RESUMO
Pulmonary surfactant, a lipoprotein complex, is essential for normal lung function, and deficiency of surfactant can result in respiratory-distress syndrome (RDS) in the prematurely born infant. Some studies have pointed towards a genetic contribution to the aetiology of RDS. Because the surfactant protein B (SP-B) is important for optimal surfactant function and because it is involved in the pathogenesis of pulmonary disease, we investigated the genetic variability of the SP-B gene in individuals with and without RDS. We identified a 2.5 kb BamHI polymorphism and studied its location, nature and frequency. We localized this polymorphism in the first half of intron 4 and found that it is derived by gain or loss in the number of copies of a motif that consists of two elements, a 20 bp conserved sequence and a variable number of CA dinucleotides. Variability in the number of motifs resulting from either deletion (in 55.3% of the cases with the variation) or insertion (44.7%) of motifs was observed in genomic DNAs from unrelated individuals. Analysis of 219 genomic DNAs from infants with (n = 82) and without (n = 137) RDS showed that this insertion/deletion appears with significantly higher frequency in the RDS population (29.3 as against 16.8%, P < 0.05).
Assuntos
Variação Genética , Proteolipídeos/genética , Surfactantes Pulmonares/genética , Sequências Repetitivas de Ácido Nucleico/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/genética , Sequência de Bases , População Negra , Clonagem Molecular , Desoxirribonuclease BamHI , Frequência do Gene , Genoma Humano , Humanos , Lactente , Recém-Nascido , Íntrons/genética , Dados de Sequência Molecular , Mutagênese Insercional , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Surfactantes Pulmonares/deficiência , Análise de Sequência de DNA , Deleção de Sequência , Homologia de Sequência do Ácido Nucleico , População BrancaRESUMO
Alzheimer's disease is characterized by the accumulation of the beta/A4 fragment of the amyloid precursor protein in the hippocampal regions of the brain. We report here the isolation of genomic clones carrying exons 15, 16 and 17 of the beta/A4 coding region of the rabbit amyloid precursor protein gene. The complete sequence of these exons predicts that all three peptides are identical to their human counterparts. An unexpectedly high concentration of CpG dinucleotides seen in exon 15 were conserved and continued into the intron 15 region. MspI/HpaII southern blot analysis revealed the presence of a number of methylated CpG dinucleotides in the cloned region of the gene. These data suggest that the rabbit amyloid precursor protein gene could provide a new and useful model for the study of this important gene.
