Haplotype Analisis of Familial Amyloidotic Polyneuropathy: an Evidence for Multiple Origins of the Val→met Mutation
The variant of transthyretin (TTR, also called prealbumin) has been identified as a major component of amyloid fibrils of familial amyloidotic polyneuropathy (FAP). In particular, the variant with30 Val→Met substitution has been commonly found in FAP of various ethnic groups. To understand the origin and spread of the Val→Met mutation, we have analyzed DNA polymorphisms associated with the TTR gene in six Japanese FAP families and several Portuguese FAP patients. Three distinct haplotypes associated with the Val→Met mutation were identified in Japanese FAP families, one of which was also found in Portuguese patients. Nucleotide sequence analysis revealed that the Val→Met mutation is caused by a C-T transition at a CpG dinucleotide sequence of mutation hotspot on the anti-sense strand of TTR gene DNA. These results suggest that the Val→Met mutation has frequently recurred in human population to generate FAP families in various ethnic groups.
KeywordsAmyloid Fibril Sodium Lauryl Sulfate Nucleotide Sequence Analysis Distinct Haplotype Familial Amyloidotic Polyneuropathy
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- 3.Saraiva, M.J.M., Costa, P.P., Birken, S. and Goodman, D.S.(1983) Trans. Assoc. Amer. Phys. 96, 261–270.Google Scholar
- 7.Saraiva, M.J.M., Sherman, W. and Goodman, D.S. (1986) J. Lab. Clin. Med. 108, 17–22.Google Scholar
- 11.Benson, M.D. and Dwulet, F.E. (1985) Clin. Res. 33, 590a (Abstr.).Google Scholar
- 15.Yoshioka, K., Sasaki, H., Yoshioka, N., Furuya, H., Harada, T., Kito, S. and Sakaki, Y. (1986) Mol. Biol. Med. 3, 319–328.Google Scholar