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SNP genotyping to screen for a common deletion in CHARGE Syndrome

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Title SNP genotyping to screen for a common deletion in CHARGE Syndrome
 
Creator Lalani, Seema
Safiullah, Arsalan
Fernbach, Susan
Phillips, Michael
Bacino, Carlos
Molinari, Laura
Glass, Nancy
Towbin, Jeffrey
Craigen, William
Belmont, John
 
Description BACKGROUND:CHARGE syndrome is a complex of birth defects including coloboma, choanal atresia, ear malformations and deafness, cardiac defects, and growth delay. We have previously hypothesized that CHARGE syndrome could be caused by unidentified genomic microdeletion, but no such deletion was detected using short tandem repeat (STR) markers spaced an average of 5 cM apart. Recently, microdeletion at 8q12 locus was reported in two patients with CHARGE, although point mutation in CHD7 on chromosome 8 was the underlying etiology in most of the affected patients.METHODS:We have extended our previous study by employing a much higher density of SNP markers (3258) with an average spacing of approximately 800 kb. These SNP markers are diallelic and, therefore, have much different properties for detection of deletions than STRs.RESULTS:A global error rate estimate was produced based on Mendelian inconsistency. One marker, rs431722 exceeded the expected frequency of inconsistencies, but no deletion could be demonstrated after retesting the 4 inconsistent pedigrees with local flanking markers or by FISH with the corresponding BAC clone. Expected deletion detection (EDD) was used to assess the coverage of specific intervals over the genome by deriving the probability of detecting a common loss of heterozygosity event over each genomic interval. This analysis estimated the fraction of unobserved deletions, taking into account the allele frequencies at the SNPs, the known marker spacing and sample size.CONCLUSIONS:The results of our genotyping indicate that more than 35% of the genome is included in regions with very low probability of a deletion of at least 2 Mb.
 
Publisher BioMed Central
 
Date 2005
2006-05-06
 
Type article
 
Format application/pdf
 
Identifier DOI:10.1186/1471-2350-6-8
http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=14162
 
Source BMC Medical Genetics Vol. 6, no. 1 (2005)
 
Language eng
 
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