scholarly journals Pedigree Analysis of Idiopathic Epilepsy In Children of South Kerala

2012 ◽  
Vol 01 (01) ◽  
pp. 024-029
Author(s):  
Amar Jayanthi. A.
Keyword(s):  
Genetic Factors ◽  
Age Of Onset ◽  
Association Studies ◽  
Positive Family History ◽  
Susceptibility Gene ◽  
Pedigree Analysis ◽  
Idiopathic Epilepsy ◽  
Major Health Problem ◽  
Neurology Clinic ◽  
Mode Of Inheritance

Abstract Background and aims: Epilepsy is a major health problem in infancy and childhood. Genetic factors are implicated in the etiology of epilepsy. A familial susceptibility to seizures have been recognized but the exact mode of inheritance remains unclear. The chief objective was to determine the inheritance pattern and to correlate its prevalence among closer relatives on the basis of sex, degree of relationship and age of onset of the disease. Materials and methods: A pedigree analysis of 100 clinically diagnosed children with idiopathic epilepsy seen between 1994 and 1997 at the Paediatric Neurology Clinic of Government Medical College, Thiruvananthapuram was done. The mode of inheritance was tested according to the genetic hypothesis of segregation analysis. Results: Positive family history was observed in 49% of the probands. A high proportion of probands with an early onset of disease showed involvement of family members and a significant sex predisposition for females was obtained. Relatives of female probands were affected more than those of males. Mothers were found to transmit the disease to offsprings more than the epileptic fathers. Conclusion: The results of pedigree analysis supported the hypothesis of an autosomal multifactorial mode of inheritance, with 86% heritability and a lower threshold for the disease to manifest. The application of modern genetic principles like identification of susceptibility gene to epilepsy, linkage and association studies would advance our understanding of the etiology of seizure disorders. Genetic factors may play a major role in the predisposition of relatives to epilepsy in families of probands with idiopathic epilepsy. The present study may aid in the genetic counselling of parents with epilepsy.

scholarly journals Identification of Parkinson’s Disease-Causing Genes via Omics Data

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinran Cui ◽  
Chen Xu ◽  
Liyuan Zhang ◽  
Yadong Wang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Factors ◽  
Association Studies ◽  
Susceptibility Gene ◽  
Clinical Manifestations ◽  
Eqtl Analysis ◽  
Genome Wide Association Studies ◽  
Accuracy Of Results ◽  
Neurogenic Disease

Parkinson’s disease (PD) is the second most frequent neurogenic disease after Alzheimer’s disease. The clinical manifestations include mostly motor disorders, such as bradykinesia, myotonia, and static tremors. Since the cause of this pathological features remain unclear, there is currently no radical treatment for PD. Environmental and genetic factors are thought to contribute to the pathology of PD. To identify the genetic factors, some studies employed the Genome-Wide Association Studies (GWAS) method and detected certain genes closely related to PD. However, the functions of these gene mutants in the development of PD are unknown. Combining GWAS and expression Quantitative Trait Loci (eQTL) analysis, the biological meaning of mutation could be explained to some extent. Therefore, the present investigation used Summary data-based Mendelian Randomization (SMR) analysis to integrate of two PD GWAS datasets and four eQTL datasets with the objective of identifying casual genes. Using this strategy, we found six Single Nucleotide Polymorphism (SNP) loci which could cause the development of PD through altering the susceptibility gene expression, and three risk genes: Synuclein Alpha (SNCA), Mitochondrial Poly(A) Polymerase (MTPAP), and RP11-305E6.4. We proved the accuracy of results through case studies and inferred the functions of these genes in PD. Overall, this study provides insights into the genetic mechanism behind PD, which is crucial for the study of the development of this disease and its diagnosis and treatment.

scholarly journals Association ofFTOPolymorphisms with Early Age of Obesity in Obese Italian Subjects

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Federica Sentinelli ◽  
Michela Incani ◽  
Federica Coccia ◽  
Danila Capoccia ◽  
Valentina Maria Cambuli ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Association Studies ◽  
Strong Association ◽  
Italian Population ◽  
Dependent Manner ◽  
Major Health Problem ◽  
Risk Alleles ◽  
Obese Subjects ◽  
Dose Dependent

Obesity is recognized as a major health problem worldwide. Genetic factors play a major role in obesity, and genomewide association studies have provided evidence that several common variants within the fat mass- and obesity-associated (FTO) gene are significantly associated with obesity. Very limited data is available onFTOin the Italian population. Aims of our study are to investigate: (1) the association ofFTOgene SNPs rs9939609 and rs9930506 with body mass index (BMI) and obesity-related parameters in a large cohort (n=752) of Italian obese subjects; (2) the association between the twoFTOSNPs and age of onset of obesity. Our results demonstrate a strong association betweenFTOSNPs rs9939609 (P<0.043) and rs9930506 (P<0.029) with BMI in the Italian population.FTOrs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI+1.4 kg/m2per G allele). We also observed that the association with BMI of the twoFTOvariants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability inFTOon BMI in a large Italian population.

scholarly journals Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype

2010 ◽  
Vol 17 (2) ◽  
pp. R109-R121 ◽  
Author(s):  
Mark H Greene ◽  
Christian P Kratz ◽  
Phuong L Mai ◽  
Christine Mueller ◽  
June A Peters ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cancer Susceptibility ◽  
Association Studies ◽  
Positive Family History ◽  
Susceptibility Gene ◽  
Germ Cell Tumors ◽  
Cancer Site ◽  
Testicular Development ◽  
Testicular Germ Cell ◽  
Mild Phenotype

Familial aggregations of testicular germ cell tumor (FTGCT) have been well described, suggesting the existence of a hereditary TGCT subset. Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four- to sixfold and eight- to tenfold increases in TGCT risk respectively. Segregation analyses suggest an autosomal recessive mode of inheritance. Linkage analyses have identified several genomic regions of modest interest, although no high-penetrance cancer susceptibility gene has been mapped yet. These data suggest that the combined effects of multiple common alleles, each conferring modest risk, might underlie familial testicular cancer. Families display a mild phenotype: the most common number of affected families is 2. Age at diagnosis is 2–3 years younger for familial versus sporadic cases. The ratio of familial seminoma to nonseminoma is 1.0. FTGCT is more likely to be bilateral than sporadic TGCT. This syndrome is cancer site specific. Testicular microlithiasis is a newly recognized FTGCT component. Candidate gene-association studies have implicated the Y chromosome gr/gr deletion and PDE11A gene mutations as genetic modifiers of FTGCT risk. Two genomewide association studies of predominantly sporadic but also familial cases of TGCT have implicated the KIT-ligand, SPRY4, and BAK1 genes as TGCT risk modifiers. All five loci are involved in normal testicular development and/or male infertility. These genetic data provide a novel insight into the genetic basis of FTGCT, and an invaluable guide to future TGCT research.

scholarly journals Towards a Central Role of ISL1 in the Bladder Exstrophy–Epispadias Complex (BEEC): Computational Characterization of Genetic Variants and Structural Modelling

Genes ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 609 ◽  
Author(s):  
Amit Sharma ◽  
Tikam Dakal ◽  
Michael Ludwig ◽  
Holger Fröhlich ◽  
Riya Mathur ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Association Studies ◽  
Critical Role ◽  
Susceptibility Gene ◽  
Bladder Exstrophy ◽  
Sequence Variants ◽  
Genome Wide Association Studies ◽  
Sequence Motifs ◽  
Conserved Sequence

Genetic factors play a critical role in the development of human diseases. Recently, several molecular genetic studies have provided multiple lines of evidence for a critical role of genetic factors in the expression of human bladder exstrophy-epispadias complex (BEEC). At this point, ISL1 (ISL LIM homeobox 1) has emerged as the major susceptibility gene for classic bladder exstrophy (CBE), in a multifactorial disease model. Here, GWAS (Genome wide association studies) discovery and replication studies, as well as the re-sequencing of ISL1, identified sequence variants (rs9291768, rs6874700, c.137C > G (p.Ala46Gly)) associated with CBE. Here, we aimed to determine the molecular and functional consequences of these sequence variants and estimate the dependence of ISL1 protein on other predicted candidates. We used: (i) computational analysis of conserved sequence motifs to perform an evolutionary conservation analysis, based on a Bayesian algorithm, and (ii) computational 3D structural modeling. Furthermore, we looked into long non-coding RNAs (lncRNAs) residing within the ISL1 region, aiming to predict their targets. Our analysis suggests that the ISL1 protein specific N-terminal LIM domain (which harbors the variant c.137C > G), limits its transcriptional ability, and might interfere with ISL1-estrogen receptor α interactions. In conclusion, our analysis provides further useful insights about the ISL1 gene, which is involved in the formation of the BEEC, and in the development of the urinary bladder.

The Epidemiology of the Genetic Liability for Schizophrenia

2000 ◽  
Vol 34 (1_suppl) ◽  
pp. A47-A55 ◽  
Author(s):  
Joachim Hallmayer
Keyword(s):  
Large Scale ◽  
Genetic Factors ◽  
Association Studies ◽  
Molecular Genetic ◽  
Positive Family History ◽  
Adoption Studies ◽  
Genetic Liability ◽  
Risk Increase ◽  
Increased Risk ◽  
Prevention Trials

Objective The low incidence of schizophrenia prohibits large scale prevention trials, and the question arises whether such studies become more feasible by taking into account genetic factors. The aim of the paper was to inform preventive endeavours with an account of the genetic background to schizophrenia. Method The family, twin and adoptive studies of schizophrenia are reviewed and recent molecular genetic data presented. Results Children of a parent diagnosed with schizophrenia have a ten-fold increased risk of developing the disorder. Twin and adoption studies strongly suggest the risk increase is mainly due to genetic factors. On an individual level, a positive family history is the strongest known risk factor for schizophrenia. For a prevention study, very large numbers of families have to be screened in order to reach a sufficient sample size. Conclusions One obvious way to increase the accuracy of predicting who is at high risk of developing schizophrenia would be to find specific mutations in the human genome. Attempts to isolate specific genes by means of linkage and association studies have been unsuccessful so far and, given the number of genes involved, it is extremely unlikely that the predictive value of individual genes will be high enough to warrant intervention. Genetic studies also suggest the genetic liability extends beyond the traditional clinical phenotypes. Prevention trials might become possible by adopting a broader approach.

Dilated Cardiomyopathy in Standard Schnauzers: Retrospective Study of 15 Cases

2017 ◽  
Vol 53 (1) ◽  
pp. 38-44 ◽  
Author(s):  
Mark W. Harmon ◽  
Stacey B. Leach ◽  
Kenneth E. Lamb
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Medical Records ◽  
Autosomal Recessive ◽  
Age Of Onset ◽  
Pedigree Analysis ◽  
Common Ancestry ◽  
Autosomal Recessive Mode ◽  
Familial Predisposition ◽  
Mode Of Inheritance

ABSTRACT Dilated cardiomyopathy (DCM) is the most common myocardial disorder of dogs, typically affecting large and giant breeds. The purpose of this study was to describe the clinical features of DCM in standard schnauzers. Medical records for 15 standard schnauzers diagnosed with DCM were reviewed. The median age at diagnosis of DCM was 1.6 yr, with all dogs developing left-sided congestive heart failure (CHF). The median age of onset of CHF was 1.6 yr, and was significantly shorter in males (1.5 yr) than for females (2.35 yr). The median survival time after diagnosis of CHF was 22 days, and was shorter in males (13 days) than females (62 days). The occurrence of early onset DCM in multiple closely related standard schnauzers suggests a familial predisposition in this breed. Pedigree analysis confirmed common ancestry for all DCM affected dogs with a most likely autosomal recessive mode of inheritance.

scholarly journals Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ionel Sandovici ◽  
Constanze M. Hammerle ◽  
Sam Virtue ◽  
Yurena Vivas-Garcia ◽  
Adriana Izquierdo-Lahuerta ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Homeostasis ◽  
Association Studies ◽  
Susceptibility Gene ◽  
Chow Diet ◽  
Genome Wide Association Studies ◽  
Cell Plasticity ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

AbstractWhen exposed to nutrient excess and insulin resistance, pancreatic β-cells undergo adaptive changes in order to maintain glucose homeostasis. The role that growth control genes, highly expressed in early pancreas development, might exert in programming β-cell plasticity in later life is a poorly studied area. The imprinted Igf2 (insulin-like growth factor 2) gene is highly transcribed during early life and has been identified in recent genome-wide association studies as a type 2 diabetes susceptibility gene in humans. Hence, here we investigate the long-term phenotypic metabolic consequences of conditional Igf2 deletion in pancreatic β-cells (Igf2βKO) in mice. We show that autocrine actions of IGF2 are not critical for β-cell development, or for the early post-natal wave of β-cell remodelling. Additionally, adult Igf2βKO mice maintain glucose homeostasis when fed a chow diet. However, pregnant Igf2βKO females become hyperglycemic and hyperinsulinemic, and their conceptuses exhibit hyperinsulinemia and placentomegalia. Insulin resistance induced by congenital leptin deficiency also renders Igf2βKO females more hyperglycaemic compared to leptin-deficient controls. Upon high-fat diet feeding, Igf2βKO females are less susceptible to develop insulin resistance. Based on these findings, we conclude that in female mice, autocrine actions of β-cell IGF2 during early development determine their adaptive capacity in adult life.

Effect of Marriage on Pre-existing Psychoses: A Convenient or Futile Solution for Severe Mental Disorders?

2020 ◽  
Vol 2 (3-4) ◽  
pp. 273-276
Author(s):  
Prakash B. Behere ◽  
Aniruddh P. Behere ◽  
Debolina Chowdhury ◽  
Amit B. Nagdive ◽  
Richa Yadav
Keyword(s):  
Mental Disorders ◽  
Age Of Onset ◽  
Social Stigma ◽  
Positive Family History ◽  
Mental Illnesses ◽  
Psychotic Symptoms ◽  
Antipsychotic Treatment ◽  
Contractual Relationship ◽  
History Of ◽  
Paranoid Type

Marriage can be defined as the state of being united as spouses in a consensual and contractual relationship recognized by law. The general population generally believes marriage to be a solution to mental illnesses. It can be agreed that mental disorders and marital issues have some relation. Parents of patients with psychoses expect that marriage is the solution to the illness and often approach doctors and seek validation about the success of the marriage of their mentally ill child, which is a guarantee no doctor can give in even normal circumstances. Evidence on sexual functioning in patients of psychosis is limited and needs further understanding. Studies show about 60%–70% women of the schizophrenia spectrum and illness to experience sexual difficulties. Based on available information, sexual dysfunction in population with psychosis can be attributed to a variety of psychosocial factors, ranging from the psychotic symptoms in itself to social stigma and institutionalization and also due to the antipsychotic treatment. Despite the decline in sexual activity and quality of life in general, it is very rarely addressed by both the treating doctor and by the patient themselves hence creating a lacuna in the patient’s care and availability of information regarding the illness’ pathophysiology. Patients become noncompliant with medications due to this undesirable effect and hence it requires to be given more attention during treatment. It was also found that paranoid type of schizophrenia patient had lower chances of separation than patients with other types of schizophrenia. The risk of relapse in cases with later age of onset of the disease, lower education, a positive family history of psychosis or a lower income increased more than other populations.

scholarly journals Genetic Determinants of Paget’s Disease of Bone

2021 ◽  
Author(s):  
Navnit S. Makaram ◽  
Stuart H. Ralston
Keyword(s):  
Genetic Factors ◽  
Association Studies ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Genome Wide Association Studies ◽  
Paget's Disease Of Bone ◽  
Genome Wide ◽  
Family Based

Abstract Purpose of Review To provide an overview of the role of genes and loci that predispose to Paget’s disease of bone and related disorders. Recent Findings Studies over the past ten years have seen major advances in knowledge on the role of genetic factors in Paget’s disease of bone (PDB). Genome wide association studies have identified six loci that predispose to the disease whereas family based studies have identified a further eight genes that cause PDB. This brings the total number of genes and loci implicated in PDB to fourteen. Emerging evidence has shown that a number of these genes also predispose to multisystem proteinopathy syndromes where PDB is accompanied by neurodegeneration and myopathy due to the accumulation of abnormal protein aggregates, emphasising the importance of defects in autophagy in the pathogenesis of PDB. Summary Genetic factors play a key role in the pathogenesis of PDB and the studies in this area have identified several genes previously not suspected to play a role in bone metabolism. Genetic testing coupled to targeted therapeutic intervention is being explored as a way of halting disease progression and improving outcome before irreversible skeletal damage has occurred.

Power comparison of Cochran-Armitage trend test against allelic and genotypic tests in large-scale case-control genetic association studies

2016 ◽  
Vol 27 (9) ◽  
pp. 2657-2673 ◽  
Author(s):  
Mathieu Emily
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Disease Model ◽  
Trend Test ◽  
Genome Wide Association Studies ◽  
Power Functions ◽  
Power Comparison ◽  
Powerful Test ◽  
Armitage Trend Test ◽  
Mode Of Inheritance

The Cochran-Armitage trend test (CA) has become a standard procedure for association testing in large-scale genome-wide association studies (GWAS). However, when the disease model is unknown, there is no consensus on the most powerful test to be used between CA, allelic, and genotypic tests. In this article, we tackle the question of whether CA is best suited to single-locus scanning in GWAS and propose a power comparison of CA against allelic and genotypic tests. Our approach relies on the evaluation of the Taylor decompositions of non-centrality parameters, thus allowing an analytical comparison of the power functions of the tests. Compared to simulation-based comparison, our approach offers the advantage of simultaneously accounting for the multidimensionality of the set of features involved in power functions. Although power for CA depends on the sample size, the case-to-control ratio and the minor allelic frequency (MAF), our results first show that it is largely influenced by the mode of inheritance and a deviation from Hardy–Weinberg Equilibrium (HWE). Furthermore, when compared to other tests, CA is shown to be the most powerful test under a multiplicative disease model or when the single-nucleotide polymorphism largely deviates from HWE. In all other situations, CA lacks in power and differences can be substantial, especially for the recessive mode of inheritance. Finally, our results are illustrated by the comparison of the performances of the statistics in two genome scans.

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