High Resolution Genomic Analysis of 18q- Using Oligo-microarray Comparative Genomic Hybridization (aCGH)

Overview

Journal Am J Med Genet A

Specialty Genetics

Date 2009 Jun 18

PMID 19533772

Citations 23

Authors

Patricia L Heard

Erika M Carter

Analisa C Crandall

Courtney Sebold

Daniel E Hale

Jannine D Cody

Affiliations

Soon will be listed here.

Abstract

The advent of oligonucleotide array comparative genomic hybridization (aCGH) has revolutionized diagnosis of chromosome abnormalities in the genetics clinic. This new technology also has valuable potential as a research tool to investigate larger genomic rearrangements that are typically diagnosed via routine karyotype. aCGH was used as a tool for the high-resolution analysis of chromosome content in individuals with known deletions of chromosome 18. The aim of this study was to clarify the precise location of the breakpoints as well as to determine the presence of occult translocations creating additional deletions and duplications. One hundred eighty-nine DNA samples from individuals with 18q deletions were analyzed. No breakpoint clusters were identified, as no more than two individuals had breakpoints within 2 kb of each other. Only two regions of 18q were never found to be haploid, suggesting the existence of haplolethal genes in those regions. Of the individuals with only a chromosome 18 abnormality, 17% (n = 29) had interstitial deletions. Six percent (n = 11) had a region of duplication immediately proximal to the deletion. Eight percent (n = 15) had more complex rearrangements with captured (non-18q) telomeres thus creating a trisomic region. The 15 captured telomeres originated from a limited number of other telomeres (4q, 10q, 17p, 18p, 20q, and Xq). These data were converted into a format for ease of viewing and analysis by creating custom tracks for the UCSC Genome Browser. Taken together, these findings confirm a higher level of variability and genomic complexity surrounding deletions of 18q than has previously been appreciated.

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