Dinucleotide repeats in the human surfactant protein-B gene and respiratory-distress syndrome.
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).
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey 17033.
J
J
Floros
S V
SV
Veletza
P
P
Kotikalapudi
L
L
Krizkova
A M
AM
Karinch
C
C
Friedman
S
S
Buchter
K
K
Marks
D001483:Base Sequence; D044383:Black People; D003001:Cloning, Molecular; D015245:Deoxyribonuclease BamHI; D005787:Gene Frequency; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011510:Proteolipids / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000172:deficiency / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D044465:White People
D011510:Proteolipids; D011663:Pulmonary Surfactants; D015245:Deoxyribonuclease BamHI