Preferential mutation of the neurofibromatosis type 1 gene in paternally derived chromosomes.
An interesting feature of neurofibromatosis type 1 (NF1) is its high mutation rate of 1 x 10(-4) per gamete per generation. The molecular basis for frequent NF1 mutation in unknown; the gene is not deletion prone. We have found that in all ten families examined, the apparent new NF1 mutation occurred on the paternally-derived chromosome. The probability of observing this result by chance is less than 0.001 assuming an equal frequency of mutation of paternal and maternal NF1 genes. We hypothesize a role for genomic imprinting that may either enhance mutation of the paternal NF1 gene or confer protection from mutation to the maternal NF1 gene.
Stephens
K
K
Department of Medicine, University of Washington School of Medicine, Seattle 98195.
Kayes
L
L
Riccardi
V M
VM
Rising
M
M
Sybert
V P
VP
Pagon
R A
RA
D002877:Chromosomes, Human; D004247:DNA / Q000235:genetics; D005260:Female; D016514:Genes, Neurofibromatosis 1; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D010334:Paternity; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
D005819:Genetic Markers; D004247:DNA