of the variance in fertility between males and females. We show that the fertility distribution for both sexes is discontinuous, that the average female has a larger number of offspring per individual than the average male, and that highly fertile males outnumber highly fertile females so that the total number of offspring produced by males and females is balanced. Results indicate that a few males are responsible for a relative higher fertility of the average female and that interactions between polyandric females with monogamic and polygynic males are common. Among the Yanomami, a relatively unacculturated hunter-gatherer-horticulturist tribe, similar differences in fertility distribution of both sexes are apparent. The data suggest that human populations contain statistically distinct subpopulations, with different reproductive strategies, suggesting the existence of complex interactions among human populations which are not evident from the study of individuals or groups.

Inheritance conditions for object life cycle diagrams

NARCIS (Netherlands)

Lipeck, U.W.; Saake, Gunter; Hartel, Peter; Vossen, G.; Jungclaus, Ralf; Wieringa, Roelf J.; Feenstra, Remco

Inheritance is the main principle in object-oriented design methods to support structuring and reuse of object behaviour descriptions. Most proposals restrict the formal use of inheritance to method interfaces and method effect specifcations. We propose to extend the inheritance relation to cover

Current perspectives on mitochondrial inheritance in fungi

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Xu J

2015-08-01

Full Text Available Jianping Xu,1,2 He Li2 1Department of Biology, McMaster University, Hamilton, Canada; 2The Key Laboratory for Non-Wood Forest Cultivation and Conservation of the Federal Ministry of Education, Central South University of Forestry and Technology, Changsha, People’s Republic of China Abstract: The mitochondrion is an essential organelle of eukaryotes, generating the universal energy currency, adenosine triphosphate, through oxidative phosphorylation. However, aside from generation of adenosine triphosphate, mitochondria have also been found to impact a diversity of cellular functions and organ system health in humans and other eukaryotes. Thus, inheriting and maintaining functional mitochondria are essential for cell health. Due to the relative ease of conducting genetic and molecular biological experiments using fungi, they (especially the budding yeast Saccharomyces cerevisiae have been used as model organisms for investigating the patterns of inheritance and intracellular dynamics of mitochondria and mitochondrial DNA. Indeed, the diversity of mitochondrial inheritance patterns in fungi has contributed to our broad understanding of the genetic, cellular, and molecular controls of mitochondrial inheritance and their evolutionary implications. In this review, we briefly summarize the patterns of mitochondrial inheritance in fungi, describe the genes and processes involved in controlling uniparental mitochondrial DNA inheritance in sexual crosses in basidiomycete yeasts, and provide an overview of the molecular and cellular processes governing mitochondrial inheritance during asexual budding in S. cerevisiae. Together, these studies reveal that complex regulatory networks and molecular processes are involved in ensuring the transmission of healthy mitochondria to the progeny. Keywords: uniparental inheritance, biparental inheritance, mating type, actin cable, mitochore, mitochondrial partition 

[Sex education and knowledge of venerial disease among public school 9th graders].

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Nielsen, Jacob Lauesgaard; Boelskifte, Jane; Falk, Jørgen; Lauszus, Finn Friis; Rasmussen, Kjeld Leisgård

2009-03-30

A study on knowledge of venereal diseases, opinions on sexual matters, and satisfaction with sex education at school. A questionnaire was handed out on the same day in all ninth grade classes in the municipality of Viborg without prior notification of teachers and pupils. A total of 394 of 398 questionnaires were answered and returned. Only 36% were fully satisfied with the sex education imparted at school, while 70% of the teenagers were satisfied with the quantity. Satisfaction was similar between genders, but more marked among those without sexual debut as 66% were satisfied, while just 47% of those with sexual debut thought sex education was satisfactory (p Knowledge of venereal disease like hiv/aids, chlamydia and herpes simplex was high (> 80% of pupils). A total of 58% of boys and 76% of girls identified chlamydia as the most common venereal disease (p sexual debut increased knowledge of chlamydia's status as the most common venereal disease to 85% among girls (p Knowledge of the symptoms and risks of chlamydia is rather limited. The girls were more aware of the fact that it may cause sterility (p sexual debut was not associated with gender but with own sexual debut. Those with no sexual debut guessed better than the pupils with sexual debut, as 77% of boys and 81% of girls with no sexual debut guessed correctly. The sex education curriculum should be differentiated with regard to sexual debut or not in order to increase satisfaction with teaching and increase the school's contribution to improve sexual knowledge and behaviour.

SEX-DETector: A Probabilistic Approach to Study Sex Chromosomes in Non-Model Organisms

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Muyle, Aline; Käfer, Jos; Zemp, Niklaus; Mousset, Sylvain; Picard, Franck; Marais, Gabriel AB

2016-01-01

We propose a probabilistic framework to infer autosomal and sex-linked genes from RNA-seq data of a cross for any sex chromosome type (XY, ZW, and UV). Sex chromosomes (especially the non-recombining and repeat-dense Y, W, U, and V) are notoriously difficult to sequence. Strategies have been developed to obtain partially assembled sex chromosome sequences. Most of them remain difficult to apply to numerous non-model organisms, either because they require a reference genome, or because they are designed for evolutionarily old systems. Sequencing a cross (parents and progeny) by RNA-seq to study the segregation of alleles and infer sex-linked genes is a cost-efficient strategy, which also provides expression level estimates. However, the lack of a proper statistical framework has limited a broader application of this approach. Tests on empirical Silene data show that our method identifies 20–35% more sex-linked genes than existing pipelines, while making reliable inferences for downstream analyses. Approximately 12 individuals are needed for optimal results based on simulations. For species with an unknown sex-determination system, the method can assess the presence and type (XY vs. ZW) of sex chromosomes through a model comparison strategy. The method is particularly well optimized for sex chromosomes of young or intermediate age, which are expected in thousands of yet unstudied lineages. Any organisms, including non-model ones for which nothing is known a priori, that can be bred in the lab, are suitable for our method. SEX-DETector and its implementation in a Galaxy workflow are made freely available. PMID:27492231

[Dilated cardiomyopathy (DCM) in dogs--pathological, clinical, diagnosis and genetic aspects].

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Broschk, C; Distl, O

2005-10-01

Dilated cardiomyopathy (DCM) is a heart disease which is often found in humans and animals. The age of onset of this progressive disease varies between 3 and 7 years of age. A juvenile form of DCM has been found in Portuguese Water Dogs and Doberman Pinscher Dogs. Some breeds such as Doberman pinscher, Newfoundland, Portuguese Water dog, Boxer, Great Dane, Cocker Spaniel and Irish Wolfhound exhibit a higher prevalence to DCM. There also seems to be a sex predisposition as male dogs are affected more often than female dogs and in Great Danes an X-linked recessive inheritance is likely. In Newfoundland and Boxer an autosomal dominant inheritance was found whereas an autosomal recessive inheritance was described in Portuguese Water Dogs. Atrial fibrillation as a cause or consequence of DCM is assumed for certain breeds. The causes of DCM are widely unknown in dogs. A genetic basis for this heart disease seems to exist. Apart from a few exceptions the mode of inheritance and the possible underlying gene mutations are not known for DCM in dogs. In humans mutations in several genes responsible for DCM have been identified. Comparative genetic analyses in dogs using genes causing DCM in men and a genome-wide scan with anonymus markers were not able to detect causative mutations or genomic regions harboring gene loci linked to DCM. The investigation of the genetic basis of canine DCM may lead to new insights into the pathogenesis of DCM and may result in new therapeutic approaches and breeding strategies.

Linking acute kidney injury to chronic kidney disease: the missing links.

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Kaballo, Mohammed A; Elsayed, Mohamed E; Stack, Austin G

2017-08-01

Acute kidney injury (AKI) is considered to be a major public health problem around the globe, and it is associated with major adverse clinical outcomes and significant health care costs. There is growing evidence suggesting that AKI is associated with the subsequent development of chronic kidney disease (CKD). While recovery of kidney function occurs in the majority of patients surviving an AKI episode, a large number of patients do not recover completely. Similarly, CKD is a well-known risk factor for the development of AKI. Recent studies suggest that both AKI and CKD are not separate disease entities but are in fact components of a far more closely interconnected disease continuum. However, the true nature of this relationship is complex and poorly understood. This review explores potential relationships between AKI and CKD, and seeks to uncover a number of "missing links" in this tentative emerging relationship.

Danon’s disease as a cause of hypertrophic cardiomyopathy

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I. V. Leontyeva

2015-01-01

Full Text Available Hypertrophic cardiomyopathy is the most common inherited disease of the myocardium. The causes of the disease are heterogeneous; its primary form results from mutations in the genes encoding cardiac sarcomeric proteins; its secondary (metabolic and syndromic forms develop due to mutations in the genes encoding non-sarcomeric proteins. Glycogenosis is the most common cause of the metabolic ones of hypertrophic cardiomyopathy. Danon’s disease (lysosome-associated membrane protein 2 (LAMP2-cardiomyopathy is a form of glycogenosis and it is characterized by a typical triad: hypertrophic cardiomyopathy, mental retardation, and skeletal myopathy. The disease occurs with mutations in the LAMP2 gene; X-linked dominant inheritance. LAMP2-cardiomyopathy does not virtually differ in its clinical manifestations from the severe form of hypertrophic cardiomyopathy, which results from mutations in the sarcomeric protein genes. The disease is characterized by a poor progressive course with the high probability of causing sudden death or with the progression of severe heart failure. Implantation of a cardioverter defibrillator is a main method to prevent sudden cardiac death. 

Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity

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2013-01-01

Background Ancestral environmental exposures to a variety of environmental factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The present work examined the potential transgenerational actions of the insecticide dichlorodiphenyltrichloroethane (DDT) on obesity and associated disease. Methods Outbred gestating female rats were transiently exposed to a vehicle control or DDT and the F1 generation offspring bred to generate the F2 generation and F2 generation bred to generate the F3 generation. The F1 and F3 generation control and DDT lineage rats were aged and various pathologies investigated. The F3 generation male sperm were collected to investigate methylation between the control and DDT lineage male sperm. Results The F1 generation offspring (directly exposed as a fetus) derived from the F0 generation exposed gestating female rats were not found to develop obesity. The F1 generation DDT lineage animals did develop kidney disease, prostate disease, ovary disease and tumor development as adults. Interestingly, the F3 generation (great grand-offspring) had over 50% of males and females develop obesity. Several transgenerational diseases previously shown to be associated with metabolic syndrome and obesity were observed in the testis, ovary and kidney. The transgenerational transmission of disease was through both female (egg) and male (sperm) germlines. F3 generation sperm epimutations, differential DNA methylation regions (DMR), induced by DDT were identified. A number of the genes associated with the DMR have previously been shown to be associated with obesity. Conclusions Observations indicate ancestral exposure to DDT can promote obesity and associated disease transgenerationally. The etiology of disease such as obesity may be in part due to environmentally induced epigenetic transgenerational inheritance. PMID:24228800

Chronic Inflammation Links Cancer and Parkinson’s disease

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Zhiming eLi

2016-06-01

Full Text Available An increasing number of genetic studies suggest that the pathogenesis of Parkinson’s disease (PD and cancer share common genes, pathways, and mechanisms. Despite a disruption in a wide range of similar biological processes, the end result is very different: uncontrolled proliferation and early neurodegeneration. Thus, the links between the molecular mechanisms that cause PD and cancer remain to be elucidated. We propose that chronic inflammation in neurons and tumors contributes to a microenvironment that favors the accumulation of DNA mutations and facilitates disease formation. This article appraises the key role of microglia, establishes the genetic role of COX2 and CARD15 in PD and cancer, and discusses prevention and treatment with this new perspective in mind. We examine the evidence that chronic inflammation is an important link between cancer and PD.

X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis.

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Fullwood, P; Jones, J; Bundey, S; Dudgeon, J; Fielder, A R; Kilpatrick, M W

1993-03-01

A four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult.

25 CFR 91.9 - Inheritance of improvements.

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Inheritance of improvements. 91.9 Section 91.9 Indians..., OSAGE RESERVATION, OKLAHOMA § 91.9 Inheritance of improvements. (a) Upon the death of the owner of... of the county courts, State of Oklahoma, and shall be subject to inheritance or bequest in accordance...

Cost-effectiveness of genotyping in inherited arrhythmia syndromes: are we getting value for the money?

NARCIS (Netherlands)

Wilde, Arthur A. M.; Pinto, Yigal M.

2009-01-01

Over the last decade, the identification of the diverse genetic basis of most important inherited arrhythmia syndromes has remarkably changed our attitude toward these life-threatening diseases. Just over 10 years ago, long-QT syndrome (LQTS) was considered one disease entity, Brugada -QT syndrome

Evidence for mito-nuclear and sex-linked reproductive barriers between the hybrid Italian sparrow and its parent species.

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Cassandra N Trier

2014-01-01

Full Text Available Studies of reproductive isolation between homoploid hybrid species and their parent species have rarely been carried out. Here we investigate reproductive barriers between a recently recognized hybrid bird species, the Italian sparrow Passer italiae and its parent species, the house sparrow P. domesticus and Spanish sparrow P. hispaniolensis. Reproductive barriers can be difficult to study in hybrid species due to lack of geographical contact between taxa. However, the Italian sparrow lives parapatrically with the house sparrow and both sympatrically and parapatrically with the Spanish sparrow. Through whole-transcriptome sequencing of six individuals of each of the two parent species we identified a set of putatively parent species-diagnostic single nucleotide polymorphism (SNP markers. After filtering for coverage, genotyping success (>97% and multiple SNPs per gene, we retained 86 species-informative, genic, nuclear and mitochondrial SNP markers from 84 genes for analysis of 612 male individuals. We show that a disproportionately large number of sex-linked genes, as well as the mitochondria and nuclear genes with mitochondrial function, exhibit sharp clines at the boundaries between the hybrid and the parent species, suggesting a role for mito-nuclear and sex-linked incompatibilities in forming reproductive barriers. We suggest that genomic conflict via interactions between mitochondria and sex-linked genes with mitochondrial function ("mother's curse" at one boundary and centromeric drive at the other may best explain our findings. Hybrid speciation in the Italian sparrow may therefore be influenced by mechanisms similar to those involved in non-hybrid speciation, but with the formation of two geographically separated species boundaries instead of one. Spanish sparrow alleles at some loci have spread north to form reproductive barriers with house sparrows, while house sparrow alleles at different loci, including some on the same chromosome

Can Neglected Tropical Diseases Compromise Human Wellbeing in Sex-, Age-, and Trait-Specific Ways?

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David C Geary

2016-04-01

Full Text Available Traits that facilitate competition for reproductive resources or that influence mate choice have evolved to signal resilience to infectious disease and other stressors. As a result, the dynamics of competition and choice can, in theory, be used to generate predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species, including humans. These dynamics and associated vulnerabilities are reviewed for nonhuman species, focusing on traits that are compromised by exposure to parasites. Using the same approach, sex-, age-, and trait-specific vulnerabilities to parasitic disease are illustrated for children's and adolescent's physical growth and fitness. Suggestions are then provided for widening the assessment of human vulnerabilities to include age-appropriate measures of behavioral (e.g., children's play and cognitive (e.g., language fluency traits. These are traits that are likely to be compromised by infection in age- and sex-specific ways. Inclusion of these types of measures in studies of neglected tropic diseases has the potential to provide a more nuanced understanding of how these diseases undermine human wellbeing and may provide a useful means to study the efficacy of associated treatments.

Biparental chloroplast inheritance leads to rescue from cytonuclear incompatibility.

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Barnard-Kubow, Karen B; McCoy, Morgan A; Galloway, Laura F

2017-02-01

Although organelle inheritance is predominantly maternal across animals and plants, biparental chloroplast inheritance has arisen multiple times in the angiosperms. Biparental inheritance has the potential to impact the evolutionary dynamics of cytonuclear incompatibility, interactions between nuclear and organelle genomes that are proposed to be among the earliest types of genetic incompatibility to arise in speciation. We examine the interplay between biparental inheritance and cytonuclear incompatibility in Campanulastrum americanum, a plant species exhibiting both traits. We first determine patterns of chloroplast inheritance in genetically similar and divergent crosses, and then associate inheritance with hybrid survival across multiple generations. There is substantial biparental inheritance in C. americanum. The frequency of biparental inheritance is greater in divergent crosses and in the presence of cytonuclear incompatibility. Biparental inheritance helps to mitigate cytonuclear incompatibility, leading to increased fitness of F 1 hybrids and recovery in the F 2 generation. This study demonstrates the potential for biparental chloroplast inheritance to rescue cytonuclear compatibility, reducing cytonuclear incompatibility's contribution to reproductive isolation and potentially slowing speciation. The efficacy of rescue depended upon the strength of incompatibility, with a greater persistence of weak incompatibilities in later generations. These findings suggest that incompatible plastids may lead to selection for biparental inheritance. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Sex and gender differences in depression - proclivity in women

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Ignacio Zarragoitía Alonso

2013-04-01

Full Text Available The article presents and analyzes the major factors involved in depression, taking into account those related to biological, psychological and social issues linked to sex and gender. Ultimately, these sex and gender-associated factors determine that the condition is present more often in women than in men, nearly doubling the cases. In addition, the article describes the singularities of depressive disorders in different reproductive periods when the disease acquires clinical specificity in accordance with sexual and hormonal functions. Finally, the way in which gender roles can intervene in how depression is approached in women vis-à-vis men is covered.

Serum sex hormone and growth arrest-specific protein 6 levels in male patients with coronary heart disease

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Rui Zhao

2016-01-01

Full Text Available Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease. Moreover, the tyrosine kinase receptor Axl, the ligand of which is growth arrest-specific protein 6 (GAS6, is expressed in the vasculature, and serum GAS6 levels are associated with endothelial dysfunction and cardiovascular events. Testosterone regulates GAS6 gene transcription directly, which inhibits calcification of vascular smooth muscle cells and provides a mechanistic insight into the cardioprotective action of androgens. This study was designed to determine the correlation between serum GAS6 and testosterone levels in male patients with coronary heart disease (CHD. We recruited 225 patients with CHD and 102 apparently healthy controls. Serum concentrations of GAS6 and soluble Axl were quantified by an enzyme-linked immunosorbent assay. Levels of high-sensitivity C-reactive protein, testosterone, estradiol, and other routine biochemical markers were also measured. Testosterone decreased from 432.69 ± 14.40 to 300.76 ± 6.23 ng dl−1 (P < 0.001 and GAS6 decreased from 16.20 ± 0.31 to 12.51 ± 0.19 ng ml−1 (P < 0.001 in patients with CHD, compared with control subjects. Multiple linear regression analysis showed that serum testosterone and GAS6 levels were positively associated in male patients with CHD. Alterations in GAS6 levels may influence the development of CHD. Downregulation of GAS6/Axl signaling in the presence of low sex hormone levels during disease progression is a potential mechanism by which GAS6 affects CHD. This study provides novel results regarding the influence of sex hormones on serum GAS6 levels in patients with CHD.

Sex and Gender Differences in Gastroesophageal Reflux Disease

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Kim, Young Sun; Kim, Nayoung; Kim, Gwang Ha

2016-01-01

It is important to understand sex and gender-related differences in gastroesophageal reflux disease (GERD) because gender-related biologic factors might lead to better prevention and therapy. Non-erosive reflux disease (NERD) affects more women than men. GERD symptoms are more frequent in patients with NERD than in those with reflux esophagitis. However, men suffer pathologic diseases such as reflux esophagitis, Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC) more frequently than women. The prevalence of reflux esophagitis is significantly increased with age in women, especially after their 50s. The mean age of EAC incidence in women is higher than in men, suggesting a role of estrogen in delaying the onset of BE and EAC. In a chronic rat reflux esophagitis model, nitric oxide was found to be an aggravating factor of esophageal injury in a male-predominant way. In addition, the expression of esophageal occludin, a tight junction protein that plays an important role in the esophageal defense mechanism, was up-regulated in women. This explains the male predominance of reflux esophagitis and delayed incidence of BE or EAC in women. Moreover, the symptoms such as heartburn, regurgitation, and extra-esophageal symptoms have been more frequently reported by women than by men, suggesting that sex and gender play a role in symptom perception. Differential sensitivity with augmented symptoms in women might have diagnostic and therapeutic influence. Furthermore, recent studies have suggested that hormone replacement therapy has a protective effect against esophageal cancer. However, an anti-inflammatory role of estrogen remains compelling, which means further study is necessary in this area. PMID:27703114

Differentiating views of inheritance : The free association task as a method to assess social representations of wealth, inherit, and bequeath

NARCIS (Netherlands)

Stark, Jennifer; Kogler, C.; Gaisbauer, Helmut; Sedmak, Clemens; Kirchler, Erich

2016-01-01

Inheritance and in particular inheritance taxes have emerged as topics of steadily increasing interest in public as well as scientific discourse and debate. The present study investigates laypeople’s differentiated social representations of inheritance with the aim of shedding light on distinct

Linking adult hippocampal neurogenesis with human physiology and disease.

Science.gov (United States)

Bowers, Megan; Jessberger, Sebastian

2016-07-01

We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Sex drives intracellular conflict in yeast.

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Harrison, E; MacLean, R C; Koufopanou, V; Burt, A

2014-08-01

Theory predicts that sex can drive the evolution of conflict within the cell. During asexual reproduction, genetic material within the cell is inherited as a single unit, selecting for cooperation both within the genome as well as between the extra-genomic elements within the cell (e.g. plasmids and endosymbionts). Under sexual reproduction, this unity is broken down as parental genomes are distributed between meiotic progeny. Genetic elements able to transmit to more than 50% of meiotic progeny have a transmission advantage over the rest of the genome and are able to spread, even where they reduce the fitness of the individual as a whole. Sexual reproduction is therefore expected to drive the evolution of selfish genetic elements (SGEs). Here, we directly test this hypothesis by studying the evolution of two independent SGEs, the 2-μm plasmid and selfish mitochondria, in populations of Saccharomyces cerevisiae. Following 22 rounds of sexual reproduction, 2-μm copy number increased by approximately 13.2 (±5.6) copies per cell, whereas in asexual populations copy number decreased by approximately 5.1 (±1.5) copies per cell. Given that the burden imposed by this parasite increases with copy number, these results support the idea that sex drives the evolution of increased SGE virulence. Moreover, we found that mitochondria that are respiratory-deficient rapidly invaded sexual but not asexual populations, demonstrating that frequent outcrossed sex can drive the de novo evolution of genetic parasites. Our study highlights the genomic perils of sex and suggests that SGEs may play a key role in driving major evolutionary transitions, such as uniparental inheritance. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Genomic regions associated with the sex-linked inhibitor of dermal melanin in Silkie chicken

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Ming TIAN,Rui HAO,Suyun FANG,Yanqiang WANG,Xiaorong GU,Chungang FENG,Xiaoxiang HU,Ning LI

2014-09-01

Full Text Available A unique characteristic of the Silkie chicken is its fibromelanosis phenotype. The dermal layer of its skin, its connective tissue and shank dermis are hyperpigmented. This dermal hyperpigmentation phenotype is controlled by the sex-linked inhibitor of dermal melanin gene (ID and the dominant fibromelanosis allele. This study attempted to confirm the genomic region associated with ID. By genotyping, ID was found to be closely linked to the region between GGA_rs16127903 and GGA_rs14685542 (8406919 bp on chromosome Z, which contains ten functional genes. The expression of these genes was characterized in the embryo and 4 days after hatching and it was concluded that MTAP, encoding methylthioadenosinephosphorylase, would be the most likely candidate gene. Finally, target DNA capture and sequence analysis was performed, but no specific SNP(s was found in the targeted region of the Silkie genome. Further work is necessary to identify the causal ID mutation located on chromosome Z.

Clinical approach to inherited metabolic diseases in the neonatal period: a 20-year survey

NARCIS (Netherlands)

Saudubray, J. M.; Ogier, H.; Bonnefont, J. P.; Munnich, A.; Lombes, A.; Hervé, F.; Mitchel, G.; Poll The, B.; Specola, N.; Parvy, P.

1989-01-01

Every newborn with unexplained neurological deterioration, ketosis, metabolic acidosis or hypoglycaemia should be suspected of having an inherited error of intermediary metabolism. Many of these conditions can be diagnosed clinically with the aid of simple laboratory investigations. Since a

Inheritance of resistance to cotton blue disease Herança da resistência do algodoeiro à doença-azul

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Osmério Pupim Junior

2008-05-01

Full Text Available The objective of this work was to determine the inheritance of cotton blue disease resistance by cotton plants. Populations derived from the CD 401 and Delta Opal resistant varieties were evaluated, through a greenhouse test with artificial inoculation by viruliferous aphids. Cotton blue disease resistance is conditioned by one dominant gene, both in CD 401 and Delta Opal varieties.O objetivo deste trabalho foi determinar a herança da resistência do algodoeiro à doença-azul. Populações derivadas das variedades resistentes CD 401 e Delta Opal foram avaliadas em casa de vegetação, por meio da inoculação de pulgões virulíferos. A resistência à doença-azul do algodoeiro é condicionada por um gene dominante, tanto em 'DC 401' quanto em 'Delta Opal'.

Disease-specific hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes.

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Li, Qian; Luo, Changying; Luo, Chengjuan; Wang, Jianmin; Li, Benshang; Ding, Lixia; Chen, Jing

2017-08-01

Hematopoietic stem cell transplantation (HSCT) using an optimized conditioning regimen is essential for the long-term survival of patients with inherited bone marrow failure syndromes (IBMFS). We report HSCT in 24 children with Fanconi anemia (FA, n = 12), Diamond-Blackfan anemia (DBA, n = 7), and dyskeratosis congenita (DC, n = 5) from a single HSCT center. The graft source was peripheral blood stem cells (n = 19) or cord blood stem cells (n = 5). FA and DC patients received reduced-intensity conditioning, while DBA patients had myeloablative conditioning. The median numbers of infused mononuclear cells and CD34+ cells were 14.20 × 10 8 /kg and 4.3 × 10 6 /kg, respectively. The median time for neutrophil and platelet recovery was 12 and 18 days, respectively. Complete donor engraftment was achieved in 23 of 24 patients. There was one primary graft failure. During a median follow-up of 27.5 months (range, 2-130 months), the overall survival in all patients was 95.8%. The incidence of grade II-III acute graft versus host disease (GvHD) and chronic GvHD was 29.2% and 16.7%, respectively. We conclude that HSCT can be a curative option for patients with IBMFS. Modification of the conditioning regimen based on the type of disease may lead to encouraging long-term outcomes.

X-Linked Dyskeratosis Congenita Is Predominantly Caused by Missense Mutations in the DKC1 Gene

OpenAIRE

Knight, S.W.; Heiss, N.S.; Vulliamy, T.J.; Greschner, S.; Stavrides, G.; Pai, G.S.; Lestringant, G.; Varma, N.; Mason, P.J.; Dokal, I.; Poustka, A.

1999-01-01

Dyskeratosis congenita is a rare inherited bone marrow-failure syndrome characterized by abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia. More than 80% of patients develop bone-marrow failure, and this is the major cause of premature death. The X-linked form of the disease (MIM 305000) has been shown to be caused by mutations in the DKC1 gene. The gene encodes a 514-amino-acid protein, dyskerin, that is homologous to Saccharomyces cerevisiae Cbf5p and rat Nap57 proteins. B...

Cancer resistance as an acquired and inheritable trait

DEFF Research Database (Denmark)

Koch, Janne; Hau, Jann; Jensen, Henrik Elvang

2014-01-01

AIM: To induce cancer resistance in wild-type mice and detect if the resistance could be inherited to the progeny of the induced resistant mice. Furthermore to investigate the spectrum and immunology of this inherited cancer resistance. MATERIALS AND METHODS: Resistance to with live S180 cancer c...... of the resistance is unknown but may involve epigenetic mechanisms. Other examples of inheritability of acquired phenotypic changes exist but, to our knowledge, this is the first demonstration of acquired, inherited cancer resistance.......AIM: To induce cancer resistance in wild-type mice and detect if the resistance could be inherited to the progeny of the induced resistant mice. Furthermore to investigate the spectrum and immunology of this inherited cancer resistance. MATERIALS AND METHODS: Resistance to with live S180 cancer...... cells in BALB/c mice was induced by immunization with inactivated S180 cancer cells. The immunization was performed by either frozen/thawed or irradiated cancer cells or cell-free ascitic fluid (CFAF). RESULTS: In all instances the induced resistance was demonstrated to be inheritable. The phenotype...

The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease.

Science.gov (United States)

Hendriksz, Christian J; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Klünemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Then Bergh, Florian; Topçu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A

2017-05-01

Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups ("clinical niches") have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Several clinical niches have been identified that harbor patients at increased risk of NP-C.

Inheritance of tristyly in Oxalis tuberosa (Oxalidaceae).

Science.gov (United States)

Trognitz, B R; Hermann, M

2001-05-01

Frequencies of floral morphs in progenies obtained from a complete set of diallelic crosses among three accessions of tristylous, octoploid oca (Oxalis tuberosa) were used for a Mendelian analysis of floral morph inheritance. The frequencies observed had the best fit to a model of tetrasomic inheritance with two diallelic factors, S, s and M, m, with S being epistatic over M. No explanation could be found for the unexpected formation of a small percentage of short-styled individuals in crosses between the mid-styled and the long-styled parent. For the acceptance of models of disomic and octosomic inheritance several additional assumptions would have to be made and therefore these modes of inheritance are less likely. Dosage-dependent inheritance of floral morph was rejected. Only a small frequency (36%) of the cross progenies flowered, in contrast to the greater propensity for flowering of O. tuberosa accessions held at gene banks.

Effect of Sex Hormones on Progression of Diabetic Renal Disease in ...

African Journals Online (AJOL)

Effect of Sex Hormones on Progression of Diabetic Renal Disease in Experimental Model of Streptozotocin Induced Diabetic Rats. ... into five groups 8 rats each, normal control, diabetic, gonadectomized diabetic, 17 beta estradiol is given to female and testosterone propionate to male diabetic and gonadectomized diabetic.

Wilson’s Disease: An Inherited, Silent, Copper Intoxication Disease

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Uta Merle

2016-07-01

Full Text Available Wilson’s disease is a rare, autosomal recessive, genetic, copper overload disease, which evokes multiple motor or neuropsychiatric symptoms and liver disease. It is the consequence of a variety of different mutations affecting the ATP7B gene. This gene encodes for a class IB, P-type, copper-transporting ATPase, which is located in the trans-Golgi network of the liver and brain, and mediates the excretion of excess copper into the bile. When functionally inactive, the excess copper is deposited in the liver, brain, and other tissues. Free copper induces oxidative stress, lipid peroxidation, and lowers the apoptotic threshold of the cell. The symptoms in affected persons can vary widely and usually appear between the ages of 6 years and 20 years, but there are also cases in which the disease manifests in advanced age. In this review, we discuss the considerations in diagnosis, clinical management, and treatment of Wilson’s disease. In addition, we highlight experimental efforts that address the pathogenesis of Wilson’s disease in ATP7B deficient mice, novel analytical techniques that will improve the diagnosis at an early stage of disease onset, and treatment results with copper-chelating agents.

Discrepancies in the laws on identifying foetal sex and terminating a pregnancy in India.

Science.gov (United States)

Rahman, Talha A; Siddiqui, Ayesha T

2007-01-01

Laws that regulate the identification of a foetus and the termination of a pregnancy in India are shaped by their social context. The Medical Termination of Pregnancy Act, 1971, discriminates against unmarried women by not recognising that unwanted pregnancies in unmarried women could result in at least as much anguish and suffering as that experienced by married women. While the MTP Act permits the abortion of foetuses with disabilities, the Pre-conception and Pre-natal Diagnostic Techniques (Prohibition of Sex Selection) Act's ban on identifying the foetus's sex prevents the use of sex-detection to identify foetuses at high risk of sex-linked diseases.

Gastric adenocarcinoma in a patient with X-linked agammaglobulinemia and HIV: Case report and review of the literature

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Joud Hajjar

2016-09-01

Full Text Available X-linked agammaglobulinemia (XLA is an X-linked inherited disease usually caused by a germline mutation in the BTK gene leading to Bruton’s tyrosine kinase deficiency, which results in the impaired development of B-lymphocytes and a subsequent lack of immunoglobulin production. Patients with XLA have an increased susceptibility to bacterial and viral infections, and multiple case reports have been published regarding an association between XLA and gastrointestinal (GI malignancy. Here, we describe a case of a 25-year-old man with XLA and HIV, who developed gastric adenocarcinoma. Previously reported cases of XLA and GI malignancy are also reviewed and summarized.

SWJ:39-42 Inheritance of Pod Colour in Cowpea INHERITANCE

African Journals Online (AJOL)

Dr. Ahmed

two additional pod pigmentation genes; one conditions green pods ... Hybridization experiments were conducted in the screen house to study the pattern of inheritance of ... to breeders because its understanding could lead to the development.

Inheritance

OpenAIRE

Lippert, Sandra

2013-01-01

In ancient Egypt inheritance was conveyed either through the legal order of succession, favoring sonsover daughters, children over siblings, and older over younger, or through written declarations thatallowed for individualized arrangements. Adoption was the common means by which a childlessperson could acquire an heir. The initial tendency towards a sole heir (preferably the eldest son) wasreplaced by the division of parental property among all children, although the eldest son continued top...

Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?

Science.gov (United States)

Procopio, V; Manti, S; Bianco, G; Conti, G; Romeo, A; Maimone, F; Arrigo, T; Cutrupi, M C; Salpietro, C; Cuppari, C

2018-01-30

Uncertainty remains on the pathogenetic mechanisms, model of inheritance as well as genotype-phenotype correlation of FMF disease. To investigate the impact of genetic factors on the FMF phenotype and the disease inheritance model. A total of 107 FMF patients were enrolled. Patients were diagnosed clinically. All patients underwent genetic analysis of the FMF locus on 16p13.3. 9 distinct mutations were detected. Specifically, the 85.98% of patients showed a heterozygous genotype. The most common genotypes were p.Met680Ile/wt and p.Met694Val/wt. The most frequent clinical findings were fever, abdominal pain, joint pain, thoracic pain, and erysipelas-like erythema. Analysis of clinical data did not detect any significant difference in clinical phenotype among heterozygous, homozygous as well as compound homozygous subjects, further supporting the evidence that, contrary to the recessive autosomal inheritance, heterozygous patients fulfilled the criteria of clinical FMF. Moreover, subjects with p.Met694Val/wt and p.Met680Ile/wt genotype reported the most severe clinical phenotype. p.Ala744Ser/wt, p.Glu148Gln/Met680Ile, p.Met680Ile/Met680Ile, p.Met680Ile/Met694Val, p.Pro369Ser/wt, p.Met694Ile/wt, p.Glu148Gln/Glu148Gln, p.Lys695Arg/wt resulted in 100% pathogenicity. The existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance with incomplete penetrance and variable expressivity cannot be excluded in FMF. Copyright © 2017 Elsevier B.V. All rights reserved.

Inheritance patterns and identification of microsatellite markers linked to the rice blast resistance in BC2F1 population of rice breeding

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Gous Miah

2015-03-01

Full Text Available The BC2F1 population was derived from a cross between rice variety, MR219 (susceptible to blast and Pongsu Seribu 1 (resistant to blast. The objectives of this research were to know the inheritance pattern of blast resistance and to identify the linked markers associated with blast resistance in BC2F1 population. Sixteen microsatellite markers were found as polymorphic between the parents related to blast resistant genes (Pi-genes. Among the selected blast resistant linked markers, two markers RM6836 and RM8225 showed expected testcross ratio (1:1 for single-gene model in the BC2F1 population with the association between resistant and susceptible progeny. A total of 333-BC2F1 plants were challenged with the most virulent pathotype P7.2 of Magnaporthe oryzae. Chi-square (χ2 analysis for phenotypic segregation in single-gene model showed goodness of fit (P = 0.4463 to the expected segregation ratio (1:1. In marker segregation analysis, two polymorphic markers (RM6836 and RM8225 clearly showed goodness of fit to the expected segregation testcross ratio (1:1 for the single-gene model. The marker RM8225 and RM6836 showed significant R2 values higher than 10 for the trait of the blast lesions degree (BLD. The positions of RM6836 and RM8225 markers on rice chromosome 6 and the distance between these two markers is 0.2 cM. We conclude that single dominant gene control the blast resistance in Pongsu Seribu 1 located on chromosome 6, which is linked to RM8225 and RM6836 microsatellite markers. This information could be useful in marker-assisted selection for blast resistance in rice breeding involving Pongsu Seribu 1.

Sex comb on midleg (Scm) is a functional link between PcG-repressive complexes in Drosophila.

Science.gov (United States)

Kang, Hyuckjoon; McElroy, Kyle A; Jung, Youngsook Lucy; Alekseyenko, Artyom A; Zee, Barry M; Park, Peter J; Kuroda, Mitzi I

2015-06-01

The Polycomb group (PcG) proteins are key regulators of development in Drosophila and are strongly implicated in human health and disease. How PcG complexes form repressive chromatin domains remains unclear. Using cross-linked affinity purifications of BioTAP-Polycomb (Pc) or BioTAP-Enhancer of zeste [E(z)], we captured all PcG-repressive complex 1 (PRC1) or PRC2 core components and Sex comb on midleg (Scm) as the only protein strongly enriched with both complexes. Although previously not linked to PRC2, we confirmed direct binding of Scm and PRC2 using recombinant protein expression and colocalization of Scm with PRC1, PRC2, and H3K27me3 in embryos and cultured cells using ChIP-seq (chromatin immunoprecipitation [ChIP] combined with deep sequencing). Furthermore, we found that RNAi knockdown of Scm and overexpression of the dominant-negative Scm-SAM (sterile α motif) domain both affected the binding pattern of E(z) on polytene chromosomes. Aberrant localization of the Scm-SAM domain in long contiguous regions on polytene chromosomes revealed its independent ability to spread on chromatin, consistent with its previously described ability to oligomerize in vitro. Pull-downs of BioTAP-Scm captured PRC1 and PRC2 and additional repressive complexes, including PhoRC, LINT, and CtBP. We propose that Scm is a key mediator connecting PRC1, PRC2, and transcriptional silencing. Combined with previous structural and genetic analyses, our results strongly suggest that Scm coordinates PcG complexes and polymerizes to produce broad domains of PcG silencing. © 2015 Kang et al.; Published by Cold Spring Harbor Laboratory Press.

Curcumin, Inflammation, and Chronic Diseases: How Are They Linked?

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Yan He

2015-05-01

Full Text Available It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

Autosomal-recessive and X-linked forms of hereditary motor and sensory neuropathy in childhood.

Science.gov (United States)

Ouvrier, Robert; Geevasingha, Nimeshan; Ryan, Monique M

2007-08-01

The hereditary motor and sensory neuropathies (HMSNs, Charcot-Marie-Tooth neuropathies) are the most common degenerative disorders of the peripheral nervous system. In recent years a dramatic expansion has occurred in our understanding of the molecular basis and cell biology of the recessively inherited demyelinating and axonal neuropathies, with delineation of a number of new neuropathies. Mutations in some genes cause a wide variety of clinical, neurophysiologic, and pathologic phenotypes, rendering diagnosis difficult. The X-linked forms of HMSN represent at least 10%-15% of all HMSNs and have an expanded disease spectrum including demyelinating, intermediate, and axonal neuropathies, transient central nervous system (CNS) dysfunction, mental retardation, and hearing loss. This review presents an overview of the recessive and X-linked forms of HMSN observed in childhood, with particular reference to disease phenotype and neurophysiologic and pathologic abnormalities suggestive of specific diagnoses. These findings can be used by the clinician to formulate a differential diagnosis and guide targeted genetic testing.

On the Possible Link between Vitamin D Deficiency and Cardiovascular Disease

Science.gov (United States)

... the Possible Link Between Vitamin D Deficiency and Cardiovascular Disease Should We D-Lighten Our Lives? Pelle G. ... Individuals with heart failure, hypertension, stroke, and other cardiovascular diseases (CVD) tend to have lower vitamin D levels ...

Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states.

Science.gov (United States)

Cunningham, Timothy J; Ford, Earl S; Croft, Janet B; Merrick, Melissa T; Rolle, Italia V; Giles, Wayne H

2014-01-01

Adverse childhood experiences (ACEs) before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD) in the general population. Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs) and their corresponding 95% confidence intervals (CIs) for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61), sexual abuse (PR =1.69, 95% CI: 1.36, 2.10), living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81), witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72), and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80) during childhood compared to those with no individual ACEs. Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.55, 2.80) compared to none was associated with a higher likelihood of COPD among women only. ACEs are related to COPD, especially among women. These findings underscore the need for further research that examines sex-specific differences and the possible mechanisms linking ACEs and COPD. This work adds to a growing body of research suggesting that ACEs may contribute to health problems later in life and suggesting a need for program and policy solutions.

Ten inherited disorders in purebred dogs by functional breed groupings

OpenAIRE

Oberbauer, A. M.; Belanger, J. M.; Bellumori, T.; Bannasch, D. L.; Famula, T. R.

2015-01-01

Background Analysis of 88,635 dogs seen at the University of California, Davis Veterinary Medical Teaching Hospital from 1995 to 2010 identified ten inherited conditions having greater prevalence within the purebred dog population as compared to the mixed-breed dog population: aortic stenosis, atopy/allergic dermatitis, gastric dilatation volvulus (GDV), early onset cataracts, dilated cardiomyopathy, elbow dysplasia, epilepsy, hypothyroidism, intervertebral disk disease (IVDD), and hepatic po...

Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune diseases in Denmark 1989-2008.

Science.gov (United States)

Frisch, Morten; Nielsen, Nete Munk; Pedersen, Bo Vestergaard

2014-01-01

Autoimmune diseases have been little studied in gay men and lesbians. We followed 4.4 million Danes, including 9,615 same-sex married (SSM) persons, for 47 autoimmune diseases in the National Patient Registry between 1989 and 2008. Poisson regression analyses provided first hospitalization rate ratios (RRs) comparing rates between SSM individuals and persons in other marital status categories. SSM individuals experienced no unusual overall risk of autoimmune diseases. However, the risk of autoimmune thyroid dysfunction was increased, notably Hashimoto's thyroiditis (women(SSM), RR = 2.92; 95% confidence interval (CI) 1.74-4.55) and Graves' disease (men(SSM), RR = 1.88; 95% CI 1.08-3.01). There was also an excess of primary biliary cirrhosis (women(SSM), RR = 4.09; 95% CI 1.01-10.7), and of psoriasis (men(SSM), RR = 2.48; 95% CI 1.77-3.36), rheumatic fever (men(SSM), RR = 7.55; 95% CI 1.87-19.8), myasthenia gravis (men(SSM), RR = 5.51; 95% CI 1.36-14.4), localized scleroderma (men(SSM), RR = 7.16; 95% CI 1.18-22.6) and pemphigoid (men(SSM), RR = 6.56; 95% CI 1.08-20.6), while Dupuytren's contracture was reduced (men(SSM), RR = 0.64; 95% CI 0.39-0.99). The excess of psoriasis was restricted to same-sex married men with HIV/AIDS (men(SSM), RR = 10.5; 95% CI 6.44-15.9), whereas Graves' disease occurred in excess only among same-sex married men without HIV/AIDS (men(SSM), RR = 1.99; 95% CI 1.12-3.22). Lesbians and immunologically competent gay men in same-sex marriage face no unusual overall risk of autoimmune diseases. However, the observed increased risk of thyroid dysfunction in these lesbians and gay men deserves further study.

The scurs inheritance: new insights from the French Charolais breed

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Gautier Mathieu

2009-07-01

Full Text Available Abstract Background Polled animals are valued in cattle industry because the absence of horns has a significant economic impact. However, some cattle are neither polled nor horned but have so-called scurs on their heads, which are corneous growths loosely attached to the skull. A better understanding of the genetic determinism of the scurs phenotype would help to fine map the polled locus. To date, only one study has attempted to map the scurs locus in cattle. Here, we have investigated the inheritance of the scurs phenotype in the French Charolais breed and examined whether the previously proposed localisation of the scurs locus on bovine chromosome 19 could be confirmed or not. Results Our results indicate that the inheritance pattern of the scurs phenotype in the French Charolais breed is autosomal recessive with complete penetrance in both sexes, which is different from what is reported for other breeds. The frequency of the scurs allele (Sc reaches 69.9% in the French Charolais population. Eleven microsatellite markers on bovine chromosome 19 were genotyped in 267 offspring (33 half-sib and full-sib families. Both non-parametric and parametric linkage analyses suggest that in the French Charolais population the scurs locus may not map to the previously identified region. A new analysis of an Angus-Hereford and Hereford-Hereford pedigree published in 1978 enabled us to calculate the frequency of the Sc allele in the Hereford breed (89.4% and to study the penetrance of this allele in males heterozygous for both polled and scurs loci (40%. This led us to revise the inheritance pattern of the scurs phenotype proposed for the Hereford breed and to suggest that allele Sc is not fully but partially dominant in double heterozygous males while it is always recessive in females. Crossbreeding involving the Charolais breed and other breeds gave results similar to those reported in the Hereford breed. Conclusion Our results suggest the existence of

The scurs inheritance: new insights from the French Charolais breed.

Science.gov (United States)

Capitan, Aurélien; Grohs, Cécile; Gautier, Mathieu; Eggen, André

2009-07-06

Polled animals are valued in cattle industry because the absence of horns has a significant economic impact. However, some cattle are neither polled nor horned but have so-called scurs on their heads, which are corneous growths loosely attached to the skull. A better understanding of the genetic determinism of the scurs phenotype would help to fine map the polled locus. To date, only one study has attempted to map the scurs locus in cattle. Here, we have investigated the inheritance of the scurs phenotype in the French Charolais breed and examined whether the previously proposed localisation of the scurs locus on bovine chromosome 19 could be confirmed or not. Our results indicate that the inheritance pattern of the scurs phenotype in the French Charolais breed is autosomal recessive with complete penetrance in both sexes, which is different from what is reported for other breeds. The frequency of the scurs allele (Sc) reaches 69.9% in the French Charolais population. Eleven microsatellite markers on bovine chromosome 19 were genotyped in 267 offspring (33 half-sib and full-sib families). Both non-parametric and parametric linkage analyses suggest that in the French Charolais population the scurs locus may not map to the previously identified region. A new analysis of an Angus-Hereford and Hereford-Hereford pedigree published in 1978 enabled us to calculate the frequency of the Sc allele in the Hereford breed (89.4%) and to study the penetrance of this allele in males heterozygous for both polled and scurs loci (40%). This led us to revise the inheritance pattern of the scurs phenotype proposed for the Hereford breed and to suggest that allele Sc is not fully but partially dominant in double heterozygous males while it is always recessive in females. Crossbreeding involving the Charolais breed and other breeds gave results similar to those reported in the Hereford breed. Our results suggest the existence of unknown genetics factors modifying the expression of the

Sex-Specificity of Oxidative Stress in Newborns Leading to a Personalized Antioxidant Nutritive Strategy.

Science.gov (United States)

Lavoie, Jean-Claude; Tremblay, André

2018-03-27

Oxidative stress is a critical process that triggers several diseases observed in premature infants. Growing recognition of the detriment of oxidative stress in newborns warrants the use of an antioxidant strategy that is likely to be nutritional in order to restore redox homeostasis. It appears essential to have a personalized approach that will take into account the age of gestation at birth and the sex of the infant. However, the link between sex and oxidative stress remains unclear. The aim of this study was to find a common denominator explaining the discrepancy between studies related to sex-specific effects of oxidative stress. Results highlight a specificity of sex in the levels of oxidative stress markers linked to the metabolism of glutathione, as measured in the intracellular compartments. Levels of all sex-dependent oxidative stress markers are greater and markers associated to a better antioxidant defense are lower in boys compared to girls during the neonatal period. This sex-specific discrepancy is likely to be related to estrogen metabolism, which is more active in baby-girls and promotes the activation of glutathione metabolism. our observations suggest that nutritive antioxidant strategies need to target glutathione metabolism and, therefore, should be personalized considering, among others, the sex specificity.

Sex-Specificity of Oxidative Stress in Newborns Leading to a Personalized Antioxidant Nutritive Strategy

Directory of Open Access Journals (Sweden)

Jean-Claude Lavoie

2018-03-01

Full Text Available Oxidative stress is a critical process that triggers several diseases observed in premature infants. Growing recognition of the detriment of oxidative stress in newborns warrants the use of an antioxidant strategy that is likely to be nutritional in order to restore redox homeostasis. It appears essential to have a personalized approach that will take into account the age of gestation at birth and the sex of the infant. However, the link between sex and oxidative stress remains unclear. The aim of this study was to find a common denominator explaining the discrepancy between studies related to sex-specific effects of oxidative stress. Results highlight a specificity of sex in the levels of oxidative stress markers linked to the metabolism of glutathione, as measured in the intracellular compartments. Levels of all sex-dependent oxidative stress markers are greater and markers associated to a better antioxidant defense are lower in boys compared to girls during the neonatal period. This sex-specific discrepancy is likely to be related to estrogen metabolism, which is more active in baby-girls and promotes the activation of glutathione metabolism. Conclusion: our observations suggest that nutritive antioxidant strategies need to target glutathione metabolism and, therefore, should be personalized considering, among others, the sex specificity.

Changes in bone structure of Corriedale sheep with inherited rickets: a peripheral quantitative computed tomography assessment.

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Dittmer, Keren E; Firth, Elwyn C; Thompson, Keith G; Marshall, Jonathan C; Blair, Hugh T

2011-03-01

An inherited skeletal disease with gross and microscopic features of rickets has been diagnosed in Corriedale sheep in New Zealand. The aim of this study was to quantify the changes present in tibia from sheep with inherited rickets using peripheral quantitative computed tomography. In affected sheep, scans in the proximal tibia, where metaphysis becomes diaphysis, showed significantly greater trabecular bone mineral content (BMC) and bone mineral density (BMD). The sheep with inherited rickets had significantly greater BMC and bone area in the mid-diaphysis of the proximal tibia compared to control sheep. However, BMD in the mid-diaphysis was significantly less in affected sheep than in controls, due to the greater cortical area and lower voxel density values in affected sheep. From this it was concluded that the increased strain on under-mineralised bone in sheep with inherited rickets led to increased bone mass in an attempt to improve bone strength. Copyright © 2010 Elsevier Ltd. All rights reserved.

Investigating stakeholders' perceptions of the link between high STD rates and the current Baltimore City Public Schools' sex education curriculum

Science.gov (United States)

Bolden, Shenell L. T.

The purpose of this exploratory study was to examine key stakeholders' perceptions of the current Baltimore City Public Schools' (BCPS) sex education curriculum and to gain insight into how they believe the curriculum could be modified to be more effective. A mixed methods approach using qualitative and quantitative data collection consisting of a survey, focus group interview, and individual interviews was conducted to gather information on stakeholders' perceptions. The stakeholders included: (1) former students who received their sex education courses in the Baltimore City Public School system (BCPS); (2) teachers in BCPS who were affiliated with the sex education curriculum; (3) health care professionals who screened and/or treated East Baltimore City residents for a sexually transmitted disease (STD) and; (4) one policy maker who was responsible for creating sex education curriculum at the national level. Analysis of the quantitative data from former Baltimore City Public School students revealed a general satisfaction with the current sex education curriculum. However, qualitative data from the same group of stakeholders revealed several changes they thought should be implemented into the program in an effort to improve the current curriculum. Findings from the other groups after qualitative analysis of the interviews suggest three major themes in support of curriculum change: (1) a blended curriculum that integrates both the cognitive and affective learning domains; (2) knowledge of prevention of STD's and pregnancy; and (3) authentic teaching and learning. Results from this study strongly suggest that the Baltimore City Public School system is apathetic to the sexual health needs of students and, therefore, is inadvertently contributing to the high rate of sexually transmitted diseases among young people. Keywords: Abstinence, Affective domain, Indoctrination, Behavior Modification, Cognitive domain, Sex education curriculum, Sexually Transmitted Diseases.

Sex allocation in a species with paternal genome elimination : The roles of crowding and female age in the mealybug Planococcus citri

NARCIS (Netherlands)

Ross, Laura; Langenhof, Minke B. W.; Pen, Ido; Beukeboom, Leo W.; West, Stuart A.; Shuker, David M.

Background: In species with paternal genome elimination, both sexes are diploid. However, in males the chromosomes inherited from the father are deactivated during early development and eliminated from the germ line. Sex allocation theory predicts that, all else being equal, females should bias

Wilson's Disease

Science.gov (United States)

... yellowing of the skin and the whites of the eye (jaundice) Golden-brown eye discoloration (Kayser-Fleischer rings) Fluid buildup ... is inherited as an autosomal recessive trait, which means that to develop the disease you must inherit one copy of the ...

Retinitis pigmentosa: genes and disease mechanisms.

Science.gov (United States)

Ferrari, Stefano; Di Iorio, Enzo; Barbaro, Vanessa; Ponzin, Diego; Sorrentino, Francesco S; Parmeggiani, Francesco

2011-06-01

Retinitis pigmentosa (RP) is a group of inherited disorders affecting 1 in 3000-7000 people and characterized by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium of the retina which lead to progressive visual loss. RP can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. While usually limited to the eye, RP may also occur as part of a syndrome as in the Usher syndrome and Bardet-Biedl syndrome. Over 40 genes have been associated with RP so far, with the majority of them expressed in either the photoreceptors or the retinal pigment epithelium. The tremendous heterogeneity of the disease makes the genetics of RP complicated, thus rendering genotype-phenotype correlations not fully applicable yet. In addition to the multiplicity of mutations, in fact, different mutations in the same gene may cause different diseases. We will here review which genes are involved in the genesis of RP and how mutations can lead to retinal degeneration. In the future, a more thorough analysis of genetic and clinical data together with a better understanding of the genotype-phenotype correlation might allow to reveal important information with respect to the likelihood of disease development and choices of therapy.

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes.

Science.gov (United States)

Christie, Joshua R; Beekman, Madeleine

2017-03-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes-specifically their organization into host cells and their uniparental (maternal) inheritance-enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller's ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes-despite their asexual mode of reproduction-can readily undergo adaptive evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

[The effects of a sex education program on knowledge related to sexually transmitted diseases and sexual autonomy among university students].

Science.gov (United States)

Shin, YunHee; Chun, YoungKyung; Cho, SungMi; Cho, YeRyung

2005-12-01

The purpose of this study was to evaluate the effects of a sex education program, which was based on the Health Belief Model, on knowledge related to sexually transmitted diseases and sexual autonomy among university students. A non-equivalent control group, pretest-posttest design was used. The four session program was delivered to 18 students during 4 weeks; the control group consisted of 23 students. The theme of the first session was "sex, gender, and sexuality: all our concern", "dangerous sex" for the second session, "safe sex" for the third session, and "right sex for you and me" for the fourth session. At follow-up, the knowledge related to sexually transmitted diseases and sexual autonomy were significantly greater in the intervention group than in the control group. A sex education program with several sessions within the theoretical frame of HBM was effective to improve knowledge related to sexually transmitted diseases and sexual autonomy. The results suggest the potential of a systematic sexual education program to teach healthy sex and to extend the program for other various populations.

Risk factors for sexually transmitted diseases among sex workers in the interior of Piaui, Brazil

Directory of Open Access Journals (Sweden)

Jardeliny Corrêa da Penha

Full Text Available OBJECTIVE: To identify the risk factors for STD among female sex workers and the characteristics of this population, and to verify the association between condom use by their male partners and clients. METHOD: Cross-sectional and correlational study conducted with 73 sex workers registered at the Sex Workers´ Association of the municipality of Picos -PI, Brazil. Data were collected in September and October 2010 using a questionnaire to obtain sociodemographic information and the participants´ background in the sex industry. Ethical aspects were observed. RESULTS: There was no significant association between most of the sociodemographic variables and background in the sex industry and condom use by male partners or clients. However, there was a significant association with years in the sex industry (p = 0.029. Sex workers who had been in the industry for the longest used condoms for protection against sexually transmitted diseases. CONCLUSION: It is essential to create health promotion strategies that observe the real-life experiences of sex workers.

Inherited chromosomally integrated human herpesvirus 6 as a predisposing risk factor for the development of angina pectoris.

Science.gov (United States)

Gravel, Annie; Dubuc, Isabelle; Morissette, Guillaume; Sedlak, Ruth H; Jerome, Keith R; Flamand, Louis

2015-06-30

Inherited chromosomally integrated human herpesvirus-6 (iciHHV-6) results in the germ-line transmission of the HHV-6 genome. Every somatic cell of iciHHV-6+ individuals contains the HHV-6 genome integrated in the telomere of chromosomes. Whether having iciHHV-6 predisposes humans to diseases remains undefined. DNA from 19,597 participants between 40 and 69 years of age were analyzed by quantitative PCR (qPCR) for the presence of iciHHV-6. Telomere lengths were determined by qPCR. Medical records, hematological, biochemical, and anthropometric measurements and telomere lengths were compared between iciHHV-6+ and iciHHV-6- subjects. The prevalence of iciHHV-6 was 0.58%. Two-way ANOVA with a Holm-Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on continuous outcomes. Two-way logistic regression with a Holm-Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on disease prevalence. Of 50 diseases monitored, a single one, angina pectoris, is significantly elevated (3.3×) in iciHHV-6+ individuals relative to iciHHV-6- subjects (P = 0.017; 95% CI, 1.73-6.35). When adjusted for potential confounding factors (age, body mass index, percent body fat, and systolic blood pressure), the prevalence of angina remained three times greater in iciHHV-6+ subjects (P = 0.015; 95%CI, 1.23-7.15). Analyses of telomere lengths between iciHHV-6- without angina, iciHHV-6- with angina, and iciHHV-6+ with angina indicate that iciHHV-6+ with angina have shorter telomeres than age-matched iciHHV-6- subjects (P = 0.006). Our study represents, to our knowledge, the first large-scale analysis of disease association with iciHHV-6. Our results are consistent with iciHHV-6 representing a risk factor for the development of angina.

Testamental inheritance: Just a legal osmosis?

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Đorđević-Crnobrnja Jadranka

2011-01-01

Full Text Available Bequeath, a dispose of personal property by the last will is an example of intervention of legislation within the complex of customary law. This influence is not unusual but certainly is less frequent than the influence of customary into civil law, especially so in their interaction within inheritance. This paper therefore tries to explain this example of legal osmosis in practice. In addition, the practice in testament inheritance shows also an influence of customary law into legislation. Hence, the paper will also try to discuss a relationship between customary and civil laws and succeeding problems in inheritance at the levels of individual and that of the society.

Young men’s shame about their desire for other men predicts risky sex and moderates the knowledge - self-efficacy link.

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Mina ePark

2014-10-01

Full Text Available Background: Recent findings suggest that a strong negative social emotion (i.e., shame increases YMSM’s sexual risk-taking. Unchangeable shame (e.g., desire for other men might undermine (moderate the link between knowledge and self-efficacy or between self-efficacy and unprotected anal intercourse (UAI: This may be less likely for changeable shame (e.g., shame about risky sexual behavior.Aim: To test the hypotheses that shame (i.e., sexual desire shame, but not shame about behavior (i.e., sexual behavior shame, will be positively related to UAI and will moderate the relationship between knowledge and self-efficacy and/or self-efficacy and UAI among YMSM.Method: In an online national study, 1177 young adult (18-24 year old MSM reported one or more acts of UAI in the past 90 days with a casual partner. Eligible MSM filled out a survey in which they provided information about their knowledge of safer sex, self-efficacy for safer sex, reported levels of shame, and reported past 90-day UAI. Results: Sexual desire shame was negatively correlated with knowledge and self-efficacy and positively correlated with UAI: The pattern reversed for sexual behavior shame. Sexual desire shame significantly lowered the knowledge to self-efficacy and the self-efficacy to UAI links. Sexual behavior shame also reduced the link from knowledge to self-efficacy, but not the self-efficacy to UAI link. Conclusion: The present study shows that there are different types of shame that may produce different effects with different implications for health behavior. Sexual desire shame may better reflect an emotion that is activated prior to risky behavior (e.g., when men reflect upon or feel desire for another man. Sexual behavior shame, on the other hand, better reflects what has already happened: Thus, those higher in knowledge, efficacy, and therefore safer sex are least likely to experience shame behavior.

Mitochondrial Dysfunction in Parkinson's Disease

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P. C. Keane

2011-01-01

Full Text Available Parkinson's disease (PD is a progressive, neurodegenerative condition that has increasingly been linked with mitochondrial dysfunction and inhibition of the electron transport chain. This inhibition leads to the generation of reactive oxygen species and depletion of cellular energy levels, which can consequently cause cellular damage and death mediated by oxidative stress and excitotoxicity. A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD. This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD. This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc of PD patients and to highlight the important need for further research in this area.

Cerebral, cerebellar, and colobomatous anomalies in three related males: Sex-linked inheritance in a newly recognized syndrome with features overlapping with Joubert syndrome

NARCIS (Netherlands)

Kroes, Hester Y.; Nievelstein, Rutger-Jan A. J.; Barth, Peter G.; Nikkels, Peter G. J.; Bergmann, Carsten; Gooskens, Rob H. J. M.; Visser, Gepke; van Amstel, Hans-Kristian Ploos; Beemer, Frits A.

2005-01-01

We present a so far unrecognized X-linked mental retardation syndrome with features overlapping with Joubert syndrome (JBS). Two brothers showed hypotonia, mental retardation, ocular abnormalities with impaired vision and colobomas and a breathing pattern compatible with JBS. Neuroimaging revealed

Inheritance of proportionate dwarfism in Angus cattle.

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Latter, M R; Latter, B D H; Wilkins, J F; Windsor, P A

2006-04-01

To determine the mode of inheritance of congenital proportionate dwarfism in Angus and Angus crossbred cattle, initially detected in two commercial beef herds in northern New South Wales. Matings of normal carrier sires to unrelated cows of diverse breeds, and of one carrier sire to his unaffected daughters. An unrelated Piedmontese bull was also mated to unaffected daughters of the carrier sires. Two carrier Angus bulls and nine unaffected daughters, all of whom were completely indistinguishable from normal animals, were purchased for controlled breeding studies under known nutritional and disease conditions. Affected and carrier individuals were examined for the presence of obvious chromosomal abnormalities. Angus dwarfism has been successfully reproduced under controlled experimental conditions over successive years using unrelated dams and is undoubtedly heritable. The high frequency of occurrence of affected individuals (23/61 = 0.38 +/- .06) among the progeny of matings of the Angus sires to unrelated females of diverse breeding is not compatible with recessive inheritance, because of the negligible frequency of proportionate dwarfism in the breeds of the dams. Both paternal and maternal transmission of the defect was demonstrated, so that imprinting in the strict sense of a gene that is only expressed when received from the male parent appears not to be involved. Tested individuals showed no evidence of gross chromosomal abnormality. Dominant autosomal inheritance with incomplete penetrance was indicated by the lack of expression of the defective gene in the two Angus sires and in three unaffected daughters who produced dwarf calves from matings to the Piedmontese bull. The mode of inheritance is that of a single autosomal dominant gene with a penetrance coefficient of 0.75 +/- 0.12, estimated from the observed incidence of 23/61 affected offspring of the two carrier Angus bulls mated to unrelated dams. Simple genetic models involving either (i) an unstable

Bardet-Biedl Syndrome

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... Linked Retinoschisis (XLRS) X-Linked Retinitis Pigmentosa (XLRP) Usher Syndrome Other Retinal Diseases Glossary News & Research News & Research ... the autosomal recessive pattern of inheritance. In this type of inheritance both parents, called carriers, have one ...

Widow cleansing and inheritance among the Luo in Kenya: the need for additional women-centred HIV prevention options.

Science.gov (United States)

Perry, Brian; Oluoch, Lennah; Agot, Kawango; Taylor, Jamilah; Onyango, Jacob; Ouma, Lilian; Otieno, Caroline; Wong, Christina; Corneli, Amy

2014-01-01

The customs of widow cleansing and widow inheritance are practiced in several communities throughout sub-Saharan Africa. In the Nyanza Province of Kenya, according to tradition, Luo widows are expected to engage in sexual intercourse with a "cleanser," without the use of a condom, in order to remove the impurity ascribed to her after her husband's death. Luo couples, including widows, are also expected to engage in sex preceding specific agricultural activities, building homes, funerals, weddings, and other significant cultural and social events. Widows who are inherited for the purpose of fulfilling cultural obligation have a higher prevalence of HIV than those who remain un-inherited or are inherited for the purpose of companionship. As part of a larger descriptive qualitative study to inform study procedures for FEM-PrEP, an HIV prevention pre-exposure prophylaxis clinical trial, we conducted 15 semi-structured interviews (SSIs) with widows, 15 SSIs with inheritors, and four focus group discussions with widows in the Bondo and Rarieda districts in Nyanza Province to explore the HIV risk context within widow cleansing and inheritance practices. Thematic qualitative analysis was used to analyze the data. The majority of widows reported in the demographic questionnaire being inherited, and most widows in the SSIs described participating in the cleansing ritual. We identified two main themes related to HIV prevention within the context of widow cleansing and inheritance: 1) widows must balance limiting their risk for HIV infection with meeting cultural expectations and ensuring that their livelihood needs are met, and 2) sexual abstinence undermines cultural expectations in widowhood while the use of condoms is deemed inappropriate in fulfilling culturally prescribed sexual rituals, and is often beyond the widow's ability to negotiate. Women-controlled HIV prevention methods such as antiretroviral-based oral pre-exposure prophylaxis, vaginal gels, and vaginal rings

Towards unifying inheritance and automatic program specialization

DEFF Research Database (Denmark)

Schultz, Ulrik Pagh

2002-01-01

and specialization of classes (inheritance) are considered different abstractions. We present a new programming language, Lapis, that unifies inheritance and program specialization at the conceptual, syntactic, and semantic levels. This paper presents the initial development of Lapis, which uses inheritance...... with covariant specialization to control the automatic application of program specialization to class members. Lapis integrates object-oriented concepts, block structure, and techniques from automatic program specialization to provide both a language where object-oriented designs can be e#ciently implemented...

The relative importance of inheritances in Norway

OpenAIRE

Johansson, Marianne Lefsaker

2014-01-01

In a very influential paper, Piketty (2011) finds that inherited wealth is of increasing importance in France. He describes a U-shaped pattern in the long-run development of inheritance flows. Two driving factors in this development are the relative ratio of wealth of the deceased to wealth of the living, and the wealth-income ratio. In periods with high economic growth, wealth of the past is weakened and inheritances as share of national income decreases. As soon as growth declines, however,...

Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNAs.

Science.gov (United States)

Schuster, Andrew; Skinner, Michael K; Yan, Wei

Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats. Over 200 differentially expressed sncRNAs were identified and the tRNA-derived sncRNAs, namely 5' halves of mature tRNAs (5' halves), displayed the most dramatic changes. Gene targets of the altered miRNAs and tRNA 5' halves revealed associations between the altered sncRNAs and differentially DNA methylated regions. Dysregulated sncRNAs appear to correlate with mRNA profiles associated with the previously observed vinclozolin-induced disease phenotypes. Data suggest potential connections between sperm-borne RNAs and the vinclozolin-induced epigenetic transgenerational inheritance phenomenon.

Magnetic resonance imaging in Pelizaeus-Merzbacher disease

International Nuclear Information System (INIS)

Journel, H.; Roussey, M.; Allaire, C.; Le Marec, B.; Gandon, Y.; Carsin, M.

1987-01-01

Pelizaeus-Merzbacher's disease is a progressive encephalopathy with demyelination of the cerebral white matter. The diagnosis cannot be made on clinical or biological grounds: pathological investigation is necessary to confirm tigroid demyelination. CT scanning failure to visualize this type of anomaly but detection is now possible with the advent of magnetic resonance imaging (MRI). The authors studied the case of a boy who, at the age of 8 presented with symptoms characeristic of the disease, rotatory nystagmus, progressive encephalopathy, and inherited X-linked recessive traits. Magnetic resonance imaging revealed a high signal in the supra-tentorial white matter and the usual contrast was inverted. The authors believe that MRI can make an important contribution to the diagnosis of the disease. (orig.)

Inherited Bone Marrow Failure Syndromes (IBMFS)

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The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

Chlorhexidine rinse for prevention of urethritis in men linked to oral sex

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Kolahi Jafar

2010-06-01

Full Text Available Abstract Background Oral sex among teenagers is on the rise. Similarity between the oral flora and organisms recovered from nongonococcal urethritis and prostatitis, points to retrograde entry of bacteria from oral cavity into the urethra following insertive oral intercourse. Presentation of the hypothesis Chlorhexidine has a wide spectrum of anti-bactericidal activity encompassing gram positive and negative bacteria. It is also effective against HIV and HBV. It produced large and prolonged reductions in salivary bacterial counts within 7-h of its use. Hence, it would seem logic to postulate that rinsing with chlorhexidine before oral sex will be effective for prevention of retrograde entry of bacteria from oral cavity into the urethra. The recommendation for rinsing will be: 15 ml of a 0.12% or 10 ml of 0.2% chlorhexidine rinse for 30 seconds. Also other drug delivery systems such as chlorhexidine chewing gum or spray can be used. Testing the hypothesis Men suffering from recurrent nongonococcal urethritis or prostatitis are good subjects for testing the hypothesis. They perform genital safe sex via consistent use of condom. Yet they generally received unprotected insertive oral intercourse. Chlorhexidine can be used for prevention of recurrences of the disease. Implications of the hypothesis The chlorhexidine will be a new, easy, attractive and effective method for reduction of nongonococcal urethritis, prostatitis and epidydimitis following insertive oral intercourse. It is poorly absorbed from skin, mucosa and gastrointestinal tract indicating systemic safety of chlorhexidine. The agent does not cause any bacterial resistance and supra-infection.

Bone Marrow Transplantation (BMT) and Gene Replacement ...

African Journals Online (AJOL)

Abstract. Background: Sickle cell anemia (SCA) forms one of the neglected tropical disease of genetic aetiology. Unlike many complex genetic diseases inherited on a multiallelic pattern, SCA is a hemoglobinopathy of Mendelian type genetic inheritance. The SCA trait is inherited through a recessive autosomal link, with the ...

The contribution of the mitochondrial genome to sex-specific fitness variance.

Science.gov (United States)

Smith, Shane R T; Connallon, Tim

2017-05-01

Maternal inheritance of mitochondrial DNA (mtDNA) facilitates the evolutionary accumulation of mutations with sex-biased fitness effects. Whereas maternal inheritance closely aligns mtDNA evolution with natural selection in females, it makes it indifferent to evolutionary changes that exclusively benefit males. The constrained response of mtDNA to selection in males can lead to asymmetries in the relative contributions of mitochondrial genes to female versus male fitness variation. Here, we examine the impact of genetic drift and the distribution of fitness effects (DFE) among mutations-including the correlation of mutant fitness effects between the sexes-on mitochondrial genetic variation for fitness. We show how drift, genetic correlations, and skewness of the DFE determine the relative contributions of mitochondrial genes to male versus female fitness variance. When mutant fitness effects are weakly correlated between the sexes, and the effective population size is large, mitochondrial genes should contribute much more to male than to female fitness variance. In contrast, high fitness correlations and small population sizes tend to equalize the contributions of mitochondrial genes to female versus male variance. We discuss implications of these results for the evolution of mitochondrial genome diversity and the genetic architecture of female and male fitness. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Participation of Polycomb group gene extra sex combs in hedgehog signaling pathway

International Nuclear Information System (INIS)

Shindo, Norihisa; Sakai, Atsushi; Yamada, Kouji; Higashinakagawa, Toru

2004-01-01

Polycomb group (PcG) genes are required for stable inheritance of epigenetic states across cell divisions, a phenomenon termed cellular memory. PcG proteins form multimeric nuclear complex which modifies the chromatin structure of target site. Drosophila PcG gene extra sex combs (esc) and its vertebrate orthologs constitute a member of ESC-E(Z) complex, which possesses histone methyltransferase activity. Here we report isolation and characterization of medaka esc homolog, termed oleed. Hypomorphic knock-down of oleed using morpholino antisense oligonucleotides resulted in the fusion of eyes, termed cyclopia. Prechordal plate formation was not substantially impaired, but expression of hedgehog target genes was dependent on oleed, suggesting some link with hedgehog signaling. In support of this implication, histone methylation, which requires the activity of esc gene product, is increased in hedgehog stimulated mouse NIH-3T3 cells. Our data argue for the novel role of esc in hedgehog signaling and provide fundamental insight into the epigenetic mechanisms in general

Conformal symmetry inheritance in null fluid spacetimes

International Nuclear Information System (INIS)

Tupper, B O J; Keane, A J; Hall, G S; Coley, A A; Carot, J

2003-01-01

We define inheriting conformal Killing vectors for null fluid spacetimes and find the maximum dimension of the associated inheriting Lie algebra. We show that for non-conformally flat null fluid spacetimes, the maximum dimension of the inheriting algebra is seven and for conformally flat null fluid spacetimes the maximum dimension is eight. In addition, it is shown that there are two distinct classes of non-conformally flat generalized plane wave spacetimes which possess the maximum dimension, and one class in the conformally flat case

Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?

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Dubal Dena B

2012-11-01

Full Text Available Abstract Biologic sex and gonadal hormones matter in human aging and diseases of aging such as Alzheimer’s – and the importance of studying their influences relates directly to human health. The goal of this article is to review the literature to date on sex and hormones in mouse models of Alzheimer’s disease (AD with an exclusive focus on interpreting the relevance of findings to the human condition. To this end, we highlight advances in AD and in sex and hormone biology, discuss what these advances mean for merging the two fields, review the current mouse model literature, raise major unresolved questions, and offer a research framework that incorporates human reproductive aging for future studies aimed at translational discoveries in this important area. Unraveling human relevant pathways in sex and hormone-based biology may ultimately pave the way to novel and urgently needed treatments for AD and other neurodegenerative diseases.

New and emerging technologies for the treatment of inherited retinal diseases: a horizon scanning review.

Science.gov (United States)

Smith, J; Ward, D; Michaelides, M; Moore, A T; Simpson, S

2015-09-01

The horizon scanning review aimed to identify new and emerging technologies in development that have the potential to slow or stop disease progression and/or reverse sight loss in people with inherited retinal diseases (IRDs). Potential treatments were identified using recognized horizon scanning methods. These included a combination of online searches using predetermined search terms, suggestions from clinical experts and patient and carer focus groups, and contact with commercial developers. Twenty-nine relevant technologies were identified. These included 9 gene therapeutic approaches, 10 medical devices, 5 pharmacological agents, and 5 regenerative and cell therapies. A further 11 technologies were identified in very early phases of development (typically phase I or pre-clinical) and were included in the final report to give a complete picture of developments 'on the horizon'. Clinical experts and patient and carer focus groups provided helpful information and insights, such as the availability of specialised services for patients, the potential impacts of individual technologies on people with IRDs and their families, and helped to identify additional relevant technologies. This engagement ensured that important areas of innovation were not missed. Most of the health technologies identified are still at an early stage of development and it is difficult to estimate when treatments might be available. Further, well designed trials that generate data on efficacy, applicability, acceptability, and costs of the technologies, as well as the long-term impacts for various conditions are required before these can be considered for adoption into routine clinical practice.

Preimplantation genetic diagnosis of X-linked diseases examined by indirect linkage analysis.

Science.gov (United States)

Borgulova, I; Putzova, M; Soldatova, I; Krautova, L; Pecnova, L; Mika, J; Kren, R; Potuznikova, P; Stejskal, D

2015-01-01

Many centers of assisted reproduction in the Czech Republic offer preimplantation genetic diagnosis with fluorescent in situ hybridization (FISH) to couples requiring preimplantation genetic diagnosis (PGD) of X-linked diseases. However, this process results in discarding all male embryos and is not able to distinguish a carrier or healthy female embryo in X-linked recessive disorders. The main aim of this study was to summarize a six-year period of PGD of X-linked monogenic diseases using indirect linkage analysis. We wanted to accentuate the advantage indirect analysis of PGD using multiple displacement amplification (MDA) followed by short tandem repeat (STR) analysis. We present forty-six PGD cycles, including pre-case haplotyping (PGH) panel, for fifteen X-linked diseases. Embryo transfer was made thirty-eight times and gravidity was confirmed in thirteen female probands with a success rate of pregnancy calculated at 42 %. PGD procedure using MDA amplification followed by STR analysis provides help in identifying genetic defects within embryos prior to implantation. The reliability of the method was also supported by high pregnancy rate compared to other publications, which commonly achieved a 30-35 % success rate (Tab. 2, Fig. 1, Ref. 33).

Pseudodominant inheritance pattern in a family with CMT2 caused by GDAP1 mutations

NARCIS (Netherlands)

van Paassen, Barbara W.; Bronk, Marieke; Verhamme, Camiel; van Ruissen, Fred; Baas, Frank; van Spaendonck-Zwarts, Karin Y.; de Visser, Marianne

2017-01-01

We report a family in which an autosomal dominantly inherited Charcot-Marie-Tooth (CMT) disease type 2 was suspected. The affected family members (proband, sister, father, and paternal aunt) showed intrafamilial clinical variability. The proband needed walking aids since adolescence because of

Legal Portion in Russian Inheritance Law

Science.gov (United States)

Inshina, Roza; Murzalimova, Lyudmila

2013-01-01

In this paper the authors describe the right to inherit as one of the basic human rights guaranteed by the Constitution of the Russian Federation. The state has set rules according to which after a person's death, his or her property is inherited by other persons. The Russian civil legislation establishes the institution of legal portions that is…

The role of inheritance in structuring hyperextended rift systems

Science.gov (United States)

Manatschal, Gianreto; Lavier, Luc; Chenin, Pauline

2015-04-01

A long-standing question in Earth Sciences is related to the importance of inheritance in controlling tectonic processes. In contrast to physical processes that are generally applicable, assessing the role of inheritance suffers from two major problems: firstly, it is difficult to appraise without having insights into the history of a geological system; and secondly all inherited features are not reactivated during subsequent deformation phases. Therefore, the aim of our presentation is to give some conceptual framework about how inheritance may control the architecture and evolution of hyperextended rift systems. We use the term inheritance to refer to the difference between an "ideal" layer-cake type lithosphere and a "real" lithosphere containing heterogeneities and we define 3 types of inheritance, namely structural, compositional and thermal inheritance. Moreover, we assume that the evolution of hyperextended rift systems reflects the interplay between their inheritance (innate/"genetic code") and the physical processes at play (acquired/external factors). Thus, by observing the architecture and evolution of hyperextended rift systems and integrating the physical processes, one my get hints on what may have been the original inheritance of a system. Using this approach, we focus on 3 well-studied rift systems that are the Alpine Tethys, Pyrenean-Bay of Biscay and Iberia-Newfoundland rift systems. For the studied examples we can show that: 1) strain localization on a local scale and during early stages of rifting is controlled by inherited structures and weaknesses 2) the architecture of the necking zone seems to be influenced by the distribution and importance of ductile layers during decoupled deformation and is consequently controlled by the thermal structure and/or the inherited composition of the curst 3) the location of breakup in the 3 examples is not significantly controlled by the inherited structures 4) inherited mantle composition and rift

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes

Science.gov (United States)

Christie, Joshua R.; Beekman, Madeleine

2017-01-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes—specifically their organization into host cells and their uniparental (maternal) inheritance—enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller’s ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes—despite their asexual mode of reproduction—can readily undergo adaptive evolution. PMID:28025277

The ecology of sex explains patterns of helping in arthropod societies.

Science.gov (United States)

Davies, Nicholas G; Ross, Laura; Gardner, Andy

2016-08-01

Across arthropod societies, sib-rearing (e.g. nursing or nest defence) may be provided by females, by males or by both sexes. According to Hamilton's 'haplodiploidy hypothesis', this diversity reflects the relatedness consequences of diploid vs. haplodiploid inheritance. However, an alternative 'preadaptation hypothesis' instead emphasises an interplay of ecology and the co-option of ancestral, sexually dimorphic traits for sib-rearing. The preadaptation hypothesis has recently received empirical support, but remains to be formalised. Here, we mathematically model the coevolution of sex-specific helping and sex allocation, contrasting these hypotheses. We find that ploidy per se has little effect. Rather, the ecology of sex shapes patterns of helping: sex-specific preadaptation strongly influences who helps; a freely adjustable sex ratio magnifies sex biases and promotes helping; and sib-mating, promiscuity, and reproductive autonomy also modulate the sex and abundance of helpers. An empirical survey reveals that patterns of sex-specific helping in arthropod taxa are consistent with the preadaptation hypothesis. © 2016 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

Assessment of Functional Effects of Unclassified Genetic Variants

NARCIS (Netherlands)

Couch, Fergus J.; Rasmussen, Lene Juel; Hofstra, Robert; Monteiro, Alvaro N. A.; Greenblatt, Marc S.; de Wind, Niels

2008-01-01

Inherited predisposition to disease is often linked to reduced activity of a disease associated gene product. Thus, quantitation of the influence of inherited variants on gene function can potentially be used to predict the disease relevance of these variants. While many disease genes have been

Assessment of Functional Effects of Unclassified Genetic Variants

NARCIS (Netherlands)

Couch, Fergus J.; Rasmussen, Lene Juel; Hofstra, Robert; Monteiro, Alvaro N. A.; Greenblatt, Marc S.; de Wind, Niels

Inherited predisposition to disease is often linked to reduced activity of a disease associated gene product. Thus, quantitation of the influence of inherited variants on gene function can potentially be used to predict the disease relevance of these variants. While many disease genes have been

Mitochondrial DNA inheritance in the human fungal pathogen Cryptococcus gattii.

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Wang, Zixuan; Wilson, Amanda; Xu, Jianping

2015-02-01

The inheritance of mitochondrial DNA (mtDNA) is predominantly uniparental in most sexual eukaryotes. In this study, we examined the mitochondrial inheritance pattern of Cryptococcus gattii, a basidiomycetous yeast responsible for the recent and ongoing outbreak of cryptococcal infections in the US Pacific Northwest and British Columbia (especially Vancouver Island) in Canada. Using molecular markers, we analyzed the inheritance of mtDNA in 14 crosses between strains within and between divergent lineages in C. gattii. Consistent with results from recent studies, our analyses identified significant variations in mtDNA inheritance patterns among strains and crosses, ranging from strictly uniparental to biparental. For two of the crosses that showed uniparental mitochondrial inheritance in standard laboratory conditions, we further investigated the effects of the following environmental variables on mtDNA inheritance: UV exposure, temperature, and treatments with the methylation inhibitor 5-aza-2'-deoxycytidine and with the ubiquitination inhibitor ammonium chloride. Interestingly, one of these crosses showed no response to these environmental variables while the other exhibited diverse patterns ranging from complete uniparental inheritance of the MATa parent mtDNA, to biparental inheritance, and to a significant bias toward inheritance of the MATα parental mtDNA. Our results indicate that mtDNA inheritance in C. gattii differs from that in its closely related species Cryptococcus neoformans. Copyright © 2015 Elsevier Inc. All rights reserved.

Does Customary Law Discriminate Balinese Women’s Inheritance Rights?

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Hanna Christine Ndun

2018-05-01

Full Text Available There is a stereotype with regard to the rights of the Balinese women on inheriting under the Balinese tradi-tional customary law. It is generally assumed that the law discriminates Balinese women as well as against the human rights principle of equality. This article analyzes the contemporary problems of such issue and would demonstrate the actual principles, rules and practices, including the essential concept of the rights under the Balinese traditional customary law of inheritance. This issue has been explored under a normative legal approach where the resources are primarily taken from the relevant national legal instruments and court decisions, instead of textbooks and journals. An interview has also been commenced for clarifying some aspects of the issue. This article concludes that there has been a generally misleading on viewing the Balinese customary law as discriminating women on an inheritance issue, as in fact, the law also provides rules for supporting women’s rights for inheriting. The law in a certain way has properly preserved the right of women for inheriting in which women under the law have also enjoyed rights for inheriting, especially the daughter and widow. In contrast, the Balinese men that are generally perceived as the ultimate gender enjoying privileges rights to inherit, in the practice of inheritance in the traditional community are also subject to some discrimination. The law has provided a set of rule of inheritance both for men and women where they are subject to certain equal rule and condition. The law also clarifies that both genders are enjoying equal rights on inheritance in a certain portion and situation binding under the principle of balancing between rights and obligation for each side.

Sex Differences Influencing Micro- and Macrovascular Endothelial Phenotype In Vitro.

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Huxley, Virginia H; Kemp, Scott S; Schramm, Christine; Sieveking, Steve; Bingaman, Susan; Yu, Yang; Zaniletti, Isabella; Stockard, Kevin; Wang, Jianjie

2018-06-09

(macro- versus microvessel) and sex influenced multiple phenotypic characteristics. Statistical model analysis of EC growth demonstrated an hierarchy of variable importance, recapitulated for other phenotypic characteristics, wherein predictions assuming EC homogeneity Sex Sex and Vessel Origin. Further, patterns of EC mRNA expression by vessel origin and by sex did not predict protein expression. Overall the study demonstrated that accurate assessment of sex-linked EC dysfunction first requires understanding of EC function by position in the vascular tree and by sex. Results from a single EC tissue source/species/sex cannot provide universal insight into the mechanisms regulating in vivo endothelial function in health, no less disease. (250) This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Norrie's disease in an Asian family.

OpenAIRE

Harendra de Silva, D G; de Silva, D B

1988-01-01

Norrie's disease, a congenital progressive oculo-acoustico-cerebral degenerative condition, is a sex linked recessive disorder. Previously described as atrophia oculi congeneti, it is associated with bilateral pseudotumour of the retina, lens, and corneal opacities, and phthisis bulbi. Some patients develop progressive deterioration of mental function and hearing. We report a Sri Lankan family with typical features of Norrie's disease.

The impact of mating systems and dispersal on fine-scale genetic structure at maternally, paternally and biparentally inherited markers.

Science.gov (United States)

Shaw, Robyn E; Banks, Sam C; Peakall, Rod

2018-01-01

For decades, studies have focused on how dispersal and mating systems influence genetic structure across populations or social groups. However, we still lack a thorough understanding of how these processes and their interaction shape spatial genetic patterns over a finer scale (tens-hundreds of metres). Using uniparentally inherited markers may help answer these questions, yet their potential has not been fully explored. Here, we use individual-level simulations to investigate the effects of dispersal and mating system on fine-scale genetic structure at autosomal, mitochondrial and Y chromosome markers. Using genetic spatial autocorrelation analysis, we found that dispersal was the major driver of fine-scale genetic structure across maternally, paternally and biparentally inherited markers. However, when dispersal was restricted (mean distance = 100 m), variation in mating behaviour created strong differences in the comparative level of structure detected at maternally and paternally inherited markers. Promiscuity reduced spatial genetic structure at Y chromosome loci (relative to monogamy), whereas structure increased under polygyny. In contrast, mitochondrial and autosomal markers were robust to differences in the specific mating system, although genetic structure increased across all markers when reproductive success was skewed towards fewer individuals. Comparing males and females at Y chromosome vs. mitochondrial markers, respectively, revealed that some mating systems can generate similar patterns to those expected under sex-biased dispersal. This demonstrates the need for caution when inferring ecological and behavioural processes from genetic results. Comparing patterns between the sexes, across a range of marker types, may help us tease apart the processes shaping fine-scale genetic structure. © 2017 John Wiley & Sons Ltd.

Inherited cardiomyopathies and sports participation.

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Zorzi, A; Pelliccia, A; Corrado, D

2018-03-01

Competitive sports activity is associated with an increased risk of sudden cardiovascular death in adolescents and young adults with inherited cardiomyopathies. Many young subjects aspire to continue competitive sport after a diagnosis of cardiomyopathy and the clinician is frequently confronted with the problem of eligibility and the request of designing specific exercise programs. Since inherited cardiomyopathies are the leading cause of sudden cardiovascular death during sports performance, a conservative approach implying disqualification of affected athletes from most competitive athletic disciplines is recommended by all the available international guidelines. On the other hand, we know that the health benefits of practicing recreational sports activity can overcome the potential arrhythmic risk in these patients, provided that the type and level of exercise are tailored on the basis of the specific risk profile of the underlying cardiomyopathy. This article will review the available evidence on the sports-related risk of sudden cardiac death and the recommendations regarding eligibility of individuals affected by inherited cardiomyopathies for sports activities.

SHBG (Sex Hormone Binding Globulin)

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... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

Continuous infusion of recombinant activated factor VII for bleeding control after lobectomy in a patient with inherited factor VII deficiency.

Science.gov (United States)

Miyata, Naoko; Isaka, Mitsuhiro; Kojima, Hideaki; Maniwa, Tomohiro; Takahashi, Shoji; Takamiya, Osamu; Ohde, Yasuhisa

2016-03-01

Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation disorder with limited available information, especially in patients undergoing major thoracic surgery. In addition, an optimal management strategy for the disease has not been defined. We herein report a case involving a 61-year-old man with asymptomatic FVII deficiency who underwent a right middle and lower lobectomy to treat lung cancer. To the best of our knowledge, the present report is the first to describe the use of recombinant activated FVII continuous infusion for bleeding control after a major thoracic surgery in a patient with inherited FVII deficiency.

Why does biparental plastid inheritance revive in angiosperms?

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Zhang, Quan; Sodmergen

2010-03-01

It is widely believed that plastid and mitochondrial genomes are inherited through the maternal parent. In plants, however, paternal transmission of these genomes is frequently observed, especially for the plastid genome. A male gametic trait, called potential biparental plastid inheritance (PBPI), occurs in up to 20% of angiosperm genera, implying a strong tendency for plastid transmission from the male lineage. Why do plants receive organelles from the male parents? Are there clues in plastids that will help to elucidate the evolution of plants? Reconstruction of the ancestral state of plastid inheritance patterns in a phylogenetic context provides insights into these questions. In particular, a recent report demonstrated the unilateral occurrence of PBPI in angiosperms. This result implies that nuclear cytoplasmic conflicts, a basic driving force for altering the mode of organelle inheritance, might have arisen specifically in angiosperms. Based on existing evidence, it is likely that biparental inheritance may have occurred to rescue angiosperm species with defective plastids.

Widow inheritance and HIV/AIDS in rural Uganda.

Science.gov (United States)

Mabumba, E D; Mugyenyi, P; Batwala, V; Mulogo, E M; Mirembe, J; Khan, F A; Liljestrand, J

2007-10-01

Despite current efforts to combat HIV/AIDS through behavioural change, ingrained socio-cultural practices such as widow inheritance in south-western Uganda has not changed. Low education, unemployment, dowry, widows' socioeconomic demands and the inheritor's greed for the deceased's wealth, influence widow inheritance. Voluntary counselling and testing is needed for the widows and their inheritors; formal dowry should be removed from marriage and widow inheritance stripped of its sexual component.

Does the mode of plastid inheritance influence plastid genome architecture?

Directory of Open Access Journals (Sweden)

Kate Crosby

Full Text Available Plastid genomes show an impressive array of sizes and compactnesses, but the forces responsible for this variation are unknown. It has been argued that species with small effective genetic population sizes are less efficient at purging excess DNA from their genomes than those with large effective population sizes. If true, one may expect the primary mode of plastid inheritance to influence plastid DNA (ptDNA architecture. All else being equal, biparentally inherited ptDNAs should have a two-fold greater effective population size than those that are uniparentally inherited, and thus should also be more compact. Here, we explore the relationship between plastid inheritance pattern and ptDNA architecture, and consider the role of phylogeny in shaping our observations. Contrary to our expectations, we found no significant difference in plastid genome size or compactness between ptDNAs that are biparentally inherited relative to those that are uniparentally inherited. However, we also found that there was significant phylogenetic signal for the trait of mode of plastid inheritance. We also found that paternally inherited ptDNAs are significantly smaller (n = 19, p = 0.000001 than those that are maternally, uniparentally (when isogamous, or biparentally inherited. Potential explanations for this observation are discussed.

Sex Differences in the Hepatic Cholesterol Sensing Mechanisms in Mice

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Ingemar Björkhem

2013-09-01

Full Text Available Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with the expression studies of hepatic cholesterol uptake and transport in female and male mice fed with a high-fat diet with or without cholesterol. Lack of dietary cholesterol led to a stronger response of the sterol sensing mechanism in females, resulting in higher expression of cholesterogenic genes compared to males. With cholesterol in the diet, the genes were down-regulated in both sexes; however, males maintained a more efficient hepatic metabolic flux through the pathway. Females had higher content of hepatic cholesterol but this was likely not due to diminished excretion but rather due to increased synthesis and absorption. Dietary cholesterol and sex were not important for gallbladder bile acids composition. Neither sex up-regulated Cyp7a1 upon cholesterol loading and there was no compensatory up-regulation of Abcg5 or Abcg8 transporters. On the other hand, females had higher expression of the Ldlr and Cd36 genes. These findings explain sexual dimorphism of cholesterol metabolism in response to dietary cholesterol in a high-fat diet in mice, which contributes to understanding the sex-basis of cholesterol-associated liver diseases.

The inheritance of groin hernia

DEFF Research Database (Denmark)

Burcharth, J; Pommergaard, H C; Rosenberg, Jacob

2013-01-01

Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias.......Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias....

Breed x sex effects on birth weight in Brahman-Simmental embryo transfer calves

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Brahman cross calves exhibit unusual inheritance of birth weight: Brahman-sired crossbreds out of Bos taurus females are heavier with greater difference between sexes than calves of the reciprocal cross. The objective of this work was to compare birth weight in various crosses of Brahman, Simmenta...

DNA Methylation and Sex Allocation in the Parasitoid Wasp Nasonia vitripennis.

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Cook, Nicola; Pannebakker, Bart A; Tauber, Eran; Shuker, David M

2015-10-01

The role of epigenetics in the control and evolution of behavior is being increasingly recognized. Here we test whether DNA methylation influences patterns of adaptive sex allocation in the parasitoid wasp Nasonia vitripennis. Female N. vitripennis allocate offspring sex broadly in line with local mate competition (LMC) theory. However, recent theory has highlighted how genomic conflict may influence sex allocation under LMC, conflict that requires parent-of-origin information to be retained by alleles through some form of epigenetic signal. We manipulated whole-genome DNA methylation in N. vitripennis females using the hypomethylating agent 5-aza-2'-deoxycytidine. Across two replicated experiments, we show that disruption of DNA methylation does not ablate the facultative sex allocation response of females, as sex ratios still vary with cofoundress number as in the classical theory. However, sex ratios are generally shifted upward when DNA methylation is disrupted. Our data are consistent with predictions from genomic conflict over sex allocation theory and suggest that sex ratios may be closer to the optimum for maternally inherited alleles.

Links between circadian rhythms and psychiatric disease

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Ilia N Karatsoreos

2014-05-01

Full Text Available Determining the cause of psychiatric disorders is a goal of modern neuroscience, and will hopefully lead to the discovery of treatments to either prevent or alleviate the suffering caused by these diseases. One roadblock to attaining this goal is the realization that neuropsychiatric diseases are rarely due to a single gene polymorphism, environmental exposure, or developmental insult. Rather, it is a complex interaction between these various influences that likely leads to the development of clinically relevant syndromes. Our lab is exploring the links between environmental exposures and neurobehavioral function by investigating how disruption of the circadian (daily clock alters the structure and function of neural circuits, with the hypothesis that disrupting this crucial homeostatic system can directly contribute to altered vulnerability of the organism to other factors that interact to produce psychiatric illness. This review explores some historical and more recent findings that link disrupted circadian clocks to neuropsychiatric disorders, particularly depression, mania, and schizophrenia. We take a comparative approach by exploring the effects observed in human populations, as well as some experimental models used in the laboratory to unravel mechanistic and causal relationships between disruption of the circadian clock and behavioral abnormalities. This is a rich area of research that we predict will contribute greatly to our understanding of how genes, environment, and development interact to modulate an individual’s vulnerability to psychiatric disorders.

Law & psychiatry: Murder, inheritance, and mental illness.

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Gold, Azgad; Appelbaum, Paul S

2011-07-01

Should a murderer be allowed to inherit the victim's estate? The question dates from biblical times, but most jurisdictions today have statutes in place that bar inheritance by convicted murderers. However, a special problem arises when the killer has a severe mental illness and has been found not guilty by reason of insanity. Should such people, who have not been convicted of a crime, be permitted to collect their inheritance? Jurisdictions vary in their responses, with the rules reflecting a mix of practical and moral considerations influenced by different perspectives about what determines the behavior of persons with mental illness.

Autonomic and inflammatory consequences of posttraumatic stress disorder and the link to cardiovascular disease.

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Brudey, Chevelle; Park, Jeanie; Wiaderkiewicz, Jan; Kobayashi, Ihori; Mellman, Thomas A; Marvar, Paul J

2015-08-15

Stress- and anxiety-related disorders are on the rise in both military and general populations. Over the next decade, it is predicted that treatment of these conditions, in particular, posttraumatic stress disorder (PTSD), along with its associated long-term comorbidities, will challenge the health care system. Multiple organ systems are adversely affected by PTSD, and PTSD is linked to cancer, arthritis, digestive disease, and cardiovascular disease. Evidence for a strong link between PTSD and cardiovascular disease is compelling, and this review describes current clinical data linking PTSD to cardiovascular disease, via inflammation, autonomic dysfunction, and the renin-angiotensin system. Recent clinical and preclinical evidence regarding the role of the renin-angiotensin system in the extinction of fear memory and relevance in PTSD-related immune and autonomic dysfunction is also addressed. Copyright © 2015 the American Physiological Society.

Extreme concentrations of endogenous sex hormones, ischemic heart disease, and death in women

DEFF Research Database (Denmark)

Benn, Marianne; Voss, Sidsel Skou; Holmegard, Haya N.

2015-01-01

OBJECTIVE - : Sex hormones may be critical determinants of ischemic heart disease and death in women, but results from previous studies are conflicting. To clarify this, we tested the hypothesis that extreme plasma concentrations of endogenous estradiol and testosterone are associated with risk...... for ischemic heart disease, 36% (18%-58%) higher for any death, and 38% (15%-65%) higher for death from other causes than cardiovascular disease and cancer. These results were similar for postmenopausal women alone. CONCLUSIONS - : In women, extreme low concentrations of endogenous estradiol were associated...

Pathogenic mechanisms linking periodontal diseases with adverse pregnancy outcomes.

Science.gov (United States)

Cetin, I; Pileri, P; Villa, A; Calabrese, S; Ottolenghi, L; Abati, S

2012-06-01

In the last 2 decades, a large proportion of studies have focused on the relationship between maternal periodontal disease and poor obstetric outcomes. The aim of the present review is to summarize the current knowledge about human studies on the pathogenetic mechanisms linking periodontal diseases with adverse pregnancy outcomes. A search of the medical literature was conducted using NIH (National Institute of Health) Pubmed through April 2011. Articles were identified with the Medical Subject Heading (MeSH) and free text terms "small for gestational age (SGA)," "preeclampsia," "preterm labor," and "periodontal disease." Experimental human studies have shown that periodontal pathogens may disseminate toward placental and fetal tissues accompanied by an increase in inflammatory mediators in the placenta. As such, new inflammatory reactions within the placental tissues of the pregnant woman may occur, the physiological levels of prostaglandin E(2) (PGE(2)) and tumor necrosis factor-α (TNF-α) in the amniotic fluid may increase and eventually lead to premature delivery. Although many data from clinical trials suggest that periodontal disease may increase the adverse pregnancy outcome, the exact pathogenetic mechanism involved remains controversial. The findings explain the potential link between periodontal infections and adverse pregnancy outcomes. First, periodontal bacteria can directly cause infections both of the uteroplacenta and the fetus; second, systemic inflammatory changes induced by periodontal diseases can activate responses at the maternal-fetal interface. Of note, associative studies have produced different results in different population groups and no conclusive evidence has still been produced for the potential role of preventive periodontal care to reduce the risk factors of preterm birth.

Is there a sex effect in colon cancer? Disease characteristics, management, and outcomes in routine clinical practice.

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Quirt, J S; Nanji, S; Wei, X; Flemming, J A; Booth, C M

2017-02-01

The incidence of colon cancer varies by sex. Whether women and men show differences in extent of disease, treatment, and outcomes is not well described. We used a large population-based cohort to evaluate sex differences in colon cancer. Using the Ontario Cancer Registry, all cases of colon cancer treated with surgery in Ontario during 2002-2008 were identified. Electronic records of treatment identified use of surgery and adjuvant chemotherapy. Pathology reports for a random 25% sample of all cases were obtained, and disease characteristics, treatment, and outcomes in women and men were compared. A Cox proportional hazards model was used to identify factors associated with overall (os) and cancer-specific survival (css). The study population included 7249 patients who underwent resection of colon cancer; 49% ( n = 3556) were women. Stage of disease and histologic grade did not vary by sex. Compared with men, women were more likely to have right-sided disease (55% vs. 44%, p ≤ 0.001). Surgical procedure and lymph node yield did not differ by sex. Adjuvant chemotherapy was delivered to 18% of patients with stage ii and 64% of patients with stage iii disease; when adjusted for patient- and disease-related factors, use of adjuvant chemotherapy was similar for women and men [relative risk: 0.99; 95% confidence interval (ci): 0.94 to 1.03]. Adjusted analyses demonstrated that os [hazard ratio (hr): 0.80; 95% ci: 0.75 to 0.86] and css (hr: 0.82; 95% ci: 0.76 to 0.90) were superior for women compared with men. Long-term survival after colon cancer is significantly better for women than for men, which is not explained by any substantial differences in extent of disease or treatment delivered.

Determination of epigenetic inheritance, genetic inheritance, and estimation of genome DNA methylation in a full-sib family of Cupressus sempervirens L.

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Avramidou, Evangelia V; Doulis, Andreas G; Aravanopoulos, Filippos A

2015-05-15

Genetic inheritance and epigenetic inheritance are significant determinants of plant evolution, adaptation and plasticity. We studied inheritance of restriction site polymorphisms by the f-AFLP method and epigenetic DNA cytosine methylation inheritance by the f-MSAP technique. The study involved parents and 190 progeny of a Cupressus sempervirens L. full-sib family. Results from AFLP genetic data revealed that 71.8% of the fragments studied are under Mendelian genetic control, whereas faithful Mendelian inheritance for the MSAP fragments was low (4.29%). Further, MSAP fragment analysis showed that total methylation presented a mean of 28.2%, which was higher than the midparent value, while maternal inheritance was higher (5.65%) than paternal (3.01%). Interestingly de novo methylation in the progeny was high (19.65%) compared to parental methylation. Genetic and epigenetic distances for parents and offspring were not correlated (R(2)=0.0005). Furthermore, we studied correlation of total relative methylation and CG methylation with growth (height, diameter). We found CG/CNG methylation (N: A, C, T) to be positively correlated with height and diameter, while total relative methylation and CG methylation were positively correlated with height. Results are discussed in light of further research needed and of their potential application in breeding. Copyright © 2015 Elsevier B.V. All rights reserved.

X-Linked Recessive Form of Nephrogenic Diabetes Insipidus in A 7-Year-Old Boy

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Janchevska A.

2014-12-01

Full Text Available Nephrogenic diabetes insipidus (NDI is caused by the inability of renal collecting duct cells to respond to arginine vasopressin (AVP/antidiuretic hormone (ADH. We present the case of a 7-year-old boy with a history of excretion of large amounts of dilute urine and polydipsia since infancy. The boy had several vomiting episodes with mild dehydration during the first 3 years of life. There was no evidence of headaches, dizziness or visual problems. He drinks between 2 and 3 L/day and has 24-hour diuresis of 2 liters, now. He has prepubertal appearance with appropriate weight [+0.85 standard deviation score (SDS] and height (+0.15 SDS for his age. His intelligence was also normal. The water deprivation test showed low urine osmolality after 8 hours of dehydration. After desmopressin administration, urine osmolality remained low. Serum osmolality was in the normal range for sex and age before and after desmopressin administration. This indicated a nephrogenic form of diabetes insipidus. Molecular analyses revealed a P286L [p.Pro(CCC286Leu(CTC] mutation in the AVPR2 gene, that was inherited from his mother. This patient is the first case with genetically confirmed X-linked inherited form of NDI in the Republic of Macedonia. Molecular analysis confirmed the clinical diagnosis and enabled genetic advice for this family.

A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets

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Tetsuya Kawahara

2015-01-01

Full Text Available X-linked hypophosphatemic rickets (XLH is a dominant inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. Inactivating mutations in the gene encoding phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX have been found to be associated with XLH. Here, we report a 16-year-old female patient affected by hypophosphatemic rickets. We evaluated her serum fibroblast growth factor 23 (FGF23 levels and conducted sequence analysis of the disease-associated genes of FGF23-related hypophosphatemic rickets: PHEX, FGF23, dentin matrix protein 1, and ectonucleotide pyrophosphatase/phosphodiesterase 1. She was diagnosed with XLH based on her clinical features and family history. Additionally, we observed elevated FGF23 levels and a novel PHEX exon 9 mutation (c.947G>T; p.Gly316Val inherited from her father. Although bioinformatics showed that the mutation was neutral, Gly316 is perfectly conserved among humans, mice, and rats, and there were no mutations in other FGF23-related rickets genes, suggesting that in silico analysis is limited in determining mutation pathogenicity. In summary, we present a female patient and her father with XLH harboring a novel PHEX mutation that appears to be causative of disease. Measurement of FGF23 for hypophosphatemic patients is therefore useful for the diagnosis of FGF23-dependent hypophosphatemia.

Intergenerational epigenetic inheritance in reef-building corals

KAUST Repository

Liew, Yi Jin

2018-02-22

The notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants and metazoans. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals). Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

Intergenerational epigenetic inheritance in reef-building corals

KAUST Repository

Liew, Yi Jin; Howells, Emily J.; Wang, Xin; Michell, Craig; Burt, John A.; Idaghdour, Youssef; Aranda, Manuel

2018-01-01

The notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants and metazoans. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals). Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

Application of an Image Cytometry Protocol for Cellular and Mitochondrial Phenotyping on Fibroblasts from Patients with Inherited Disorders

DEFF Research Database (Denmark)

Fernandez-Guerra, Paula; Lund, Martin; Corydon, T J

2015-01-01

Cellular phenotyping of human dermal fibroblasts (HDFs) from patients with inherited diseases provides invaluable information for diagnosis, disease aetiology, prognosis and assessing of treatment options. Here we present a cell phenotyping protocol using image cytometry that combines measurements...... on a parallel one. We analysed HDFs from healthy individuals after treatment with various concentrations of hydrogen peroxide (H2O2) for different intervals, to mimic the physiological effects of oxidative stress. Our results show that cell number, viability, TRS and MMP decreased, while MSL increased both...... in a time- and concentration-dependent manner. To assess the use of our protocol for analysis of HDFs from patients with inherited diseases, we analysed HDFs from two patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD), one with a severe clinical phenotype and one with a mild...

Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

NARCIS (Netherlands)

Z. Zelinkova (Zuzana); E. Bultman (Evelien); L. Vogelaar (Lauran); C. Bouziane (Cheima); E.J. Kuipers (Ernst); C.J. van der Woude (Janneke)

2012-01-01

textabstractAIM: To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients. METHODS: All IBD patients attending the IBD outpatient clinic of a referral hospital were identifed through the electronic diagnosis

Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations.

Science.gov (United States)

Arai, Yuuki; Maeda, Akiko; Hirami, Yasuhiko; Ishigami, Chie; Kosugi, Shinji; Mandai, Michiko; Kurimoto, Yasuo; Takahashi, Masayo

2015-01-01

The aim of this study was to gain information about disease prevalence and to identify the responsible genes for inherited retinal dystrophies (IRD) in Japanese populations. Clinical and molecular evaluations were performed on 349 patients with IRD. For segregation analyses, 63 of their family members were employed. Bioinformatics data from 1,208 Japanese individuals were used as controls. Molecular diagnosis was obtained by direct sequencing in a stepwise fashion utilizing one or two panels of 15 and 27 genes for retinitis pigmentosa patients. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes, that is, ABCA4 for Stargardt disease, was conducted. Limited availability of intrafamily information and decreasing family size hampered identifying inherited patterns. Differential disease profiles with lower prevalence of Stargardt disease from European and North American populations were obtained. We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%. This study found 43 novel sequence variants. In silico analysis suggests that 20 of 25 novel missense variants are pathogenic. EYS mutations had the highest prevalence at 23.5%. c.4957_4958insA and c.8868C>A were the two major EYS mutations identified in this cohort. EYS mutations are the most prevalent among Japanese patients with IRD.

Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations

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Yuuki Arai

2015-01-01

Full Text Available The aim of this study was to gain information about disease prevalence and to identify the responsible genes for inherited retinal dystrophies (IRD in Japanese populations. Clinical and molecular evaluations were performed on 349 patients with IRD. For segregation analyses, 63 of their family members were employed. Bioinformatics data from 1,208 Japanese individuals were used as controls. Molecular diagnosis was obtained by direct sequencing in a stepwise fashion utilizing one or two panels of 15 and 27 genes for retinitis pigmentosa patients. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes, that is, ABCA4 for Stargardt disease, was conducted. Limited availability of intrafamily information and decreasing family size hampered identifying inherited patterns. Differential disease profiles with lower prevalence of Stargardt disease from European and North American populations were obtained. We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%. This study found 43 novel sequence variants. In silico analysis suggests that 20 of 25 novel missense variants are pathogenic. EYS mutations had the highest prevalence at 23.5%. c.4957_4958insA and c.8868C>A were the two major EYS mutations identified in this cohort. EYS mutations are the most prevalent among Japanese patients with IRD.

Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.

Science.gov (United States)

Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G; Sergouniotis, Panagiotis I; O'Sullivan, James; Lamb, Janine A; Perveen, Rahat; Hall, Georgina; Newman, William G; Bishop, Paul N; Roberts, Stephen A; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C; Nemeth, Andrea H; Black, Graeme C M

2016-05-01

To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Case series. A total of 562 patients diagnosed with IRD. We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Diagnostic yield of genomic testing. Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15-45) uplift in diagnostic yield. We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Possible X linked congenital mitochondrial cardiomyopathy in three families.

OpenAIRE

Orstavik, K H; Skjörten, F; Hellebostad, M; Hågå, P; Langslet, A

1993-01-01

Familial cases of childhood congestive cardiomyopathy with X linked recessive inheritance and abnormalities of heart muscle mitochondria have been previously reported. We report here three families with possible X linked congestive cardiomyopathy and specific mitochondrial abnormalities. The heart disorder presented as endocardial fibroelastosis with neonatal death in two brothers in one family, and as heart failure and death in infancy in two brothers in the other two families. In one family...

Comparison of sexual risky factors of men who have sex with men and sex-buying men as groups vulnerable to sexually transmitted diseases.

Science.gov (United States)

Jung, Minsoo; Lee, Joongyub; Kwon, Dong Seok; Park, Byung-Joo

2012-05-01

It is necessary to examine groups carrying out sexually risky behavior because the prevalence of sexually transmitted diseases (STDs) is high among them. In this study, the prevalence of STDs among homosexuals and sex-buying men in South Korea was investigated, along with their sexual risk factors. Men who have sex with men (MSMs, n=108) were recruited in Seoul and Busan by applying the time location sampling method, while sex-buying men (n=118) were recruited from a john school in Gyeonggi province, the suburbs of Seoul. Dependent variables included past or present infection with syphilis, Chlamydia, gonorrhea, and human immunodeficiency virus. Independent variables included health behavior, social support, sexual behavior, and safe sex. It was found that when the MSMs were non-drunk while having sexual intercourse (odds ratio [OR], 0.132), they showed a higher STD infection rate when they had a higher number of anal sex partners (OR, 5.872), rarely used condoms (OR, 1.980), had lower self-efficacy (OR, 0.229), and were more anxious about becoming infected with an STD (OR, 3.723). However, the men who paid for sex showed high STD infections when they had more sex partners (OR, 2.286) and lower education levels (OR, 3.028). STD infections among the two groups were high when they were engaged with many sex partners and not having protected sex. In other words, there was a gap in risky sex behavior within such groups, which was significantly related to the possibility of developing an STD. Therefore, the preventive intervention against STDs for these groups needs to be expanded to include management of sex behaviors.

Inheritance and wealth inequality: Evidence from population registers

OpenAIRE

Elinder, Mikael; Erixson, Oscar; Waldenström, Daniel

2016-01-01

We use new population-wide register data on inheritances and wealth in Sweden to estimate the causal impact of inheritances on wealth inequality. We find that inheritances reduce relative wealth inequality (e.g., the Gini coefficient falls by 5–10 percent) but that absolute dispersion increases. Examining different parts of the wealth distribution, we find that the top decile's wealth share decreases substantially, whereas the wealth share of the bottom half increases from a negative to a pos...

The Role of Gene Therapy in the Treatment of Retinal Diseases: A Review.

Science.gov (United States)

Campa, C; Gallenga, C E; Bolletta, E; Perri, P

2017-01-01

Gene therapy represents the therapeutic delivery of nucleic acid polymers into patient cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ. It is not surprising therefore that several clinical trials are now ongoing in this field. The purpose of this review was to provide an update on gene therapy for retinal diseases, discussing differences in treatment strategies, vector designs and surgical techniques. Research was performed on PubMed, ClinicalTrials.gov, and Home Genetic Reference. We additionally utilized the internet database for genetics of retinal diseases, the portal for rare diseases and orphan drugs and the NCBI database Online Mendelian Inheritance in Man. No restriction was applied on the language of publications. We present the available results of current active clinical trials for inherited retinal disease such as Leber's congenital amaurosis type 2, choroideremia, Stargardt disease, achromatopsia and juvenile X-linked retinoschisis. We also illustrate a new approach of this therapy for the treatment of much more common ocular diseases such as age-related macular degeneration and diabetic retinopathy. Gene therapy represents an emerging and promising therapeutic approach for the treatment not only of rare inherited retinal diseases but also much more common retinal pathologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Organelle Genome Inheritance in Deparia Ferns (Athyriaceae, Aspleniineae, Polypodiales

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Li-Yaung Kuo

2018-04-01

Full Text Available Organelle genomes of land plants are predominately inherited maternally but in some cases can also be transmitted paternally or biparentally. Compared to seed plants (>83% genera of angiosperms and >12% genera of gymnosperms, plastid genome (plastome inheritance has only been investigated in fewer than 2% of fern genera, and mitochondrial genome (mitogenome from only one fern genus. We developed a new and efficient method to examine plastome and mitogenome inheritance in a fern species—Deparia lancea (Athyriaceae, Aspleniineae, Polypodiales, and found that plastid and mitochondrial DNAs were transmitted from only the maternal parentage to a next generation. To further examine whether both organelle genomes have the same manner of inheritance in other Deparia ferns, we sequenced both plastid and mitochondrial DNA regions of inter-species hybrids, and performed phylogenetic analyses to identify the origins of organellar DNA. Evidence from our experiments and phylogenetic analyses support that both organelle genomes in Deparia are uniparentally and maternally inherited. Most importantly, our study provides the first report of mitogenome inheritance in eupolypod ferns, and the second one among all ferns.

Non Inherited Maternal HLA Antigens in Susceptibility to Familial Rheumatoid Arthritis

Science.gov (United States)

Guthrie, Katherine A.; Tishkevich, Natalia R.; Nelson, J. Lee

2009-01-01

Objectives Some rheumatoid arthritis (RA) patients lack RA-associated HLA alleles. Prior studies investigated non-inherited maternal HLA alleles (NIMA) in RA risk with conflicting results. Methods We examined NIMA in a large cohort of families from the North American Rheumatoid Arthritis Consortium. Results Among 620 patients with one or both parents HLA-genotyped, RA patients informative for analysis included 176 without HLA-DRB1*04 and 86 without the HLA shared epitope (SE). The frequency of NIMA encoding HLA-DR4 or the SE was compared to the non-inherited paternal allele (NIPA). DR4-encoding NIMA vs. NIPA revealed no significant difference (27% vs. 20%). However, parity is known to modulate RA risk and analyses stratified by sex and age of onset showed significant variation among women. Interestingly, among women with onset <45 years DR4-encoding NIMA was increased compared to NIPA; among women ≥45 years at onset the reverse was observed (31% vs. 16% compared to 10% vs. 60%, p=0.008). DR4 encoding NIMA vs. NIPA did not differ in men. The SE did not differ in men or women. Conclusions Risk of RA was associated with HLA-DR4 encoding NIMA in younger-onset women but not in older-onset women or men. These observations could help explain conflicting prior results of NIMA in RA. PMID:18684745

Ricci inheritance symmetry in general relativity

International Nuclear Information System (INIS)

Bokhari, A.H.; Al-Dweik, A.; Zaman, F.D.; Karim, M.; Kubel, D.

2010-01-01

In an earlier paper (see Nuovo Cimento B, 19 (2004) 1187) it was conjectured that none of the well-known spherically symmetric static space-time solutions of the Einstein equations admit non-trivial Ricci inheritance symmetry. In this paper we discuss Ricci inheritance (R I) symmetry in three well-known non static spherically symmetric space-time metrics and show that our conjecture is also valid in non-static space-time metrics.

A Disease Mutation Causing Episodic Ataxia Type I in the S1 Links Directly to the Voltage Sensor and the Selectivity Filter in Kv Channels.

Science.gov (United States)

Petitjean, Dimitri; Kalstrup, Tanja; Zhao, Juan; Blunck, Rikard

2015-09-02

The mutation F184C in Kv1.1 leads to development of episodic ataxia type I (EA1). Although the mutation has been said to alter activation kinetics and to lower expression, we show here that the underlying molecular mechanisms may be more complex. Although F184 is positioned in the "peripheral" S1 helix, it occupies a central position in the 3D fold. We show in cut-open oocyte voltage-clamp recordings of gating and ionic currents of the Shaker Kv channel expressed in Xenopus oocytes that F184 not only interacts directly with the gating charges of the S4, but also creates a functional link to the selectivity filter of the neighboring subunit. This link leads to impaired fast and slow inactivation. The effect on fast inactivation is of an allosteric nature considering that fast inactivation is caused by a linked cytosolic ball peptide. The extensive effects of F184C provide a new mechanism underlying EA. Episodic ataxia (EA) is an inherited disease that leads to occasional loss of motor control in combination with variable other symptoms such as vertigo or migraine. EA type I (EA1), studied here, is caused by mutations in a voltage-gated potassium channel that contributes to the generation of electrical signals in the brain. The mechanism by which mutations in voltage-gated potassium channels lead to EA is still unknown and there is no consistent pharmacological treatment. By studying in detail one disease-causing mutation in Kv1.1, we describe a novel molecular mechanism distinct from mechanisms described previously. This mechanism contributes to the understanding of potassium channel function in general and might lead to a better understanding of how EA develops. Copyright © 2015 the authors 0270-6474/15/3512198-09$15.00/0.

Early Inherited Risk for Anxiety Moderates the Association between Fathers’ Child-Centered Parenting and Early Social Inhibition

Science.gov (United States)

Brooker, Rebecca J.; Alto, Kathleen M.; Marceau, Kristine; Najjar, Reema; Leve, Leslie D.; Ganiban, Jody M.; Shaw, Daniel S.; Reiss, David; Neiderhiser, Jenae M.

2016-01-01

Studies of the role of the early environment in shaping children’s risk for anxiety problems have produced mixed results. It is possible that inconsistencies in previous findings result from a lack of consideration of a putative role for inherited influences moderators on the impact of early experiences. Early inherited influences not only contribute to vulnerabilities for anxiety problems throughout the lifespan, but can also modulate the ways that the early environment impacts child outcomes. In the current study, we tested the effects of child-centered parenting behaviors on putative anxiety risk in young children who differed in levels of inherited vulnerability. We tested this using a parent-offspring adoption design and a sample in which risk for anxiety problems and parenting behaviors were assessed in both mothers and fathers. Inherited influences on anxiety problems were assessed as anxiety symptoms in biological parents. Child-centered parenting was observed in adoptive mothers and fathers when children were 9 months old. Social inhibition, an early temperament marker of anxiety risk, was observed at child ages 9 and 18 months. Inherited influences on anxiety problems moderated the link between paternal child-centered parenting during infancy and social inhibition in toddlerhood. For children whose birth parents reported high levels of anxiety symptoms, greater child-centered parenting in adoptive fathers was related to greater social inhibition 9 months later. For children whose birth parents reported low levels of anxiety symptoms, greater child-centered parenting in adoptive fathers was related to less social inhibition across the same period. PMID:27572913

Early inherited risk for anxiety moderates the association between fathers' child-centered parenting and early social inhibition.

Science.gov (United States)

Brooker, R J; Alto, K M; Marceau, K; Najjar, R; Leve, L D; Ganiban, J M; Shaw, D S; Reiss, D; Neiderhiser, J M

2016-12-01

Studies of the role of the early environment in shaping children's risk for anxiety problems have produced mixed results. It is possible that inconsistencies in previous findings result from a lack of consideration of a putative role for inherited influences moderators on the impact of early experiences. Early inherited influences not only contribute to vulnerabilities for anxiety problems throughout the lifespan, but can also modulate the ways that the early environment impacts child outcomes. In the current study, we tested the effects of child-centered parenting behaviors on putative anxiety risk in young children who differed in levels of inherited vulnerability. We tested this using a parent-offspring adoption design and a sample in which risk for anxiety problems and parenting behaviors were assessed in both mothers and fathers. Inherited influences on anxiety problems were assessed as anxiety symptoms in biological parents. Child-centered parenting was observed in adoptive mothers and fathers when children were 9 months old. Social inhibition, an early temperament marker of anxiety risk, was observed at child ages 9 and 18 months. Inherited influences on anxiety problems moderated the link between paternal child-centered parenting during infancy and social inhibition in toddlerhood. For children whose birth parents reported high levels of anxiety symptoms, greater child-centered parenting in adoptive fathers was related to greater social inhibition 9 months later. For children whose birth parents reported low levels of anxiety symptoms, greater child-centered parenting in adoptive fathers was related to less social inhibition across the same period.

Terapia gênica em distrofias hereditárias de retina Gene therapy for inherited retinal dystrophies

Directory of Open Access Journals (Sweden)

Monique Côco

2009-08-01

Full Text Available As distrofias hereditárias de retina abrangem um amplo número de doenças caracterizadas por lenta e progressiva degeneração da retina. São o resultado de mutações em genes expressos em fotorreceptores e no epitélio pigmentado da retina. A herança pode ser autossômica dominante, autossômica recessiva, ligada ao X recessiva, digênica ou herança mitocondrial. Atualmente não há tratamento para essas doenças e os pacientes convivem com a perda progressiva da visão. O aconselhamento genético e o suporte para reabilitação têm indicação nestes casos. Pesquisas envolvendo a base molecular e genética dessas doenças está continuamente em expansão e ampliam as perspectivas para novas formas de tratamento. Dessa forma, a terapia gênica, que consiste na inserção de material genético exógeno em células de um indivíduo com finalidade terapêutica, tem sido a principal forma de tratamento para as distrofias hereditárias de retina. O olho é um órgão peculiar para a terapia gênica, pois é anatomicamente dividido em compartimentos, imunologicamente privilegiado e com meios transparentes. A maioria das doenças oculares tem defeitos em genes conhecidos. Além disso, há modelo animal bem caracterizado para algumas condições. Propostas para pesquisa clínica em terapia gênica nas degenerações retinianas hereditárias com defeito no gene RPE65, recentemente tiveram aprovação ética e os resultados preliminares obtidos trouxeram grandes expectativas na melhora da qualidade de vida dos pacientes.The inherited retinal dystrophies comprise a large number of disorders characterized by a slow and progressive retinal degeneration. They are the result of mutations in genes that express in either the photoreceptor cells or the retinal pigment epithelium. The mode of inheritance can be autosomal dominant, autosomal recessive, X linked recessive, digenic or mitochondrial DNA inherited. At the moment, there is no treatment for these

Peer relationships and adolescents' academic and non-academic outcomes: same-sex and opposite-sex peer effects and the mediating role of school engagement.

Science.gov (United States)

Liem, Gregory Arief D; Martin, Andrew J

2011-06-01

The literature has documented theoretical/conceptual models delineating the facilitating role of peer relationships in academic and non-academic outcomes. However, the mechanisms through which peer relationships link to those outcomes is an area requiring further research. The study examined the role of adolescents' perceptions of their relationships with same-sex and opposite-sex peers in predicting their academic performance and general self-esteem and the potentially mediating role of school engagement in linking these perceived peer relationships with academic and non-academic outcomes. The sample comprised 1,436 high-school students (670 boys, 756 girls; 711 early adolescents, 723 later adolescents). Self-report measures and objective achievement tests were used. Structural equation modelling (SEM) was performed to test the hypothesized model and its invariance across gender and age groups. Perceived same-sex peer relationships yielded positive direct and indirect links with academic performance and general self-esteem. Perceived opposite-sex peer relationships yielded positive direct and indirect links with general self-esteem and an indirect positive link with academic performance, but mediation via school engagement was not as strong as that of perceived same-sex peer relationships. These findings generalized across gender and age groups. Adolescents' same-sex and opposite-sex peer relationships seem to positively impact their academic performance and general self-esteem in distinct ways. It appears that school engagement plays an important role in mediating these peer relationship effects, particularly those of same-sex peer relationships, on academic and non-academic functioning. Implications for psycho-educational theory, measurement, and practice are discussed. ©2011 The British Psychological Society.

Spectrum Of Inherited Metabolic Disorders In Pakistani Children Presenting At A Tertiary Care Centre

International Nuclear Information System (INIS)

Cheema, H. A.; Malik, H. S.; Parkash, A.; Fayyaz, Z.

2016-01-01

Objective: To determine the frequency, presentation and outcome of various inherited metabolic diseases in children presenting in a tertiary care hospital, Lahore, Pakistan. Study Design: An observational study. Place and Duration of Study: Gastroenterology, Hepatology and Nutrition Department of The Children Hospital and Institute of Child Health, Lahore, from January 2011 to October 2014. Methodology: All children aged < 14 years with high suspicion of a metabolic disorder were inducted. Routine and radiological investigation were carried out at the study place. Comprehensive diagnostic testing of particular metabolic disorder was sent abroad. Those with a specific metabolic disorder were included in the study while those with normal metabolic work-up were excluded. All data was collected on preformed proforma. Result: A total of 239 patients were enrolled. Nineteen different types of inherited metabolic disorders were diagnosed in 180 patients; age ranged from 8 days to 14 years. Consanguinity was positive in 175 (97 percentage) among the parents of the affected children, with previously affected siblings in 64 (35.5 percentage). The most frequent disorders were inherited disorders of carbohydrate metabolism (92, 51 percentage), lipid storage disease (59, 32.7 percentage), organic acidemia and energy defects (18, 10 percentage), amino acid disorder (6, 3.3 percentage), and miscellaneous (4, 2.2 percentage). Fifty-eight (32.2 percentage) presented with acute metabolic crisis, 28 (15.5 percentage) patients presented with early onset liver failure, and 24 (13.3 percentage) with mental retardation. Out of these, 16 (8.8 percentage) expired. Conclusion: Glycogen storage disorders being the commonest followed by Gaucher disease and Galactosemia. The associated complications resulted in high morbidity and mortality. (author)

Targeted massively parallel sequencing and histological assessment of skeletal muscles for the molecular diagnosis of inherited muscle disorders.

Science.gov (United States)

Nishikawa, Atsuko; Mitsuhashi, Satomi; Miyata, Naomasa; Nishino, Ichizo

2017-02-01

Inherited skeletal muscle diseases are genetically heterogeneous diseases caused by mutations in more than 150 genes. This has made it challenging to establish a high-throughput screening method for identifying causative gene mutations in clinical practice. In the present study, we developed a useful method for screening gene mutations associated with the pathogenesis of skeletal muscle diseases. We established four target gene panels, each covering all exonic and flanking regions of genes involved in the pathogenesis of the following muscle diseases: (1) muscular dystrophy (MD), (2) congenital myopathy/congenital myasthenic syndrome, (3) metabolic myopathy and (4) myopathy with protein aggregations/rimmed vacuoles. We assigned one panel to each patient based on the results of clinical and histological analyses of biopsied muscle samples and performed high-throughput sequencing by using Ion PGM next-generation sequencer. We also performed protein analysis to confirm defective proteins in patients with major muscular dystrophies. Further, we performed muscle-derived cDNA analysis to identify splice-site mutations. We identified possible causative gene mutations in 33% of patients (62/188) included in this study. Our results showed that the MD panel was the most useful, with a diagnostic rate of 46.2%. Thus, we developed a high-throughput sequencing technique for diagnosing inherited muscle diseases. The use of this technique along with histological and protein analyses may be useful and cost-effective for screening mutations in patients with inherited skeletal muscle diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Epigenetic Inheritance Across the Landscape

Directory of Open Access Journals (Sweden)

Amy Vaughn Whipple

2016-10-01

Full Text Available The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome-environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype.

Epigenetic Inheritance across the Landscape.

Science.gov (United States)

Whipple, Amy V; Holeski, Liza M

2016-01-01

The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here, we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome-environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype.

Dynamic Inheritance and Static Analysis can be Reconciled

DEFF Research Database (Denmark)

Ernst, Erik

1998-01-01

the exibility and expressivity of staticlanguages while preserving the safety properties. It is an inheritancemechanism, with standard single inheritance as a special case. It al-lows both compile-time and run-time construction of new classes. More-over, it supports specialization of existing objects at run......-time. This helpsavoiding the combinatorial explosion in the number of classes associatedwith multiple inheritance, and it supports a better separation of con-cerns in large systems. Pre-methoding|inheritance applied to behavioraldescriptors|has been used for the construction of control structures formany years, in Beta....... With dynamic inheritance, pre-methoding becomesmore expressive, supporting control structures as rst class values whichmay be constructed and combined dynamically. Even though the conceptof pre-methoding is missing from most other languages, the basic ideacould be applied to any statically typed object...

DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice

International Nuclear Information System (INIS)

Wang, Yongan; Yang, Qing; Liu, Wei; Yu, Mingxi; Zhang, Zhou; Cui, Xiaoyu

2016-01-01

Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2 mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. - Highlights: • Maternal exposure to di (2-ethylhexyl) phthalate disturbs fetus sex determination. • DEHP upregulated Foxl2 expression potentially disturbs postnatal granulosa cell differentiation. • DEHP accelerated medulla

DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice

Energy Technology Data Exchange (ETDEWEB)

Wang, Yongan [Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024 (China); Yang, Qing [School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116024 (China); Liu, Wei, E-mail: liu_wei@dlut.edu.cn [Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024 (China); Yu, Mingxi; Zhang, Zhou; Cui, Xiaoyu [Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024 (China)

2016-09-15

Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2 mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. - Highlights: • Maternal exposure to di (2-ethylhexyl) phthalate disturbs fetus sex determination. • DEHP upregulated Foxl2 expression potentially disturbs postnatal granulosa cell differentiation. • DEHP accelerated medulla

Exocrine pancreatic insufficiency in the Eurasian dog breed - inheritance and exclusion of two candidate genes

DEFF Research Database (Denmark)

Proschowsky, Helle Friis; Fredholm, Merete

2007-01-01

Exocrine pancreatic insufficiency is considered an inherited disease in several dog breeds. Affected dogs show polyphagia, weight loss and voluminous faeces of light colour due to the lack of pancreatic enzymes. In the study described herein, we performed a segregation analysis using the SINGLES ...

[Inherited primitive and secondary polycythemia].

Science.gov (United States)

Barba, T; Boileau, J-C; Pasquet, F; Hot, A; Pavic, M

2016-07-01

Myeloproliferative disorders and secondary polycythemia cover most of the polycythemia cases encountered in daily practice. Inherited polycythemias are rare entities that have to be suspected when the classical causes of acquired polycythemia have been ruled out. Recent advances were made in the understanding of these pathologies, which are still little known to the physicians. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of inherited polycythemia. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Inheritance rules for Hierarchical Metadata Based on ISO 19115

Science.gov (United States)

Zabala, A.; Masó, J.; Pons, X.

2012-04-01

Mainly, ISO19115 has been used to describe metadata for datasets and services. Furthermore, ISO19115 standard (as well as the new draft ISO19115-1) includes a conceptual model that allows to describe metadata at different levels of granularity structured in hierarchical levels, both in aggregated resources such as particularly series, datasets, and also in more disaggregated resources such as types of entities (feature type), types of attributes (attribute type), entities (feature instances) and attributes (attribute instances). In theory, to apply a complete metadata structure to all hierarchical levels of metadata, from the whole series to an individual feature attributes, is possible, but to store all metadata at all levels is completely impractical. An inheritance mechanism is needed to store each metadata and quality information at the optimum hierarchical level and to allow an ease and efficient documentation of metadata in both an Earth observation scenario such as a multi-satellite mission multiband imagery, as well as in a complex vector topographical map that includes several feature types separated in layers (e.g. administrative limits, contour lines, edification polygons, road lines, etc). Moreover, and due to the traditional split of maps in tiles due to map handling at detailed scales or due to the satellite characteristics, each of the previous thematic layers (e.g. 1:5000 roads for a country) or band (Landsat-5 TM cover of the Earth) are tiled on several parts (sheets or scenes respectively). According to hierarchy in ISO 19115, the definition of general metadata can be supplemented by spatially specific metadata that, when required, either inherits or overrides the general case (G.1.3). Annex H of this standard states that only metadata exceptions are defined at lower levels, so it is not necessary to generate the full registry of metadata for each level but to link particular values to the general value that they inherit. Conceptually the metadata

Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.

Science.gov (United States)

Hamosh, Ada; Scott, Alan F; Amberger, Joanna S; Bocchini, Carol A; McKusick, Victor A

2005-01-01

Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (http://www.ncbi.nlm.nih.gov/omim/) is now distributed electronically by the National Center for Biotechnology Information, where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, HUGO nomenclature, MapViewer, GeneTests, patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.

The sex-shift in single disease and multimorbid asthma and rhinitis during puberty