Paternal segmental isodisomy of centromeric region on chromosome 1 as a cause of juvenile hemochromatosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE50441 | GEO | 2014/01/30
SECONDARY ACCESSION(S): PRJNA217496
REPOSITORIES: GEO
Similar Datasets
Project description:Juvenile hemochromatosis type 2A in the studied patient was caused by a homozygous mutation c.196G>T (p.G66*) in hemojuvelin. Homozygous state for this mutation evolved through interstitial segmental isodisomy encompassing the centromeric region of chromosome 1 accompanying its paternal disomy. The disomy resulted into normal karyotype SNP genotyping was performed on 3 samples - family trio. Affymetrix GeneChip Command Console software was used for image processing and CEL files were processed by Affymetrix GTC using the BRLMM-P-Plus algorithm and regional GC correction configuration for Copy Number/LOH analysis. The HapMap270 file supplied by Affymetrix was used as the reference.
2014-01-30 | E-GEOD-50441 | biostudies-arrayexpress
Project description:Analysis of the molecular etiologies of severe combined immunodeficiency (SCID) has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein tyrosine phosphatase CD45, we utilized single nucleotide polymorphisms (SNP) Cytogenetics arrays; The patient’s mother was heterozygous for an inactivating mutation in CD45, while the paternal alleles exhibited no detectable mutations. The patient exhibited a single CD45 mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele. Non-lymphoid blood cells and other mesoderm and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient who had undergone successful bone marrow transplantation. These findings represent the first reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases. Affymetrix SNP Cytogenetics arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved sorted PMBC and buccal samples. Copy number and allele analysis of Affymetrix Cytogenetics arrays was performed for the patient's and his parent's samples.
2012-02-10 | E-GEOD-35674 | biostudies-arrayexpress
Project description:Paternal segmental isodisomy of centromeric region on chromosome 1 as a cause of juvenile hemochromatosis
| PRJNA217496 | ENA
Project description:Analysis of the molecular etiologies of severe combined immunodeficiency (SCID) has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein tyrosine phosphatase CD45, we utilized single nucleotide polymorphisms (SNP) Cytogenetics arrays; The patient’s mother was heterozygous for an inactivating mutation in CD45, while the paternal alleles exhibited no detectable mutations. The patient exhibited a single CD45 mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele. Non-lymphoid blood cells and other mesoderm and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient who had undergone successful bone marrow transplantation. These findings represent the first reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases.
2012-02-10 | GSE35674 | GEO
Project description:Relapse is the commonest cause of death in acute myeloid leukaemia (AML), but the mechanisms leading to relapse are unclear. Recently, acquisition of segmental uniparental disomy (UPD) by mitotic recombination (MR) has been reported in 15-20% of AML samples at diagnosis using whole genome single nucleotide polymorphism (SNP) arrays. These cytogenetically invisible abnormalities are associated with homozygous mutations in several types of malignancy. Clonal evolution of heterozygous to homozygous mutations by MR could provide a mechanism for relapse. Keywords: DNA copy number, loss of heterozygosity
2008-05-01 | GSE7210 | GEO
Project description:β-thalassemia major can be caused by homozygous mutations of the HBB gene, most of the cases are inherited from parents who both have β-thalassemia minor. Herein, we show that a mosaic paternal uniparental isodisomy of chromosome 11p14.3-15.5 is associated with β-thalassemia major in a patient with β-thalassemia minor-that evolved to β-thalassemia major. From this case, we suggest that analysis of HBB gene for non-hematopoietic tissues should be performed in late-onset β-thalassemia major patients. Keywords: genomic
2007-05-22 | GSE7847 | GEO
Project description:Preservation of chromosome integrity is key for the survival of any organism. To assure segregation of intact chromosomes, cell division is presumed to be under strict control of cell-cycle checkpoints. Estimates of chromosomal mutation rates per generation based on cytogenetic analyses of newborns and products of conception, range between 4.57x10-5 and 3.42x10-4. In contrast, the high incidence of segmental imbalances detected by single-cell genome-wide copy number profiling indicates that the error rate per cell division might be more than an order of magnitude higher. To directly measure the de novo incidence of segmental chromosomal imbalances, we plated a single fibroblast and analyzed the genomes of the two sister cells following a single cell division. Analysis of 89 pairs of sister cells (178 single cells in total) from 5 different cell lines revealed megabase-sized chromosomal imbalances in 21 fibroblasts, 14 of which derived from 7 mitoses with complementary segmental aneuploidies in the two daughter cells. The mutation rate of segmental imbalances is thus at least 7.9%, indicating that compared to the per generation chromosome stability is at least 100 times lower in vitro and likely underestimated in vivo.
2016-05-01 | GSE75088 | GEO
Project description:Preservation of chromosome integrity is key for the survival of any organism. To assure segregation of intact chromosomes, cell division is presumed to be under strict control of cell-cycle checkpoints. Estimates of chromosomal mutation rates per generation based on cytogenetic analyses of newborns and products of conception, range between 4.57x10-5 and 3.42x10-4. In contrast, the high incidence of segmental imbalances detected by single-cell genome-wide copy number profiling indicates that the error rate per cell division might be more than an order of magnitude higher. To directly measure the de novo incidence of segmental chromosomal imbalances, we plated a single fibroblast and analyzed the genomes of the two sister cells following a single cell division. Analysis of 89 pairs of sister cells (178 single cells in total) from 5 different cell lines revealed megabase-sized chromosomal imbalances in 21 fibroblasts, 14 of which derived from 7 mitoses with complementary segmental aneuploidies in the two daughter cells. The mutation rate of segmental imbalances is thus at least 7.9%, indicating that compared to the per generation chromosome stability is at least 100 times lower in vitro and likely underestimated in vivo.
2016-05-01 | GSE75068 | GEO
Project description:Preservation of chromosome integrity is key for the survival of any organism. To assure segregation of intact chromosomes, cell division is presumed to be under strict control of cell-cycle checkpoints. Estimates of chromosomal mutation rates per generation based on cytogenetic analyses of newborns and products of conception, range between 4.57x10-5 and 3.42x10-4. In contrast, the high incidence of segmental imbalances detected by single-cell genome-wide copy number profiling indicates that the error rate per cell division might be more than an order of magnitude higher. To directly measure the de novo incidence of segmental chromosomal imbalances, we plated a single fibroblast and analyzed the genomes of the two sister cells following a single cell division. Analysis of 89 pairs of sister cells (178 single cells in total) from 5 different cell lines revealed megabase-sized chromosomal imbalances in 21 fibroblasts, 14 of which derived from 7 mitoses with complementary segmental aneuploidies in the two daughter cells. The mutation rate of segmental imbalances is thus at least 7.9%, indicating that compared to the per generation chromosome stability is at least 100 times lower in vitro and likely underestimated in vivo.
2016-05-01 | GSE75098 | GEO