Segmental duplication
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Chromosomal band 17q12 is a gene-rich region flanked by segmental duplications, making the region prone to deletions and duplications via the non-allelic homologous recombination mechanism. While deletions cause a well-described disorder with a specific phenotype called renal cysts and diabetes mellitus, the phenotype caused by reciprocal duplications is less specific, primarily because of variable expressivity, and incomplete penetrance. We present an unusual family with four children carrying the 17q12 microduplication inherited from their clinically healthy mother, who was a carrier of both the duplication and, interestingly, also of an atypical deletion of the 17q12 region. The duplication was inherited from her diabetic father and the deletion from her diabetic mother who also suffered from a renal disorder. Clinical manifestations in the family were variable, but all children showed some degree of a neurodevelopmental disorder, such as epilepsy, intellectual disability, delayed speech development, or attention deficit disorder. The simultaneous occurrence of a deletion and duplication in the same chromosomal region in one family is very rare, and to our knowledge, individuals carrying both a deletion and a duplication of this region have never been described.
- MeSH
- chromozomální delece MeSH
- duplikace chromozomů genetika MeSH
- fenotyp MeSH
- lidé MeSH
- mentální retardace * genetika MeSH
- mnohočetné abnormality * genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Repetitive sequences present a challenge for genome sequence assembly, and highly similar segmental duplications may disappear from assembled genome sequences. Having found a surprising lack of observable phenotypic deviations and non-Mendelian segregation in Arabidopsis thaliana mutants in SEC10, a gene encoding a core subunit of the exocyst tethering complex, we examined whether this could be explained by a hidden gene duplication. Re-sequencing and manual assembly of the Arabidopsis thaliana SEC10 (At5g12370) locus revealed that this locus, comprising a single gene in the reference genome assembly, indeed contains two paralogous genes in tandem, SEC10a and SEC10b, and that a sequence segment of 7 kb in length is missing from the reference genome sequence. Differences between the two paralogs are concentrated in non-coding regions, while the predicted protein sequences exhibit 99% identity, differing only by substitution of five amino acid residues and an indel of four residues. Both SEC10 genes are expressed, although varying transcript levels suggest differential regulation. Homozygous T-DNA insertion mutants in either paralog exhibit a wild-type phenotype, consistent with proposed extensive functional redundancy of the two genes. By these observations we demonstrate that recently duplicated genes may remain hidden even in well-characterized genomes, such as that of A. thaliana. Moreover, we show that the use of the existing A. thaliana reference genome sequence as a guide for sequence assembly of new Arabidopsis accessions or related species has at least in some cases led to error propagation.
Autoři prezentují šestitýdenního kojence s prenatálně diagnostikovanou střevní duplikaturou. Diagnóza byla postnatálně potvrzena pomocí ultrazvuku a MR. Byla provedena resekce kličky jejuna se střevní duplikaturou. Histologické vyšetření stěny cysty prokázalo zachovalou svalovou vrstvu a oploštělý střevní epitel.
The authors present a case report of a 6 week-old infant with prenatal appearance of intestinal duplication cyst. Diagnosis was postnatal confirmed with sonography and MRI. Resection of the jejunal bowel segment including the duplication cyst was performed. Histological examination of the cyst wall revealed a normal muscular layer with destroyed epithelium.
- MeSH
- cysta mezenteria chirurgie ultrasonografie MeSH
- kojenec MeSH
- lidé MeSH
- nemoci jejuna chirurgie patologie ultrasonografie MeSH
- prenatální diagnóza MeSH
- ultrasonografie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
Gene amplification is a frequent genetic abnormality in solid tumors, and many oncogenes are activated in this way. In acute myeloid leukemia (AML), a frequent target of gene amplification is chromosome 11, particularly chromosome region 11q23, including the MLL (myeloid/lymphoid leukemia) gene. However, the number of other amplicons from the long arm of chromosome 11 has also been described. Duplication/amplification of chromosome 11 was found by cytogenetic methods in 10 of 119 newly diagnosed patients with AML. The amplification was presented as: amplification including only the 5' segment of the MLL gene (1 patient), trisomy 11 (3 patients), partial trisomy 11q (2 patients), isochromosome 11q (1 patient), and multiple amplification of specific regions (3 patients). In two cases, amplification involved parts of not only long arm but also of short arm of the chromosome 11: 11p15 and 11p11.1 to 11p13.
- MeSH
- akutní myeloidní leukemie diagnóza genetika MeSH
- amplifikace genu MeSH
- dospělí MeSH
- duplikace genu MeSH
- hybridizace in situ fluorescenční MeSH
- karyotypizace MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 11 genetika MeSH
- prognóza MeSH
- senioři MeSH
- trizomie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Most patients with neurofibromatosis (NF1) are endowed with heterozygous mutations in the NF1 gene. Approximately 5% show an interstitial deletion of chromosome 17q11.2 (including NF1) and in most cases also a more severe phenotype. Here we report on a 7-year-old girl with classical NF1 signs, and in addition mild overgrowth (97th percentile), relatively low OFC (10th-25th percentile), facial dysmorphy, hoarse voice, and developmental delay. FISH analysis revealed a 17q11.2 microdeletion as well as an unbalanced 7p;13q translocation leading to trisomy of the 7q36.3 subtelomeric region. The patient's mother and grandmother who were phenotypically normal carried the same unbalanced translocation. The 17q11.2 microdeletion had arisen de novo. Array comparative genomic hybridization (CGH) demonstrated gain of a 550-kb segment from 7qter and loss of 2.5 Mb from 17q11.2 (an atypical NF1 microdeletion). We conclude that the patient's phenotype is caused by the atypical NF1 deletion, whereas 7q36.3 trisomy represents a subtelomeric copy number variation without phenotypic consequences. To our knowledge this is the first report that a duplication of the subtelomeric region of chromosome 7q containing functional genes (FAM62B, WDR60, and VIPR2) can be tolerated without phenotypic consequences. The 17q11.2 microdeletion (containing nine more genes than the common NF1 microdeletions) and the 7qter duplication were not accompanied by unexpected clinical features. Most likely the 7qter trisomy and the 17q11.2 microdeletion coincide by chance in our patient. Copyright (c) 2007 S. Karger AG, Basel
- MeSH
- chromozomální delece * MeSH
- cytogenetika MeSH
- dospělí MeSH
- duplikace genu * MeSH
- hybridizace in situ fluorescenční MeSH
- kojenec MeSH
- lidé MeSH
- lidské chromozomy, pár 17 * genetika MeSH
- lidské chromozomy, pár 7 * genetika MeSH
- neurofibromatózy * genetika patologie MeSH
- předškolní dítě MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- telomery genetika klasifikace MeSH
- Check Tag
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Acipenseriformes is a basal lineage of ray-finned fishes and comprise 27 extant species of sturgeons and paddlefishes. They are characterized by several specific genomic features as broad ploidy variation, high chromosome numbers, presence of numerous microchromosomes and propensity to interspecific hybridization. The presumed palaeotetraploidy of the American paddlefish was recently validated by molecular phylogeny and Hox genes analyses. A whole genome duplication in the paddlefish lineage was estimated at approximately 42 Mya and was found to be independent from several genome duplications evidenced in its sister lineage, i.e. sturgeons. We tested the ploidy status of available chromosomal markers after the expected rediploidization. Further we tested, whether paralogs of Hox gene clusters originated from this paddlefish specific genome duplication are cytogenetically distinguishable. RESULTS: We found that both paralogs HoxA alpha and beta were distinguishable without any overlapping of the hybridization signal - each on one pair of large metacentric chromosomes. Of the HoxD, only the beta paralog was unequivocally identified, whereas the alpha paralog did not work and yielded only an inconclusive diffuse signal. Chromosomal markers on three diverse ploidy levels reflecting different stages of rediploidization were identified: quadruplets retaining their ancestral tetraploid condition, semi-quadruplets still reflecting the ancestral tetraploidy with clear signs of advanced rediploidization, doublets were diploidized with ancestral tetraploidy already blurred. Also some of the available microsatellite data exhibited diploid allelic band patterns at their loci whereas another locus showed more than two alleles. CONCLUSIONS: Our exhaustive staining of paddlefish chromosomes combined with cytogenetic mapping of ribosomal genes and Hox paralogs and with microsatellite data, brings a closer look at results of the process of rediploidization in the course of paddlefish genome evolution. We show a partial rediploidization represented by a complex mosaic structure comparable with segmental paleotetraploidy revealed in sturgeons (Acipenseridae). Sturgeons and paddlefishes with their high propensity for whole genome duplication thus offer suitable animal model systems to further explore evolutionary processes that were shaping the early evolution of all vertebrates.
- MeSH
- diploidie * MeSH
- duplikace genu * MeSH
- genomika * MeSH
- genotypizační techniky MeSH
- hybridizace in situ fluorescenční * MeSH
- mikrosatelitní repetice genetika MeSH
- ribozomy genetika MeSH
- rybí proteiny genetika MeSH
- ryby genetika MeSH
- sekvenční homologie nukleových kyselin * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Chronic lymphocytic leukemia (CLL) with cytogenetics findings, such as complex karyotype and deletions of TP53 or ATM, is associated with adverse clinical outcomes. Additional chromosomal abnormalities further stratify patients into groups with diverse prognoses. Gain of 8q24 is one of the abnormalities considered as prognostically unfavorable. In our study, we performed a FISH analysis in an initial cohort of 303 consecutive CLL patients and determined the frequency of +8q to be 6.3 %. Our analysis confirmed the association with TP53/ATM aberrations and CK, as the frequency of +8q reached 26.7 % in an extended delTP53/ATM+CK cohort. M-FISH analysis enabled the identification of partner chromosomes where the segment of the duplicated 8q arm was localized. More detailed mapping of the gained 8q region using the M-BAND method determined the smallest amplified region 8q23-8qter. We observed significantly shorter overall survival (OS; 9.0 years in +8q-positive vs. 10.6 years in +8q-negative; p=0.02) and detected slightly higher MYC mRNA/protein levels in +8q-positive vs. +8q-negative patients.
- Publikační typ
- časopisecké články MeSH
- MeSH
- botanika metody MeSH
- chromozom Y * genetika MeSH
- DNA virů krev MeSH
- DNA * analýza krev MeSH
- kosti a kostní tkáň MeSH
- lidé MeSH
- mitochondriální DNA analýza dějiny genetika MeSH
- nekrotická degradace DNA MeSH
- odběr biologického vzorku metody MeSH
- polymerázová řetězová reakce využití MeSH
- posmrtné změny MeSH
- rodokmen MeSH
- segmentové duplikace MeSH
- sekvenční analýza DNA využití MeSH
- soudní genetika * dějiny metody zákonodárství a právo MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
BACKGROUND: Inversions are balanced structural chromosome rearrangements, which can influence gene expression and the risk of unbalanced chromosome constitution in offspring. Many examples of inversion polymorphisms exist in human, affecting both heterochromatic regions and euchromatin. RESULTS: We describe a novel, 15 Mb long paracentric inversion, inv(21)(q21.1q22.11), affecting more than a third of human 21q. Despite of its length, the inversion cannot be detected using karyotyping due to similar band patterns on the normal and inverted chromosomes, and is therefore likely to escape attention. Its identification was aided by the repeated observation of the same pair of 150 kb long duplications present in cis on chromosome 21 in three Czech families subjected to microarray analysis. The finding prompted us to hypothesise that this co-occurrence of two remote duplications could be associated with an inversion of the intervening segment, and this speculation turned out to be right. The inversion was confirmed in a series of FISH experiments which also showed that the second copy of each of the duplications was always located at the opposite end of the inversion. The presence of the same pair of duplications in additional individuals reported in public databases indicates that the inversion may also be present in other populations. Three out of the total of about 4000 chromosomes 21 examined in our sample carried the duplications and were inverted, corresponding to carrier frequency of about 1/660. Although the breakpoints affect protein-coding genes, the occurrence of the inversion in normal parents and siblings of our patients and the occurrence of the duplications in unaffected controls in databases indicate that this rare variant is rather non-pathogenic. The inverted segment carried an identical shared haplotype in the three families studied. The haplotypes, however, diverged very rapidly in the flanking regions, possibly pointing to an ancient founder event at the origin of the inversion. CONCLUSIONS: The identification of inv(21)(q21.1q22.11) supports the notion that paracentric inversions are the most common form of chromosomal variation and that some of them may still remain undetected.
Abnormalities of chromosome 1 are among the most frequent chromosomal aberrations in patients with multiple myeloma (MM) and are considered a poor-risk genetic feature. To define the frequency and minimal region of 1q gain, we performed immunophenotyping and fluorescence in situ hybridization, comparative genomic hybridization (CGH), and array-CGH in 30 patients in relapse and progression of MM. Gain of 1q21 was found in 15 patients (50%), and in 14 of them whole-arm gain was found. One of these 14 patients had trisomy of chromosome 1 together with whole arm 1q gain, and two others had segmental duplication together with whole arm 1q gain. Segmental duplication of 1q21.1 approximately q23.1 alone was found in one patient. These results confirmed a high frequency of 1q aberrations and revealed that the vast majority of patients with 1q aberration in relapse and progression of MM display whole arm 1q gain. Finally, we observed that 1q gain is highly associated with number of additional changes.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 1 genetika MeSH
- mnohočetný myelom genetika patologie MeSH
- progrese nemoci MeSH
- recidiva MeSH
- senioři MeSH
- srovnávací genomová hybridizace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
