RESUMO
Retinitis pigmentosa (RP) is a heterogeneous genetic disorder with autosomal dominant, autosomal recessive, and X-linked forms. We previously mapped an additional arRP locus to chromosome 6p21 (RP14) in a single extended kinship from the Dominican Republic. Aided by a second linked RP pedigree from the same region of the Dominican Republic, we have refined the disease locus to a 2-cM region that is homozygous-by-descent in both pedigrees. A complete YAC, and a partial BAC, contig of the RP14 locus was constructed between the markers D6S1560 and D6S291, encompassing approximately 2.1 Mb. The contig contains 12 YACs and 31 BACs and is characterized by 45 markers including 8 microsatellite markers, 6 gene-derived sequences/ESTs obtained from the databases, and 28 new STSs and 4 new ESTs obtained by BLAST search using DNA sequence from the ends of the BAC and YAC inserts. With a STS density of approximately 1 every 20 kilobases, this contig significantly enhances available maps of the region.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 6/genética , Genes Recessivos/genética , Homozigoto , Mapeamento por Restrição , Retinose Pigmentar/genética , Cromossomos Artificiais de Levedura/genética , Cromossomos Artificiais de Levedura/metabolismo , Cromossomos Bacterianos/genética , Clonagem Molecular , República Dominicana , Feminino , Marcadores Genéticos , Humanos , Masculino , LinhagemRESUMO
The RP14 autosomal recessive Retinitis pigmentosa (arRP) locus has been mapped to a 2cM region of chromosome 6p21.3. TULP1 (the gene encoding tubby-like protein 1) is a candidate target for the disease mutation because it maps to the RP14 minimum genetic region and because a mutation in the highly homologous mouse tub gene leads to obesity, deafness and early progressive retinal degeneration. Here we report a splice-site mutation (IVS14+1, G-->A) that is homozygous in all affected individuals (N=33) and heterozygous in all obligate carriers (N=50) from two RP14-linked kindreds. The mutation was not observed in 210 unrelated controls. The data indicate that impairment of TULP1 protein function is a rare cause of arRP and that the normal protein plays an essential role in the physiology of the retina.
Assuntos
Proteínas do Olho/genética , Genes Recessivos , Retinose Pigmentar/genética , Animais , Sequência de Bases , Sequência Conservada , Primers do DNA , República Dominicana , Feminino , Triagem de Portadores Genéticos , Homozigoto , Humanos , Masculino , Camundongos , Camundongos Mutantes , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da PolimeraseRESUMO
A cross-sectional evaluation of dental caries in primary teeth and nutritional status was conducted involving 285 Peruvian children from low socioeconomic conditions aged 3-9 y. Forty-nine percent of the children were found to be chronically malnourished (stunted) whereas acute malnutrition (wasting) was infrequent (2%). Stunted children showed a delayed exfoliation of primary teeth. The caries prevalence curve as a function of age (ie, a plot of decayed, extracted, and filled teeth vs age) was found to be shifted to the right by approximately 15 mo in stunted children as compared with well-nourished children. Children aged 7-9 y with stunted growth showed a significantly higher percentage of carious teeth than did well-nourished children of the same age (40 and 29%, respectively; p less than 0.005). Nutritional deficits that lead to chronic malnutrition not only may affect tooth exfoliation but also appear to render the primary teeth more susceptible to caries attack later in life.