Genetic mapping of neurofibromatosis.

This thesis describes a study that examines the hypothesis of genetic linkage between the autosomal dominant disorder neurofibromatosis (NF) and human chromosomes 4 and 19. Spence et al. (1983) reported positive logarithm of the odds ratio (LOD) score between peripheral NF and the GV (vitamin D binding plasma transport protein) loci on chromosome 4. Chromosome 19 was under scrutiny from reports of the co-segregation of NF and myotonic dystrophy in pedigrees. Myotonic dystrophy has been mapped to chromosome 19 through linkage to the C3 (third component of complement) locus. Twelve Utah families are evaluated for possible linkage to know markers on chromosome 4 and chromosome 19. The cumulative LOD score for GC is -3.58 (at theta = .1). In the absence of heterogeneity, this value is believed to be sufficient to nullify previous reports of linkage of GC to NF. All markers on chromosome 4, (GC inclusive) give conclusive evidence against tight linkage. Linkage analysis for C3 yielded a cumulative LOD score of -4.5 (at theta = 0.0). Other markers on chromosome 19 were either negative or at zero probability for theta = 0.0. These results support an argument toward no linkage between chromosome 19 and NF, but more data is required before a final consensus should be made.