Talk:Respiratory System - Diaphragm

About Discussion Pages

On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes: References - recent and historic that relates to the topic Additional topic information - currently prepared in draft format Links - to related webpages Topic page - an edit history as used on other Wiki sites Lecture/Practical - student feedback Student Projects - online project discussions. Links: Pubmed Most Recent | Reference Tutorial | Journal Searches Glossary Links Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link Cite this page: Hill, M.A. (2024, June 26) Embryology Respiratory System - Diaphragm. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Respiratory_System_-_Diaphragm

2012

Congenital diaphragmatic hernia candidate genes derived from embryonic transcriptomes

Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2978-83. Epub 2012 Feb 6.

Russell MK, Longoni M, Wells J, Maalouf FI, Tracy AA, Loscertales M, Ackerman KG, Pober BR, Lage K, Bult CJ, Donahoe PK. Source Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114, USA.

Abstract

Congenital diaphragmatic hernia (CDH) is a common (1 in 3,000 live births) major congenital malformation that results in significant morbidity and mortality. The discovery of CDH loci using standard genetic approaches has been hindered by its genetic heterogeneity. We hypothesized that gene expression profiling of developing embryonic diaphragms would help identify genes likely to be associated with diaphragm defects. We generated a time series of whole-transcriptome expression profiles from laser captured embryonic mouse diaphragms at embryonic day (E)11.5 and E12.5 when experimental perturbations lead to CDH phenotypes, and E16.5 when the diaphragm is fully formed. Gene sets defining biologically relevant pathways and temporal expression trends were identified by using a series of bioinformatic algorithms. These developmental sets were then compared with a manually curated list of genes previously shown to cause diaphragm defects in humans and in mouse models. Our integrative filtering strategy identified 27 candidates for CDH. We examined the diaphragms of knockout mice for one of the candidate genes, pre-B-cell leukemia transcription factor 1 (Pbx1), and identified a range of previously undetected diaphragmatic defects. Our study demonstrates the utility of genetic characterization of normal development as an integral part of a disease gene identification and prioritization strategy for CDH, an approach that can be extended to other diseases and developmental anomalies.

PMID 22315423