scholarly journals Associating Symptom Phenotype and Genotype in Preeclampsia

2018 ◽  
Vol 20 (2) ◽  
pp. 126-136 ◽  
Author(s):  
Sandra A. Founds ◽  
Eleni Tsigas ◽  
Dianxu Ren ◽  
M. Michael Barmada
Keyword(s):  
Candidate Genes ◽  
Medical Records ◽  
Genetic Disorder ◽  
Later Life ◽  
Small Sample ◽  
Nucleotide Polymorphisms ◽  
History Of ◽  
Complex Genetic Disorder ◽  
Symptom Phenotype ◽  
Visual Disturbances

Preeclampsia is a complex genetic disorder with an incompletely understood pathogenesis. Its phenotype may be better elucidated by integrating symptoms. This study aimed to identify symptoms by gestational age and associations with novel preeclampsia candidate genes. Women with a history of preeclampsia recruited from The Preeclampsia Registry completed clinical/demographic, symptom surveys and provided medical records. DNA extracted from saliva was processed with multiplexed assays for eight single-nucleotide polymorphisms (SNPs) selected to tag candidate genes and/or located in symptom susceptibility regions. Groups with versus without symptoms were compared using χ2. Associations between SNPs and symptoms were analyzed as genotype categories and presence/absence of the variant allele. Logistic regression modeling was conducted with exploratory p = .05. In 114 participants, 113 reported at least 1 of the 18 symptoms. Symptoms varied by trimester. Nine symptoms were associated with seven SNPs. Visual disturbances were associated with three SNPs and nausea/vomiting with two SNPs. Modeling adjustment for maternal age and parity resulted in 15 associations between 9 symptoms and 8 SNPs. Medical records demonstrated 100% concordance with self-reported diagnosis and 48% concordance with reported severity. Findings indicated novel symptom–genotype associations in preeclampsia. The small sample was self-selected, but results support future studies including medical records review. When validated, these results may lead to holistic phenotyping of women to characterize subsets of preeclampsia. This approach may optimize health in pregnancy and later life for mothers and offspring through prediction, prevention, and precision nursing care.

scholarly journals Current concepts in genetics of nonsyndromic clefts

2009 ◽  
Vol 42 (01) ◽  
pp. 068-081
Author(s):  
Jyotsna Murthy ◽  
L. V. K. S. Bhaskar
Keyword(s):  
Candidate Genes ◽  
Statistical Power ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Genetic Disorder ◽  
Cell Signalling ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Complex Genetic Disorder

ABSTRACTNonsyndromic cleft lip and palate is a complex genetic disorder with variable phenotype, largely attributed to the interactions of the environment and multiple genes, each potentially having certain effects. Numerous genes have been reported in studies demonstrating associations and/or linkage of the cleft lip and palate phenotypes to alleles of microsatellite markers and single nucleotide polymorphisms within specific genes that regulate transcription factors, growth factors, cell signalling and detoxification metabolisms. Although the studies reporting these observations are compelling, most of them lack statistical power. This review compiles the evidence that supports linkage and associations to the various genetic loci and candidate genes. Whereas significant progress has been made in the field of cleft lip and palate genetics in the past decade, the role of the genes and genetic variations within the numerous candidate genes that have been found to associate with the expression of the orofacial cleft phenotype remain to be determined.

scholarly journals P.079 4H leukodystrophy: a case series of siblings with an unusually mild phenotype

2019 ◽  
Vol 46 (s1) ◽  
pp. S35
Author(s):  
SM DeGasperis ◽  
G Bernard ◽  
D Pohl
Keyword(s):  
Medical Records ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Case Series ◽  
Genetic Mutation ◽  
Neurological Deficits ◽  
Motor Deficits ◽  
Severe Phenotype ◽  
Mild Phenotype ◽  
History Of

Background: 4H leukodystrophy is a genetic disorder typically characterized by hypomyelination, hypodontia and hypogonatotropic hypogonadism. Previously reported patients had considerable cognitive and motor deficits. We present a pair of siblings with a less severe phenotype. Methods: Patient data was obtained from medical records from the Children’s Hospital of Eastern Ontario. Results: The first patient was diagnosed with 4H leukodystrophy at the age of 21 years after genetic testing revealed a POLR3B mutation with a homozygous V523E variant. She has hypomyelination on MRI and a history of optic neuritis, as well as intermittent sensory and motor symptoms in the context of a diagnosis of multiple sclerosis. She has no clinical manifestations of 4H leukodystrophy. The patient is now 26 years old and has only mild neurological deficits. Her younger brother was diagnosed with 4H leukodystrophy at the age of 18 years and found to have the same genetic mutation as his sister. He has a history of seizures and mild learning disabilities. He is now 23 years old with no typical symptoms of 4H leukodystrophy. Conclusions: 4H leukodystrophy is usually associated with a severe, disabling phenotype and a poor prognosis. Our patients illustrate that a much milder phenotype exists.

scholarly journals Prader-Willi syndrome: an update on obesity and endocrine problems

2021 ◽  
Vol 26 (4) ◽  
pp. 227-236
Author(s):  
Su Jin Kim ◽  
Sung Yoon Cho ◽  
Dong-Kyu Jin
Keyword(s):  
Behavioral Problems ◽  
Genetic Disorder ◽  
Nutritional Therapy ◽  
Hormone Deficiency ◽  
Endocrine Disorders ◽  
Prader Willi Syndrome ◽  
Metabolic Complications ◽  
Obstructive Sleep ◽  
History Of ◽  
Complex Genetic Disorder

Prader-Willi syndrome (PWS) is a rare complex genetic disorder that results from a lack of expression of the paternally inherited chromosome 15q11-q13. PWS is characterized by hypotonia and feeding difficulty in early infancy and development of morbid obesity aggravated by uncontrolled hyperphagia after childhood and adolescent. Dysmorphic facial features, delayed motor and language development, various degrees of cognitive impairment, and behavioral problems are common in PWS. Without early, intensive nutritional therapy along with behavioral modification, PWS patients develop severe obesity associated with type 2 diabetes, obstructive sleep apnea, right-side heart failure, and other obesity-related metabolic complications. Hypothalamic dysfunction in PWS can lead to several endocrine disorders, including short stature with growth hormone deficiency, hypothyroidism, central adrenal insufficiency, and hypogonadism. In this review, we discuss the natural history of PWS and the mechanisms of hyperphagia and obesity. We also provide an update on obesity treatments and recommendations for screening and monitoring of various endocrine problems that can occur in PWS.

DNA sequence and haplotype variation in two candidate genes for dilated cardiomyopathy in the turkey Meleagris gallopavo

Genome ◽  
2007 ◽  
Vol 50 (5) ◽  
pp. 463-469 ◽  
Author(s):  
Kuan-chin Lin ◽  
Jun Xu ◽  
Davida Kamara ◽  
Tuoyu Geng ◽  
Kwaku Gyenai ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Candidate Genes ◽  
Troponin T ◽  
Small Sample Size ◽  
Meleagris Gallopavo ◽  
Small Sample ◽  
Snp Analysis ◽  
Chromosome 2 ◽  
Nucleotide Polymorphisms ◽  
Haplotype Variation

Determining variation in genes is fundamental to understanding their function in the disease state. Cardiac troponin T (cTnT) and phospholamban (PLN) genes have been implicated in dilated cardiomyopathy (DCM) in human and model species. To investigate the role of these 2 candidate genes in DCM in the turkey Meleagris gallopavo, understanding sequence variants and map position distribution is necessary. To this end, a total of 1854 and 1771 bp of cTnT and PLN gene sequences, respectively, were scanned for single nucleotide polymorphisms (SNPs) in a randomly bred population. A total of 15 SNPs was identified in the cTnT and PLN genomic sequences. Nine haplotypes, 5 in cTnT and 4 in PLN, were identified. Observed heterozygosities (0.02–0.39) in the turkey population were low for both genes. Within each gene, 1 SNP corresponding to a restriction enzyme site was identified and used to develop a PCR–restriction fragment length polymorphism (RFLP) genotyping assay. The PLN gene was genetically mapped to turkey chromosome 2, equivalent to Gallus gallus chromosome 3, and cTnT mapped to a turkey microchromosome. Although limited because of the relatively small sample size of 55 birds, the data from this SNP analysis of PLN and cTnT provide a foundation from which to evaluate the function of cTnT and PLN in the turkey. Information about the distribution of the SNPs and haplotypes will facilitate future association and linkage studies.

scholarly journals Genomic Identity of White Oak Species in an Eastern North American Syngameon

2019 ◽  
Vol 104 (3) ◽  
pp. 455-477 ◽  
Author(s):  
Andrew L. Hipp ◽  
Alan T. Whittemore ◽  
Mira Garner ◽  
Marlene Hahn ◽  
Elisabeth Fitzek ◽  
...  
Keyword(s):  
Gene Flow ◽  
North American ◽  
Null Distribution ◽  
Small Sample ◽  
Simple Problem ◽  
Nucleotide Polymorphisms ◽  
White Oak ◽  
Entire Genome ◽  
History Of ◽  
Multiple Species

The eastern North American white oaks, a complex of approximately 16 potentially interbreeding species, have become a classic model for studying the genetic nature of species in a syngameon. Genetic work over the past two decades has demonstrated the reality of oak species, but gene flow between sympatric oaks raises the question of whether there are conserved regions of the genome that define oak species. Does gene flow homogenize the entire genome? Do the regions of the genome that distinguish a species in one part of its range differ from the regions that distinguish it in other parts of its range, where it grows in sympatry withdifferent species? Or are there regions of the genome that are relatively conserved across species ranges? In this study, we revisit seven species of the eastern North American white oak syngameon using a set of 80 single-nucleotide polymorphisms (SNPs) selected in a previous study because they show differences among, and consistency within, the species. We test the hypothesis that there exist segments of the genome that do not become homogenized by repeated introgression, but retain distinct alleles characteristic of each species. We undertake a range-wide sampling to investigate whether SNPs that appeared to be fixed based on a relatively small sample in our previous work are fixed or nearly fixed across the range of the species. Each of the seven species remains genetically distinct across its range, given our diagnostic set of markers, with relatively few individuals exhibiting admixture of multiple species. SNPs map back to all 12 Quercus linkage groups (chromosomes) and are separated from each other by an average of 7.47 million bp (± 8.74 million bp, SD), but are significantly clustered relative to a random null distribution, suggesting that our SNP toolkit reflects genome-wide patterns of divergence while potentially being concentrated in regions of the genome that reflect a higher-than-average history of among-species divergence. This application of a DNA toolkit designed for the simple problem of identifying species in the field has two important implications. First, the eastern North American white oak syngameon is composed of entities that most taxonomists would consider “good species.” Second, and more fundamentally, species in the syngameon are genetically coherent because characteristic portions of the genome remain divergent despite a history of introgression. Understanding the conditions under which some loci diverge while others introgress is key to understanding the origins and maintenance of global tree diversity.

scholarly journals Single Nucleotide Polymorphisms in MicroRNA Binding Sites: Implications in Colorectal Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Panchalee Bhaumik ◽  
Chandrasekhar Gopalakrishnan ◽  
Balu Kamaraj ◽  
Rituraj Purohit
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cell Proliferation ◽  
In Silico ◽  
Genetic Disorder ◽  
Enrichment Analysis ◽  
Tumour Suppressor Genes ◽  
Nucleotide Polymorphisms ◽  
Altered Expression ◽  
Complex Genetic Disorder

Cancer is a complex genetic disorder, characterised by uncontrolled cell proliferation and caused by altered expression of oncogenes and tumour suppressor genes. When cell proliferation pertains to colon, it is called colorectal cancer. Most of colorectal cancer causing genes are potential targets for the miRNA (microRNA) that bind to 3′UTR (untranslated regions) of mRNA and inhibit translation. Mutations occurring in miRNA binding regions can alter the miRNA, mRNA combination, and can alter gene expression drastically. We hypothesized that 3′UTR mutation in miRNA binding site could alter the miRNA, mRNA interaction, thereby altering gene expression. Altered gene expression activity could promote tumorigenesis in colon. Therefore, we formulated a systematic in silico procedure that integrates data from various databases, followed rigorous selection criteria, and identified mutations that might alter the expression levels of cancer causing genes. Further we performed expression analysis to shed light on the potential tissues that might be affected by mutation, enrichment analysis to find the metabolic functions of the gene, and network analysis to highlight the important interactions of cancer causing genes with other genes to provide insight that complex network will be disturbed upon mutation. We provide in silico evidence for the effect of these mutations in colorectal cancer.

scholarly journals Linking migraine frequency with family history of migraine

Cephalalgia ◽  
2018 ◽  
Vol 39 (2) ◽  
pp. 229-236 ◽  
Author(s):  
Nadine Pelzer ◽  
Mark A Louter ◽  
Erik W van Zwet ◽  
Dale R Nyholt ◽  
Michel D Ferrari ◽  
...  
Keyword(s):  
Family History ◽  
Migraine With Aura ◽  
Genetic Disorder ◽  
Linear Regression Analysis ◽  
Age At Onset ◽  
Genetic Load ◽  
Migraine Frequency ◽  
History Of ◽  
Complex Genetic Disorder ◽  
Acute Headache

Background Migraine is a complex genetic disorder that is brought about by multiple genetic and environmental factors. We aimed to assess whether migraine frequency is associated with genetic susceptibility. Methods We investigated in 2829 migraine patients (14% males) whether ‘migraine frequency’ (measured as the number of migraine days per month) was related to ‘genetic load’ (measured as the number of parents affected with migraine) using a validated web-based questionnaire. In addition, we investigated associations with age-at-onset, migraine subtype, use of acute headache medication, and comorbid depression. Results We found an association between the number of migraine days per month and family history of migraine for males ( p = 0.03), but not for females ( p = 0.97). This association was confirmed in a linear regression analysis. Also, a lower age-at-onset ( p < 0.001), having migraine with aura ( p = 0.03), and a high number of medication days ( p = 0.006) were associated with a stronger family history of migraine, whereas lifetime depression ( p = 0.13) was not. Discussion Migraine frequency, as measured by the number of migraine days per month, seems associated with a genetic predisposition only in males. A stronger family history of migraine was also associated with a lower age-at-onset, a higher number of medication days, and migraine with aura. Our findings suggest that specific clinical features of migraine seem more determined by genetic factors.

Investigating the Dynamics of Suicidal Ideation

Crisis ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Nina Hallensleben ◽  
Lena Spangenberg ◽  
Thomas Forkmann ◽  
Dajana Rath ◽  
Ulrich Hegerl ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Small Sample Size ◽  
Unipolar Depression ◽  
Small Sample ◽  
History Of ◽  
Severity Of Depression ◽  
Ecological Momentary ◽  
Depressive Episodes ◽  
Ema Method ◽  
Shed Light

Abstract. Background: Although the fluctuating nature of suicidal ideation (SI) has been described previously, longitudinal studies investigating the dynamics of SI are scarce. Aim: To demonstrate the fluctuation of SI across 6 days and up to 60 measurement points using smartphone-based ecological momentary assessments (EMA). Method: Twenty inpatients with unipolar depression and current and/or lifetime suicidal ideation rated their momentary SI 10 times per day over a 6-day period. Mean squared successive difference (MSSD) was calculated as a measure of variability. Correlations of MSSD with severity of depression, number of previous depressive episodes, and history of suicidal behavior were examined. Results: Individual trajectories of SI are shown to illustrate fluctuation. MSSD values ranged from 0.2 to 21.7. No significant correlations of MSSD with several clinical parameters were found, but there are hints of associations between fluctuation of SI and severity of depression and suicidality. Limitations: Main limitation of this study is the small sample size leading to low power and probably missing potential effects. Further research with larger samples is necessary to shed light on the dynamics of SI. Conclusion: The results illustrate the dynamic nature and the diversity of trajectories of SI across 6 days in psychiatric inpatients with unipolar depression. Prediction of the fluctuation of SI might be of high clinical relevance. Further research using EMA and sophisticated analyses with larger samples is necessary to shed light on the dynamics of SI.

Participant Reactions to Suicide-Focused Research

Crisis ◽  
2020 ◽  
Vol 41 (5) ◽  
pp. 367-374
Author(s):  
Sarah P. Carter ◽  
Brooke A. Ammerman ◽  
Heather M. Gebhardt ◽  
Jonathan Buchholz ◽  
Mark A. Reger
Keyword(s):  
Medical Records ◽  
Research Study ◽  
Small Sample Size ◽  
Psychiatric Inpatient ◽  
Small Sample ◽  
Inpatient Unit ◽  
Online Laboratory ◽  
Psychiatric Inpatient Unit ◽  
Before And After ◽  
Participant Reactions

Abstract. Background: Concerns exist regarding the perceived risks of conducting suicide-focused research among an acutely distressed population. Aims: The current study assessed changes in participant distress before and after participation in a suicide-focused research study conducted on a psychiatric inpatient unit. Method: Participants included 37 veterans who were receiving treatment on a psychiatric inpatient unit and completed a survey-based research study focused on suicide-related behaviors and experiences. Results: Participants reported no significant changes in self-reported distress. The majority of participants reported unchanged or decreased distress. Reviews of electronic medical records revealed no behavioral dysregulation and minimal use of as-needed medications or changes in mood following participation. Limitations: The study's small sample size and veteran population may limit generalizability. Conclusion: Findings add to research conducted across a variety of settings (i.e., outpatient, online, laboratory), indicating that participating in suicide-focused research is not significantly associated with increased distress or suicide risk.

The use of a Domain Ontology for the Management of Essential Hypertension (Preprint)

2020 ◽  
Author(s):  
Emma Chavez ◽  
Vanessa Perez ◽  
Angélica Urrutia
Keyword(s):  
Decision Making ◽  
Essential Hypertension ◽  
Medical History ◽  
Medical Records ◽  
Medical Training ◽  
Relevant Information ◽  
Domain Ontology ◽  
Free Text ◽  
Snomed Ct ◽  
History Of

BACKGROUND : Currently, hypertension is one of the diseases with greater risk of mortality in the world. Particularly in Chile, 90% of the population with this disease has idiopathic or essential hypertension. Essential hypertension is characterized by high blood pressure rates and it´s cause is unknown, which means that every patient might requires a different treatment, depending on their history and symptoms. Different data, such as history, symptoms, exams, etc., are generated for each patient suffering from the disease. This data is presented in the patient’s medical record, in no order, making it difficult to search for relevant information. Therefore, there is a need for a common, unified vocabulary of the terms that adequately represent the diseased, making searching within the domain more effective. OBJECTIVE The objective of this study is to develop a domain ontology for essential hypertension , therefore arranging the more significant data within the domain as tool for medical training or to support physicians’ decision making will be provided. METHODS The terms used for the ontology were extracted from the medical history of de-identified medical records, of patients with essential hypertension. The Snomed-CT’ collection of medical terms, and clinical guidelines to control the disease were also used. Methontology was used for the design, classes definition and their hierarchy, as well as relationships between concepts and instances. Three criteria were used to validate the ontology, which also helped to measure its quality. Tests were run with a dataset to verify that the tool was created according to the requirements. RESULTS An ontology of 310 instances classified into 37 classes was developed. From these, 4 super classes and 30 relationships were obtained. In the dataset tests, 100% correct and coherent answers were obtained for quality tests (3). CONCLUSIONS The development of this ontology provides a tool for physicians, specialists, and students, among others, that can be incorporated into clinical systems to support decision making regarding essential hypertension. Nevertheless, more instances should be incorporated into the ontology by carrying out further searched in the medical history or free text sections of the medical records of patients with this disease.

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