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Selected AbstractsUnified sampling approach for multipoint linkage disequilibrium mapping of qualitative and quantitative traitsGENETIC EPIDEMIOLOGY, Issue 4 2002Fang-Chi Hsu Abstract Rapid development in biotechnology has enhanced the opportunity to deal with multipoint gene mapping for complex diseases, and association studies using quantitative traits have recently generated much attention. Unlike the conventional hypothesis-testing approach for fine mapping, we propose a unified multipoint method to localize a gene controlling a quantitative trait. We first calculate the sample size needed to detect linkage and linkage disequilibrium (LD) for a quantitative trait, categorized by decile, under three different modes of inheritance. Our results show that sampling trios of offspring and their parents from either extremely low (EL) or extremely high (EH) probands provides greater statistical power than sampling in the intermediate range. We next propose a unified sampling approach for multipoint LD mapping, where the goal is to estimate the map position (,) of a trait locus and to calculate a confidence interval along with its sampling uncertainty. Our method builds upon a model for an expected preferential transmission statistic at an arbitrary locus conditional on the sampling scheme, such as sampling from EL and EH probands. This approach is valid regardless of the underlying genetic model. The one major assumption for this model is that no more than one quantitative trait locus (QTL) is linked to the region being mapped. Finally we illustrate the proposed method using family data on total serum IgE levels collected in multiplex asthmatic families from Barbados. An unobserved QTL appears to be located at ,, = 41.93 cM with 95% confidence interval of (40.84, 43.02) through the 20-cM region framed by markers D12S1052 and D12S1064 on chromosome 12. The test statistic shows strong evidence of linkage and LD (chi-square statistic = 18.39 with 2 df, P -value = 0.0001). Genet. Epidemiol. 22:298,312, 2002. © 2002 Wiley-Liss, Inc. [source] Effect of genotype and environment on branching in weedy green millet (Setaria viridis) and domesticated foxtail millet (Setaria italica) (Poaceae)MOLECULAR ECOLOGY, Issue 5 2006ANDREW N. DOUST Abstract Many domesticated crops are derived from species whose life history includes weedy characteristics, such as the ability to vary branching patterns in response to environmental conditions. However, domesticated crop plants are characterized by less variable plant architecture, as well as by a general reduction in vegetative branching compared to their progenitor species. Here we examine weedy green millet and its domesticate foxtail millet that differ in the number of tillers (basal branches) and axillary branches along each tiller. Branch number in F2:3 progeny of a cross between the two species varies with genotype, planting density, and other environmental variables, with significant genotype,environment interactions (GEI). This is shown by a complex pattern of reaction norms and by variation in the pattern of significant quantitative trait loci (QTL) amongst trials. Individual and joint analyses of high and low density trials indicate that most QTL have significant GEI. Dominance and epistasis also explain some variation in branching. Likely candidate genes underlying the QTL (based on map position and phenotypic effect) include teosinte branched1 and barren stalk1. Phytochrome B, which has been found to affect response to shading in other plants, explains little or no variation. Much variation in branching is explained by QTL that do not have obvious candidate genes from maize or rice. [source] Genetic heterogeneity in rheumatoid arthritis mouse models induced by extrinsic and intrinsic factorsPATHOLOGY INTERNATIONAL, Issue 6 2010Shinichi Mizuki A cumulative effect of the susceptibility genes with polymorphic alleles may be responsible for rheumatoid arthritis (RA). The objective of this study was to clarify whether susceptibility to RA is under the control of common allelic loci between two different RA models induced by extrinsic and intrinsic factors, collagen-induced arthritis (CIA) in DBA/1 mice and arthritis in MRL/Mp (MRL) mice associated with the Fas deficient mutant gene, Faslpr, respectively. CIA was examined in mice of parental DBA/1 and MRL, (MRL × DBA/1) F1 and (MRL × DBA/1) F2 progenies. In genome-wide screening of the severity in the F2 using microsatellite markers, significant linkage was observed on chromosomes 5 and 17 at map position of D5Mit259 and H-2, respectively, associated with DBA/1 alleles, while there was no loci associated with arthritis of MRL- Faslpr mice previously identified. In a quantitative trait locus (QTL) analysis, the locus on chromosome 5 showed the highest peak at map position 35 cM (LOD score 6.0). This study may indicate that the arthritis induced by extrinsic and intrinsic factors is under the control of a different combination of susceptibility genes with common and different alleles, possibly simulating the genetic heterogeneity of RA. [source] Linkage mapping and comparative analysis of bovine expressed sequence tags (ESTs)ANIMAL GENETICS, Issue 3 2000W M Grosse Summary Bovine expressed sequence tags (ESTs) containing microsatellites are suitable markers for both linkage and comparative maps. We isolated clones from a bovine fetal thigh skeletal muscle cDNA library that were positive for a (CA)10 probe. Thirty individual clones were isolated and characterised by sequencing. Sequences from the 5, and 3, ends of a clone were considered as separate ESTs until a contiguous sequence was identified. A total of 47 ESTs were sequenced from the 5, and/or 3, ends and full sequence was obtained for the 30 clones. BLAST nucleotide analysis identified significant homology to known mammalian coding regions for 31 of the bovine ESTs, 30 of which also matched human ESTs or sequence-tagged sites (STS). The remaining 16 bovine ESTs represented novel transcripts. Microsatellites were isolated in 27 of the ESTs, 11 of which were developed into markers and placed on the MARC bovine linkage map. Human cytogenetic map positions were available for 20 of the 30 human EST orthologs, and a putative bovine map position for 17 of the sequences could be inferred using comparative mapping data. These results demonstrated that mapping bovine ESTs containing microsatellites is a plausible strategy to increase the density of gene markers on the bovine linkage and comparative maps. [source] Screening for novel ENU-induced rhythm, entrainment and activity mutantsGENES, BRAIN AND BEHAVIOR, Issue 4 2004Y. Bacon Chemical mutagenesis has provided an opportunity to develop and expand the repertoire of behavioural mutants for gene function studies. With this in mind, we have established a screen in mice for mutations affecting circadian rhythms, entrainment to light and other wheel-running parameters. The screen consists of an assessment of mouse wheel-running activity in a 12:12 h light/dark cycle for 7,10 days followed by assessment in constant darkness for up to 20 days. Responses to light are assessed using two protocols; a 15 minute light pulse given at circadian time 16 on the tenth day in constant darkness and an additional 12 h of light upon transition from light/dark conditions to constant darkness. To date, approximately 1300 progeny of chemically mutagenised mice have been screened. Computer-aided assessment of wheel-running parameters has helped in identifying abnormal phenotypes in approximately 5% of all animals screened. Inheritance testing of mice with abnormal phenotypes has confirmed the number of robustly inherited mutant phenotypes to be 1% of the total screened. Confirmed mutants including those affecting free-running period, light-responsiveness and wheel-running endurance have been identified. Thus far, low-resolution map positions have been established for four mutants by completing genome scans in backcross progeny. Mutant loci do not correspond with those previously associated with wheel-running behaviour. This result confirms that phenotype-driven approaches such as this should continue to provide material for mammalian gene function studies. [source] A Genetic Map Constructed Using a Doubled Haploid Population Derived from Two Elite Chinese Common Wheat VarietiesJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 8 2008Kun-Pu Zhang Abstract Genetic mapping provides a powerful tool for the analysis of quantitative trait loci (QTLs) at the genomic level. Herein, we report a new genetic linkage map developed from an F1 -derived doubled haploid (DH) population of 168 lines, which was generated from the cross between two elite Chinese common wheat (Triticum aestivum L.) varieties, Huapei 3 and Yumai 57. The map contained 305 loci, represented by 283 simple sequence repeat (SSR) and 22 expressed sequence tag (EST)-SSR markers, which covered a total length of 2141.7 cM with an average distance of 7.02 cM between adjacent markers on the map. The chromosomal locations and map positions of 22 new SSR markers were determined, and were found to distribute on 14 linkage groups. Twenty SSR loci showed different chromosomal locations from those reported in other maps. Therefore, this map offers new information on the SSR markers of wheat. This genetic map provides new opportunities to detect and map QTLs controlling agronomically important traits. The unique features of this map are discussed. [source] Gene expression microarray analysis and genome databases facilitate the characterization of a chromosome 22 derived homogenously staining regionMOLECULAR CARCINOGENESIS, Issue 1 2004Suzanna L. Arcand Abstract Karyotype and fluorescence in situ hybridization (FISH) analyses previously identified a homogenously staining region (HSR) derived from chromosome 22 in OV90, an epithelial ovarian cancer (EOC) cell line. Affymetrix® expression microarrays in combination with the UniGene and Human Genome Browser databases were used to identify the candidate genes comprising the amplicon of the HSR, based on comparison of expression profiles of OV90, EOC cell lines lacking HSRs and primary cultures of normal ovarian surface epithelial (NOSE) cells. A group of probe sets displaying a minimum 3-fold overexpression with a high reliability score (P-call) in OV90 were identified which represented genes that mapped within a 1,2 Mb interval on chromosome 22. A large number of probe sets, some of which represent the same genes, displayed no evidence of overexpression and/or low reliability scores (A-call). An investigation of the probe set sequences with the Affymetrix® and Sanger Institute Chromosome 22 Group databases revealed that some of the probe sets displaying discordant results for the same gene were complementary to intronic sequences and/or the antisense strand. Microarray results were validated by RT-PCR. Genomic analysis suggests that the HSR was derived from the amplification of a 1.1 Mb interval defined by the chromosomal map positions of ZNF74 and Hs.372662, at 22q11.21. The deduced amplicon is derived from a complex region of chromosome 22 that harbors low-copy repeats (LCRs). The amplicon contains 18 genes as likely targets for gene amplification. This study illustrates that large-scale expression microarray analysis in combination with genome databases is sufficient for deducing target genes associated with amplicons and stresses the importance of investigating probe set design before engaging in validation studies. © 2004 Wiley-Liss, Inc. [source] Linkage mapping and comparative analysis of bovine expressed sequence tags (ESTs)ANIMAL GENETICS, Issue 3 2000W M Grosse Summary Bovine expressed sequence tags (ESTs) containing microsatellites are suitable markers for both linkage and comparative maps. We isolated clones from a bovine fetal thigh skeletal muscle cDNA library that were positive for a (CA)10 probe. Thirty individual clones were isolated and characterised by sequencing. Sequences from the 5, and 3, ends of a clone were considered as separate ESTs until a contiguous sequence was identified. A total of 47 ESTs were sequenced from the 5, and/or 3, ends and full sequence was obtained for the 30 clones. BLAST nucleotide analysis identified significant homology to known mammalian coding regions for 31 of the bovine ESTs, 30 of which also matched human ESTs or sequence-tagged sites (STS). The remaining 16 bovine ESTs represented novel transcripts. Microsatellites were isolated in 27 of the ESTs, 11 of which were developed into markers and placed on the MARC bovine linkage map. Human cytogenetic map positions were available for 20 of the 30 human EST orthologs, and a putative bovine map position for 17 of the sequences could be inferred using comparative mapping data. These results demonstrated that mapping bovine ESTs containing microsatellites is a plausible strategy to increase the density of gene markers on the bovine linkage and comparative maps. [source] |