DNA rearrangements in the alpha 5(IV) collagen gene (COL4A5) of individuals with Alport syndrome: further refinement using pulsed-field gel electrophoresis.
Alport syndrome (AS), an X-linked kidney disorder, has been shown to be caused by mutations in the gene for the alpha 5-chain of type IV collagen (COL4A5), which maps to Xq22. On the basis of the results of conventional Southern blot analysis of AS patient DNAs, we employed pulsed-field gel electrophoresis to characterize further three gene rearrangements at the 3'-end of alpha 5(IV). We were able to construct long-range restriction maps for all three of these patients and deduce the extent and nature of each rearrangement. One of these mutations is a 450-kb simple deletion that includes 12 kb of the alpha 5(IV) gene. A second mutation has been shown to be a direct duplication of 35 kb of alpha 5(IV) genomic DNA, and a third mutation involves a complex insertion/deletion event resulting in an overall loss of 25 kb.
Vetrie
D
D
Paediatric Research Unit, United Medical School, Guy's Hospital, London, United Kingdom.
Boye
E
E
Flinter
F
F
Bobrow
M
M
Harris
A
A
D002874:Chromosome Mapping; D003094:Collagen / Q000235:genetics*; D016521:Electrophoresis, Gel, Pulsed-Field; D004720:Endonucleases / Q000378:metabolism; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D009394:Nephritis, Hereditary / Q000235:genetics*; D015183:Restriction Mapping
D003094:Collagen; D004720:Endonucleases