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.

Chromosome microdissection and cloning in human genome and genetic disease analysis.

Abstract: A procedure has been described for microdissection and microcloning of human chromosomal DNA sequences in which universal amplification of the dissected fragments by Mbo I linker adaptor and polymerase chain reaction is used. A very large library comprising 700,000 recombinant plasmid microclones from 30 dissected chromosomes of human chromosome 21 was constructed. Colony hybridization showed that 42% of the clones contained repetitive sequences and 58% contained single or low-copy sequences. The insert sizes generated by complete Mbo I cleavage ranged from 50 to 1100 base pairs with a mean of 416 base pairs. Southern blot analysis of microclones from the library confirmed their human origin and chromosome 21 specificity. Some of these clones have also been regionally mapped to specific sites of chromosome 21 by using a regional mapping panel of cell hybrids. This chromosome microtechnology can generate large numbers of microclones with unique sequences from defined chromosomal regions and can be used for processes such as (i) isolating corresponding yeast artificial chromosome clones with large inserts, (ii) screening various cDNA libraries for isolating expressed sequences, and (iii) constructing region-specific libraries of the entire human genome. The studies described here demonstrate the power of this technology for high-resolution genome analysis and explicate their use in an efficient search for disease-associated genes localized to specific chromosomal regions.

Paternal nondisjunction in trisomy 21: excess of male patients

Abstract: Paternal nondisjunction accounts for approximately 5% of cases of trisomy 21. We have studied 36 cases of free trisomy 21, in which the supernumerary chromosome was of paternal origin, with DNA markers in the pericentromeric region and along the long arm of chromosome 21. Fifteen of the paternal cases were consistent with meiosis II errors, 8 with mitotic errors and only 7 with meiosis I nondisjunction. This contrasts markedly with maternally derived trisomy 21, in which meiosis I errors predominate. An excess of males was observed in the meiotic cases (21 males:6 females), highly significantly different from a 1.06 ratio. A significant difference in mean maternal age was found between cases of paternal origin (28.1 years) and those of maternal origin (31.8 years, n = 429). This indicates that the maternal age effect is confined to maternal nondisjunction.

Trisomy of the G protein-coupled K+ channel gene, Kcnj6, affects reward mechanisms, cognitive functions, and synaptic plasticity in mice.

Abstract: G protein-activated inwardly rectifying K+ channels (GIRK) generate slow inhibitory postsynaptic potentials in the brain via Gi/o protein-coupled receptors. GIRK2, a GIRK subunit, is widely abundant in the brain and has been implicated in various functions and pathologies, such as learning and memory, reward, motor coordination, and Down syndrome. Down syndrome, the most prevalent cause of mental retardation, results from the presence of an extra maternal chromosome 21 (trisomy 21), which comprises the Kcnj6 gene (GIRK2). The present study examined the behaviors and cellular physiology properties in mice harboring a single trisomy of the Kcnj6 gene. Kcnj6 triploid mice exhibit deficits in hippocampal-dependent learning and memory, altered responses to rewards, hampered depotentiation, a form of excitatory synaptic plasticity, and have accentuated long-term synaptic depression. Collectively the findings suggest that triplication of Kcnj6 gene may play an active role in some of the abnormal neurological phenotypes found in Down syndrome.

Linkage of the Wiskott-Aldrich syndrome with polymorphic DNA sequences from the human X chromosome.

Abstract: The Wiskott-Aldrich syndrome (WAS) is one of several human immunodeficiency diseases inherited as an X-linked trait. The location of WAS on the X chromosome is unknown. We have studied 10 kindreds segregating for WAS for linkage with cloned, polymorphic DNA markers and have demonstrated significant linkage between WAS and two loci, DXS14 and DXS7, that map to the proximal short arm of the X chromosome. Maximal logarithm of odds (lod scores) for WAS-DXS14 and WAS-DXS7 were 4.29 (at theta = 0.03) and 4.12 (at theta = 0.00), respectively. Linkage data between WAS and six marker loci indicate the order of the loci to be (DXYS1-DXS1)-WAS-DXS14-DXS7-(DXS84-OTC). These results suggest that the WAS locus lies within the pericentric region of the X chromosome and provide an initial step toward identifying the WAS gene and improving the genetic counseling of WAS families.

Chromosome-level homeology in paleopolyploid soybean (Glycine max) revealed through integration of genetic and chromosome maps.

Abstract: Soybean has 20 chromosome pairs that are derived from at least two rounds of genomewide duplication or polyploidy events although, cytogenetically, soybean behaves like a diploid and has disomic inheritance for most loci. Genetically anchored genomic clones were used as probes for fluorescence in situ hybridization (FISH) to determine the level of postpolyploid chromosomal rearrangements and to integrate the genetic and physical maps to (1) assign linkage groups to specific chromosomes, (2) assess chromosomal structure, and (3) determine the distribution of recombination along the length of a chromosome. FISH mapping of seven putatively gene-rich BACs from linkage group L (chromosome 19) revealed that most of the genetic map correlates to the highly euchromatic long arm and that there is extensive homeology with another chromosome pair, although colinearity of some loci does appear to be disrupted. Moreover, mapping of BACs containing high-copy sequences revealed sequestration of high-copy repeats to the pericentromeric regions of this chromosome. Taken together, these data present a model of chromosome structure in a highly duplicated but diploidized eukaryote, soybean.