A gene dosage map of Chromosome 18: A map with clinical utility

Abstract

Purpose: Microarray technology has revolutionized the field of clinical genetics with the ability to detect very small copy number changes. However, challenges remain in linking genotype with phenotype. Our goal is to enable a clinical geneticist to align the molecular karyotype information from an individual patient with the annotated genomic content, so as to provide a clinical prognosis. Methods: We have combined data regarding copy number variations, microdeletion syndromes, and classical chromosome abnormalities, with the sparse but growing knowledge about the biological role of specific genes to create a genomic map of Chromosome 18 with clinical utility. Results: We have created a draft model of such a map, drawing from our longstanding interest in and data regarding the abnormalities of Chromosome 18. Conclusion: We have taken the first step toward creating a genomic map that can be used by the clinician in counseling and directing preventive or symptomatic care of individuals with Chromosome 18 abnormalities. Genet Med 2009:11(11):778 -782.

Global analyses of Chromosome 17 and 18 genes of lung telocytes compared with mesenchymal stem cells, fibroblasts, alveolar type II cells, airway epithelial cells, and lymphocytes

“…It has been reported that chromosomes 17 and 18 contained many disease-associated genes [32-37]. The present study initially demonstrated TCs-specific genes, of which 16 and 10 up-regulated and 68 and 22 down-regulated, in chromosomes 17 and 18, respectively.…”

Linking chromosome abnormality and copy number variation

“…In our first effort to do this for chromosome 18, we found dosage information on 86 of the 253 known genes on chromosome 18 [Cody et al, 2009]. Therefore, one-third of genes could be provisionally assigned a dosage category using existing information.…”

“…In addition, critical regions for the phenotypes associated with numerous chromosome abnormalities have been identified. A selected list is as follows: 1p36 [Redon et al, 2005]; 4p [Maas et al, 2008]; 5p [Zhang et al, 2005]; 9p [Barbaro et al, 2009]; 11q [Coldren et al, 2008]; 13q [Kirchhoff et al, 2009]; 18q [Cody et al, 2009]; and 21 [Korbel et al, 2009]. Although these types of data identify regions and rarely identify singles genes, these data are never-the-less an important resource for information about potential annotation of specific genes.…”

“…We have created a first draft gene dosage map and a critical regions map for chromosome 18 [Cody et al, 2009]. This map is a demonstration of how these data can be compiled and used for gaining clinical insight into a new patient recently diagnosed with a genomic copy number change.…”

The Chromosome 18 Clinical Resource Center

“…By following the directions in the section of the management guides labeled, “How to create a personalized syndrome description,” the exact base pair coordinates of the copy number change can be used to create a map view of the dosage sensitive genes and the phenotypes known to be associated with that region of the chromosome (Cody et al, ). In the case of 18p‐ used as an illustration here, the patient has a 3 Mb terminal deletion of 18p.…”