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.

Islet autoimmunity in children with Down's syndrome.

Abstract: There is an unexplained excess of type 1 diabetes and other organ-specific autoimmune diseases in children with Down's syndrome, but the immunogenetic characteristics of diabetes in Down's syndrome have not been investigated. We studied the frequency of islet autoantibodies in 106 children with Down's syndrome and no history of autoimmunity and analyzed HLA class II genotypes in 222 children with Down's syndrome, 40 children with Down's syndrome and type 1 diabetes, 120 age- and sex-matched children with type 1 diabetes, and 621 healthy control subjects. Co-occurrence of at least two islet autoantibody markers was observed in 6 of 106 nondiabetic children with Down's syndrome compared with 13 of 2,860 healthy age-matched children (P < 0.001). There was an excess of diabetes-associated HLA class II genotypes in children with Down's syndrome and type 1 diabetes compared with age- and sex-matched healthy control subjects (P < 0.001). Down's syndrome children with type 1 diabetes were, however, less likely to carry the highest risk genotype DR4-DQ8/DR3-DQ2 than children with type 1 diabetes from the general population (P = 0.01) but more likely to carry low-risk genotypes (P < 0.0001). The frequency of subclinical islet autoimmunity is increased in Down's syndrome, and susceptibility to type 1 diabetes in Down's syndrome is partially HLA mediated. Other factors, possibly including genes on chromosome 21, may increase the penetrance of type 1 diabetes in Down's syndrome.

47,XX,UPD(7)mat,+r(7)pat/46,XX,UPD(7)mat mosaicism in a girl with Silver-Russell syndrome (SRS): possible exclusion of the putative SRS gene from a 7p13-q11 region

Abstract: Maternal uniparental disomy for chromosome 7 (UPD7) may present with a characteristic phenotype reminiscent of Silver-Russell syndrome (SRS). Previous studies have suggested that approximately 10% of SRS patients have maternal UPD7. We describe a girl with a mos47,XX,+mar/46,XX karyotype associated with the features of SRS. Chromosome painting using a chromosome 7 specific probe pool showed that the small marker was a ring chromosome 7 (r(7)). PCR based microsatellite marker analysis of the patient detected only one maternal allele at each of 16 telomeric loci examined on chromosome 7, but showed both paternal and maternal alleles at four centromeric loci. Considering her mosaic karyotype composed of diploid cells and cells with partial trisomy for 7p13-q11, the allele types obtained at the telomeric loci may reflect the transmission of one maternal allele in duplicate, that is, maternal UPD7 (complete isodisomy or homodisomy 7), whereas those at the centromeric loci were consistent with biparental contribution to the trisomic region. It is most likely that the patient originated in a 46,XX,r(7) zygote, followed by duplication of the maternally derived whole chromosome 7 in an early mitosis, and subsequent loss of the paternally derived ring chromosome 7 in a subset of somatic cells. The cell with 46,XX,r(7) did not survive thereafter because of the monosomy for most of chromosome 7. If the putative SRS gene is imprinted, it can be ruled out from the 7p11-q11 region, because biparental alleles contribute to the region in our patient. Keywords: maternal uniparental disomy; chromosome 7; Silver-Russell syndrome; monosomy duplication

Construction of a 750-kb bacterial clone contig and restriction map in the region of human chromosome 21 containing the progressive myoclonus epilepsy gene.

Abstract: The gene responsible for progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is located on human chromosome 21q22.3 in a region defined by recombination breakpoints and linkage disequilibrium. As part of an effort to clone the EPM1 gene on the basis of its chromosomal location, we have constructed a 753-kb bacterial clone contig that encompasses the region containing the gene. Because DNA markers from the region did not identify intact yeast artificial chromosome (YAC) clones after screening several libraries, we built the contig from cosmid clones and used bacterial artificial chromosome (BAC) and bacteriophage P1 clones to fill gaps. In addition to constructing the clone contig, we determined the locations of the EcoRI, SacII, EagI, and NotI restriction sites in the clones, resulting in a high-resolution restriction map of the region. Most of the contig is represented by a level of redundancy that allows the orders of most restriction sites to be determined, provides multiple data points supporting the clone orders and orientations, and allows a set of clones with a minimum degree of overlap to be chosen for efficient additional analysis. The clone and restriction maps are in excellent agreement with maps generated of the region by other methods. These ordered bacterial clones and the mapping information obtained from them provide valuable reagents for isolating candidate genes for EPM1, as well as for determining the nucleotide sequence of a 750 kb region of the human genome.

Mapping of four distinct BCR-related loci to chromosome region 22q11: order of BCR loci relative to chronic myelogenous leukemia and acute lymphoblastic leukemia breakpoints.

Abstract: A probe derived from the 3' region of the BCR gene (breakpoint cluster region gene) detects four distinct loci in the human genome. One of the loci corresponds to the complete BCR gene, whereas the others contain a 3' segment of the gene. After HindIII cleavage of human DNA, these four loci are detected as 23-, 19-, 13-, and 9-kilobase-pair fragments, designated BCR4, BCR3, BCR2, and BCR1, respectively, with BCR1 deriving from the original complete BCR gene. All four BCR loci segregate 100% concordantly with human chromosome 22 in a rodent-human somatic cell hybrid panel and are located at chromosome region 22q11.2 by chromosomal in situ hybridization. The BCR2 and BCR4 loci are amplified in leukemia cell line K562 cells, indicating that they fall within the amplification unit that includes immunoglobulin lambda light chain locus (IGL) and ABL locus on the K562 Philadelphia chromosome (Ph1); additionally, in chronic myelogenous leukemia-derived mouse-human hybrids retaining a Ph1 chromosome in the absence of the 9q+ and normal chromosome 22, BCR2 and BCR4 loci are retained, whereas the 3' region of BCR1 and the BCR3 locus are lost, indicating that BCR3 is distal to BCR1 on chromosome 22. Similarly, in mouse-human hybrids retaining a Ph1 chromosome derived from an acute lymphoblastic leukemia-in the absence of the 9q+ and 22, only BCR2 and BCR4 loci are retained, indicating that the breakpoint in this acute lymphoblastic leukemia, as in chronic myelogenous leukemia, is proximal to the BCR1 3' region, but distal to the IGLC locus and the BCR2 and BCR4 3' loci. Thus, the order of loci on chromosome 22 is centromere----BCR2, BCR4, and IGL----BCR1----BCR3----SIS, possibly eliminating BCR2 and BCR4 loci as candidate targets for juxtaposition to the ABL gene in the acute lymphoblastic leukemia Ph1 chromosome.