1,720,972 research outputs found
Directly transmitted unbalanced chromosome abnormalities and euchromatic variants
No full textIn total, 200 families were reviewed with directly transmitted, cytogenetically visible unbalanced chromosome abnormalities (UBCAs) or euchromatic variants (EVs). Both the 130 UBCA and 70 EV families were divided into three groups depending on the presence or absence of an abnormal phenotype in parents and offspring. No detectable phenotypic effect was evident in 23/130 (18%) UBCA families ascertained mostly through prenatal diagnosis (group 1). In 30/130 (23%) families, the affected proband had the same UBCA as other phenotypically normal family members (group 2). In the remaining 77/130 (59%) families, UBCAs had consistently mild consequences (group 3). In the 70 families with established EVs of 8p23.1, 9p12, 9q12, 15q11.2, and 16p11.2, no phenotypic effect was apparent in 38/70 (54%). The same EV was found in affected probands and phenotypically normal family members in 30/70 families (43%) (group 2), and an EV co-segregated with mild phenotypic anomalies in only 2/70 (3%) families (group 3). Recent evidence indicates that EVs involve copy number variation of common paralogous gene and pseudogene sequences that are polymorphic in the normal population and only become visible at the cytogenetic level when copy number is high. The average size of the deletions and duplications in all three groups of UBCAs was close to 10 Mb, and these UBCAs and EVs form the "Chromosome Anomaly Collection" at http://www.ngrl.org.uk/Wessex/collection. The continuum of severity associated with UBCAs and the variability of the genome at the sub-cytogenetic level make further close collaboration between medical and laboratory staff essential to distinguish clinically silent variation from pathogenic rearrangement. <br/
Terminal 3p deletions: phenotypic variability, chromosomal non-penetrance, or gene modification?
No full textA transmitted deletion of 2q13 to 2q14.1 causes no phenotypic abnormalities
No full textAn imbalance of genetic material, especially monosomy, will usually give rise to an abnormal phenotype. A few instances of proximal 2q deletions have been published, but previous cases (q12-q14,1 q12-q14.2,2 q14-q213 4) have been associated with clinical features such as mental retardation, facial dysmorphism, heart defects, and renal and digital anomalies.3 We ascertained an interstitial deletion of chromosome 2 at q13-q14.1 (fig 1) in a clinically normal G6, P2, SAB3 woman aged 38. She had been referred for chromosome analysis following three successive miscarriages at 81/2, before 11, and at 7 weeks' gestation. Her current pregnancy was chromosomally normal at amniocentesis and continuing at 26 weeks. Testing of her two previous children was not being pursued at the time of writing. This deletion was subsequently found to have been transmitted by her G2, P2 mother who had no associated phenotype nor history of miscarriages
Absence of 22q11 deletions in 211 patients with developmental delay analysed using PCR
No full textThe 22q11 deletion syndrome has been described by the acronym "CATCH 22" (Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcaemia resulting from 22q11 deletions). Previous studies have indicated that other features such as growth retardation, developmental delay, renal abnormalities, psychiatric problems, and neurological abnormalities may also be associated with the deletion. There have been several estimates of the prevalence of the 22q11 deletion, ranging from 1 in 3000 to 1 in 10 000 live births. It is possible, however, that the frequency of the deletion has been underestimated because of the large phenotypic variability, or the failure to identify mildly affected subjects in the absence of more severely affected relatives. Ninety percent of patients have a common 3 Mb deletion and 7% have a nested 1.5 Mb deletion
Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster
No full textUsing a combination of multiplex amplifiable probe hybridization and semiquantitative fluorescence in situ hybridization (SQ-FISH), we analyzed DNA copy number variation across chromosome band 8p23.1, a region that is frequently involved in chromosomal rearrangements. We show that a cluster of at least three antimicrobial beta-defensin genes (DEFB4, DEFB103, and DEFB104) at 8p23.1 are polymorphic in copy number, with a repeat unit >/=240 kb long. Individuals have 2-12 copies of this repeat per diploid genome. By segregation, microsatellite dosage, and SQ-FISH chromosomal signal intensity ratio analyses, we deduce that individual chromosomes can have one to eight copies of this repeat unit. Chromosomes with seven or eight copies of this repeat unit are identifiable by cytogenetic analysis as a previously described 8p23.1 euchromatic variant. Analysis of RNA from different individuals by semiquantitative reverse-transcriptase polymerase chain reaction shows a significant correlation between genomic copy number of DEFB4 and levels of its messenger RNA (mRNA) transcript. The peptides encoded by these genes are potent antimicrobial agents, especially effective against clinically important pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, and DEFB4 has been shown to act as a cytokine linking the innate and adaptive immune responses. Therefore, a copy number polymorphism involving these genes, which is reflected in mRNA expression levels, is likely to have important consequences for immune system function
Repetitive DNA and chromosomal rearrangements: speciation-related events in plant genomes
No full textChromosomal change is one of the more hotly debated potential mechanisms of speciation. It has long been argued over whether--and to what degree--changes in chromosome structure contribute to reproductive isolation and, ultimately, speciation. In this review we do not aim to completely analyze accumulated data about chromosomal speciation but wish to draw attention to several critical points of speciation-related chromosomal change, namely: (a) interrelations between chromosomal rearrangements and repetitive DNA fraction; (b) mobility of ribosomal DNA clusters; and (c) rDNA and transposable elements as perpetual generators of genome instabilit
Deletions of 2q14 that include the homeobox engrailed 1 (EN1) transcription factor are compatible with a normal phenotype
No full textA novel transmitted 2-3 Mb deletion of 2q14.1-q14.2 was found in an affected boy from a consanguineous family with a possible diagnosis of PEHO syndrome (OMIM 260565). BAC FISH showed that the deletion included a minimum of 20 genes including the homeobox engrailed 1 gene (EN1). However, the same deletion was also found in his phenotypically normal father and brother (family 1). The phenotype of the proband may, therefore, have been coincidental to the deletion, a result of a recessive condition within or outside the deleted segment or possibly due to variable dosage compensation of EN1 by the paralogous EN2 gene at 7q36. BAC FISH also showed that this deletion overlapped with a previously reported transmitted deletion of 2q13-q14.1 that had no phenotypic consequences (family 2). The deleted regions contained a total of 32 genes and comprise the final 5.25 Mb of the ancestral chromosome 2B from which chromosome 2 was formed in man. These families provide further evidence that heterozygous deletions of regions of low gene density are compatible with a normal phenotype
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Transmitted duplication of 12q21.32-12q22 includes 48 genes and has no apparent phenotypic consequences
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