The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that promotes white cell maturation, participates in the metabolism of pulmonary surfactant. Little is known on the production of GM-CSF during pregnancy or the neonatal period. We studied how the concentrations of GM-CSF in amniotic fluid (AF) or in tracheal aspirates (TA) of newborn infants are influenced by length of gestation, postnatal age, as well as conditions affecting the mother or the fetus. One hundred and forty-three AF samples from 143 pregnant patients (gestational age range, 28-42 wk) and 202 TA samples from 82 neonates (gestational age, 24-42.5 wk, postnatal age 0.2 d to 4 wk) were analyzed for GM-CSF using ELISA. In patients with intact membranes, AF GM-CSF increased as a function of gestational age; the concentrations were below 7.5 ng/L (detection limit of the assay) (n = 5), 18.6 +/- 2.3 ng/L (n = 56), and 56.7 +/- 7.9 ng/L (n = 58) at gestational ages between 28 and 32 wk, between 32 and 37 wk, and in term patients, respectively (linear regression: r = 0.404, p = 0.001). Among patients at less than 33 wk of gestation, those with intact membranes had a median AF GM-CSF concentration under the detection limit (n = 7), whereas in those with preterm premature rupture of membranes, the concentration was 50.1 +/- 22.2 ng/L (n = 16) (p = 0.002). Among term patients, those in labor had higher AF GM-CSF than those without signs of labor. TA GM-CSF at less than 12 h of age correlated with gestational age (r = 0.654, p = 0.0002, n = 28); thereafter, TA GM-CSF increased, and gestation dependence disappeared. We conclude that GM-CSF in AF and in fetal lung liquid is developmentally regulated and GM-CSF production increases in inflammatory conditions during pregnancy.