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Copy Number Abnormalities (copy + number_abnormality)
Selected AbstractsCandidate glioblastoma development gene identification using concordance between copy number abnormalities and gene expression level changesGENES, CHROMOSOMES AND CANCER, Issue 10 2007Ken C. Lo Copy number abnormalities (CNAs) in tumor cells are presumed to affect expression levels of genes located in region of abnormality. To investigate this relationship we have surveyed the losses, gains and amplifications in 30 glioblastomas using array comparative genome hybridization and compared these data with gene expression changes in the same tumors using the Affymetrix U133Plus2.0 oligonucleotide arrays. The two datasets were overlaid using our in-house overlay tool which highlights concordance between CNAs and expression level changes for the same tumors. In this survey we have highlighted genes frequently overexpressed in amplified regions on chromosomes 1, 4, 11, and 12 and have identified novel amplicons on these chromosomes. Deletions of specific regions on chromosomes 9, 10, 11, 14, and 15 have also been correlated with reduced gene expression in the regions of minimal overlap. In addition we describe a novel approach for comparing gene expression levels between tumors based on the presence or absence of chromosome CNAs. This genome wide screen provides an efficient and comprehensive survey of genes which potentially serve as the drivers for the CNAs in GBM. © 2007 Wiley-Liss, Inc. [source] Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency,HUMAN MUTATION, Issue 8 2010Fang-Yuan Li Abstract Systemic primary carnitine deficiency (CDSP) is caused by recessive mutations in the SLC22A5 (OCTN2) gene encoding the plasmalemmal carnitine transporter and characterized by hypoketotic hypoglycemia, and skeletal and cardiac myopathy. The entire coding regions of the OCTN2 gene were sequenced in 143 unrelated subjects suspected of having CDSP. In 70 unrelated infants evaluated because of abnormal newborn screening (NBS) results, 48 were found to have at least 1 mutation/unclassified missense variant. Twenty-eight of 33 mothers whose infants had abnormal NBS results were found to carry at least 1 mutation/unclassified missense variant, including 11 asymptomatic mothers who had 2 mutations. Therefore, sequencing of the OCTN2 gene is recommended for infants with abnormal NBS results and for their mothers. Conversely, 52 unrelated subjects were tested due to clinical indications other than abnormal NBS and only 14 of them were found to have at least one mutation/unclassified variant. Custom designed oligonucleotide array CGH analysis revealed a heterozygous ,1.6 Mb deletion encompassing the entire OCTN2 gene in one subject who was apparently homozygous for the c.680G>A (p.R227H) mutation. Thus, copy number abnormalities at the OCTN2 locus should be considered if by sequencing, an apparently homozygous mutation or only one mutant allele is identified. ©2010 Wiley-Liss, Inc. [source] Genome-Wide Analysis of Subependymomas Shows Underlying Chromosomal Copy Number Changes Involving Chromosomes 6, 7, 8 and 14 in a Proportion of CasesBRAIN PATHOLOGY, Issue 4 2008Kathreena M. Kurian Abstract Subependymomas (SE) are slow-growing brain tumors that tend to occur within the ventricles of middle-aged and elderly adults. The World Health Organization classifies these tumors within the ependymoma group. Previous limited analysis of this tumor type had not revealed significant underlying cytogenetic abnormalities. We have used microarray comparative genomic hybridization to study a series of SE (n = 12). A whole-genome array at 0.97-Mb resolution showed copy number abnormalities in five of 12 cases (42%). Two cases (17%) showed regions of loss on chromosome 6. More detailed analysis of all cases using a chromosome 6 tile-path array confirmed the presence of overlapping regions of loss in only these two cases. One of these cases also showed trisomy chromosome 7. Monosomy of chromosome 8 was seen in a further two cases (17%), and a partial loss on chromosome 14 was observed in one additional case. This is the first array-based, genome-wide study of SE. The observation that five of 12 cases examined (42%) at 0.97-Mb resolution showed chromosomal copy number abnormalities is a novel finding in this tumor type. [source] Developmental perspectives on copy number abnormalities of the 22q11.2 regionCLINICAL GENETICS, Issue 3 2010TY Tan Tan TY, Gordon CT, Amor DJ, Farlie PG. Developmental perspectives on copy number abnormalities of the 22q11.2 region. The 22q11.2 chromosomal landscape predisposes to genomic rearrangements that are associated with a variety of clinical phenotypes. The most well known of these include the 22q11.2 deletion and Cat-eye syndromes (CES), but more recently other copy number abnormalities have been recognised, especially with increased use of microarrays in the investigation of patients with congenital malformations or cognitive impairment. In addition, mutations in the TBX1 gene have been found in patients with phenotypes reminiscent of 22q11.2 syndromes. Recent advances in our understanding of 22q11.2 genes and their interactions provide insight into the mechanisms underlying the phenotypic variability of the 22q11.2 syndromes, and suggest a possible common developmental pathway perturbed by copy number abnormalities of this locus. [source] | |||||||||||||