RESUMO
Familial dysautonomia (FD) is an autosomal recessive disorder characterized by developmental arrest in the sensory and autonomic nervous systems and by Ashkenazi Jewish ancestry. We previously had mapped the defective gene (DYS) to an 11-cM segment of chromosome 9q31-33, flanked by D9S53 and D9S105. By using 11 new polymorphic loci, we now have narrowed the location of DYS to <0.5 cM between the markers 43B1GAGT and 157A3. Two markers in this interval, 164D1 and D9S1677, show no recombination with the disease. Haplotype analysis confirmed this candidate region and revealed a major haplotype shared by 435 of 441 FD chromosomes, indicating a striking founder effect. Three other haplotypes, found on the remaining 6 FD chromosomes, might represent independent mutations. The frequency of the major FD haplotype in the Ashkenazim (5 in 324 control chromosomes) was consistent with the estimated DYS carrier frequency of 1 in 32, and none of the four haplotypes associated with FD was observed on 492 non-FD chromosomes from obligatory carriers. It is now possible to provide accurate genetic testing both for families with FD and for carriers, on the basis of close flanking markers and the capacity to identify >98% of FD chromosomes by their haplotype.
Assuntos
Doenças do Sistema Nervoso Autônomo/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 9/genética , Ligação Genética/genética , Haplótipos/genética , Alelos , Feminino , Efeito Fundador , Frequência do Gene/genética , Marcadores Genéticos/genética , Testes Genéticos , Variação Genética/genética , Heterozigoto , Humanos , Judeus/genética , Desequilíbrio de Ligação/genética , Masculino , Mutação/genética , Linhagem , Polimorfismo Genético/genética , Recombinação Genética/genéticaRESUMO
A holographic technique by which two dissimilar optical fields can be subtracted to yield only their difference is presented. The principle underlying this technique is that of optical interference between a holographically reconstructed field and a direct real-time one. Experimental verification is presented for the three cases of image-plane, fourier-transform, and Fresnel side-band holograms. Also considered is the application of this concept to change detection between photographic transparencies of some scene taken at different times.