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
Fifty Kingella kingae organisms, isolated from tonsillar cultures of day care center attendees during an 11-month period, and 60 isolates derived from epidemiologically unrelated individuals, including 19 isolates from respiratory carriers and 41 isolates from patients with invasive infections, were typed by immunoblotting, pulsed-field gel electrophoresis, and ribotyping. One strain, defined by unique immunoblotting, pulsed-field gel electrophoresis, and ribotyping patterns, represented 14 day care isolates (28%) and was frequently isolated during the first half of the follow-up period; a second strain represented 23 (46%) isolates and prevailed during the last 5 months. Children frequently carried the same strain continuously or intermittently for weeks or months, when it was replaced by a new strain. Epidemiologically unrelated organisms showed greater variability, and no strain represented >5% of isolates. The present results support person-to-person transmission of K. kingae among young children in the day care setting.