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Xenoduplex Analysis—A Method for Comparative Gene Mapping Using Hybrid Panels

Marklund, Lena; Jeon, Jin-Tae; Andersson, Leif
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
Publicado em /04/1998 EN
Relevância na Pesquisa
46.02%
Somatic cell hybrid (SCH) panels and radiation hybrid (RH) panels are powerful resources for comparative gene mapping because gene assignments are made without the detection of genetic polymorphism as needed for linkage mapping. A frequently encountered problem, however, is that the gene specific primers may amplify homologous PCR products of equal length from the donor and recipient species of the panel. Here, we describe a simple solution to this problem in which we utilize the formation of interspecies heteroduplexes that can be easily distinguished from the corresponding homoduplexes by native polyacrylamide gel electrophoresis. We denote these DNA–DNA interspecies hybrids, xenoduplexes (xeno = Gr. Xenos, foreigner). A merit of the method is that the formation of xenoduplexes strongly suggests that the PCR products from the two species represent homologous sequences. The method is thus particularly useful for comparative gene mapping when the PCR primers have been designed by use of sequence information from other species. In this study we have successfully used xenoduplex analysis and a pig-rodent SCH panel to map seven porcine genes (ACADM, AT3, HOXD, IL8RB, LEPR, PAX8, PKLR) for which no previous sequence information was available. The assignment of the leptin receptor gene (LEPR) to pig chromosome 6q32–35 excluded LEPR as a candidate gene for a QTL on pig chromosome 4 with a major effect on fatness.

The genome data base (GDB)—a human gene mapping repository

Pearson, P.L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 25/04/1991 EN
Relevância na Pesquisa
45.91%
The types of gene mapping data and its organization in the Genome Data Base (GDB) recently established at Johns Hopkins Medical School are described. The database provides a continuous online environment for data perusal and editing and is used as the informatics core for running the human gene mapping workshops. Current development is primarily concentrated on extending the types of map object, means of defining map location, map storage and representation. Experimental data structures have been created that permit storage of any type of map information, physical or genetic.

Identification and Applications of Repetitive Probes for Gene Mapping in the Mouse

Siracusa, L. D.; Jenkins, N. A.; Copeland, N. G.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1991 EN
Relevância na Pesquisa
45.97%
Interspecific mouse hybrids that are viable and fertile provide a wealth of genetic variation that is useful for gene mapping. We are using this genetic variation to develop multilocus linkage maps of the mouse genome. As an outgrowth of this work, we have identified three repetitive probes that collectively identify 28 loci dispersed on 16 of the 19 mouse autosomes and the X chromosome. These loci establish a skeleton linkage map that can be used to detect linkage over much of the mouse genome. The molecular probes are derived from the mouse mammary tumor virus envelope gene, the ornithine decarboxylase gene, and the triose phosphate isomerase gene. The ability to scan the mouse genome quickly and efficiently in an interspecific cross using these three repetitive probes makes this system a powerful tool for identifying the chromosomal location of mutations that have yet to be cloned, mapping multigenic traits, and identifying recessive protooncogene loci associated with murine neoplastic disease. Ultimately, interspecific hybrids in conjunction with repetitive and single-copy probes will provide a rapid means to access virtually any gene of interest in the mouse genome at the molecular level.

Comparison of the power and accuracy of biallelic and microsatellite markers in population-based gene-mapping methods.

Xiong, M; Jin, L
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1999 EN
Relevância na Pesquisa
46%
Because of their great abundance and amenability to fully automated genotyping, single-nucleotide polymorphisms (SNPs) and simple insertion/deletion are emerging as a new generation of markers for positional cloning. Although the efficiency and cost associated with the markers are important in the mapping of human disease genes, the power to detect the linkage between the marker and the disease locus, as well as the accuracy of the estimation of the map location of the disease gene, dictate the selection of the markers. Both the power and the accuracy depend not only on the type of the markers but also on other factors, such as the age of the disease mutation, the magnitude of the genetic effect, the marker-allele distribution in the population, mutation rates of marker loci, the frequency of the disease allele, the recombination fraction, and the methods for mapping the human disease genes. In this article, we develop a mathematical framework and the analytical formulas for calculation of the power and the accuracy and investigate the impact that the aforementioned factors have on the power and the accuracy, by using two population-based gene-mapping methods-likelihood-based linkage-disequilibrium mapping and the transmission/disequilibrium test...

Modeling uncertainty in a database for physical gene mapping data.

Miller, P. L.; Shifman, M. A.; Kidd, K. K.
Fonte: American Medical Informatics Association Publicador: American Medical Informatics Association
Tipo: Artigo de Revista Científica
Publicado em //1991 EN
Relevância na Pesquisa
45.98%
We are building a database for the storage, retrieval, and graphical display of physical gene mapping data. To allow this information to be analyzed robustly, such a database must confront the inherent uncertainty of the data as a central design issue. The paper describes the overall database design, the types of gene mapping data which the system will contain, the types of uncertainty in the data, and certain of the design issues involved in allowing the database to handle uncertainty in a comprehensive fashion. Only if a full appreciation of uncertainty is built into the system from its inception will a physical gene mapping database be truly robust and successful.

Revised karyotyping and gene mapping of the Biomphalaria glabrata embryonic (Bge) cell line

Odoemelam, Edwin; Raghavan, Nithya; Miller, Andrè; Bridger, Joanna M.; Knight, Matty
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.94%
The fresh water snail Biomphalaria glabrata (2n = 36) belongs to the taxonomic class Gastropoda (family Planorbidae) and is integral to the spread of the human parasitic disease schistosomiasis. The importance of this mollusc is such that it has been selected as a model molluscan organism for whole genome sequencing. In order to understand the structure and organisation of the B. glabrata’s genome it is important that gene-mapping studies are established. Thus, we have studied the genomes of two B. glabrata embryonic (Bge) cell line isolates 1 and 2 grown in separate laboratories, but both derived from Eder L. Hansen’s original culture from the 1970s. This cell line continues to be an important tool and model system for schistosomiasis and B. glabrata. Using these cell line isolates, we have investigated the genome content and established a revised karyotype based on chromosome size and centromere position for these cells. Unlike the original karyotype (2n = 36) established for the cell line, our investigations now show the existence of extensive aneuploidy in both cell line isolates to the extent that the total complement of chromosomes in both greatly exceeds the original cell line’s diploid number of 36 chromosomes. The isolates...

Combining gene mapping and phenotype assessment for fast mutation finding in non-consanguineous autosomal recessive retinitis pigmentosa families

Hebrard, Maxime; Manes, Gaël; Bocquet, Béatrice; Meunier, Isabelle; Coustes-Chazalette, Delphine; Hérald, Emilie; Sénéchal, Audrey; Bolland-Augé, Anne; Zelenika, Diana; Hamel, Christian P
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.97%
Among inherited retinal dystrophies, autosomal recessive retinitis pigmentosa (arRP) is the most genetically heterogenous condition with 32 genes currently known that account for ∼60 % of patients. Molecular diagnosis thus requires the tedious systematic sequencing of 506 exons. To rapidly identify the causative mutations, we devised a strategy that combines gene mapping and phenotype assessment in small non-consanguineous families. Two unrelated sibships with arRP had whole-genome scan using SNP microchips. Chromosomal regions were selected by calculating a score based on SNP coverage and genotype identity of affected patients. Candidate genes from the regions with the highest scores were then selected based on phenotype concordance of affected patients with previously described phenotype for each candidate gene. For families RP127 and RP1459, 33 and 40 chromosomal regions showed possible linkage, respectively. By comparing the scores with the phenotypes, we ended with one best candidate gene for each family, namely tubby-like protein 1 (TULP1) and C2ORF71 for RP127 and RP1459, respectively. We found that RP127 patients were compound heterozygous for two novel TULP1 mutations, p.Arg311Gln and p.Arg342Gln, and that RP1459 patients were compound heterozygous for two novel C2ORF71 mutations...

Identification of a Novel Gene for Diabetic Traits in Rats, Mice, and Humans

Tsaih, Shirng-Wern; Holl, Katie; Jia, Shuang; Kaldunski, Mary; Tschannen, Michael; He, Hong; Andrae, Jaime Wendt; Li, Shun-Hua; Stoddard, Alex; Wiederhold, Andrew; Parrington, John; Ruas da Silva, Margarida; Galione, Antony; Meigs, James; Hoffmann, Raymon
Fonte: Genetics Society of America Publicador: Genetics Society of America
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
46.02%
The genetic basis of type 2 diabetes remains incompletely defined despite the use of multiple genetic strategies. Multiparental populations such as heterogeneous stocks (HS) facilitate gene discovery by allowing fine mapping to only a few megabases, significantly decreasing the number of potential candidate genes compared to traditional mapping strategies. In the present work, we employed expression and sequence analysis in HS rats (Rattus norvegicus) to identify Tpcn2 as a likely causal gene underlying a 3.1-Mb locus for glucose and insulin levels. Global gene expression analysis on liver identified Tpcn2 as the only gene in the region that is differentially expressed between HS rats with glucose intolerance and those with normal glucose regulation. Tpcn2 also maps as a cis-regulating expression QTL and is negatively correlated with fasting glucose levels. We used founder sequence to identify variants within this region and assessed association between 18 variants and diabetic traits by conducting a mixed-model analysis, accounting for the complex family structure of the HS. We found that two variants were significantly associated with fasting glucose levels, including a nonsynonymous coding variant within Tpcn2. Studies in Tpcn2 knockout mice demonstrated a significant decrease in fasting glucose levels and insulin response to a glucose challenge relative to those in wild-type mice. Finally...

Isolation of a fertile wheat-barley addition line carrying the entire barley chromosome 1H

Islam, A.; Shepherd, K.
Fonte: Kluwer Academic Publ Publicador: Kluwer Academic Publ
Tipo: Artigo de Revista Científica
Publicado em //2000 EN
Relevância na Pesquisa
45.91%
The isolation of six of the seven possible additions of barley chromosomes to the wheat genome reported 18 years ago has made an important contribution to gene mapping in barley, first with genes controlling isozymes and more recently DNA (molecular) markers. A fertile addition line involving barley chromosome 1H,which carries genes controlling several characters of economic importance, could not be isolated at that time because it caused extreme meiotic abnormalities leading to complete sterility when added to wheat. Later the short arm of barley chromosome 1H was added to wheat as a fertile ditelosomic addition, but the non-availability of the entire barley chromosome 1H addition line has hampered the location of barley genes to the long arm of this chromosome. This problem has now been overcome cytogenetically as described herein. The resultant self-fertile disomic-monotelodisomic addition line carrying a pair of barley chromosome 6H and a heteromorphic 1H/1HS pair is more stable, and makes the wheat-barley addition line series complete for gene mapping work and will provide a vehicle for the possible transfer of useful genes from this barley chromosome to wheat.; A.K.M. Rafiqul Islam and Kenneth W. Shepherd

Expression profiling and mapping of defence response genes associated with the barley-Pyrenophora teres incompatible interaction

Bogacki, P.; Oldach, K.; Williams, K.
Fonte: Wiley-Blackwell Publishing Ltd. Publicador: Wiley-Blackwell Publishing Ltd.
Tipo: Artigo de Revista Científica
Publicado em //2008 EN
Relevância na Pesquisa
45.95%
Barley net- and spot-form of net blotch disease are caused by two formae of the hemibiotrophic fungus Pyrenophora teres (P. t. f. teres and P. t. f. maculata). In the present study, suppression subtractive hybridization (SSH) was used in combination with quantitative real-time reverse transcriptase PCR to identify and profile the expression of defence response (DR) genes in the early stages of both barley–P. teres incompatible and compatible interactions. From a pool of 307 unique gene transcripts identified by SSH, 45 candidate DR genes were selected for temporal expression profiling in infected leaf epidermis. Differential expression profiles were observed for 28 of the selected candidates, which were grouped into clusters depending on their expression profiles within the first 48 h after inoculation. The expression profiles characteristic of each gene cluster were very similar in both barley–P. t. f. teres and barley–P. t. f. maculata interactions, indicating that resistance to both pathogens could be mediated by induction of the same group of DR genes. Chromosomal map locations for 21 DR genes were identified using four doubled-haploid mapping populations. The mapped DR genes were distributed across all seven barley chromosomes...

Multiple trait analysis for genetic mapping of quantitative trait loci for carcass and beef quality

Koshkoih, Ali Esmailizadeh
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2007
Relevância na Pesquisa
45.98%
The use of molecular markers to identify quantitative trait loci ( QTL ) affecting economically important traits has become a key approach in animal genetics, both for understanding the genetic basis of these traits and to help design novel breeding programs. The general goal of the present work was to map QTL for economically important traits in beef cattle. Because of the practical limitations of phenotypic selection for meat quality, these traits are ideal candidates for the use of marker - assisted selection. Thus, the thesis specifically focused on carcass and beef quality traits. Six half - sib families were generated by mating six Limousin x Jersey crossbred sires to purebred Jersey or Limousin cows, producing 784 backcross progeny ( 366 and 418 progeny in Australia and New Zealand, respectively ). The six crossbred sires and all the backcross progeny were genotyped for 285 microsatellite markers ( on average 189 informative loci per sire family ) spread across the 29 bovine autosomes. A large number of traits were recorded on backcross progeny. In the first phase of the research, a single - QTL model based on regression interval mapping was used to map QTL for a wide range of economically important traits in the beef industry. Chromosome - wise significant evidence for linkage was found on BTA12 ( P < 0.01 ) and BTA16 ( P < 0.05 ) for age at puberty. Thirteen QTL were found to affect calving ease related traits ( birth weight...

Stochastic search gene suggestion: Hierarchical Bayesian model selection meets gene mapping

Swartz, Michael D.
Fonte: Universidade Rice Publicador: Universidade Rice
Tipo: Thesis; Text Formato: 182 p.; application/pdf
ENG
Relevância na Pesquisa
45.98%
This dissertation introduces a novel approach for addressing the complexities of mapping a complex disease by adjusting a Bayesian Model Selection method. Mapping the genes for a complex disease, such as Rheumatoid Arthritis, involves finding multiple genetic loci that may contribute to the onset of the disease. Pairwise testing of the loci leads to the problem of multiple testing. To avoid multiple tests, one can look at haplotypes, or linear sets of loci, but this results in a contingency table with sparse counts, especially when using marker loci with multiple alleles. In order to jointly consider all loci in the problem, we applied a Hierarchical Bayesian Model Selection method to a conditional logistic regression model used in gene mapping. We chose Stochastic Search Variable Selection for its use of latent indicator variables to indicate those covariates, in this case genes, important to the model. We extended the latent variable structure to mirror genetics through a latent allele indicator conditional on a latent locus indicator. We also examined using a prior correlation structure on the allele coefficients that mirrors linkage disequilibrium, a between-locus genetic correlation structure. Ultimately, we ruled out the usefulness of a dependent covariance structure on the prior for allele main effects...

The LASSO linear mixed model for mapping quantitative trait loci

Foster, Scott David
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado Formato: 1731251 bytes; 92431 bytes; application/pdf; application/pdf
Publicado em //2006 EN
Relevância na Pesquisa
56.06%
This thesis concerns the identification of quantitative trait loci (QTL) for important traits in cattle line crosses. One of these traits is birth weight of calves, which affects both animal production and welfare through correlated effects on parturition and subsequent growth. Birth weight was one of the traits measured in the Davies' Gene Mapping Project. These data form the motivation for the methods presented in this thesis. Multiple QTL models have been previously proposed and are likely to be superior to single QTL models. The multiple QTL models can be loosely divided into two categories : 1 ) model building methods that aim to generate good models that contain only a subset of all the potential QTL ; and 2 ) methods that consider all the observed marker explanatory variables. The first set of methods can be misleading if an incorrect model is chosen. The second set of methods does not have this limitation. However, a full fixed effect analysis is generally not possible as the number of marker explanatory variables is typically large with respect to the number of observations. This can be overcome by using constrained estimation methods or by making the marker effects random. One method of constrained estimation is the least absolute selection and shrinkage operator (LASSO). This method has the appealing ability to produce predictions of effects that are identically zero. The LASSO can also be specified as a random model where the effects follow a double exponential distribution. In this thesis...

Ascertainment, diagnostic evaluation and gene mapping of South Australian families with possible X-linked mental retardation.

Al Raisi, Zahiya Abdulhameed Ahmed
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2009
Relevância na Pesquisa
45.98%
Mental retardation is a disorder that affects the lives of many individuals and their families worldwide. The underlying causes are heterogeneous and despite efforts to reveal them, the aetiology remains unknown for 50% of cases. Estimates of the prevalence of MR have varied between one and three percent in different studies, because of differences in definition, classification and approach to ascertainment. Most studies show that MR is about 30% more prevalent in males than females suggesting that XLMR is an important contributor to MR. Previous studies estimated that XLMR has a prevalence of 1.83 males (Herbst et al., 1980). The aim of the thesis was the ascertainment, diagnostic evaluation and gene mapping of South Australian families with possible XLMR. The South Australian Clinical Genetics Service's database (Kintrak) identified 33 families with possible XLMR of unknown cause. The clinical features and diagnostic evaluation of these families were documented. Six of these families were large enough for linkage mapping but only 2 of them agreed to participate in the current study. For one family the gene was localised between markers DXS8067 and DXS1062. Two candidate genes within the linkage interval, PHF6 and GRIA3 were screened for a mutation but no pathological mutation was found. The linkage mapping of the second family is still in progress. One of the 33 families was suspected to have Borjeson-Forssman-Lehmann syndrome and was screened for PHF6 but no mutation was found. Tarpey et al. (2007) identified protein truncating mutations in UPF3B in some patients with Lujan Fryns Syndrome (XLMR with Marfanoid body build). Therefore...

Linkage disequilibrium in the neurofibromatosis 1 (NF1) region: implications for gene mapping.

Jorde, L B; Watkins, W S; Viskochil, D; O'Connell, P; Ward, K
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1993 EN
Relevância na Pesquisa
45.97%
To test the usefulness of linkage disequilibrium for gene mapping, we compared physical distances and linkage disequilibrium among eight RFLPs in the neurofibromatosis 1 (NF1) region. Seven of the polymorphisms span most of the NF1 gene, while the remaining polymorphism lies approximately 70 kb 3' to a stop codon in exon 49. By using Centre d'Etude du Polymorphisme Humain (CEPH) kindreds, 91-110 unrelated parents were genotyped. A high degree of disequilibrium is maintained among the seven intragenic polymorphisms (r > .82, P < 10(-7)), even though they are separated by as much as 340 kb. The 3' polymorphism is only 68 kb distal to the next polymorphism, but disequilibrium between the 3' polymorphism and all others is comparatively low (magnitude of 4 < .33, P values .27-.001). This result was replicated in three sets of unrelated kindreds: the Utah CEPH families, the non-Utah CEPH families, and an independent set of NF1 families. Trigenic, quadrigenic, three-locus, and four-locus disequilibrium measures were also estimated. There was little evidence of higher-order linkage disequilibrium. As expected for a disease with multiple mutations, no disequilibrium was observed between the disease gene and any of the RFLPs. The observed pattern of high disequilibrium within the gene and a loss of disequilibrium 3' to the stop codon could have implications for gene mapping studies. These are discussed...

Genomic Restructuring in the Tasmanian Devil Facial Tumour: Chromosome Painting and Gene Mapping Provide Clues to Evolution of a Transmissible Tumour

Deakin, Janine E.; Bender, Hannah S.; Pearse, Anne-Maree; Rens, Willem; O'Brien, Patricia C. M.; Ferguson-Smith, Malcolm A.; Cheng, Yuanyuan; Morris, Katrina; Taylor, Robyn; Stuart, Andrew; Belov, Katherine; Amemiya, Chris T.; Murchison, Elizabeth P.; Pap
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.91%
Devil facial tumour disease (DFTD) is a fatal, transmissible malignancy that threatens the world's largest marsupial carnivore, the Tasmanian devil, with extinction. First recognised in 1996, DFTD has had a catastrophic effect on wild devil numbers, and intense research efforts to understand and contain the disease have since demonstrated that the tumour is a clonal cell line transmitted by allograft. We used chromosome painting and gene mapping to deconstruct the DFTD karyotype and determine the chromosome and gene rearrangements involved in carcinogenesis. Chromosome painting on three different DFTD tumour strains determined the origins of marker chromosomes and provided a general overview of the rearrangement in DFTD karyotypes. Mapping of 105 BAC clones by fluorescence in situ hybridisation provided a finer level of resolution of genome rearrangements in DFTD strains. Our findings demonstrate that only limited regions of the genome, mainly chromosomes 1 and X, are rearranged in DFTD. Regions rearranged in DFTD are also highly rearranged between different marsupials. Differences between strains are limited, reflecting the unusually stable nature of DFTD. Finally, our detailed maps of both the devil and tumour karyotypes provide a physical framework for future genomic investigations into DFTD.

Gene mapping and gene enrichment by the avidin-biotin interaction: use of cytochrome-c as a polyamine bridge.

Sodja, A; Davidson, N
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1978 EN
Relevância na Pesquisa
45.97%
A modification of previously described methods of electron microscopic gene mapping and of gene enrichment based on the avidin-biotin interaction is presented. The modification consists of coupling cytochrome-c instead of pentane diamine to the oxidized 2', 3' terminus of an RNA by Schiff base formation and BH-4 reduction. The RNA-cytochrome-c conjugate is purified by a simple chromatographic procedure; several biotins are attached to the cytochrome moiety by acylation. The extended arm between biotin and RNA gives efficient electron microscopic gene mapping of DNA:RNA-biotin hybrids with avidin-ferritin and avidin-polymethacylate sphere labels and efficient gene enrichment by buoyant banding of DNA:RNA-biotin:avidin-spheres in CsCl. A 1400 fold enrichment (thus, 25% pure) and a 90% yield of long Drosophila DNA strands with 5S RNA genes is achieved.

Gene mapping and gene enrichment by the avidin-biotin interaction: use of cytochrome-c as a polyamine bridge

Sodja, Ann; Davidson, Norman
Fonte: Instituto de Tecnologia da Califórnia Publicador: Instituto de Tecnologia da Califórnia
Tipo: Article; PeerReviewed Formato: application/pdf
Publicado em /02/1978
Relevância na Pesquisa
45.97%
A modification of previously described methods of electron microscopic gene mapping and of gene enrichment based on the avidin-biotin interaction is presented. The modification consists of coupling cytochrome-c instead of pentane tane diamine to the oxidized 2', 3' terminus of an RNA by Schiff base formation and reduction. The RNA-cytochrome-c conjugate is purified by a simple chromatographic procedure; several biotins are attached to the cytochrome moiety by acylation. The extended arm between biotin and RNA gives efficient electron microscopic gene mapping of DNA:RNA-biotin hybrids with avidin-ferritin and avidin-polymethacylate sphere labels and efficient gene enrichment by buoyant banding of DNA:RNA-biotin:avidin-spheres in CsCl. A 1400 fold enrichment (thus, 25% pure) and a 90% yield of long Drosophila DNA strands with 5S RNA genes is achieved.

From brain determination to testis determination: Evolution of the mammalian sex-determining gene

Graves, Jennifer
Fonte: CSLI Publications Publicador: CSLI Publications
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
55.93%
In mammals, sex is determined by an XY male:XX female sex chromosome system in which a male-dominant gene on the Y chromosome (SRY) determines testis formation. Sex chromosomes evolved from an ordinary autosome pair as the Y chromosome was progressively degraded. The Y chromosome has lost nearly all of its 1500 original genes, and those that survived did so because they evolved a critical role in male determination or differentiation. SRY is typical of Y-borne genes. Comparative gene mapping and sequencing shows that SRY arose quite recently as a degraded version of the SOX3 gene on the X chromosome. SOX3 is expressed predominantly in brain, and so is more likely to be a brain-determining than a testis-determining gene. The male-dominant action of SRY may be an illusion, as its structure suggests that it works by interfering with the action of a related gene, which in turn inhibits testis development. This hypothesis can give a good account of how a brain-determining gene acquired a role in testis determination via differential dosage of SOX3. SRY has no central role in sex determination and it can be replaced as a trigger and lost, as have many other Y-borne genes in recent evolutionary history. The absence of SRY in two species of the mole vole (Ellobius) suggests that its useful life is already running out.

Mapeamento de um gene de Leishmania major que confere resistência a pentamidina por deleção e inserção de elementos transposicionais; Mapping of a Leishmania major gene/locus that confers pentamidine resistance by deletion and insertion of transposable element

Coelho, Adriano C.; Tosi, Luiz R. O.; Cotrim, Paulo C.
Fonte: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo Publicador: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; Formato: application/pdf
Publicado em 01/04/2004 ENG
Relevância na Pesquisa
45.92%
A Pentamidina (PEN) é um composto alternativo para o tratamento de pacientes com leishmaniose que apresentam resistência ao antimônio, cujo alvo celular continua incerto. Uma abordagem para se identificar prováveis alvos seria a identificação e super-expressão de genes capazes de mediar resistência a PEN. A partir de uma genoteca construída com o DNA de Leishmania major em um vetor - cosmídio que se desenvolve tanto em bactérias como nas células do parasita, isolamos um locus que após transfecção é capaz de produzir resistência a PEN às células do parasita. Almejando o mapeamento desse locus de leishmania, o inserto clonado nesse cosmídio foi deletado através de duas digestões parciais sucessivas com enzimas de restrição, seguida de transfecção em células selvagens, super-expressão gênica, indução e testes funcionais na presença de PEN. Para determinar o gene de Leishmania relacionado com a resistência a PEN, o seqüenciamento de nucleotídeos foi executado após inserção de elementos transposicionais de Drosophila melanogaster no interior do inserto deletado para atuar como 'ilhas de iniciadores'. Descrevemos aqui o mapeamento desse locus, após a inserção transposicional, que além de facilitar o seqüenciamento de nucleotídeos de grandes fragmentos de DNA...