Shaikh, T. H., Gai, X., Perin, J. C., Glessner, J. T., Xie, H., Murphy, K. et al. High-resolution mapping and analysis of copy number variations in the human genome: a data resource for clinical and research applications. Genome Res. 19, 1682-1690

Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Genome Research (Impact Factor: 14.63). 08/2009; 19(9):1682-90. DOI: 10.1101/gr.083501.108
Source: PubMed


We present a database of copy number variations (CNVs) detected in 2026 disease-free individuals, using high-density, SNP-based oligonucleotide microarrays. This large cohort, comprised mainly of Caucasians (65.2%) and African-Americans (34.2%), was analyzed for CNVs in a single study using a uniform array platform and computational process. We have catalogued and characterized 54,462 individual CNVs, 77.8% of which were identified in multiple unrelated individuals. These nonunique CNVs mapped to 3272 distinct regions of genomic variation spanning 5.9% of the genome; 51.5% of these were previously unreported, and >85% are rare. Our annotation and analysis confirmed and extended previously reported correlations between CNVs and several genomic features such as repetitive DNA elements, segmental duplications, and genes. We demonstrate the utility of this data set in distinguishing CNVs with pathologic significance from normal variants. Together, this analysis and annotation provides a useful resource to assist with the assessment of CNVs in the contexts of human variation, disease susceptibility, and clinical molecular diagnostics.

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    • "Estimated frequency in the human population is 4.70% (Canham et al., 2015). The loss at 16p11.2 contains three related genes TP53TG3, TP53TG3C, and TP53TG3B and it was reported previously in healthy population (Shaikh et al., 2009;de Smith et al., 2007). Estimated frequency in the human population is 5.14% (Canham et al., 2015). "
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    • "She also described some difficulties with fine motor skills and visual integration . Duplications of this region of chromosome 2q13 are not reported in normal CNV databases [Itsara et al., 2009; Shaikh et al., 2009; Macdonald et al., 2014] "
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    ABSTRACT: Copy number variation (CNV) in the long arm of chromosome 2 has been implicated in developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), congenital anomalies, and psychiatric disorders. Here we describe 14 new subjects with recurrent deletions and duplications of chromosome 2q11.2, 2q13, and 2q11.2-2q13. Though diverse phenotypes are associated with these CNVs, some common features have emerged. Subjects with 2q11.2 deletions often exhibit DD, speech delay, and attention deficit hyperactivity disorder (ADHD), whereas those with 2q11.2 duplications have DD, gastroesophageal reflux, and short stature. Congenital heart defects (CHDs), hypotonia, dysmorphic features, and abnormal head size are common in those with 2q13 deletions. In the 2q13 duplication cohort, we report dysmorphic features, DD, and abnormal head size. Two individuals with large duplications spanning 2q11.2-2q13 have dysmorphic features, hypotonia, and DD. This compilation of clinical features associated with 2q CNVs provides information that will be useful for healthcare providers and for families of affected children. However, the reduced penetrance and variable expressivity associated with these recurrent CNVs makes genetic counseling and prediction of outcomes challenging. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
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    • " including those by Itsara et al. (1/1557), Shaikh et al. (1/2026) and Xu et al. (3/6533) [Itsara et al., 2009; Shaikh et al., 2009; Xu et al., 2011]. This suggests that this change is likely to be benign. "
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