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* Context.--Rapid advancements in the understanding and manipulation of tumor-immune interactions have led to the approval of immune therapies for patients with non-small cell lung cancer. Certain immune checkpoint inhibitor therapies require the use of companion diagnostics, but methodologic variability has led to uncertainty around test selection and implementation in practice. Objective.--To develop evidence-based guideline recommendations for the testing of immunotherapy/immunomodulatory biomarkers, including programmed death ligand-1 (PD-L1) and tumor mutation burden (TMB), in patients with lung cancer. Design.--The College of American Pathologists convened a panel of experts in non-small cell lung cancer and biomarker testing to develop evidence-based recommendations in accordance with the standards for trustworthy clinical practice guidelines established by the National Academy of Medicine. A systematic literature review was conducted to address 8 key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were created from the available evidence, certainty of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework. Results.--Six recommendation statements were developed. Conclusions.--This guideline summarizes the current understanding and hurdles associated with the use of PD-L1 expression and TMB testing for immune checkpoint inhibitor therapy selection in patients with advanced non-small cell lung cancer and presents evidence-based recommendations for PD-L1 and tMb testing in the clinical setting. doi: 10.5858/arpa.2023-0536-CP), The advent of immune modulatory therapy has led to a radical shift in the treatment paradigm for patients with a wide range of cancers. The clinical impact of these therapies, [...]

Immune checkpoint therapies have been shown in numerous clinical trials to have significant clinical benefits for lung cancer patients, and there are increasing numbers of indications and therapies available. (1-13) [...]

Background Establishing a molecular genetic diagnosis of focal segmental glomerulosclerosis (FSGS)/steroid-resistant nephrotic syndrome (SRNS) can be useful for predicting post-transplant recurrence. Monogenic causes are reportedly present in approximately 20-30% of patients with FSGS/SRNS. However, the characteristics of patients who are likely to have a monogenic cause remain to be determined. Methods Pediatric recipients with SRNS and/or biopsy-proven FSGS who underwent their first kidney transplantation at our center between 1999 and 2019 were analyzed. Patients with secondary FSGS/SRNS were excluded. The recipients were divided into three groups: familial/syndromic, presumed primary, and undetermined FSGS/SRNS. Patients who met all of the following criteria were categorized as having presumed primary FSGS/SRNS: (i) nephrotic syndrome, (ii) complete or partial remission with initial steroid therapy and/or additional immunosuppressive therapies, and (iii) diffuse foot process effacement on electron microscopy in the native kidney biopsy. All patients underwent genetic testing using next-generation sequencing. Results Twenty-four patients from 23 families were analyzed in this study. Pathogenic or likely pathogenic variants in FSGS/SRNS-related genes were identified in four of four families, zero of eight families, and 10 of 11 families with familial/syndromic, presumed primary, and undetermined FSGS/SRNS, respectively. Post-transplant recurrence only occurred in patients with presumed primary FSGS/SRNS. Conclusions Our systematic approach based on precise clinicopathological findings including nephrotic syndrome, treatment responses, and diffuse foot process effacement might be useful to differentiate pediatric kidney transplant recipients with FSGS/SRNS who are likely to have a monogenic cause from patients who are not, and to predict post-transplant recurrence. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., Author(s): Kenichiro Miura [sup.1] , Naoto Kaneko [sup.1] , Taeko Hashimoto [sup.1] [sup.2] , Kiyonobu Ishizuka [sup.1] , Yoko Shirai [sup.1] , Masataka Hisano [sup.3] , Hiroko Chikamoto [sup.1] , [...]

Author(s): Benjamin Steinman [sup.1] , Marcela Del Rio [sup.1] , Anna Zolotnitskaya [sup.1] , Nicole Hayde [sup.1] Author Affiliations: (1) grid.414114.5, 0000 0004 0566 7955, Division of Pediatric Nephrology, Children's [...]

Our institution developed and continuously improved a Neurodevelopmental Reflex (NDR) algorithm to help physicians with genetic test ordering for neurodevelopmental disorders (NDDs). To assess its performance, we performed a retrospective study of 511 patients tested through NDR from 2018 to 2019. SNP Microarray identified pathogenic/likely pathogenic copy number variations in 27/511 cases (5.28%). Among the 484 patients tested for Fragile X FMR1 CGG repeats, a diagnosis (0.20%) was established for one male mosaic for a full mutation, a premutation, and a one-CGG allele. Within the 101 normocephalic female patients tested for MECP2, two patients were found to carry pathogenic variants (1.98%). This retrospective study suggested the NDR algorithm effectively established diagnoses for patients with NDDs with a yield of 5.87%., Author(s): Xiaoli Du [sup.1] , Jennifer Elaine Glass [sup.1] , Stephanie Balow [sup.1] [sup.2] , Lisa M. Dyer [sup.1] [sup.2] , Pamela A. Rathbun [sup.1] [sup.3] , Qiaoning Guan [sup.1] [...]

Alport syndrome spectrum can be considered as a group of genetic diseases affecting the major basement membrane collagen type IV network in various organs including the ear, eye, and kidney. The living donor candidate evaluation is an ever-changing landscape. Recently, next-generation sequence (NGS) panels have become readily available and provide opportunities to genetically screen recipient and donor candidates for collagen network gene variants. In this review, our aim is to provide a comprehensive update on the role of genetic testing for the evaluation of potential living kidney donors to kidney candidates with Alport syndrome spectrum. We examine the utility of genetic testing in the evaluation of potential donors for recipients with Alport syndrome spectrum, and discuss risks and unresolved challenges. Suggested algorithms in the context of related and unrelated donation are offered. In contemporary practice, an approach to the evaluation of living donor candidates for transplant candidates with Alport syndrome spectrum can incorporate genetic testing in algorithms tailored for donor-recipient relationship status. Ongoing research is needed to inform optimal practice., Author(s): Yasar Caliskan [sup.1] , Krista L. Lentine [sup.1] Author Affiliations: (1) grid.262962.b, 0000 0004 1936 9342, Saint Louis University Center for Abdominal Transplantation, , 1201 S. Grand Blvd, 63110, [...]

Genetic testing is essential for patients with a suspected hereditary myopathy. More than 50% of patients clinically diagnosed with a myopathy carry a variant of unknown significance in a myopathy gene, often leaving them without a genetic diagnosis. Limb-girdle muscular dystrophy (LGMD) type R4/2E is caused by mutations in [beta]-sarcoglycan (SGCB). Together, [beta]-, [alpha]-, [gamma]-, and [delta]-sarcoglycan form a 4-protein transmembrane complex (SGC) that localizes to the sarcolemma. Biallelic loss-of-function mutations in any subunit can lead to LGMD. To provide functional evidence for the pathogenicity of missense variants, we performed deep mutational scanning of SGCB and assessed SGC cell surface localization for all 6,340 possible amino acid changes. Variant functional scores were bimodally distributed and perfectly predicted pathogenicity of known variants. Variants with less severe functional scores more often appeared in patients with slower disease progression, implying a relationship between variant function and disease severity. Amino acid positions intolerant to variation mapped to points of predicted SGC interactions, validated in silico structural models, and enabled accurate prediction of pathogenic variants in other SGC genes. These results will be useful for clinical interpretation of SGCB variants and improving diagnosis of LGMD; we hope they enable wider use of potentially life-saving gene therapy., Introduction Recessive mutations in [beta]-sarcoglycan (SGCB) cause limb-girdle muscular dystrophy type R4/2E (LGMDR4/2E), resulting in muscle wasting, progressive weakness, degeneration of skeletal muscle, and often premature death (1, 2). [beta]-Sarcoglycan [...]

Byline: Harsh. Sheth, Dhairya. Pancholi, Riddhi. Bhavsar, Ashraf. Mannan, Aparna. Ganapathy, Mayank. Chowdhury, Sudhir. Shah, Dhawal. Solanki, Frenny. Sheth, Jayesh. Sheth Background: Neurological diseases are phenotypically and genotypically heterogeneous. Clinical [...]

Background This nationwide study assessed the impact of nationally agreed cancer genetics guidelines on use of BRCA1/2 germline testing, risk management advice given by health professionals to women with pathogenic BRCA1/2 variants and uptake of such advice by patients. Methods Clinic files of 883 women who had initial proband screens for BRCA1/2 pathogenic variants at 12 familial cancer clinics between July 2008-July 2009 (i.e. before guideline release), July 2010-July 2011 and July 2012-July 2013 (both after guideline release) were audited to determine reason given for genetic testing. Separately, the clinic files of 599 female carriers without a personal history of breast/ovarian cancer who underwent BRCA1/2 predictive genetic testing and received their results pre- and post-guideline were audited to ascertain the risk management advice given by health professionals. Carriers included in this audit were invited to participate in a telephone interview to assess uptake of advice, and 329 agreed to participate. Results There were no significant changes in the percentages of tested patients meeting at least one published indication for genetic testing - 79, 77 and 78% of files met criteria before guideline, and two-, and four-years post-guideline, respectively ([chl] = 0.25, p = 0.88). Rates of documentation of post-test risk management advice as per guidelines increased significantly from pre- to post-guideline for 6/9 risk management strategies. The strategies with the highest compliance amongst carriers or awareness post-release of guidelines were annual magnetic resonance imaging plus mammography in women 30-50 years (97%) and annual mammography in women > 50 years (92%). Of women aged over 40 years, 41% had a risk-reducing bilateral mastectomy. Amongst women aged > 40 years, 75% had a risk-reducing salpingo-oophorectomy. Amongst women who had not had a risk-reducing bilateral mastectomy, only 6% took risk-reducing medication. Fear of side-effects was cited as the main reasons for not taking these medicines by 73% of women. Conclusions Guidelines did not change the percentages of tested patients meeting genetic testing criteria but improved documentation of risk management advice by health professionals. Effective approaches to enhance compliance with guidelines are needed to improve risk management and quality of care. Keywords: Guidelines, Compliance, Genetic testing, Cancer risk, BRCA1 and BRCA2, Author(s): Bettina Meiser[sup.1], Rajneesh Kaur[sup.1], April Morrow[sup.1], Michelle Peate[sup.1,2], W. K. Tim Wong[sup.1,3], Emily McPike[sup.1], Elisa Cops[sup.4], Cassandra Nichols[sup.5], Rachel Austin[sup.6], Miriam Fine[sup.7], Letitia Thrupp[sup.4], Robyn Ward[sup.8,9], Finlay Macrae[sup.10,11], Janet [...]

Byline: Dhanya. Narayanan, Moni. Tuteja, Adam. McIntyre, Robert. Hegele, Nadege. Calmels, Cathy. Obringer, Vincent. Laugel, Kausik. Mandal, Shubha. Phadke Background: Cockayne syndrome is an autosomal recessive disorder caused by biallelic [...]

'The Pregnancy and Health Profile' (PHP) is a free prenatal genetic screening and clinical decision support (CDS) software tool for prenatal providers. PHP collects family health history (FHH) during intake and provides point-of-care risk assessment for providers and education for patients. This pilot study evaluated patient and provider responses to PHP and effects of using PHP in practice. PHP was implemented in four clinics. Surveys assessed provider confidence and knowledge and patient and provider satisfaction with PHP. Data on the implementation process were obtained through semi-structured interviews with administrators. Quantitative survey data were analyzed using Chi square test, Fisher's exact test, paired t tests, and multivariate logistic regression. Open-ended survey questions and interviews were analyzed using qualitative thematic analysis. Of the 83% (513/618) of patients that provided feedback, 97% felt PHP was easy to use and 98% easy to understand. Thirty percent (21/71) of participating physicians completed both pre- and post-implementation feedback surveys [13 obstetricians (OBs) and 8 family medicine physicians (FPs)]. Confidence in managing genetic risks significantly improved for OBs on 2/6 measures (p values ≤0.001) but not for FPs. Physician knowledge did not significantly change. Providers reported value in added patient engagement and reported mixed feedback about the CDS report. We identified key steps, resources, and staff support required to implement PHP in a clinical setting. To our knowledge, this study is the first to report on the integration of patient-completed, electronically captured and CDSenabled FHH software into primary prenatal practice. PHP is acceptable to patients and providers. Key to successful implementation in the future will be customization options and interoperability with electronic health records. Keywords Family health history * Personalized risk assessment * Clinical decision support * Prenatal care * Genetic screening, Introduction Family health history (FHH) has been called 'the cheapest genetic test' [1] or the first genetic test [2], and it has long been recognized as an essential aspect of [...]

Schizophrenia is a common disease with a complex aetiology, probably involving multiple and heterogeneous genetic factors. Here, by analysing the exome sequences of 2,536 schizophrenia cases and 2,543 controls, we demonstrate a polygenic burden primarily arising from rare (less than 1 in 10,000), disruptive mutations distributed across many genes. Particularly enriched gene sets include the voltage-gated calcium ion channel and the signalling complex formed by the activity-regulated cytoskeleton-associated scaffold protein (ARC) of the postsynaptic density, sets previously implicated by genome-wide association and copy-number variation studies. Similar to reports in autism, targets of the fragile X mental retardation protein (FMRP, product of FMR1) are enriched for case mutations. No individual gene-based test achieves significance after correction for multiple testing and we do not detect any alleles of moderately low frequency (approximately 0.5 to 1 per cent) and moderately large effect. Taken together, these data suggest that population-based exome sequencing can discover risk alleles and complements established gene-mapping paradigms in neuropsychiatric disease. Exome sequence analysis of more than 5,000 schizophrenia cases and controls identifies a polygenic burden primarily arising from rare, disruptive mutations distributed across many genes, among which are those encoding voltage-gated calcium ion channels and the signalling complex formed by the ARC protein of the postsynaptic density; as in autism, mutations were also found in homologues of known targets of the fragile X mental retardation protein. Pathogenic mechanisms in schizophrenia Two major sequencing studies of the exome -- the protein-coding portion of the genome -- in schizophrenia sufferers and their relatives are published in this issue of Nature. Together they provide strong pointers to specific pathogenic mechanisms that disrupt the glutamatergic synapses in schizophrenia. In particular, mutations that influence the action of the scaffold protein ARC (activity-regulated cytoskeleton-associated protein) are prominently involved, as are mutations in targets of the fragile X mental retardation protein (FMRP). Defects in FMRP have previously been shown to be associated with autism spectrum disorders., Author(s): Shaun M. Purcell [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] , Jennifer L. Moran [sup.1] , Menachem Fromer [sup.1] [sup.2] [sup.3] [sup.4] , Douglas Ruderfer [sup.2] [sup.3] , Nadia Solovieff [sup.4] [...]

Each year, tens of thousands of young people worldwide die suddenly after their hearts stop beating for no apparent reason. Genetic testing for inherited heart rhythm disorders can potentially offer [...]

Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder characterized by radiosensitivity, genomic instability, and predisposition to cancer. A-T is caused by biallelic mutations in the ataxia-telangiectasia mutated (ATM) gene, but [...]

Thus far, the focus of personalized medicine has been the prevention and treatment of conditions that affect adults. Although advances in genetic technology have been applied more frequently to prenatal diagnosis than to fetal treatment, genetic and genomic information is beginning to influence pregnancy management. Recent developments in sequencing the fetal genome combined with progress in understanding fetal physiology using gene expression arrays indicate that we could have the technical capabilities to apply an individualized medicine approach to the fetus. Here I review recent advances in prenatal genetic diagnostics, the challenges associated with these new technologies and how the information derived from them can be used to advance fetal care. Historically, the goal of prenatal diagnosis has been to provide an informed choice to prospective parents. We are now at a point where that goal can and should be expanded to incorporate genetic, genomic and transcriptomic data to develop new approaches to fetal treatment., The goal of personalized medicine is to optimize health and develop individualized therapy for disease by combining a person's genetic and genomic data with information about their lifestyle and exposures. [...]

Hantavirus pulmonary syndrome (HPS) is a manifestation of an emerging zoonosis caused by New World viruses of the family Bunyaviridae, genus Hantavirus. Hantavirus is transmitted to humans by inhalation of [...]

To the Editor: Last year I sent a vial of my spit to a prominent direct-to-consumer genetic testing company. The company's Web site promised that, in return, I would get [...]

[CD8.sup.+] T cells play a critical role in the immune response to viral pathogens. Persistent human cytomegalovirus (HCMV) infection results in a strong increase in the number of virus-specific, quiescent effector-type [CD8.sup.+] T cells with constitutive cytolytic activity, but the molecular pathways involved in the induction and maintenance of these cells are unknown. We show here that HCMV infection induced acute and lasting changes in the transcriptomes of virus-reactive T cells collected from HCMV-seropositive patients at distinct stages of infection. Enhanced cell cycle and metabolic activity was restricted to the acute phase of the response, but at all stages, HCMV-specific [CD8.sup.+] T cells expressed the Th1-associated transcription factors T-bet (TBX21) and eomesodermin (EOMES), in parallel with continuous expression of IFNG mRNA and IFN-γ-regulated genes. The cytolytic proteins granzyme B and perforin as well as the fractalkine-binding chemokine receptor CX3CR1 were found in virus-reactive cells throughout the response. During HCMV latency, virus-specific [CD8.sup.+] T cells lacked the typical features of exhausted cells found in other chronic infections. Persistent effector cell traits together with the permanent changes in chemokine receptor usage of virus-specific, nonexhausted, long-lived [CD8.sup.+] T cells may be crucial to maintain lifelong protection from HCMV reactivation., Introduction Depending on the clearance or persistence of a virus, virus-specific [CD8.sup.+] T cells may have diverse fates after a primary immune response. In the case of cleared viruses, a [...]

The large-scale, consortium-based genomewide study aims to identify genetic risk factors that may be useful in identifying subtypes of asthma and determining whether intermediate phenotypes are causally linked to the disease. The results indicate that asthma is genetically heterogeneous and a few common alleles are associated with disease risk at all ages.

The article discusses the risks associated with presymptomatic direct-to-Consumer (DTC) genetic testing. The U.S. Food and Drug Administration (FDA) has written letters to various companies voicing concerns over companies encouraging consumers to undertake DTC genetic testing without adequate clinical guidance.

Decision analytic modeling was used to evaluate the trade-off between costs, clinical effectiveness and benefit of an array genomic hybridization (AGH) testing strategy compared to a conventional testing strategy. Deterministic sensitivity analysis revealed that AGH after first-line cytogenetic testing was uninformative and does not provide good value for money compared to using AGH as first-line testing.

An evidence-based summary of clinical cytogenetic testing comparing chromosomal microarray (CMA) to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation is presented. The evidence strongly support the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA).

The article discusses the latest trends and recent progress in the field of treatment and management of pancreatic cancer. The need for a great degree of improvement in all aspects of treatment of pancreatic cancer is highlighted.

The application of the whole-genome sequencing technique for the genetic diagnosis of the Charcot-Marie-Tooth disorder is analyzed. The sequencing approach is shown to be extremely useful for analyzing the diagnostic information of the patients.

Several simulations are conducted to explain the impact of the various uncertainties observed in population incidence rates and genotype frequencies on the lifetime risk estimates of different populations. The significance of the different epidemiologic parameters in estimating the risk estimates in personal genomic profiles is also demonstrated.

The article discusses the benefits and uses of genetics and genetic testing in the clinical evaluation of cardiomyopathy among individuals and families for improved outcomes. The case of a 24-year-old man with familial cardiomyopathy is highlighted to help identify others in the family who are at a risk of developing the disease.

Family narratives of genetic disease address multigenerational legacies of illness, guide expectations about future diagnoses and anticipated losses, and promote continuity and coherence. Yet contemporary families with histories of genetic [...]

Completion of the genome sequence of Streptococcus sanguinis SK36 necessitates tools for further characterization of this species. It is often desirable to insert antibiotic resistance markers and other exogenous genes into the chromosome; therefore, we sought to identify a chromosomal site for ectopic expression of foreign genes, and to verify that insertion into this site did not affect important cellular phenotypes. We designed three plasmid constructs for insertion of erm, aad9 or tetM resistance determinants into a genomic region encoding only a small (65 aa) hypothetical protein. To determine whether this insertion affected important cellular properties, SK36 and its erythromycin-resistant derivative, JFP36, were compared for: (i) growth in vitro, (ii) genetic competence, (iii) biofilm formation and (iv) virulence for endocarditis in the rabbit model of infective endocarditis (IE). The spectinomycin-resistant strain, JFP56, and tetracycline-resistant strain, JFP76, were also tested for virulence in vivo. Insertion of erm did not affect growth, competence or biofilm development of JFP36. Recovery of bacteria from heart valves of co-inoculated rabbits was similar to wild-type for JFP36, JFP56 and JFP76, indicating that IE virulence was not significantly affected. The capacity for mutant complementation in vivo was explored in an avirulent ssaB mutant background. Expression of ssaB from its predicted promoter in the target region restored IE virulence. Thus, the chromosomal site utilized is a good candidate for further manipulations of S. sanguinis. In addition, the resistant strains developed may be further applied as controls to facilitate screening for virulence factors in vivo.

Saccharomyces cerevisiae can be infected with four amyloid-based prions: [URE3], [[PSI.sup.+]], [[PIN.sup.+]], and [[SWI.sup.+]], due to self-propagating aggregation of Ure2p, Sup35p, Rnq1p and Swi1p, respectively. We searched for new prions of yeast by fusing random segments of yeast DNA to SUP35MC, encoding the Sup35 protein lacking its own prion domain, selecting clones in which Sup35MC function was impaired. Three different clones contained parts of the Q/N-rich amino-terminal domain of Mca1p/Yca1p with the Sup35 part of the fusion protein partially inactive. This inactivity was dominant, segregated 4:0 in meiosis, and was efficiently transferred by cytoplasmic mixing. The inactivity was cured by overexpression of Hsp104, but the prion could arise again in the cured strain (reversible curing). Overproduction of the Mca1 N-terminal domain induced the de novo appearance of the prion form of the fusion. The prion state, which we name [MCA], was transmitted to the chromosomally encoded Mca1p based on genetic, cytological and biochemical tests. cytoduction | metacaspase | prion

OBJECTIVE: To conduct clinical and molecular genetic analyses of the members of an extended family in Central Indiana with a high prevalence of restless legs syndrome (RLS). PARTICIPANTS AND METHODS: [...]

A surveillance program for influenza A viruses (H5N1) was conducted in live bird and food markets in central Thailand during July 2006-August 2007. Twelve subtype H5N1 viruses were isolated. The [...]

Forkhead box class O (FoxO) transcription factors are key regulators of growth, metabolism, life span, and stress resistance. FoxOs integrate signals from different pathways and guide the cellular response to varying energy and stress conditions. FoxOs are modulated by several signaling pathways, e.g., the insulin-TOR signaling pathway and the stress induced JNK signaling pathway. Here, we report a genome wide RNAi screen of kinases and phosphatases aiming to find regulators of dFoxO activity in Drosophila S2 cells. By using a combination of transcriptional activity and localization assays we identified several enzymes that modulate dFoxO transcriptional activity, intracellular localization and/or protein stability. Importantly, several currently known dFoxO regulators were found in the screening, confirming the validity of our approach. In addition, several interesting new regulators were identified, including protein kinase C and glycogen synthase kinase 3[beta], two proteins with important roles in insulin signaling. Furthermore, several mammalian orthologs of the proteins identified in Drosophila also regulate FOXO activity in mammalian cells. Our results contribute to a comprehensive understanding of FoxO regulatory processes. dFoxO | insulin signaling | PKC

Byline: Wendy Ferguson, MBBch, MRCPI (Rotunda Hospital, Parnell Square, Dublin 1, wferguson@rotunda.ie); Mary Cafferkey, MB, FRCpath, FFpath (Rotunda Hospital, Parnell Square, Dublin 1, The Rainbow Clinic, The Children's University Hospital, [...]

OBJECTIVE: To determine the influence of a positive genetic test for hypertrophic cardiomyopathy (HCM) on clinical outcome. PATIENTS AND METHODS: A cohort of 203 unrelated patients with HCM (mean [+ [...]

Genomic imprinting is interpreted as a phenomenon, in which some genes inherited from one parent are not completely expressed due to modification of the genome caused during gametogenesis. Subsequently, the expression level of an allele at the imprinted gene is changed dependent on the parental origin, which is referred to as the parent-of-origin effect. In livestock, some QTL for reproductive performance and meat productivity have been reported to be imprinted. So far, methods detecting imprinted QTL have been proposed on the basis of interval mapping, where only a single QTL was tested at a time. In this study, we developed a Bayesian method for simultaneously mapping multiple QTL, allowing the inference about expression modes of QTL in an outbred [F.sub.2] family. The inference about whether a QTL is Mendelian or imprinted was made using Markov chain Monte Carlo estimation by comparing the goodness-of-fits between models, assuming the presence and the absence of parent-of-origin effect at a QTL. We showed by the analyses of simulated data sets that the Bayesian method can effectively detect both Mendelian QTL and imprinted QTL.

Author(s): Marcia Cruz-Correa[sup.1,2,8] , Julyann Pérez-Mayoral[sup.1,2] , Julie Dutil[sup.3] , Miguel Echenique[sup.4] , Rafael Mosquera[sup.5] , Keila Rivera-Román[sup.6] , Sharee Umpierre[sup.1] , Segundo Rodriguez-Quilichini[sup.1] , Maria Gonzalez-Pons[sup.1,2] , Myrta I. [...]

A study to examine the results of carrier screening of Ashkenazi Jews for gaucher disease (GD) is presented.

Recent discoveries in the molecular pathogenesis of both polycythemia vera (PV) and congenital polycythemia (CP) underline the prospect of a genetic diagnosis in these disorders. At the forefront are the [...]

The details of a genetic screen used to isolate genes responsible for the growth of axons with myelin sheaths during the development of the central nervous system in zebrafish are presented.

Policy makers have suggested that information about genetic risk factors, which are associated with low risk and for which preventive strategies exist, should not be considered 'exceptional' and should not warrant special safeguards, such as data protection or specialist pre-test counselling. There is scant research on how such risk factors are perceived, and to explore this we conducted qualitative interviews with 42 participants who had undergone testing in the South West of England for a low risk genetic susceptibility to deep vein thrombosis (DVT). Generally the participants, who were mostly women, thought the test was less serious than a genetic test for a predisposition to breast cancer or a non-genetic, diagnostic test for diabetes. They had used the genetic information to reduce their risk of DVTs by avoiding oral contraceptives and hormone replacement therapy but had not changed their lifestyle. Many considered pre-test genetic counselling unnecessary. However, a subgroup of participants, who were often less educated or at a high risk, were distressed and/or confused about thrombophilia and thought pre-test counselling would have been helpful. The findings indicate an emerging interpretation of genetics not as revealing exceptional or 'in depth' knowledge about one's health and identity but as occasionally relevant surface information, which participants use to make specific health decisions but not to transform their everyday lives. However, the views of the subgroup indicate that some participants interpret thrombophilia as serious and/or need special support. Keywords. Genetic testing; Genetic risk; Thrombophilia; Deep vein thrombosis; Patient perceptions; UK

The issue of genetic testing of individuals by insurance companies while providing health insurance to them is discussed.