139 research outputs found
A Computational Method for the Rate Estimation of Evolutionary Transpositions
Genome rearrangements are evolutionary events that shuffle genomic
architectures. Most frequent genome rearrangements are reversals,
translocations, fusions, and fissions. While there are some more complex genome
rearrangements such as transpositions, they are rarely observed and believed to
constitute only a small fraction of genome rearrangements happening in the
course of evolution. The analysis of transpositions is further obfuscated by
intractability of the underlying computational problems.
We propose a computational method for estimating the rate of transpositions
in evolutionary scenarios between genomes. We applied our method to a set of
mammalian genomes and estimated the transpositions rate in mammalian evolution
to be around 0.26.Comment: Proceedings of the 3rd International Work-Conference on
Bioinformatics and Biomedical Engineering (IWBBIO), 2015. (to appear
Homologs of genes and anonymous loci on human Chromosome 13 map to mouse Chromosomes 8 and 14
To enhance the comparative map for human Chromosome (Chr) 13, we identified clones for human genes and anonymous loci that cross-hybridized with their mouse homologs and then used linkage crosses for mapping. Of the clones for four genes and twelve anonymous loci tested, cross-hybridization was found for six, COL4A1, COL4A2, D13S26, D13S35, F10, and PCCA. Strong evidence for homology was found for COL4A1, COL4A2, D13S26, D13S35, and F10, but only circumstantial homology evidence was obtained for PCCA. To genetically map these mouse homologs ( Cf10, Col4a1, Col4a2, D14H13S26, D8H13S35 , and Pcca-rs ), we used interspecific and intersubspecific mapping panels. D14H13S26 and Pcca-rs were located on the distal portion of mouse Chr 14 extending by ∼30 cM the conserved linkage between human Chr 13 and mouse Chr 14, assuming that Pcca-rs is the mouse homolog of PCCA. By contrast, Cf10, Col4a1, Col4a2 , and D8H13S35 mapped near the centromere of mouse Chr 8, defining a new conserved linkage. Finally, we identified either a closely linked sequence related to Col4a2 , or a recombination hot-spot between Col4a1 and Col4a2 that has been conserved in humans and mice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47022/1/335_2004_Article_BF00352413.pd
Limited Lifespan of Fragile Regions in Mammalian Evolution
An important question in genome evolution is whether there exist fragile
regions (rearrangement hotspots) where chromosomal rearrangements are happening
over and over again. Although nearly all recent studies supported the existence
of fragile regions in mammalian genomes, the most comprehensive phylogenomic
study of mammals (Ma et al. (2006) Genome Research 16, 1557-1565) raised some
doubts about their existence. We demonstrate that fragile regions are subject
to a "birth and death" process, implying that fragility has limited
evolutionary lifespan. This finding implies that fragile regions migrate to
different locations in different mammals, explaining why there exist only a few
chromosomal breakpoints shared between different lineages. The birth and death
of fragile regions phenomenon reinforces the hypothesis that rearrangements are
promoted by matching segmental duplications and suggests putative locations of
the currently active fragile regions in the human genome
IL-33 activates tumor stroma to promote intestinal polyposis
Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the ApcMin/+ mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in ApcMin/+ polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in ApcMin/+ polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment
Lysyl oxidase ( Lox ) maps between Grl-1 and Adrb-2 on mouse Chromosome 18
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47002/1/335_2004_Article_BF00352234.pd
Conserved linkage of neurotrophin-3 and von Willebrand factor on mouse Chromosome 6
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47003/1/335_2004_Article_BF00357095.pd
Report of the National Heart, Lung, and Blood Institute Working Group on epigenetics and hypertension
Hypertension, defined as a condition associated with 65140-mm Hg systolic blood pressure or 6590-mm Hg diastolic blood pressure, affects >1 billion people worldwide,1 and in 2009 it cost the US healthcare system more than 3.6 trillion more over the next 10 years.
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