SNP array mapping of 20p deletions: Genotypes, Phenotypes and Copy Number Variation

• Published in: Human mutation Vol. 30; no. 3; pp. 371 - 378
• Main Authors: Kamath, Binita M., Thiel, Brian D., Gai, Xiaowu, Conlin, Laura K., Munoz, Pedro S., Glessner, Joseph, Clark, Dinah, Warthen, Daniel M., Shaikh, Tamim H., Mihci, Ercan, Piccoli, David A., Grant, Struan F.A., Hakonarson, Hakon, Krantz, Ian D., Spinner, Nancy B.
• Format: Journal Article
• Language: English
• Published: 01.03.2009
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/humu.20863

The use of array technology to define chromosome deletions and duplications is bringing us closer to establishing a genotype/phenotype map of genomic copy number alterations. We studied 21 patients and 5 relatives with deletions of the short arm of chromosome 20 using the Illumina HumanHap550 SNP array to 1) more accurately determine the deletion sizes, 2) identify and compare breakpoints, 3) establish genotype/phenotype correlations and 4) investigate the use of the HumanHap550 platform for analysis of chromosome deletions. Deletions ranged from 95kb to 14.62Mb, and all of the breakpoints were unique. Eleven patients had deletions between 95kb and 4Mb and these individuals had normal development, with no anomalies outside of those associated with Alagille syndrome. The proximal and distal boundaries of these eleven deletions constitute a 5.4MB region, and we propose that haploinsufficiency for only 1 of the 12 genes in this region causes phenotypic abnormalities. This defines the JAG1 associated critical region, in which deletions do not confer findings other than those associated with Alagille syndrome. The other 10 patients had deletions between 3.28Mb and 14.62Mb, which extended outside the critical region, and notably, all of these patients, had developmental delay. This group had other findings such as autism, scoliosis and bifid uvula. We identified 47 additional polymorphic genome-wide copy number variants (>20 SNPs), with 0–5 variants called per patient. Deletions of the short arm of chromosome 20 are associated with relatively mild and limited clinical anomalies. The use of SNP arrays provides accurate high-resolution definition of genomic abnormalities.