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Genetic Investigations (genetic + investigation)
Kinds of Genetic Investigations Selected AbstractsHighly variable microsatellite loci for studies of introduced populations of the small Indian mongoose (Herpestes javanicus)MOLECULAR ECOLOGY RESOURCES, Issue 4 2002C.-G. Thulin Abstract During their introduction, non-native species typically undergo founder events that reduce genetic variation. To allow a high-resolution genetic investigation of introduced populations of the small Indian mongoose (Herpestes javanicus), we developed primers for nine variable microsatellite loci. Their applicability was assessed in 10 mongooses from the large Fijian population, which originated from a single pair from Calcutta, India. The number of alleles ranged from two to five per locus, possibly as a result of preservation of initial variability and in situ mutations during the rapid population expansion after introduction. [source] Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients susceptible to malignant hyperthermia who show definite IVCT results: identification of three novel mutationsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2002H. Rueffert Background: The ryanodine receptor of the skeletal muscle (RYR1) seems to be of outstanding importance in the pathogenesis of malignant hyperthermia (MH). It has been shown that point mutations in the RYR1 gene are strongly associated with the MH phenotype. A correctly determined phenotype is the basic prerequisite for adequate genetic MH screening. In this study we examined only those MH susceptible patients for the presence of potential RYR1 mutations who showed strong pathological muscle responses in the in vitro contracture test (IVCT). Methods: A total of 56 MHS index patients who complied with the following IVCT criteria were included in the molecular genetic investigation: Contracture forces ,4 mN at a caffeine concentration of 2.0 mmol/l and ,8 mN at a halothane concentration of 0.44 mmol/l. DNA sequences of exons 2, 6, 9, 11, 12, 14, 15, 17, 39, 40, 45, 46, 102 of the RYR1 gene were analysed by the direct sequencing technique. Furthermore, if an MH mutation was identified in an index patient, all relatives were screened for their family specific RYR1 defect. Results: In 39 index patients an RYR1 mutation was detected: Arg163Cys (n = 2), Asp166Asn (n = 1), Gly341Arg (n = 2), Arg401His (n = 2), Arg614Cys (n = 12), Asp2129Glu (n = 1),Vol2168Met (n = 1), Thr2206Met (n = 9), Ala2428Thr (n = 1), Gly2434Arg (n = 2), Arg2435His (n = 1), Arg2452Trp (n = 1), Arg2454His (n = 4). Three new RYR1 mutations were identified. We found a potential MH mutation in a further 130 relatives of the 39 index patients. Thirty-seven individuals were classified as MHS exclusively by molecular genetic techniques and did not have to undergo the IVCT. Conclusions: The ascertained high rate of successful MH mutation screening (69.64%) is obviously associated with the more clearly defined MHS diagnosis in the IVCT. According to the EMHG guidelines for the molecular genetic detection of MH susceptibility, a positive MH disposition could be determined in numerous persons by a less invasive technique. [source] Spastic Paraplegia, Optic Atrophy, and Neuropathy: New Observations, Locus Refinement, and Exclusion of Candidate GenesANNALS OF HUMAN GENETICS, Issue 3 2009Lúcia Inęs Macedo-Souza Summary SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with marker D11S1889). Three genes located in this newly defined critical region were sequenced, but no pathogenic mutation was detected. The gene responsible for SPOAN remains elusive. [source] Investigation of Adducin 2 (beta) DNA polymorphisms in genetic predisposition to diabetic nephropathy in Type 1 diabetesDIABETIC MEDICINE, Issue 8 2008D. Currie Abstract Aims Adducin 2 (beta) (ADD2) is a biological and positional candidate gene proposed to confer genetic risk for diabetic nephropathy. This study aimed to comprehensively investigate all common and putatively functional polymorphisms in the genomic region encompassing this gene. Methods Tag single nucleotide polymorphisms (n = 23) derived from phase II of the International HapMap Project and in silico functional variants (n = 2) were genotyped in 1467 White individuals from the British Isles (cases, n = 718; control subjects, n = 749) by a combination of Sequenom iPLEX and TaqMan technologies. Results ,2 analysis of genotype and allele frequencies in cases vs. control subjects revealed weak evidence for association of one variant at the 5% level of significance (rs10164951, P = 0.02). Adjusting for multiple testing in the present case,control collection negated this association. Conclusions We selected an appropriate subset of variants suitable for genetic investigations of the ADD2 gene and report the first investigation of polymorphisms in ADD2 with diabetic nephropathy. Our results suggest that common polymorphisms and putatively functional variants in the ADD2 gene do not strongly influence genetic susceptibility to diabetic nephropathy in this White population with Type 1 diabetes. [source] Genetic aspects of pathological gambling: a complex disorder with shared genetic vulnerabilitiesADDICTION, Issue 9 2009Daniela S. S. Lobo ABSTRACT Aims To summarize and discuss findings from genetic studies conducted on pathological gambling (PG). Methods Searches were conducted on PubMed and PsychInfo databases using the keywords: ,gambling and genes', ,gambling and family' and ,gambling and genetics', yielding 18 original research articles investigating the genetics of PG. Results Twin studies using the Vietnam Era Twin Registry have found that: (i) the heritability of PG is estimated to be 50,60%; (ii) PG and subclinical PG are a continuum of the same disorder; (iii) PG shares genetic vulnerability factors with antisocial behaviours, alcohol dependence and major depressive disorder; (iv) genetic factors underlie the association between exposure to traumatic life-events and PG. Molecular genetic investigations on PG are at an early stage and published studies have reported associations with genes involved in the brain's reward and impulse control systems. Conclusions Despite the paucity of studies in this area, published studies have provided considerable evidence of the influence of genetic factors on PG and its complex interaction with other psychiatric disorders and environmental factors. The next step would be to investigate the association and interaction of these variables in larger molecular genetic studies with subphenotypes that underlie PG. Results from family and genetic investigations corroborate further the importance of understanding the biological underpinnings of PG in the development of more specific treatment and prevention strategies. [source] Response to intraarterial induction chemotherapy: A prognostic parameter in oral and oropharyngeal cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2006Adorján F. Kovács MD Abstract Background. Patients with head and neck cancer and good pathologic response to neoadjuvant systemic induction chemotherapy have a better prognosis for survival than do those with stable or progressive disease. Thus, induction chemotherapy could theoretically help in stratifying further treatment, but toxicity is much too high. The prognostic implication of superselective intraarterial high-dose cisplatin administered by a femoral approach, which has much less toxicity, is not yet known. Methods. One hundred eighty-seven unselected consecutive patients with previously untreated oral and oropharyngeal squamous cell carcinoma received intraarterial high-dose cisplatin for induction and were assessed for response by visual examination and palpation. This treatment was followed by surgery and adjuvant radiation with concomitant systemic chemotherapy. Omission of a modality depended on individual contraindications and not on preselection. The consequence of omissions has been the constitution of several treatment arms. The overall and disease-free survival in relation to clinical local response after intraarterial induction chemotherapy was calculated using the Kaplan,Meier method. Additional analysis excluded bias caused by stages and treatment arms. Results. Explorative statistics using the log-rank and chi-square tests demonstrated a strong prognostic relevance of response to intraarterial chemotherapy irrespective of stage and treatment. Conclusions. Our results are encouraging for prospective randomized studies and molecular genetic investigations with intraarterial chemotherapy. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] Annotated chromosome maps for renal disease,HUMAN MUTATION, Issue 3 2009Amy Jayne McKnight Abstract A combination of linkage analyses and association studies are currently employed to promote the identification of genetic factors contributing to inherited renal disease. We have standardized and merged complex genetic data from disparate sources, creating unique chromosomal maps to enhance genetic epidemiological investigations. This database and novel renal maps effectively summarize genomic regions of suggested linkage, association, or chromosomal abnormalities implicated in renal disease. Chromosomal regions associated with potential intermediate clinical phenotypes have been integrated, adding support for particular genomic intervals. More than 500 reports from medical databases, published scientific literature, and the World Wide Web were interrogated for relevant renal-related information. Chromosomal regions highlighted for prioritized investigation of renal complications include 3q13,26, 6q22,27, 10p11,15, 16p11,13, and 18q22. Combined genetic and physical maps are effective tools to organize genetic data for complex diseases. These renal chromosome maps provide insights into renal phenotype-genotype relationships and act as a template for future genetic investigations into complex renal diseases. New data from individual researchers and/or future publications can be readily incorporated to this resource via a user-friendly web-form accessed from the website: www.qub.ac.uk/neph-res/CORGI/index.php. Hum Mutat 0, 1,8, 2008. © 2008 Wiley-Liss, Inc. [source] Is late onset depression a prodrome to dementia?INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 11 2002Isaac Schweitzer Abstract Background Recent research suggests there are clinical and biological differences between late onset depression (LOD) and early-onset depression (EOD). Objectives In this paper we review clinical, epidemiological, structural neuroimaging and genetic investigations of late life depression that have been performed over the past two decades and offer evidence that LOD is often a prodromal disorder for dementia. Results LOD patients are more likely to have cognitive impairment and to have more deep white matter lesions (DWMLs). Evidence concerning cortical and temporal lobe atrophy is conflicting, while the ApoE 4 allele is not associated with LOD. Conclusions It is likely that LOD is not a prodrome for a particular type of dementia, but the majority of patients who do develop dementia will acquire Alzheimer's disease (AD) or a vascular dementia, as these are by far the most common causes of dementia. This issue requires further clarification with follow-up of patients over the long term. Copyright © 2002 John Wiley & Sons, Ltd. [source] Parents of Children with Intellectual Disabilities: Their Expectations and Experience of Genetic CounsellingJOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES, Issue 3 2003Owen Barr Background, Following the birth of a child, parents and other family members have to adapt to their new circumstances. This process takes time and can become more complex when the child is suspected or diagnosed as having intellectual disabilities. When a child has a disability, parents often seek answers as to the origin and nature of the condition as part of the adaptation process. For some parents, this will result in genetic investigations and could lead to the provision of personal genetics about the child and parents. Materials and methods, This paper reports a mixed-method project that combined questionnaires prior to and interviews after an appointment with a geneticist. The project sought to identify the expectations and experience of parents who had a child referred to specialist genetics services. Results and conclusions, The findings identify that parents felt largely unprepared for their appointment and reported feelings of failing to maximize the opportunity present. The need for more effective liaison between specialist regional and local primary care and learning disability services is also highlighted. Parents made practical suggestions relevant to all the above services about how they could be better supported at this difficult stage in the adaptation process. [source] Canine inhertited retinal degenerations: update on molecular genetic research and its clinical applicationJOURNAL OF SMALL ANIMAL PRACTICE, Issue 10 2002C-T. Lin Inherited retinal degenerations in the dog include generalized progressive retinal atrophy, retinal pigment epithelial dystrophy, congenital stationary night blindness and day blindness (hemeralopia). The clinical phenotype and pathology of these diseases closely resemble some types of human inherited retinal degeneration, in particular retinitis pigmentosa, one of the most common inherited causes of blindness in man. Molecular genetic investigations aim to identify the genetic mutations underlying the canine inherited retinal degenerations. Two major research strategies, candidate gene analysis and linkage analysis, have been used. To date, candidate gene analysis has definitively identified the genetic mutations underlying nine inherited retinal degenerations, each in a different breed of dog, and linkage studies have identified genetic markers for a further retinal degeneration which is found in at least six different breeds. This review outlines the research strategy behind candidate gene and linkage studies and summarises recent results in the search for genetic causes of canine inherited retinal degenerations. The aim is to increase awareness of this rapidly changing field and to show how the research can be used to develop genetic tests for these diseases and thereby reduce the incidence of inherited eye disease in dogs. [source] Diagnosis of malignant hyperthermia susceptibility during CABG surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2003T. Girard A 55-year-old man presented for coronary artery bypass graft (CABG) surgery. Malignant hyperthermia (MH) was suspected in his family. This case report describes a diagnostic approach to obtain a definite MH diagnosis by performing an in vitro contracture test at the time of CABG surgery in combination with molecular genetic investigations. [source] Characterization of novel sugarcane expressed sequence tag microsatellites and their comparison with genomic SSRsPLANT BREEDING, Issue 4 2006L. R. Pinto Abstract Microsatellites or simple sequence repeats (SSRs) are one of the most suitable markers for genome analysis as they have great potential to aid breeders to develop new improved sugarcane varieties. The development of SSR derived from expressed sequence tags (EST) opens new opportunities for genetic investigations at a functional level. In the present work, the polymorphism obtained with a subset of 51 EST,SSRs derived from sucest was compared with those generated by 50 genomic SSRs (gSSR) in terms of number of alleles, polymorphism information content, discrimination power and their ability to establish genetic relationships among 18 sugarcane clones including three Saccharum species (S. officinarum, S. barberi, S. sinense). The majority of EST,SSRs loci had four to six alleles in contrast to the seven to nine observed for the gSSRs loci. Approximately, 35% of the gSSRs had PIC values around 0.90 in contrast to 15% of the EST,SSRs. However, the mean discrimination power of the two types of SSR did not differ significantly as much as the average genetic similarity (GS) based on Dice coefficient. The correlation between GS of the two types of SSRs was high (r = 0.71/P = 0.99) and significant. Although differences were observed between dendrograms obtained with each SSR type, both were in good agreement with pedigree information. The S. officinarum clone IJ76-314 was grouped apart from the other clones evaluated. The results here demonstrate that EST,SSRs can be successfully used for genetic relationship analysis, extending the knowledge of genetic diversity of sugarcane to a functional level. [source] First Evidence of Genetic Imbalances in AngiofibromasTHE LARYNGOSCOPE, Issue 2 2002Bernhard Schick MD Abstract Objective/Hypothesis Angiofibromas are clinically well characterized by their origin at the posterior lateral nasal wall close to the sphenopalatine foramen, their occurrence in male adolescent patients, and the histological findings of a benign fibrovascular neoplasm with irregular, endothelium-lined vascular spaces in a fibrous stroma. However, their etiology and genetic causes remain unknown. The present study addresses genetic imbalances in angiofibromas. Study Design The present pilot study compared genomic hybridization in three angiofibromas to search for chromosomal abnormalities in this rare tumor. Methods Fluorescence-marked normal DNA and angiofibroma DNA were compared using genomic hybridization screening to detect chromosomal abnormalities. Their binding ratio to metaphase chromosomes were analyzed by special digital image analysis. Results Chromosomal gains and losses showing a high level of agreement were detected in all three angiofibromas. Specifically, DNA gains were observed on chromosomes 3q, 4q, 5q, 6q, 7q, 8q, 12p, 12q, 13q, 14q, 18q, 21q, and X, and DNA losses were screened on chromosomes 17, 19p, 22q, and Y. Finding chromosomal abnormalities at the sex chromosomes X and Y of this rare tumor is remarkable. Concurrent chromosomal gain on 8q12q22 was noted in all three tumor specimens. Conclusions Comparative genomic hybridization is suitable for screening angiofibromas on a genetic level. The results on these screens indicate that further genetic investigations of this rare benign tumor may provide more details about the tumor's genetic abnormalities and perhaps clarify the etiology of angiofibromas. [source] Genetics and delusional disorderBEHAVIORAL SCIENCES & THE LAW, Issue 3 2006Alastair G. Cardno M.B., M.R.C.Psych., Ph.D. This article gives an overview of genetic research approaches and their application to delusional disorder. Most studies have been based on small samples and have had other methodological limitations, so it is not clear whether there is a genetic contribution to the aetiology of delusional disorder. It is unlikely that delusional disorder is strongly related genetically to affective disorder or schizophrenia, but more subtle relationships cannot be ruled out. The rarity of multiply affected families prohibits linkage studies and, to date, molecular genetic investigations have been mainly limited to small association studies of dopamine receptor polymorphisms. A range of considerably larger, epidemiologically rigorous studies is required, but the uncommonness and other features of the disorder put strong limitations on the prospects for ascertaining adequate samples. Copyright © 2006 John Wiley & Sons, Ltd. [source] Hagfish embryos again,the end of a long droughtBIOESSAYS, Issue 9 2007Nicholas D. Holland Hagfishes have long held a key place in discussions of early vertebrate evolution. Frustratingly, one basis for such discussions,namely hagfish embryology,is very incompletely known, because the embryos of these animals are notoriously difficult to obtain.1,2 Fortunately, a recent publication on a Far Eastern hagfish3 describes a workable procedure for obtaining embryos and then uses this precious material to show that the hagfish neural crest arises by cell delamination as in other vertebrates,and not by epithelial outpouchings from the wall of the neural tube as previously claimed.4 Importantly, because hagfish embryos should now be available on a regular basis, the way is open for additional morphological and developmental genetic investigations to help evaluate existing evolutionary scenarios and perhaps suggest new ones. BioEssays 29:833,836, 2007. © 2007 Wiley Periodicals, Inc. [source] Recombinant human TSH testing is a valuable tool for differential diagnosis of congenital hypothyroidism during l -thyroxine replacementCLINICAL ENDOCRINOLOGY, Issue 2 2003Laura Fugazzola Summary objective The differential diagnosis of congenital hypothyroidism (CH) is aimed to distinguish transitory from permanent forms, to optimize l-thyroxine (l-T4) therapy to replacement or TSH-suppressive regimens, and to reach accurate definition of the clinical and biochemical phenotype for subsequent genetic investigations and counselling. Therefore, l -T4 therapy is presently withdrawn in most instances and investigations are performed in a disturbing hypothyroid state. design The availability of recombinant human TSH (rhTSH) prompted us to assess its efficacy in the differential diagnosis of CH during l-T4 therapy. patients and measurements Eight adult patients with permanent CH remained on l -thyroxine and underwent a new protocol for rhTSH (Thyrogen®) testing with injections [4 g/kg/day intramuscularly (i.m.)] at days 1, 2 and 3. At day 3, 123I was administered and uptake obtained after 2 and 24 h. Serum TSH and thyroglobulin (Tg) levels were measured at days 1,4. Neck ultrasound was carried out in all cases. results Serum TSH reached levels > 20 mU/l at day 2 and remained above 30 mU/l on days 3 and 4. Stimulation of Tg levels was seen in five patients with peak at day 4. Lingual thyroid was documented at scintigraphy (TS) in three Tg-responsive patients who were previously diagnosed as having thyroid agenesia. In one patient with dyshormonogenesis and high Tg, TS confirmed the presence of goitre with positive perchlorate test. TS was negative in the remaining four cases. All tests indicated complete agenesia in one, whereas a minimal Tg response was marker of nearly complete agenesia in another. The last two TS-negative patients had hypoplastic glands at ultrasound, and refractoriness to TSH stimulation was confirmed by absent Tg response. conclusions We report the first application of rhTSH for differential diagnosis of patients with permanent CH, avoiding the undesirable transient hypothyroidism consequent to l-T4 withdrawal. The data obtained led to the change of the diagnosis at presentation in 4/8 patients and to a more accurate description of the clinical picture in all patients. The proposed protocol has been proved to cause Tg increases even in the presence of small amounts of responsive thyroid cells. The rhTSH testing led to the desired disease characterization, thus allowing specific management and targeted genetic analyses. [source] | |||||||||||||