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At least 109 records · Page 6Linked to original sources
PubMed2001

Absence of deleted in azoospermia (DAZ) genes in spermatozoa of infertile men with somatic DAZ deletions.

OBJECTIVE: To determine the presence or absence of the deleted in azoospermia (DAZ) gene clusters in the Y-bearing spermatozoa in semen of severely oligozoospermic men or in testicular biopsy samples of azoospermic men with somatic DAZ deletions. DESIGN: Prospective study. SETTING: Academic hospital. PATIENT(S): Nineteen patients attending our clinics for therapeutic intracytoplasmic injection of sperm. INTERVENTION(S): Peripheral blood lymphocytes were used to obtain somatic DNA for analysis using the polymerase chain reaction. Analysis of chromosomes X and Y and the detection of the DAZ gene clusters were carried out with the fluorescence in situ hybridization technique in spermatozoa remaining after intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S): Presence or absence of the DAZ gene clusters in matched somatic DNA and Y-bearing spermatozoa. RESULT(S): Seven patients appeared to have a somatic DAZ deletion. Three-color fluorescence in situ hybridization showed that all Y-bearing spermatozoa examined from these men carried the same deletion. CONCLUSION(S): The DAZ deletions present in the seven men would all have been transmitted if they had fathered sons through artificial fertilization techniques using the sperm cells examined in this study.

DNA↗
PubMed1997

Screening for deletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in azoospermia and severe oligozoospermia.

OBJECTIVE: To evaluate the occurrence and prevalence of microdeletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in patients with azoospermia or severe oligozoospermia. DESIGN: Controlled clinical study. SETTING: University infertility clinic. PATIENT(S): Infertile men (n = 168) with nonobstructive, idiopathic azoospermia or severe oligozoospermia and normal LH. The control group consisted of proven fathers (n = 86). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis; polymerase chain reaction amplification of the loci sY84, sY143, sY254, and sY255; serum FSH, LH, and T; testicular volume. RESULT(S): Deletions involving the sY254 and sY255 DAZ loci were found in three azoospermic patients and two men with sperm concentration < 1 x 10(6)/mL. Serum FSH was elevated in four patients and was normal in one. All five patients had decreased testicular volumes compared with controls. No deletions involving the sY84 and sY143 loci were found. The four loci were amplified normally in the control group. CONCLUSION(S): The estimated frequency of deletions involving the DAZ locus is 3% in azoospermic-severely oligozoospermic men consulting an infertility clinic. Polymerase chain reaction amplification of the DAZ locus is useful for the diagnosis of microdeletions of the Y chromosome. Deletions involving more proximal regions of the Y chromosome seem to be rare.

Adult↗
PubMed2002

A deletion-generator compound element allows deletion saturation analysis for genomewide phenotypic annotation.

With the available eukaryotic genome sequences, there are predictions of thousands of previously uncharacterized genes without known function or available mutational variant. Thus, there is an urgent need for efficient genetic tools for genomewide phenotypic analysis. Here we describe such a tool: a deletion-generator technology that exploits properties of a double transposable element to produce molecularly defined deletions at high density and with high efficiency. This double element, called P[wHy], is composed of a "deleter" element hobo, bracketed by two genetic markers and inserted into a "carrier" P element. We have used this P[wHy] element in Drosophila melanogaster to generate sets of nested deletions of sufficient coverage to discriminate among every transcription unit within 60 kb of the starting insertion site. Because these two types of mobile elements, carrier and deleter, can be found in other species, our strategy should be applicable to phenotypic analysis in a variety of model organisms.

Animals↗
PubMed2001

Large-scale selection of lines with deletions in chromosome 1 B in wheat and applications for fine deletion mapping.

Terminal deletions of chromosome 1B in common wheat were selected on a large scale. The gametocidal gene of Aegilops cylindrica was used as the inducer of chromosome breakage. First, genes for endosperm storage proteins located on both arms of chromosome 1B were used as the selection markers. However, it was found that the chromosome breakage occurred during female gametogenesis, causing genotypic inconsistency between the embryo and endosperm. Thus, we isolated plants with terminal deletions in chromosome 1B by C-banding. Of 1327 plants examined, 128 showed aberrations in chromosome 1B: 47 in the short arm, 76 in the long arm, and 5 in both arms. The present deletions tended to have the breakpoint at more proximal regions than those produced previously by T.R. Endo and B.S. Gill. Using 33 deletion lines produced in this study and 34 lines previously produced, we mapped 39 RFLP loci and a nucleolar organizer region (NOR) on a specific region of chromosome 1B. The NOR was found to consist of two subregions with different repetitive units, which were termed NOR-Bld and NOR-Blp. Based on this fine deletion map and genotypic inconsistency between embryo and endosperm, the features of the gametocidal gene are discussed.

Chromosome Aberrations↗
PubMed1996

Deletion of small nuclear ribonucleoprotein polypeptide N (SNRPN) in Prader-Willi syndrome detected by fluorescence in situ hybridization: two sibs with the typical phenotype without a cytogenetic deletion in chromosome 15q.

The small nuclear ribonucleoprotein polypeptide N (SNRPN) gene is regarded as one of the candidates for Prader-Willi syndrome (PWS). We describe two sibs with typical PWS presenting deletion of SNRPN detected by fluorescence in situ hybridization (FISH). Neither a cytogenetically detectable 15q12 deletion nor a deletion for the D15S11, D15S10, and GABRB3 cosmid probes were found in either patient. This implies a smaller deletion limited to the PWS critical region. FISH with a SNRPN probe will permit analysis of PWS patients with limited deletions not detectable with other probes.

Adult↗
PubMed1999

Terminal deletion, del(1)(p36.3), detected through screening for terminal deletions in patients with unclassified malformation syndromes.

We report on a 4 year-old girl with a 1p36.3-pter deletion. Clinical findings included minor anomalies of face and distal limbs, patent ductus arteriosus, the Ebstein heart anomaly, and brain atrophy with seizures. Conventional GTG-banded chromosome analysis revealed a normal (46,XX) result. Subsequent analysis by fluorescent in situ hybridization (FISH) using distal probes demonstrated a deletion of 1p36.6-pter. Molecular investigations with microsatellite markers showed hemizygosity at three loci at 1p36.3 with loss of the paternal allele. The deletion of 1p36.3 is difficult to identify by banding alone; indeed, our patient represents the third reported case with a del(1)(p36.3) that was detected only after more detailed analysis. In all three cases the deletion was detected through screening of patients with multiple congenital anomalies/mental retardation syndromes suggestive of autosomal chromosome aberrations for subtelomeric submicroscopic deletions by means of FISH or microsatellite marker analysis. On the basis of these observations we highly recommend that FISH with a subtelomeric 1p probe be routinely performed in patients with similar facial phenotype, severe mental retardation and seizures, and a heart malformation, particularly the Ebstein anomaly.

Age Determination by Skeleton↗
PubMed2001

An 8-cM interstitial deletion on 4q21-q22 in DNA from an infant with hepatoblastoma overlaps with a commonly deleted region in adult liver cancers.

We performed molecular analysis of a germline interstitial deletion of chromosome 4 [del(4)(q21.22q23)], which had been observed in a male infant manifesting early-onset hepatoblastoma (HBL). The chromosomal anomaly in this child was associated with a unique congenital syndrome including HBL, atrial septal defect, ventricular septal defect, patent ductus arteriosus, mental retardation, and seizures. However, the patient did not exhibit a megalencephaly typical of 4q21-22 deletions. His HBL was associated with an increasing serum alpha-fetoprotein level and rapid growth. To define the chromosomal deletion at the molecular level in this child, we analyzed his lymphoblasts with fluorescence in situ hybridization, using as probes a panel of BAC/PAC genomic clones containing STS markers covering the 4q12-27 region. The analysis revealed that the affected chromosome had an 8-cM deletion within 4q21-q22, flanked by markers D4S2964 and D4S2966. This microdeletion overlaps with the commonly deleted region at 4q21-q22 that was recently defined in adult hepatocellular carcinomas.

Adult↗
PubMed2003

Patient with terminal duplication 3q and terminal deletion 5q: comparison with the 3q duplication syndrome and distal 5q deletion syndrome.

Partial duplication of chromosome 3q is a well-described condition of multiple congenital anomalies and developmental delay that resembles the Brachmann-de Lange syndrome. Similarly, an emerging phenotype of a distal 5q deletion syndrome has recently been described. The combination of both chromosome abnormalities has not been previously described. We report on a child with both a de novo duplication of distal 3q (q27 --> qter) and terminal deletion of 5q (q35.2 --> qter). The patient had facial anomalies, hypoplastic toenails, lymphedema of the dorsum of the feet, type I Chiari malformation, a seizure disorder, and moderate developmental delays. The phenotype is compared and contrasted to the few reports of patients with similar terminal 3q duplications and 5q deletions. Our patient did not have the characteristic phenotype of the 3q duplication syndrome, suggesting that the chromosome region responsible for this phenotype is more proximal than the terminal 3q27 region. In addition, comparison with three other reported cases of terminal 5q35 deletions suggests a possible association of terminal 5q deletions with central nervous system (CNS) structural abnormalities.

Abnormalities, Multiple↗
PubMed2006

Interstitial 2.2 Mb deletion at 9q34 in a patient with mental retardation but without classical features of the 9q subtelomeric deletion syndrome.

In a female patient with mild mental retardation an interstitial subtelomeric 9q34.3 deletion was identified by a multiplex ligation-dependent probe amplification (MLPA) based screen for subtelomeric abnormalities. Further characterization of the deletion by high-resolution tiling path array-based comparative genomic hybridization (array CGH) revealed a size of 2.2 Mb. The woman lacked the typical 9qter deletion phenotype characteristics, which is inline with the finding that both Eu-HMTase1 (EHMT) genes were present. However, she presented with mild mental retardation, some mild facial dysmorphisms and aplasia cutis. This is another example of an interstitial subtelomeric deletion, which underscores that further characterizing the precise nature of the deletion is of clinical importance. Moreover, it confirms the importance of the Eu-HMTase1 gene as the major causative factor of the classical 9qter syndrome phenotype.

Abnormalities, Multiple↗
PubMed2002

Germline BRCA1 promoter deletions in UK and Australian familial breast cancer patients: Identification of a novel deletion consistent with BRCA1:psiBRCA1 recombination.

Inherited susceptibility to breast cancer results from germline mutations in one of a number of genes including BRCA1. A significant number of BRCA1-linked familial breast cancer patients, however, have no detectable BRCA1 mutation. This could be due in part to the inability of commonly used mutation-detection techniques to identify mutations outside the BRCA1 coding region. This paper addresses the hypothesis that non-coding region mutations, specifically in the BRCA1 promoter, account for some of these cases. We describe a new and detailed restriction map of the 5' region of the BRCA1 gene including the nearby NBR2, psiBRCA1, and NBR1 genes and the isolation of a number of new informative hybridization probes suitable for Southern analysis. Using this information we screened DNA from lymphoblastoid cell-lines made from 114 UK familial breast cancer patients and detected one large deletion in the 5' region of BRCA1. We show that the breakpoints for this deletion are in BRCA1 intron 2 and between NBR2 and exon 2 of psiBRCA1, raising the possibility that this deletion arose via a novel mechanism involving BRCA1:psiBRCA1 recombination. We have also screened 60 familial breast cancer patients from the Australian population, using an amplification refractory mutation system (ARMS) technique described previously by our group, and found one patient with a genotype consistent with a BRCA1 promoter deletion. These findings indicate that germline BRCA1 promoter deletions are a rare and yet significant mutation event and that they could arise via a novel genetic mechanism.

Adult↗
PubMed1998

A detailed physical and transcriptional map of the region of chromosome 20 that is deleted in myeloproliferative disorders and refinement of the common deleted region.

Acquired deletions of the long arm of chromosome 20 are the most common chromosomal abnormality seen in polycythemia vera and are also associated with other myeloid malignancies. Such deletions are believed to mark the site of one or more tumor suppressor genes, loss of which perturbs normal hematopoiesis. A common deleted region (CDR) has previously been identified on 20q. We have now constructed the most detailed physical map of this region to date--a YAC contig that encompasses the entire CDR and spans 23 cM (11 Mb). This contig contains 140 DNA markers and 65 unique expressed sequences. Our data represent a first step toward a complete transcriptional map of the CDR. The high marker density within the physical map permitted two complementary approaches to reducing the size of the CDR. Microsatellite PCR refined the centromeric boundary of the CDR to D20S465 and was used to search for homozygous deletions in 28 patients using 32 markers. No such deletions were detected. Genetic changes on the remaining chromosome 20 may therefore be too small to be detected or may occur in a subpopulation of cells.

Centromere↗
PubMed1995

Genotype-phenotype correlation in a series of 167 deletion and non-deletion patients with Prader-Willi syndrome.

A total of 167 patients with Prader-Willi syndrome (PWS) was studied at the clinical and molecular level. Diagnosis was confirmed by the PW71 methylation test. Quantitative Southern blot hybridizations with a probe for the small nuclear ribonucleoprotein N were performed to distinguish between patients with a deletion (116 patient or 69.5%) and patients without a deletion (51 patients or 30.5%). These two types of patients differed with respect to the presence of hypopigmentation, which was more frequent in patients with a deletion (52%) than in patients without (23%), and to average birth weight of females and males, which was lower in patients with a deletion than in patients without. Newborns with PWS had a lower birth weight and length at term, but normal head circumference in comparison with a control group. This finding aids the identification of the neonatal phenotype. In addition, our data confirm an increased maternal age in the non-deletion group.

Adolescent↗
PubMed2002

Visualization of somatic deletions mediated by R/RS site-specific recombination and induction of germinal deletions caused by callus differentiation and regeneration in rice.

A transgenic rice plant expressing the recombinase of Zygosaccharomyces rouxii under the control of the CaMV 35S promoter was crossed with a transgenic plant carrying a cryptic (beta-glucuronidase) GUS reporter gene, which was activated by recombinase-mediated deletions between two specific recombination sites ( RSs). In F(1) plants, GUS activity was observed as blue spots and stripes in vascular bundles in several parts of the leaves. GUS expression was detected in all of the calli induced from F(1) seeds and throughout the regenerated plants. DNA analysis using the polymerase chain reaction and Southern blotting showed that R/ RS-mediated deletions occurred in all of the cells of the regenerated plants. Stable GUS expression was confirmed in the progeny resulting from self-pollination. Thus, the deletions obtained in the regenerated plants were genetically equivalent to the germinal deletions. These results indicate that the induction of callus differentiation and shoot regeneration is an effective manner to activate the R/ RS system and to produce plants with chromosomal deletions.

Binding Sites↗
PubMed1998

Generation of mutant mice with large chromosomal deletion by use of irradiated ES cells--analysis of large deletion around hprt locus of ES cell.

A method of generating mice from embryonic stem (ES) cells with a large chromosomal deletion produced by X-ray irradiation has been developed. Fifty-two mutant ES clones were made that carried a nested set of chromosomal deletions up to approximately 10 cM in length around the hprt locus on the X Chromosome (Chr). Germline chimeras were generated from three ES clones with deletions ranging from 200 to 700 kb. In germline male mice from two independent clones, deletions around the hprt locus yielded a runty phenotype or caused death at birth. The runty mice had approximately 1/3 the body weight and size of wild littermates and did not survive more than 3 weeks after birth. The most plausible cause of these phenotypes is defects in regions flanking the hprt locus. This method of creating mutant mice with a large chromosomal deletion is very useful for the identification and understanding of gene functions.

Animals↗
PubMed2004

Mapping genomic deletions down to the base: a quantitative copy number scanning approach used to characterise and clone the breakpoints of a recurrent 7p14.2p15.3 deletion.

With the recent advances in genomic research, it has become apparent that a substantial part of human malformation and mental retardation is caused by imbalances in genomic content. Thus, there is an increasing need for versatile methods allowing a detailed mapping and cloning of the actual rearrangements. We have combined the flexibility of real-time quantitative PCR with the knowledge of human genome sequence to perform a copy number scanning in three patients known to harbour a deletion in the 7p14p15 locus. In two of the patients the actual breakpoints were cloned and sequenced, whereas the breakpoint of the third patient was mapped to a region previously predicted to be prone for rearrangements. One patient also harboured an inversion in connection with the deletion that disrupted the HDAC9 gene. All three patients showed clinical characteristics reminiscent of the hand-foot-genital syndrome and were deleted for the entire HOXA cluster. Two patients were also deleted for DFNA5, a gene implicated in dominant nonsyndromic hearing impairment, but neither patient showed signs of reduced hearing capabilities. The described copy number scanning approach is largely independent of the genomic locus and may be a valuable tool for characterising a large spectrum of deletions.

Child, Preschool↗
PubMed2006

Deletions in the A(L) region of the h4xb plasma membrane Ca(2+) pump. High apparent affinity for Ca(2+) of a deletion mutant resembling the alternative spliced form h4zb.

Mutants of the plasma membrane Ca(2+) pump (human isoform 4xb) with deletions in the linker between domain A and transmembrane segment M3 (A(L) region) were constructed and expressed in Chinese hamster ovary cells. The total or partial removal of the amino acid segment 300-349 did not change the maximal Ca(2+) transport activity, but mutants with deletions involving residues 300-338 exhibited a higher apparent affinity for Ca(2+) than the wild type h4xb enzyme. Deletion of the putative acidic lipid interacting sequence (residues 339-349) had no observable functional consequences. The removal of either residues 300-314 or 313-338 resulted in a similar increase in the apparent Ca(2+) affinity of the pump although the increase was somewhat lower than that obtained by the deletion 300-349 suggesting that both deletions affected the same structural determinant. The results show that alterations in the region of the alternative splicing site A change the sensitivity to Ca(2+) of the human isoform 4 of the PMCA.

Alternative Splicing↗
PubMed1998

A protocol for detection of mitochondrial DNA deletions: characterization of a novel deletion.

OBJECTIVES: To develop a protocol capable of identifying deletions in mitochondrial DNA and use it to identify the breakpoints of a mtDNA deletion in a patient with chronic progressive external ophthalmoplegia (CPEO). DESIGN AND METHODS: Deletions in mtDNA were identified by a combination of long range PCR and Southern blotting. The precise breakpoints were determined by automated DNA sequencing. RESULTS: A series of DNA samples from patients with suspected mitochondrial disease was subjected to a protocol, which combines long range PCR and Southern blotting. We found a unique deletion in a patient with CPEO and we identified the precise location of this deletion through DNA sequencing. CONCLUSIONS: Long range PCR has the advantages of speed, minimal samples requirements, and sensitivity. Southern blotting is better able to evaluate heteroplasmy and detect duplications. We suggest a protocol that enables us to identify precisely the breakpoints in a unique mutation of mtDNA in a patient with CPEO.

Adolescent↗
PubMed2000

SMA carrier testing--validation of hemizygous SMN exon 7 deletion test for the identification of proximal spinal muscular atrophy carriers and patients with a single allele deletion.

To facilitate the detection of carriers of a hemizygous survival motor neuron (SMN) exon 7 deletion we have modified the quantitative SMN exon 7 assay described by McAndrew et al (1997). The major changes include quantitative analysis of the amount of SMN exon 7-specific fluorescently-labelled PCR product on an automated sequencer, and the monitoring of the completeness of a DraI digestion necessary to distinguish the PCR products of exons 7 of SMN and its copy gene. In our method the amount of SMN exon 7 PCR product is compared with the amount of a co-amplified PCR product of the retinoblastoma (RB1) exon containing a DraI restriction site. By co-amplification using the same primers of plasmids included in the reaction as internal standards containing SMN exon 7 with a 36-nucleotide deletion and RB1 exon 13 with a 19-nucleotide deletion, respectively, the relative amplification efficacy can be monitored. The assay has been validated in 63 ascertained carriers and 28 ascertained non-carriers. The sensitivity of the test is approximately 97%, the specificity approaches 100%. In four out of six SMA patients without a homozygous deletion we detected a hemizygous deletion. The implications of the use of this assay for carrier testing and for confirmation of the clinical diagnosis of SMA are discussed.

Cyclic AMP Response Element-Binding Protein↗