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Candidate Gene Analysis (candidate + gene_analysis)
Selected AbstractsGenetics and Asthma Disease Susceptibility in the US Latino PopulationMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 2 2010Joan Reibman MD Abstract The US Latino population is heterogeneous with diversity in environmental exposures and socioeconomic status. Moreover, the US Hispanic population derives from numerous countries previously under Spanish rule, and many Hispanics have complex proportions of European, Native American, and African ancestry. Disparities in asthma severity and control are due to complex interactions between environmental exposures, socioeconomic factors, and genetic variations. In addition, diseases within the Latino community may also differ by country of origin. Although US Census data show low asthma rates in the Hispanic population as a whole, there is a lot of variability in the prevalence and morbidity of asthma, with a prevalence of 5.0% in Mexican Americans versus 17.0% in Puerto Ricans. The diversity and population admixture make the study of the genetics of asthma complex in Latino populations. However, an understanding of the genetics of asthma in all populations, including the Latino population, can enhance risk identification, help us to target pharmacological therapy, and guide environmental regulations, all of which can promote a reduction in health disparities. The inclusion of markers of ancestral diversity and the incorporation of techniques to adjust for stratification now make these studies feasible in complex populations, including the Latino population. To date, studies using linkage analyses, genome-wide associations, or candidate gene analyses have identified an association of asthma or asthma-related phenotypes with candidate genes, including interleukin 13, ,-2 adrenergic receptor, a disintegrin and metalloproteinase 33, orosomucoid 1-like 3, and thymic stromal lymphopoietin. As reviewed here, although these genes have been identified in diverse populations, limited studies have been performed in Latino populations, and they have had variable replication. There is a need for the development of registries with well-phenotyped pediatric and adult Latino populations and subgroups for inclusion in the rapidly expanding field of genetic studies, and these studies need to be used to reduce health disparities. Mt Sinai J Med 77:140,148, 2010. © 2010 Mount Sinai School of Medicine [source] Genetic variation of the human glycine receptor subunit genes GLRA3 and GLRB and susceptibility to idiopathic generalized epilepsiesAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 6 2001Diana Sobetzko Abstract Alterations of glycine receptor ,1 and , subunit genes have been associated with hypertonic motor disorders in both mice and humans. Mutations in genes encoding other ligand- and voltage-gated ion channels have been identified in rare monogenic forms of idiopathic generalized epilepsies (IGE). We tested the hypothesis that allelic variants of the glycine receptor subunit genes, GLRA3 and GLRB, both localized on chromosome 4q, confer susceptibility to common subtypes of IGE. Mutation screening was carried out in index patients of 14 IGE families. No pathogenic mutation was found, but two intronic polymorphisms were detected in the GLRB gene, and four intronic, three exonic, and one 3,-UTR polymorphisms were identified for the GLRA3 gene. Subsequent screening for exonic and 3,-UTR polymorphisms in GLRA3 showed no statistical difference between a group of sporadic IGE patients (n,=,104) and a control group (n,=,141). The genotype frequencies for exonic and 3,-UTR polymorphisms in GLRA3 showed no statistically significant difference between IGE patients (n,=,104) and an ethnically matched control group (n,=,141). Thus, no association between IGE and alterations in GLRA3 or GLRB genes could be detected, indicating that both genes do not play a major causative role in the epileptogenesis of common IGE subtypes. Still, these novel single nucleotide polymorphisms may be useful markers for candidate gene analyses of other disorders. © 2001 Wiley-Liss, Inc. [source] Power calculations for likelihood ratio tests for offspring genotype risks, maternal effects, and parent-of-origin (POO) effects in the presence of missing parental genotypes when unaffected siblings are availableGENETIC EPIDEMIOLOGY, Issue 1 2007E. Rampersaud Abstract Genotype-based likelihood-ratio tests (LRT) of association that examine maternal and parent-of-origin effects have been previously developed in the framework of log-linear and conditional logistic regression models. In the situation where parental genotypes are missing, the expectation-maximization (EM) algorithm has been incorporated in the log-linear approach to allow incomplete triads to contribute to the LRT. We present an extension to this model which we call the Combined_LRT that incorporates additional information from the genotypes of unaffected siblings to improve assignment of incompletely typed families to mating type categories, thereby improving inference of missing parental data. Using simulations involving a realistic array of family structures, we demonstrate the validity of the Combined_LRT under the null hypothesis of no association and provide power comparisons under varying levels of missing data and using sibling genotype data. We demonstrate the improved power of the Combined_LRT compared with the family-based association test (FBAT), another widely used association test. Lastly, we apply the Combined_LRT to a candidate gene analysis in Autism families, some of which have missing parental genotypes. We conclude that the proposed log-linear model will be an important tool for future candidate gene studies, for many complex diseases where unaffected siblings can often be ascertained and where epigenetic factors such as imprinting may play a role in disease etiology. Genet. Epidemiol. © 2006 Wiley-Liss, Inc. [source] Third international meeting on the genetic epidemiology of complex traits, April 4,6, 2002, Cambridge, UKHUMAN MUTATION, Issue 3 2002Sally John Abstract The Third International Meeting on the Genetic Epidemiology of Complex Traits was held at Churchill College, Cambridge, UK on April 4,6, 2002. The event was organized by the Twin Research and Genetic Epidemiology Unit, St Thomas' Hospital, London and sponsored by Roche Genetics and Insightful. It provided an interactive forum for discussion of topical issues relating to the genetic analysis of complex diseases and traits. Topics discussed included linkage disequilibrium mapping and candidate gene analysis, as well as cutting edge advances in both technologies and statistical analysis methods. Details of the meeting can be found at http://www.twin-research.ac.uk/. Hum Mutat20:227,229, 2002. © 2002 Wiley-Liss, Inc. [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] The genetics of inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2001T. Ahmad Recent epidemiological, clinical and molecular studies have provided strong evidence that inherited predisposition is important in the pathogenesis of chronic inflammatory bowel diseases. The model most consistent with the epidemiological data suggests that Crohn's disease and ulcerative colitis are related polygenic diseases, sharing some but not all susceptibility genes. Investigators throughout the world have applied the complementary techniques of genome-wide scanning and candidate gene analysis. Four areas of linkage have been widely replicated on chromosomes 16 (IBD1), 12 (IBD2), 6 (IBD3,the HLA region), and most recently on chromosome 14. Fine mapping of these regions is underway. Of the ,positional' candidate genes, most attention has centred on the genes of the major histocompatibility complex. Genes within this region may determine disease susceptibility, behaviour, complications and response to therapy. Hope continues that studies of inflammatory bowel disease genetics will provide fresh insight into disease pathogenesis and soon deliver clinical applications. [source] Mechanisms of Regulation of Litter Size in Pigs on the Genome LevelREPRODUCTION IN DOMESTIC ANIMALS, Issue 2007O Distl Contents Improvement in litter size has become of great interest in pig industry as good fecundity is directly related to a sow's productive life. Genetic regulation of litter size is complex and the main component traits so far defined are ovulation rate, embryonic survival, uterus capacity, foetal survival and pre-weaning losses. Improvements using concepts of the quantitative genetics let expect only slow genetic progress due to its low heritability of approximately 0.09 for number of piglets born alive. Marker assisted selection allows to dissect litter size in its component traits and using molecular genetic markers for the components of litter size traits promises more progress and advantages in optimum balancing of the different physiological mechanisms influencing litter size. In this review, efforts being made to unravel the genetic determinants of litter size are accounted and discussed. For litter size traits, more than 50 quantitative trait loci (QTL) were mapped and in more than 12 candidate genes associations confirmed. The number of useful candidate genes is much larger as shown by expression profiles and in addition, much more QTL can be assumed. These functional genomic approaches, both QTL mapping and candidate gene analysis, have to be merged for a better understanding of a wider application across different pig breeds and lines. Newly developed tools based on microarray techniques comprising DNA variants or expressed tags of many genes or even the whole genome appear useful for in depth understanding of the genetics of litter size in pigs. [source] Neutrophil dysfunction in a family with a SAPHO syndrome,like phenotypeARTHRITIS & RHEUMATISM, Issue 10 2008Polly J. Ferguson SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) is an inflammatory disorder of the bone, skin, and joints. We describe a family with multiple affected members who segregate a SAPHO syndrome,like phenotype, and we report the results of neutrophil studies and candidate gene analysis. We obtained written informed consent and a family history and reviewed medical records. We collected DNA and sequenced candidate genes, and we performed functional studies on neutrophils isolated from the proband and her mother. The pedigree segregated chronic osteomyelitis and cutaneous inflammation in a pattern that suggested an autosomal-dominant disorder. No coding sequence mutations were detected in PSTPIP1,PSTPIP2, LPIN2, SH3BP2, or NCF4. Analysis of neutrophil function in the proband, including nitroblue tetrazolium tests, myeloperoxidase assays, neutrophil chemotaxis, and neutrophil chemotaxis assays, revealed no identifiable abnormalities. However, an abnormality in the luminol, but not the isoluminol, respiratory burst assays following stimulation with phorbol myristate acetate (PMA) was detected in neutrophils isolated from the affected proband. Internal oxidant production was also reduced in the proband and her mother when neutrophils were treated with fMLP with or without platelet-activating factor, PMA alone, or tumor necrosis factor , alone. This family segregates a disorder characterized by chronic inflammation of the skin and bone. Functional differences in neutrophils exist between affected individuals and controls. The biologic significance of this defect remains unknown. Identification of the gene defect will help identify an immunologic pathway that, when dysregulated, causes inflammation of the skin and bone. [source] | |||||||||||||