lecture 4 BIMM-09

lecture 4 BIMM-09 - Model organisms in the understanding of...

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1 Model organisms in the understanding of the molecular basis of human development and disease, Conservation of developmental patterning genes and circuits in both vertebrates and invertebrates was invisible before the advent of molecular studies on developmental genes in model organisms
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2 Mammals have organized clusters of homeotic genes, or Hom/Hox genes (from their origin as homeobox containing genes), that resemble the clusters of Fy Hox genes Drosophila Hox gene cluster mouse Hox gene clusters (4)
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3 W. McGinnis, et al. (1984) Cell 37: 406 Evidence that a wide variety of animal genomes have (Hox) genes that are similar to Fy homeotic genes example of a "zoo Southern" blot experiment
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4 W. McGinnis, et al. (1984) Cell 37: 406 Mammals also have homeobox DNA sequences similar to fy homeotic genes, another zoo blot
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5 03_10_3.jpg Like the fy Hox genes, the Mouse Hox genes are are expressed in diFFerent cellular zones on the anterior posterior axis oF mouse embryos
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6 Changes in the localized patterns of Hox gene expression patterns are correlated with changes in animal morphology during evolution chicken Hoxc6 transcripts snake Hoxc6 transcripts
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7 Mutation of the mouse Hox10a, b, and c genes results in extra ribs in the body (a homeotic transformation) Axial skeletons of a triple Hox mutant at embryonic day 18.5 - lumbar and sacral vertebrae develop small ribs normal mouse axial skeleton of an embryo of the same stage
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8 The conservation of Hox gene clusters and functions means that the last common ancestor of Fruit ±ies and mammals had some version of a Hox cluster of anterior-posterior patterning genes
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9 Posterior Hox genes of mammals also control the developmental patterning of limbs
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10 Overlapping Hox gene expression patterns control proximal- distal and anterior-posterior vertebrate limb patterning Different Hox genes from the "a" cluster are activated in different zones of the limb bud proximal-distal axis Different Hox genes from the "d" cluster are activated in different zones of the limb bud anterior-posterior axis
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11 Human limb defects and Hox mutations • In an inherited synpolydactyly syndome, which has mild dominant and severe recessive limb defects, all affected individuals are either heterozygous or homozygous for a version of the HOXD13 gene that has suffered an expansion of a stretch of alanine codons. (Muragaki, et al. Science 272, 548) • In a family with hand-foot-genital syndrome, all
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lecture 4 BIMM-09 - Model organisms in the understanding of...

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