TY - JOUR
T1 - Genetic modifiers of muscular dystrophy
T2 - Implications for therapy
AU - Heydemann, Ahlke
AU - Doherty, Katherine R.
AU - McNally, Elizabeth M.
N1 - Funding Information:
AH, KRD and EMM are supported by the NIH. EMM is also supported by the Muscular Dystrophy Association, the Heart Research Foundation, and the Burroughs Wellcome Foundation.
PY - 2007/2
Y1 - 2007/2
N2 - The genetic understanding of the muscular dystrophies has advanced considerably in the last two decades. Over 25 different individual genes are now known to produce muscular dystrophy, and many different "private" mutations have been described for each individual muscular dystrophy gene. For the more common forms of muscular dystrophy, phenotypic variability can be explained by precise mutations. However, for many genetic mutations, the presence of the identical mutation is associated with marked phenotypic range that affects muscle function as well as cardiac function. The explanation for phenotype variability in the muscular dystrophies is only now being explored. The availability of genetically engineered animal models has allowed the generation of single mutations on the background of highly inbred strain. Phenotypic variation that is altered by genetic background argues for the presence of genetic modifier loci that can ameliorate or enhance aspects of the dystrophic phenotype. A number of individual genes have been implicated as modifiers of muscular dystrophy by studies in genetically engineered mouse models of muscular dystrophy. The value of these genes and products is that the pathways identified through these experiments may be exploited for therapy.
AB - The genetic understanding of the muscular dystrophies has advanced considerably in the last two decades. Over 25 different individual genes are now known to produce muscular dystrophy, and many different "private" mutations have been described for each individual muscular dystrophy gene. For the more common forms of muscular dystrophy, phenotypic variability can be explained by precise mutations. However, for many genetic mutations, the presence of the identical mutation is associated with marked phenotypic range that affects muscle function as well as cardiac function. The explanation for phenotype variability in the muscular dystrophies is only now being explored. The availability of genetically engineered animal models has allowed the generation of single mutations on the background of highly inbred strain. Phenotypic variation that is altered by genetic background argues for the presence of genetic modifier loci that can ameliorate or enhance aspects of the dystrophic phenotype. A number of individual genes have been implicated as modifiers of muscular dystrophy by studies in genetically engineered mouse models of muscular dystrophy. The value of these genes and products is that the pathways identified through these experiments may be exploited for therapy.
KW - Dysferlin
KW - Dystrophin
KW - Modifier
KW - Muscular dystrophy
KW - Sarcoglycan
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U2 - 10.1016/j.bbadis.2006.06.013
DO - 10.1016/j.bbadis.2006.06.013
M3 - Review article
C2 - 16916601
AN - SCOPUS:33846384302
SN - 0925-4439
VL - 1772
SP - 216
EP - 228
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 2
ER -