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.
Department of Medicine, University of Washington School of Medicine, Seattle 98195.
K
K
Stephens
L
L
Kayes
V M
VM
Riccardi
M
M
Rising
V P
VP
Sybert
R A
RA
Pagon
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