The vertebrate retina is comprised of seven major cell types that are generated in overlapping but well-defined intervals. To identify genes that might regulate retinal development, gene expression in the developing retina was profiled at multiple time points using serial analysis of gene expression (SAGE). The expression patterns of 1,051 genes that showed developmentally dynamic expression by SAGE were investigated using in situ hybridization. A molecular atlas of gene expression in the developing and mature retina was thereby constructed, along with a taxonomic classification of developmental gene expression patterns. Genes were identified that label both temporal and spatial subsets of mitotic progenitor cells. For each developing and mature major retinal cell type, genes selectively expressed in that cell type were identified. The gene expression profiles of retinal Müller glia and mitotic progenitor cells were found to be highly similar, suggesting that Müller glia might serve to produce multiple retinal cell types under the right conditions. In addition, multiple transcripts that were evolutionarily conserved that did not appear to encode open reading frames of more than 100 amino acids in length (“noncoding RNAs”) were found to be dynamically and specifically expressed in developing and mature retinal cell types. Finally, many photoreceptor-enriched genes that mapped to chromosomal intervals containing retinal disease genes were identified. These data serve as a starting point for functional investigations of the roles of these genes in retinal development and physiology.

WHAT'S KNOWN ON THIS SUBJECT:Infants with biliary atresia (BA) have better outcomes if detected and treated early, typically before 8 weeks of age. Making an early diagnosis is difficult, however, because newborns appear healthy and start developing disease at an unknown time. WHAT THIS STUDY ADDS:Patients with BA have elevated direct/ conjugated bilirubin (DB/CB) levels at birth. BA could be detected earlier if: (1) all newborns have DB/CB levels measured, including those not jaundiced; and (2) all elevated DB/CB levels are followed, independent of total bilirubin measurements. abstract OBJECTIVES: Healthy infants are thought to acquire biliary atresia (BA) in the first weeks of life. Because those diagnosed earlier have better outcomes, we were interested in determining the earliest time BA could be detected. We started by examining the immediate postnatal period, hypothesizing that newborns would not yet have acquired disease and still have normal direct/conjugated bilirubin (DB/CB) levels. PATIENTS AND METHODS:Newborn DB/CB levels were obtained retrospectively from birth hospitals. Subjects with BA were born between 2007 and 2010 and cared for at Texas Children's Hospital. Those with BA splenic malformation syndrome or born prematurely were excluded. Control subjects were term newborns who later never developed neonatal liver disease. RESULTS:Of the 61 subjects with BA, 56% had newborn DB/CB levels measured. All DB/CB levels exceeded laboratory norms and rose over time. At 24 to 48 hours of life, subjects with BA had mean DB levels significantly higher than those of controls (1.4 Ϯ 0.43 vs. 0.19 Ϯ 0.075 mg/dL, P Ͻ .0001), even while their mean total bilirubin (TB) levels remained below phototherapy limits. Finally, despite the elevated DB/CB levels, the majority of patients (79%) had normal DB:TB ratios Յ0.2. CONCLUSIONS:Patients with BA have elevated DB/CB levels shortly after birth. To detect affected infants earlier and improve outcomes, the results suggest two possibilities: (1) screen all newborns for elevated DB/CB levels, rather than just those who appear jaundiced; and then (2) follow all newborns with elevated DB/CB levels, rather than just those with DB:TB ratios Ͼ0.2. Pediatrics 2011;128:e1428-e1433 Drs Harpavat, Finegold, and Karpen designed the study, analyzed and interpreted the data, revised the article, and approved the final version for publication; Dr Harpavat acquired the data and wrote the original draft; and Dr Karpen initiated the idea and provided overall supervision for the project.A companion to this article can be found on page e1598 and online at www.pediatrics.org/cgi

No abstract