Chromosome 21

About: Chromosome 21 is a research topic. Over the lifetime, 4736 publications have been published within this topic receiving 206655 citations. The topic is also known as: chr21 & Homo sapiens chromosome 21.

The role of non-disjunction in aneuploidy in man. An overview.

Abstract: Non-disjunction plays a major role in generating aneuploidy in man. About 50% of spontaneous abortions are chromosomally abnormal and among these, trisomies constitute the major group (∼50%), followed by monosomy X (18%), triploidy (17%), tetraploidy (6%) and others. Over 30% of all trisomies are due to trisomy for chromosome 16. There seems to be an association between maternal radiation history and spontaneous abortions in the sence that the work reported, mothers of chromosomally abnormal foetuses have received higher mean gonadal doses relative to comparable controls. About 6% of babies who die perinatally are chromosomally abnormal and the majority are trisomics especially for group E chromosomes. The results of six major surveys of consecutive newborns show that 6 out of 1000 (0.6%) carry one or another kind of chromosome anomally. The breakdown is as follows: 0.22%, sex-chromosomal abnormalities; 0.14%, autosomal trisomies (+D, +E and +G); 0.19%, balanced structural rearrangements and 0.06%, unbalanced structural rearrangements and others. The frequency of “clinically significant” anomalies has been estimated to be about one-half of the total of all chromosomal abnormalities detected in newborns. The spontaneous “mutation rate” for numerical anomalies of chromosomes which result in liveborn children is about 15 × 10 −4 per gamete per generation (9.3 × 10 −4 for sex-chromosomal aneuploidies and 5.7 × 10 −4 for autosomal trisomies). Autosomal aneuploidies are associated with more severe phenotypic effects than sex-chromosomal aneuploidies. The majority of the sex-chromosomal aneuploidies are constituted by XXY, XYY, XXX and XO genotypes (and mosaics). Of these, while the XYY genotype can arise only through second division paternal non-disjunction, the others can arise as a result of either first or second division non-disjunction in either the father or the mother. There is evidence showing that in about 80% of XO (Turner's syndrome) individuals, the single remaining X is of maternal origin suggesting loss of the paternal-X. The frequency of sex-chromosomal aneuploidies in children born to survivors of the Hiroshima and Nagasaki bombings is higher than in controls, but the difference is not significant. Down's syndrome, which is one of the relatively better known autosomal aneuploidies in man, is due to trisomy for chromosome 21, translocation of chromosome 21 with another autosome (usually chromosome 14) or mosaicism for an extra chromosome 21. Trisomy 21 which accounts for 95% of the cases, is due to non-disjunction during gametogenesis in one of the parents, more often in the mother. With quinacrine fluorescent techniques, evidence has been obtained which shows that non-disjunction can occur either in the father or in the mother at first or second meiotic division. The incidence of primary trisomies for chromosome 21 shows a strong correlation with increasing maternal age and this is very extensively documented (gradual increase in risk from maternal age about 20 to 30–31 and a steeper increase thereafter). The data on the association between an increase in paternal age and Down's syndrome are conflicting although some data suggest that the risk may be high for fathers above 55 years of age. Satellite associations between acrocentric chromosomes have been observed in metaphase preparations of chromosomes of lymphocytes, but the questions of whether there are preferential associations between certain chromosomes, and if so, what their relevance is for trisomy, are not yet settled. Consequently it may be premature to extrapolate the findings in somatic cells to germ cells and to the possible origin of trisomies, including that of trisomy 21. The results of 9 retrospective and 3 prospective studies designed to examine whether parental irradiation may increase the risk of producing Down's syndrome have been published. The available evidence does suggest that there is no correlation between paternal radiation and Down's syndrome in the progeny, but is conflicting on the question of correlation between maternal irradiation and Down's syndrome. Thus, after nearly two decades of work on this aspect, no unequivocal answers are available. Both trisomy 18 (Edward's syndrome) and trisomy 13 (Patau's syndrome) are associated with severe phenotypic effects; the incidence rates are about one on 10 000 and one in 15 000 births, respectively. These trisomies are not compatible with survival to adulthood. Other, relatively rare trisomies include those for chromosomes 8 and 22. In Fig. 1 is presented a broad summary of the frequencies of different chromosomal anomalies and thier effects, relating these to one million conceptions (under the assumption that 15% of all conceptions are spontaneously aborted and 2% of the children die perinatally and making use of the different frequencies cited in the text with respect to the kinds of anomalies). The technique of fusion of human spermatozoa with golden hamster eggs, the details of which were published recently, appears to be a promising one since, this permits a direct analysis of the chromosome constitution of human spermatozoa and hopefully, studies on the effects of physical and chemical agents at a level that has hitherto been impossible.

Chromosomal localization of the human placental lactogen-growth hormone gene cluster to 17q22-24.

Abstract: Recombinant plasmid HCS-pBR322 containing a 550-base-pair (bp) insert of cDNA to human placental lactogen (hPL) mRNA was 3H-labeled by nick translation and hybridized in situ to human chromosome preparations in the presence of 10% dextran sulfate. A high percentage of cells (80%) were found to exhibit label on the distal end of the long arm of chromosome 17. Silver grains on this region constituted 25.5% of all labeled sites, allowing assignment of the hPL and growth hormone (hGH) genes, which have over 90% nucleotide homology in their coding sequences, to 17q22-24. A gene copy number experiment showed that both genes are present in approximately three copies per haploid genome.

Dosage compensation regulatory proteins and the evolution of sex chromosomes in Drosophila.

Abstract: In the fruitfly Drosophila melanogaster, the four male specific lethal (msl) genes are required to achieve dosage compensation of the male X chromosome. The MSL proteins are thought to interact with cis-acting sites that confer dosage compensation to nearby genes, as they are detected at hundreds of discrete sites along the length of the polytene X chromosome in males but not in females. The histone H4 acetylated isoform, H4Ac16, colocalizes with the MSL proteins at a majority of sites on the D. melanogaster X chromosome. Using polytene chromosome immunostaining of other species from the genus Drosophila, we found that X chromosome association of MSL proteins and H4Ac16 is conserved despite differences in the sex chromosome karyotype between species. Our results support a model in which cis-acting regulatory sites for dosage compensation evolve on a neo-X chromosome arm in response to the degeneration of its former homologue.

Chromosome 15 anomalies and the Prader-Willi syndrome: cytogenetic analysis.

Abstract: The behaviour of chromosome 15 is very different from that of the other acrocentric chromosomes. The cytogenetic characteristics of rearrangements associated with Prader-Willi syndrome (PWS) are analyzed as similar rearrangements irrespective of the associated phenotype (reciprocal translocations of chromosome 15, small bisatellited additional chromosomes, Robertsonian translocations, interstitial deletions, pericentric inversions). This study suggests that: (1) The proximal (15q) region and PWS seem to be indissociable; (2) chromosome 15 has an indisputable cytogenetic originality which could be related to its histochemical properties. Chromosome 15 constitutive heterochromatin usually contains much 5-methylcytosine-rich DNA and a large amount of each of the four satellite DNAs. Furthermore the existence in the proximal (15q) region of one or several palindromic sequences could be postulated to explain the great lability of this region of chromosome 15.

Understanding mental retardation in Down's syndrome using trisomy 16 mouse models.

Abstract: Mental retardation in Down's syndrome, human trisomy 21, is characterized by developmental delays, language and memory deficits and other cognitive abnormalities. Neurophysiological and functional information is needed to understand the mechanisms of mental retardation in Down's syndrome. The trisomy mouse models provide windows into the molecular and developmental effects associated with abnormal chromosome numbers. The distal segment of mouse chromosome 16 is homologous to nearly the entire long arm of human chromosome 21. Therefore, mice with full or segmental trisomy 16 (Ts65Dn) are considered reliable animal models of Down's syndrome. Ts65Dn mice demonstrate impaired learning in spatial tests and abnormalities in hippocampal synaptic plasticity. We hypothesize that the physiological impairments in the Ts65Dn mouse hippocampus can model the suboptimal brain function occuring at various levels of Down's syndrome brain hierarchy, starting at a single neuron, and then affecting simple and complex neuronal networks. Once these elements create the gross brain structure, their dysfunctional activity cannot be overcome by extensive plasticity and redundancy, and therefore, at the end of the maturation period the mind inside this brain remains deficient and delayed in its capabilities. The complicated interactions that govern this aberrant developmental process cannot be rescued through existing compensatory mechanisms. In summary, overexpression of genes from chromosome 21 shifts biological homeostasis in the Down's syndrome brain to a new less functional state.