RESUMO
A number of genetic markers, including ATP1A3, TGFB, CKMM, and PRKCG, define the genetic region on human chromosome 19 containing the myotonic dystrophy locus. These and a number of other DNA probes have been mapped to mouse chromosome 7 utilizing a mouse Mus domesticus/Mus spretus interspecific backcross segregating for the genetic markers pink-eye dilution (p) and chinchilla (cch). The establishment of a highly syntenic group conserved between mouse chromosome 7 and human chromosome 19q indicates the likely position of the homologous gene locus to the human myotonic dystrophy gene on proximal mouse chromosome 7. In addition, we have mapped the muscle ryanodine receptor gene (Ryr) to mouse chromosome 7 and demonstrated its close linkage to the Atpa-2, Tgfb-1, and Ckmm cluster of genes. In humans, the malignant hyperthermia susceptibility locus (MHS) also maps close to this gene cluster. The comparative mapping data support Ryr as a candidate gene for MHS.
Assuntos
Cromossomos Humanos Par 19 , Cromossomos , Distrofia Miotônica/genética , Animais , Mapeamento Cromossômico , Cruzamentos Genéticos , Feminino , Genes , Ligação Genética , Humanos , Masculino , Camundongos , Pigmentação/genética , Polimorfismo de Fragmento de Restrição , Receptores Colinérgicos/genética , Recombinação Genética , Canal de Liberação de Cálcio do Receptor de Rianodina , Homologia de Sequência do Ácido NucleicoRESUMO
mdx is an X-linked muscular dystrophy mutant of the mouse and a putative homolog of the human X-linked muscular dystrophy locus--Duchenne muscular dystrophy (DMD). Utilizing a C57BL/10/Mus Spretus interspecific cross in which the mdx mutation was segregating, we have constructed a detailed genetic map around the mdx locus on the mouse X chromosome. We were unable to detect recombinants between mdx and exonic probes derived from the human DMD gene. These genetic data support the contention from biochemical studies (E.P. Hoffman, R. H. Brown, and L. M. Kunkel, 1987, Cell 51: 919-928) that DMD and mdx are homologous genes.
Assuntos
Genes , Distrofia Muscular Animal/genética , Cromossomo X , Animais , Southern Blotting , Mapeamento Cromossômico , Feminino , Marcadores Genéticos/análise , Haplótipos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distrofias Musculares/genéticaRESUMO
A large number of microclones obtained by microdissection of the mouse X chromosome have been mapped using an interspecific Mus domesticus/Mus spretus cross. Clones displaying close linkage to a number of loci of known phenotype but unknown gene product, such as mdx (X-linked muscular dystrophy), have been obtained. Over a central 30 cM span of the mouse X chromosome, 17 clones have been mapped and ordered at a sufficient density to contemplate the complete physical mapping of this region that will aid in the isolation of a number of unidentified genes. Some of the mapped microclones detect moderately repetitive sequences that were clustered in several discrete regions of the mouse X chromosome.
Assuntos
Clonagem Molecular , Cruzamentos Genéticos , Desoxirribonucleases de Sítio Específico do Tipo II , Camundongos/genética , Muridae/genética , Cromossomo X , Animais , Mapeamento Cromossômico , Enzimas de Restrição do DNA , Desoxirribonuclease HpaII , Feminino , Masculino , Recombinação GenéticaRESUMO
The recent discovery of sequences at the site of the Duchenne muscular dystrophy (DMD) gene in humans has opened up the possibility of a detailed molecular analysis of the genes in humans and in related mammalian species. Until relatively recently, there was no obvious mouse model of this genetic disease for the development of therapeutic strategies. The identification of a mouse X-linked mutant showing muscular dystrophy, mdx, has provided a candidate mouse genetic homologue to the DMD locus; the relatively mild pathological features of mdx suggest it may have more in common with mutations of the Becker muscular dystrophy type at the same human locus, however. But the close genetic linkage of mdx to G6PD and Hprt on the mouse X chromosome, coupled with its comparatively mild pathology, have suggested that the mdx mutation may instead correspond to Emery Dreifuss muscular dystrophy which itself is closely linked to DNA markers at Xq28-qter in the region of G6PD on the human X chromosome. Using an interspecific mouse domesticus/spretus cross, segregating for a variety of markers on the mouse X chromosome, we have positioned on the mouse X chromosome sequences homologous to a DMD cDNA clone. These sequences map provocatively close to the mdx mutation and unexpectedly distant from sparse fur, spf, the mouse homologue of OTC (ornithine transcarbamylase) which is closely linked to DMD on the human X chromosome.
Assuntos
DNA/metabolismo , Genes , Distrofias Musculares/genética , Cromossomo X , Alelos , Animais , Mapeamento Cromossômico , Cruzamentos Genéticos , Ligação Genética , Humanos , Camundongos , Muridae , Recombinação Genética , Especificidade da EspécieRESUMO
A wild mouse (CD) karyotype in which all the chromosomes bar the X, 19, and Y, are fused as metacentrics has been used for the microdissection and microcloning of a specific mouse X chromosome region. Dissection of a proximal region of the X chromosome encompassing the genetic loci Hprt to Tfm and including mdx has yielded 650 clones. A number of the recovered clones containing sizable inserts have been confirmed as X chromosome specific. This X chromosome bank of clones provides a start point for the isolation of the mdx locus. It is now clear that microdissection and microcloning can be applied to all mouse chromosomes, including the X chromosome, yielding premapped banks of clones that will greatly aid in the isolation and characterization of important genetic loci.