High-resolution mapping of mouse chromosome 8 identifies an evolutionary chromosomal breakpoint.
The central region of mouse Chromosome (Chr) 8, containing the myodystrophy (myd) locus, is syntenic with human Chr 4q28-qter. The human neuromuscular disorder facioscapulohumeral muscular dystrophy (FSHD) maps to Chr 4q35, and myd has been proposed as a mouse homolog of FSHD. We have employed a comparative mapping approach to investigate this relationship further by extending the mouse genetic map of this region. We have ordered 12 genes in a single cross, 8 of which have human homologs on 4q28-qter. The results confirm a general relationship between the most distal genes on human 4q and the most proximal genes in the mouse 8 syntenic region. Despite chromosomal rearrangements of syntenic groups in this region, conservation of gene order is maintained between the group of genes in the human telomeric region of 4q35 and MMU8. Furthermore, this conserved telomeric HSA4q35 syntenic group maps proximal to the myd mutation and is flanked by genes with homologs on HSA8p22. At the proximal boundary of the MMU8 linkage group we have identified a single 300-kb YAC containing the genes Frgl and Pcml, which have human homologs on 4q35 and 8p22, respectively. Thus, this YAC spans an evolutionary chromosomal breakpoint. As well as providing clues about chromosomal evolution, this map of the FSHD syntenic mouse region should prove invaluable in the isolation of candidate genes for this disease.
School of Biological Sciences, The University of Manchester, 3.239 Stopford Building, Oxford Rd., Manchester M13 9PT, UK.
P K
PK
Grewal
D J
DJ
Bolland
L C
LC
Todd
J E
JE
Hewitt
D000818:Animals; D005075:Biological Evolution; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003433:Crosses, Genetic; D017931:DNA Primers; D005819:Genetic Markers; D006801:Humans; D051379:Mice / Q000235:genetics*; D008810:Mice, Inbred C57BL; D009115:Muridae; D009136:Muscular Dystrophies / Q000235:genetics; D009137:Muscular Dystrophy, Animal / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016615:Telomere
D017931:DNA Primers; D005819:Genetic Markers