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Medical Genetics (medical + genetics)
Selected AbstractsInterleukin-1 receptor antagonist and tumour necrosis factor-alpha gene polymorphisms in Turkish patients with allergic contact dermatitisCONTACT DERMATITIS, Issue 2 2009Ilgen Ertam Background: It has been shown that the family of interleukin-1 receptor antagonist (IL-1 RA) and tumour necrosis factor-alpha (TNF,) genes are polymorphic and related to some inflammatory diseases. Allergic contact dermatitis is the classic presentation of delayed-type hypersensitivity responses to exogenous agents. A number of genes playing role in inflammatory response may be associated with allergic contact dermatitis. Objectives: To investigate whether there is an association between IL-1RA and TNF, gene polymorphisms and allergic contact dermatitis in Turkish patients with allergic contact dermatitis. Methods: This study was performed by the collaboration of Departments of Dermatology and Medical Genetics, Ege University, Faculty of Medicine. A total of 50 patients (31 females and 19 males) with allergic contact dermatitis, and 100 age- and sex-matched controls (58 females and 42 males) were included in the study. IL-1RA Variable Number of Tandem Repeats (VNTR) polymorphism in intron 2 and TNF,-308G-A polymorphism were genotyped by using polymerase chain reaction and agarose gel electrophoresis. Results: The frequency of IL-1RA 1/2 (48%) genotype was significantly higher (P = 0.002) in patient group than that is found in control group (22%). The frequency of TNF, (TNF G-308A) G/G genotype was significantly higher in patient group (68%) than that is found in control group (31%) (P = 0.008). Conclusions: Our findings suggest that TNF, (G/G) gene polymorphism may play role in susceptibility to allergic contact dermatitis in Turkish patients. [source] Companion Animal Medicine in the Age of Medical GeneticsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2000Donald F. Patterson We'd like to explain what pathology means, In terms of what's wrong with the structure of genes; Know if a control or a structural locus Constitutes the exact pathological focus. With the help of the enzymes that slice DNA, And cloning techniques, we now have a way To study the actual sequence of bases; To know when those purines are not in their places.1 [source] Imprinted genes and human disease,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2010Rosanna Weksberg Abstract This issue of Seminars of Medical Genetics features a series of articles on human disorders caused by the dysregulation of imprinted genes. At the outset, there is a review of the general mechanisms by which genomic imprinting is normally regulated followed by an exploration of the clinical and molecular aspects of human imprinting disorders. As we enter an era of bioinformatics and genome-wide analyses with increasing access to high density microarrays and next generation sequencing, it is becoming apparent that the concept of a single mutation or epimutation leading to a disease is outdated. The role of the clinician will become increasingly important, in concert with these molecular advances, in terms of evaluating phenotypic variation to further our understanding of imprinting disorders. Such investigations will benefit children and families as we become better able to define recurrence risk, predict phenotype, and tailor medical management. © 2010 Wiley-Liss, Inc. [source] Identification and prioritization of quality indicators in clinical genetics: An international survey,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2009Barbara C. Zellerino Abstract The range and demand for clinical genetic services will continue to grow, and now is an ideal time to assess current service quality. Based on the previous work of quality professional organizations such as the Institute of Medicine (IOM) and The Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) which is now known as The Joint Commission (TJC), an independent group of genetic and healthcare quality professionals (InheritQual) drafted and defined a list of potential quality indicators for clinical genetics. Perspectives on the appropriateness and the practicality of each indicator were surveyed and analyzed. The Quality Special Interest Group of the American College of Medical Genetics (ACMG) chartered the survey results. After measuring the degree of consensus, an expert panel was selected to review the quality indicators based on practicality and applicability. This expert panel comprised of members of the ACMG Quality Sig workgroup met for final consensus and developed a methodology to pilot these indicators. © 2009 Wiley-Liss, Inc. [source] Evidence-based medicine and practice guidelines: Application to genetics,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2009Helga V. Toriello Abstract The Professional Practice and Guidelines Committee of the American College of Medical Genetics has the responsibility of overseeing the development of guidelines for the practice of clinical genetics. In the past, most, if not all, guidelines were primarily based on expert opinion. However, recently the goal has become to develop guidelines that are more evidence-based, or at least, to recognize the level of evidence available to the authors of these documents. This article reviews the challenges that are faced by geneticists who are charged with the development of practice guidelines. © 2009 Wiley-Liss, Inc. [source] Validation of DNA probes for preimplantation genetic diagnosis (PGD) by fluorescence in situ hybridization (FISH) R1PRENATAL DIAGNOSIS, Issue 11 2006Stanislawa Weremowicz Abstract Background Preimplantation genetic diagnosis (PGD) by fluorescence in situ hybridization (FISH) is being employed increasingly by medical centers and private companies. Validation of any clinical assay, particularly one with novel applications such as PGD by FISH, is of critical importance in the clinical setting. This importance is recognized by both the College of American Pathologists (CAP) and the American College of Medical Genetics (ACMG), who recommend validation of FISH assays in the clinical setting. Validation of FISH assays for PGD is especially significant, as only one or two cells (blastomeres) will be available for testing of a given embryo. Methods We have developed validation protocols for a variety of FISH assays, including sex identification, structural chromosomal aneusomy, and aneuploidy screening with the Vysis, Inc., PGT probe panel. Results Our validation results show good individual performance of commercially available probes, and decreasing overall efficiency as the number of probes included in an assay increases. Copyright © 2006 John Wiley & Sons, Ltd. [source] Diagnostic evaluation of developmental delay/mental retardation: An overviewAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2003Agatino Battaglia Abstract Mental retardation (MR) is one of the few clinically important disorders for which the etiopathogenesis is still poorly understood. It is a condition of great concern for public health and society. MR is currently defined as a significant impairment of cognitive and adaptive functions, with onset before age 18 years. It may become evident during infancy or early childhood as developmental delay (DD), but it is best diagnosed during the school years. MR is estimated to occur in 1,10% of the population, and research on its etiology has always been a challenge in medicine. The etiopathogenesis encompasses so many different entities that the attending physician can sometimes feel a "virtual panic," starting a wide-range diagnostic evaluation. The Consensus Conference of the American College of Medical Genetics has recently established guidelines regarding the evaluation of patients with MR [Curry et al., 1997], emphasizing the high diagnostic utility of cytogenetic studies and neuroimaging in certain clinical settings. However, since then there has been substantial progress in molecular cytogenetics and neuroimaging techniques, the use of which has allowed recognition and definition of new disorders, thus increasing the diagnostic yield. This review will focus on the most appropriate investigations shown to be, at present, necessary to define the etiology of DD/MR, in the context of recommendations for the clinical evaluation of the patient with undiagnosed MR. © 2003 Wiley-Liss, Inc. [source] Epidemiology of Huntington's disease in SloveniaACTA NEUROLOGICA SCANDINAVICA, Issue 6 2009B. Peterlin Objectives,,, The objective of this study was to estimate the prevalence of Huntington's disease (HD) in Slovenia using direct mutation analysis. Materials and methods,,, Symptomatic patients and presymptomatic individuals at risk for HD referred to the Institute of Medical Genetics between 1997 and 2007 were included in the study. The patients were ascertained through multiple sources. The prevalence was estimated on 31 December 2006. Results,,, A total of 116 and 68 individuals with CAG repeat number >36 were symptomatic and presymptomatic, respectively. The prevalence of HD in Slovenia was estimated at 5.16/105 (95% confidence interval 4.16,6.16). Conclusions,,, This is the first report on the epidemiology and prevalence of HD in Slovenia. The prevalence of HD is comparable with previously reported data in other European countries. In Slovenia, a higher proportion of individuals at risk for HD decide on predictive mutational testing as compared with the estimated numbers for Europe, United States, Canada and Australia. [source] Adapting the logical basis of tests for Hardy-Weinberg Equilibrium to the real needs of association studies in human and medical geneticsGENETIC EPIDEMIOLOGY, Issue 7 2009Katrina A. B. Goddard Abstract The standard procedure to assess genetic equilibrium is a ,2 test of goodness-of-fit. As is the case with any statistical procedure of that type, the null hypothesis is that the distribution underlying the data is in agreement with the model. Thus, a significant result indicates incompatibility of the observed data with the model, which is clearly at variance with the aim in the majority of applications: to exclude the existence of gross violations of the equilibrium condition. In current practice, we try to avoid this basic logical difficulty by increasing the significance bound to the P -value (e.g. from 5 to 10%) and inferring compatibility of the data with Hardy Weinberg Equilibrium (HWE) from an insignificant result. Unfortunately, such direct inversion of a statistical testing procedure fails to produce a valid test of the hypothesis of interest, namely, that the data are in sufficiently good agreement with the model under which the P -value is calculated. We present a logically unflawed solution to the problem of establishing (approximate) compatibility of an observed genotype distribution with HWE. The test is available in one- and two-sided versions. For both versions, we provide tools for exact power calculation. We demonstrate the merits of the new approach through comparison with the traditional ,2 goodness-of-fit test in 2×60 genotype distributions from 43 published genetic studies of complex diseases where departure from HWE was noted in either the case or control sample. In addition, we show that the new test is useful for the analysis of genome-wide association studies. Genet. Epidemiol. 33:569,580, 2009. © 2009 Wiley-Liss, Inc. [source] Phenotology of disease-linked proteins,HUMAN MUTATION, Issue 1 2005Jeffrey K. Myers Abstract Are there analogous sequence positions in families of related proteins where disease-linked mutations occur with unusually high frequency? We attempt to answer this question by examining sequence alignments for G-protein coupled receptors (GPCRs) and voltage-gated potassium channels that have a significant number of missense mutations linked to some form of human disease. When the disease-linked mutations are mapped onto the sequences for each family, there are a large number of aligned sites at which disease-linked mutations occur in more than one protein. The statistical significance of the aligned sites is judged by analysis of artificially-generated random datasets. There are a modest number of aligned sites that are statistically significant,we refer to these as "phenotologous" sequence positions. Phenotologous sites represent aligned positions at which mutations linked to disease phenotypes occur with high frequency within a family of proteins. The most interesting of these sites are those which are not conserved,such sites are apparently critical in defining structural or functional differences between related proteins. Phenotology may be used to make experimentally testable predictions regarding medical genetics, the molecular basis of disease, and protein structure,function relationships. Hum Mutat 25:90,97, 2005. © 2004 Wiley-Liss, Inc. [source] INVITED REVIEW: Quantitative trait locus mapping in natural populations: progress, caveats and future directionsMOLECULAR ECOLOGY, Issue 2 2005JON SLATE Abstract Over the last 15 years quantitative trait locus (QTL) mapping has become a popular method for understanding the genetic basis of continuous variation in a variety of systems. For example, the technique is now an integral tool in medical genetics, livestock production, plant breeding and population genetics of model organisms. Ten years ago, it was suggested that the method could be used to understand continuous variation in natural populations. In this review I: (i) clarify what is meant by natural population in the QTL context, (ii) discuss whether evolutionary biologists have successfully mapped QTL in natural populations, (iii) highlight some of the questions that have been addressed by QTL mapping in natural populations, (iv) describe how QTL mapping can be conducted in unmanipulated natural populations, (v) highlight some of the limitations of QTL mapping and (vi) try to predict some future directions for QTL mapping in natural populations. [source] Health-related quality of life measures in genetic disorders: An outcome variable for consideration in clinical trials,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2009David A. Stevenson Abstract The field of medical genetics is rapidly advancing, and therapeutic options to treat genetic syndromes are becoming increasingly available. An understanding of the pathophysiology of various genetic disorders has provided researchers the opportunity to propose and test pharmacologic agents in preclinical murine models with hopes of translation to human trials. The development of clinical trials can be costly and time consuming, particularly for rare conditions. Pilot feasibility studies should be performed when designing clinical trials for genetic disorders. The development and selection of appropriate outcome measures are particularly paramount in the implementation of clinical trials. The selection of inappropriate outcome measures can lead to non-measurable differences or clinically insignificant findings. In addition, just as age appropriate measures are needed, some instruments may not apply to populations with specific genetic disorders that have significant cognitive and physical impairment, as the measures may not be sensitive enough to identify clinically significant changes. In the last decade, health-related quality of life measures (HRQOL) have been increasingly included as an outcome measure in clinical trials. While traditional clinical outcomes are important, these newly developed instruments should be considered along with clinical indicators as measures of effect in clinical trials of interventions in genetic disorders. © 2009 Wiley-Liss, Inc. [source] Religious and spiritual issues in medical genetics,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2009Joseph B. Fanning Ph.D. Abstract This article provides an overview of a special issue on the religious and spiritual concerns that arise in the provision of genetic services. It introduces some of the challenges in defining religion and spirituality and provides contexts and summaries for the empirical and normative research that appears in the issue. © 2009 Wiley-Liss, Inc. [source] Lost in transition: Challenges in the expanding field of adult genetics,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 4 2006Matthew R.G. Taylor Abstract It is increasingly clear that medical genetics has broad relevance in adult clinical medicine. More adult patients with genetic conditions are being recognized, genetic testing for adult-onset genetic conditions is expanding, and children with genetic conditions are now more likely to survive to adulthood. While the number of patients who could benefit from medical genetic services increases, adult care providers are less well educated about clinical genetics and are not sufficiently prepared to meet the growing needs of this population. Genetics professionals may also be ill-suited for this challenge, since geneticists and genetic counselors have traditionally had greater experience in pediatric and prenatal settings. Communication between primary care physicians who treat adults and the genetics community is currently suboptimal and the identification and subsequent referral of adult patients for genetic services need improvement. Finally, published guidelines that address how to deliver genetic services to adult patients are unavailable for many genetic conditions. In this article we address the challenges of transitioning genetics services from traditional, and largely pediatric-based models to paradigms that can best address the needs of adult patients with genetic conditions. Potential solutions and the practicality of implementation of a team-based approach to adult genetic medicine, including the application of genetic counseling, are also discussed. © 2006 Wiley-Liss, Inc. [source] The global pattern of gene identity variation reveals a history of long-range migrations, bottlenecks, and local mate exchange: Implications for biological raceAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2009Keith L. Hunley Abstract Several recent studies have argued that human genetic variation conforms to a model of isolation by distance, whereas others see a predominant role for long-range migrations and bottlenecks. It is unclear whether either of these views fully describes the global pattern of human genetic variation. In this article, we use a coalescent-based simulation approach to compare the pattern of neutral genetic variation predicted by these views to the observed pattern estimated from neutral autosomal microsatellites assayed in 1,032 individuals from 53 globally-distributed populations. We find that neither view predicts every aspect of the observed pattern of variation on its own, but that a combination of the two does. Specifically, we demonstrate that the observed pattern of global gene identity variation is consistent with a history of serial population fissions, bottlenecks and long-range migrations associated with the peopling of major geographic regions, and gene flow between local populations. This history has produced a nested pattern of genetic structure that is inconsistent with the existence of independently evolving biological races. We consider the implications of our findings for methods that apportion variation into within- and between-group components and for medical genetics. Am J Phys Anthropol 2009. © 2009 Wiley-Liss, Inc. [source] Cochlear Implants in Five Cases of Auditory Neuropathy: Postoperative Findings and Progress,THE LARYNGOSCOPE, Issue 4 2001Jon K. Shallop PhD Abstract Objectives To review our experiences with some of the preoperative and postoperative findings in five children who were diagnosed with auditory neuropathy and were provided with cochlear implants. We describe changes in auditory function, which enabled these children to have significant improvement in their hearing and communication skills. Study Design Pre- and postoperatively, these children received complete medical examinations at Mayo Clinic, including related consultations in audiology, pediatrics, neurology, medical genetics, otolaryngology, psychology, speech pathology, and radiology. Methods These children typically had additional medical and audiological examinations at more than one medical center. The hearing assessments of these children included appropriate behavioral audiometric techniques, objective measures of middle ear function, acoustic reflex studies, transient (TOAE) or distortion product (DPOAE) otoacoustic emissions, auditory brainstem responses (ABR), and, in some cases, transtympanic electrocochleography (ECoG). After placement of the internal cochlear implant devices (Nucleus CI24), intraoperatively we measured electrode impedances, visually detected electrical stapedius reflexes (VESR) and neural response telemetry (NRT). These intraoperative objective measures were used to help program the speech processor for each child. Postoperatively, each child has had regular follow-up to assure complete healing of the surgical incision, to assess their general medical conditions, and for speech processor programming. Their hearing and communication skills have been assessed on a regular basis. Postoperatively, we have also repeated electrode impedance measurements, NRT measurements, otoacoustic emissions, and electrical auditory brainstem responses (EABR). We now have 1 year or more follow-up information on the five children. Results The five children implanted at Mayo Clinic Rochester have not had any postoperative medical or cochlear implant device complications. All of the children have shown significant improvements in their sound detection, speech perception abilities and communication skills. All of the children have shown evidence of good NRT results. All but case D (who was not tested) showed evidence of good postoperative EABR results. Otoacoustic emissions typically remained in the non-operated ear but, as expected, they are now absent in the operated ear. Conclusion Our experiences with cochlear implantation for children diagnosed with auditory neuropathy have been very positive. The five children we have implanted have not had any complications postoperatively, and each child has shown improved listening and communication skills that have enabled each child to take advantage of different communication and educational options. [source] Revealing the human mutomeCLINICAL GENETICS, Issue 4 2010JM Chen Chen JM, Férec C, Cooper DN. Revealing the human mutome. The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database). However, for a variety of reasons, this figure is likely to represent only a small proportion of the clinically relevant genetic variants that remain to be identified in the human genome (the ,mutome'). With the advent of next-generation sequencing, we are currently witnessing a revolution in medical genetics. In particular, whole-genome sequencing (WGS) has the potential to identify all disease-causing or disease-associated DNA variants in a given individual. Here, we use examples of recent advances in our understanding of mutational/pathogenic mechanisms to guide our thinking about possible locations outwith gene-coding sequences for those disease-causing or disease-associated variants that are likely so often to have been overlooked because of the inadequacy of current mutation screening protocols. Such considerations are important not only for improving mutation-screening strategies but also for enhancing the interpretation of findings derived from genome-wide association studies, whole-exome sequencing and WGS. An improved understanding of the human mutome will not only lead to the development of improved diagnostic testing procedures but should also improve our understanding of human genome biology. [source] How lay people respond to messages about genetics, health, and raceCLINICAL GENETICS, Issue 2 2005C Condit There is a growing movement in medical genetics to develop, implement, and promote a model of race-based medicine. Although race-based medicine may become a widely disseminated standard of care, messages that advocate race-based selection for diagnosing, screening and prescribing drugs may exacerbate health disparities. These messages are present in clinical genetic counseling sessions, mass media, and everyday talk. Messages promoting linkages among genes, race, and health and messages emphasizing genetic causation may promote both general racism and genetically based racism. This mini-review examines research in three areas: studies that address the effects of these messages about genetics on levels of genetic determinism and genetic discrimination; studies that address the effects of these messages on attitudes about race; and, studies of the impacts of race-specific genetic messages on recipients. Following an integration of this research, this mini-review suggests that the current literature appears fragmented because of methodological and measurement issues and offers strategies for future research. Finally, the authors offer a path model to help organize future research examining the effects of messages about genetics on socioculturally based racism, genetically based racism, and unaccounted for racism. Research in this area is needed to understand and mitigate the negative attitudinal effects of messages that link genes, race, and health and/or emphasize genetic causation. [source] | |||||||||||||