title: Evolutionary divergence of the mouse and human Lgn1/SMA repeat structures.
abstract: The orthologous genomic segments on mouse chromosome 13D1-D3 and human chromosome 5q11.2-q13.3 have been extensively studied because of their involvement in two distinct disease phenotypes, spinal muscular atrophy (SMA) in human and susceptibility to Legionella pneumophila (determined by Lgn1) in mice. The overlapping intervals in both species contain genomic amplifications of distinct structure, indicating an independent origin. We have endeavored to construct a comprehensive comparative gene map of the mouse and human Lgn1/SMA intervals in the hopes that the origins and maintenance of the genomic amplifications may become clear. Our comparative gene map demonstrates that the only regional gene in common between the amplified segments in mouse and human is the Lgn1 candidate Naip/NAIP. We have also determined that mice of the 129 haplotype harbor seven intact and three partial Naip transcription units arranged in a closely linked direct repeat on chromosome 13. Several, but not all, of these Naip loci are contained within the Lgn1 critical interval. We present a model for the origins of the mouse and human repetitive arrays from a common ancestral haplotype.
authors.affiliation: Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Growney
authors.forename: J M
authors.initials: JM
authors.lastname: Scharf
authors.forename: L M
authors.initials: LM
authors.lastname: Kunkel
authors.forename: W F
authors.initials: WF
authors.lastname: Dietrich
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D015139:Blotting, Southern; D002460:Cell Line; D002874:Chromosome Mapping; D017362:Cyclic AMP Response Element-Binding Protein; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D016952:Legionella pneumophila; D007877:Legionnaires' Disease / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000145:classification / Q000235:genetics*; D051616:Neuronal Apoptosis-Inhibitory Protein; D020161:Physical Chromosome Mapping; D016601:RNA-Binding Proteins; D012091:Repetitive Sequences, Nucleic Acid; D055532:SMN Complex Proteins
chemical_list: D020121:5' Untranslated Regions; D017362:Cyclic AMP Response Element-Binding Protein; C496800:NAIP protein, human; C496801:Naip1 protein, mouse; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins