Genome Rearrangements Detected by SNP Microarrays in Individuals with Intellectual Disability Referred with Possible Williams Syndrome
| Autor: | Maricela D. Gulbronson, Patricia Bray-Ward, Ariel M. Pani, Colleen A. Morris, Gordon C. Gowans, Ronald G. Gregg, Robin C. Clark, Kendra W. Kimberley, Cecilia M. Rios, Holly H. Hobart, Carolyn B. Mervis |
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| Rok vydání: | 2010 |
| Předmět: |
Williams Syndrome
medicine.medical_specialty DNA Copy Number Variations Microarray Developmental Disabilities Molecular Sequence Data Population lcsh:Medicine Genetics and Genomics/Complex Traits Biology Bioinformatics Polymorphism Single Nucleotide Genomic Instability 03 medical and health sciences Segmental Duplications Genomic 0302 clinical medicine Intellectual Disability Molecular genetics Intellectual disability medicine Humans SNP lcsh:Science education Genetics and Genomics/Genetics of Disease Oligonucleotide Array Sequence Analysis 030304 developmental biology Chromosome Aberrations Genetics and Genomics/Medical Genetics Genetics 0303 health sciences education.field_of_study Multidisciplinary Base Sequence Genome Human lcsh:R Genetics and Genomics medicine.disease 3. Good health Phenotype Genetics and Genomics/Disease Models Neurological Disorders/Neurogenetics Etiology lcsh:Q Human genome Williams syndrome Chromosomes Human Pair 7 030217 neurology & neurosurgery Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 8, p e12349 (2010) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0012349 |
| Popis: | Background Intellectual disability (ID) affects 2–3% of the population and may occur with or without multiple congenital anomalies (MCA) or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for ∼50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA. Methodology/Principal Findings High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450) region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications), one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays. Conclusions/Significance Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information from the breakpoints frequently provides additional information. |
| Databáze: | OpenAIRE |
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