Showing papers on "Chromosome 21 published in 1982"

Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells

Abstract: Human sequences related to the transforming gene (v-myc) of avian myelocytomatosis virus (MC29) are represented by at least one gene and several related sequences that may represent pseudogenes. By using a DNA probe that is specific for the complete gene (c-myc), different somatic cell hybrids possessing varying numbers of human chromosomes were analyzed by the Southern blotting technique. The results indicate that the human c-myc gene is located on chromosome 8. The analysis of hybrids between rodent cells and human Burkitt lymphoma cells, which carry a reciprocal translocation between chromosomes 8 and 14, allowed the mapping of the human c-myc gene on region (q24 leads to qter) of chromosome 8. This chromosomal region is translocated to either human chromosome 2, 14, or 22 in Burkitt lymphoma cells.

Two human c-onc genes are located on the long arm of chromosome 8

Abstract: We have used in situ chromosome hybridization techniques to map the human cellular counterparts (c-onc genes) of the transforming genes of two RNA tumor viruses on human meiotic pachytene and somatic metaphase chromosomes. We find that the human c-mos gene is located on chromosome 8 at a position corresponding to band 8q22 on the somatic map. The human c-myc gene is found on chromosome 8 at position 8q24. These regions on the long arm of chromosome 8 have been previously reported to be involved in specific translocations found in the M-2 subset of acute nonlymphoblastic leukemias. Burkitt lymphoma, and other forms of non-Hodgkin lymphoma, and a familial abnormality that predisposes to renal cell carcinoma. These results suggest that translocations of the human c-mos or c-myc genes may be causally related to neoplastic transformation.

Characterisation of a human Y chromosome repeated sequence and related sequences in higher primates

Abstract: The human Y chromosome carries 2000 copies of a tandemly repeated sequence, 2.47 kb long, which constitutes about 20% of the DNA of this chromosome. These sequences are localised on the tip of the long arm of the Y chromosome. Related sequences are present in DNA of females with a related but distinguishable restriction pattern. These autosomal sequences are distributed in tandem arrays on a number of autosomes. Related sequences are also present in gorilla and chimpanzee. In gorilla they resemble the human sequences in their restriction map but are not found on the Y chromosome whereas in chimpanzee the related sequences behave as a ‘dispersed’ repeat. Changes in the level of methylation of this sequence in different tissues of human males can be detected with the lowest levels found in sperm and placental DNA.

Chromosome 15 abnormalities and the Prader-Willi syndrome: a follow-up report of 40 cases.

Abstract: High-resolution chromosome analysis and multiple banding techniques were performed on blood samples from 40 patients with Prader-Willi syndrome (PWS) as a follow-up to our recent report in which we found interstitial deletions of 15q in four of five patients with this syndrome. Of the 40 new patients, 19 had interstitial del(15q), one had an apparently balanced 15;15 translocation, and one was mos46,XX/47,XX+idic(15) (pter leads to q11::q11 leads to pter). These data confirm our previous report and demonstrate that half of all patients with the clinical diagnosis of PWS have chromosome abnormalities involving chromosome 15 detectable by high-resolution methods. Although the majority of these involve a specific deletion of bands 15q11-q12, other alterations of chromosome 15 may be present.

Characterization of a cloned repetitive DNA sequence concentrated on the human X chromosome

Abstract: A tandemly repeated DNA sequence organized predominantly, if not entirely, in a specific manner on the human X chromosome has been cloned in pBR322 and characterized The sequence was detected as a 2-kilobase band in ethidium bromide-stained agarose gels of BamHI-digested total human nuclear DNA Although in situ hybridization of the cloned sequence to human metaphase chromosomes showed a single major site of hybridization at the centromere region of the X chromosome and minor sites of hybridization at several autosomal centromeres, Southern blot analysis of restricted total human DNA indicated that the cloned probe is related to other repeated DNAs, particularly the human alphoid DNAs Restriction enzyme analysis of the cloned fragment revealed an internal repeat structure based upon multiples of 170 base pairs, confirming this relatedness All available data, however, suggest that the 2-kilobase spacing of BamHI sites within the repeat may be specific to the X chromosome

Patterns of DNA replication of human chromosomes. II. Replication map and replication model.

Abstract: Combining higher resolution chromosome analysis and bromodeoxyuridine (BrdU) incorporation, our study demonstrates that: (1) Human chromosomes synthesize DNA in a segmental but highly coordinated fashion Each chromosome replicates according to its innate pattern of chromosome structure (banding) (2) R-positive bands are demonstrated as the initiation sites of DNA synthesis in all human chromosomes, including late-replicating chromosomes such as the LX and Y (3) Replication is clearly biphasic in the sense that late-replicating elements, such as G-bands, the Yh, C-bands, and the entire LX, initiate replication after it has been completed in the autosomal R-bands (euchromatin) with minimal or no overlap The chronological priority of R-band replication followed by G-bands is also retained in the facultative heterochromatin or late-replicating X chromosome (LX) Therefore, the inclusion of G-bands as a truly late-replicating chromatin type or G(Q)-heterochromatin is suggested (4) Lateral asymmetry (LA) in the Y chromosome can be detected after less than half-cycle in 5-bromodeoxyuridine (BrdUrd), and the presence of at least two regions of LA in this chromosome is confirmed (5) Finally, the replicational map of human chromosomes is presented, and a model of replication chronology is suggested Based on this model, a system of nomenclature is proposed to place individual mitoses (or chromosomes) within S-phase, according to their pattern of replication banding Potential applications of this methodology in clinical and theoretical cytogenetics are suggested

A new mapping method employing a meiotic rec-mutant of yeast.

Abstract: A rapid new mapping method has been developed for localizing a dominant or recessive mutation to a particular chromosome of yeast. The procedure utilizes the ability of strains homozygous for the spo11-1 mutation to undergo chromosome segregation without appreciable recombination during sporulation. The level of sporulation in spo11-1/spo11-1 diploids is reduced and asci are often immature or abnormal in appearance; spore viability is less than 1%. The first step of the mapping procedure is the construction of a haploid spo11-1 strain carrying a recessive drug-resistance marker and the unmapped mutation(s). This strain is crossed to a set of three spo11-1 mapping tester strains containing, among them, a recessive marker on each chromosome. The resulting spo11-1/spo11-1 diploids are sporulated and plated on drug-containing medium. Viable meiotic products that express the drug-resistance marker due to chromosome haploidization are selectively recovered. These meiotic products are haploid for most, but generally not all, chromosomes. The level of disomy for individual chromosomes averages 19%. Each of the recessive chromosomal markers is expressed in approximately a third of the drug-resistant segregants. Ninety-eight percent of these segregants show no evidence of intergenic recombination. Thus, two markers located on the same chromosome, but on different homologs, are virtually never expressed in the same drug-resistant clone. The utility of this mapping procedure is demonstrated by confirming the chromosomal location of seven known markers, as well as by the assignment of a previously unmapped mutation, spo12-1, to chromosome VIII. In addition, the analysis of the products of spo11-1 meiosis indicates that several markers previously assigned to either chromosome XIV or chromosome XVII are actually on the same chromosome.

Human cytoplasmic superoxide dismutase cDNA clone: a probe for studying the molecular biology of Down syndrome

Abstract: The gene locus for human cytoplasmic superoxide dismutase (SOD-1; superoxide:superoxide oxidoreductase, EC 1.15.1.1) is located in or near a region of chromosome 21 known to be involved in Down syndrome. To approach the molecular biology of this genetic disease we have constructed a SOD-1 cDNA clone. Poly(A)-containing RNA enriched for human SOD-1 mRNA was isolated, used to synthesize double-stranded cDNA, and inserted into the endonuclease Pst I site of the plasmid pBR322. The chimeric molecules were used to transform Escherichia coli. Two clones containing SOD-1 cDNA inserts were identified by their ability to hybridize specifically with mRNA coding for SOD-1. Each of these clones carries a 650-base-pair insert, as was determined by restriction enzyme digestion and electron microscopic heteroduplex analysis. Hybridization of labeled cloned cDNA to RNA blots revealed two distinct SOD-1 mRNA classes of 500 and 700 nucleotides. The data suggest that both are polyadenylylated and are coded by chromosome 21.

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.

Single-copy and amplified CAD genes in Syrian hamster chromosomes localized by a highly sensitive method for in situ hybridization.

Abstract: Syrian hamster cells resistant to N-(phosphonacetyl)-L-aspartate (PALA), a specific inhibitor of the aspartate transcarbamylase activity of the multifunctional protein CAD, overproduce this protein as a result of amplification of the CAD gene. The authors have used a sensitive in situ hybridization technique to localize CAD genes in spreads of metaphase chromosomes from several independent PALA-resistant lines and from wild-type PALA-sensitive cells. The amplified genes were always found within chromosomes, usually in an expanded region of the short arm of chromosome B9. In wild-type cells, the CAD gene was also on the short arm of chromosome B9. In one mutant line, 90 to 100 CAD genes were found within an expanded B9 chromosome and 10 to 15 more were near the distal end of one arm of several different chromosomes. Another line contained most of the genes in a telomeric chromosome or large chromosome fragment. The amplified genes were in chromosomal regions that were stained in a banded pattern by trypsin-Giemsa. A few double minute chromosomes were observed in a very small fraction of the total spreads examined. The in situ hybridizations were performed in the presence of 10% dextran sulfate 500, which increases the signal by as much as 100-fold.more » Using recombinant DNA plasmids nick-translated with -/sup 125/I)dCTP to high specific radioactivity, 10 CAD genes in a single chromosomal region were revealed after 1 week of autoradiographic exposure, and the position of the unique gene could be seen after 1 month.« less

Localization of human variable and constant region immunoglobulin heavy chain genes on subtelomeric band q32 of chromosome 14

Abstract: Analysis of a group of human/rodent somatic cell hybrids with nucleic acid probes prepared from cloned human variable region (VH), junctional (JH), and constant region (C epsilon) heavy chain immunoglobulin genes indicates that all of these IgH genes are localized on the subtelomeric (q32) band of chromosome 14. Somatic cell hybrids were isolated in selective medium after fusing human fibroblasts with hprt- Chinese hamster cells. The human parental cells contained two translocation chromosomes representing a reciprocal translocation between chromosomes X and 14. Only those hybrid cell lines retaining a complete human autosome 14 or the X/14 translocation chromosome (i.e. containing band 14q32) retained the human IgH genes. Retention of these genes did not correlate with the presence of the other translocation chromosome, 14/X. These results indicate that all human IgH genes (VH, JH, and CH) map to the same chromosomal band (14q32) which is commonly involved in reciprocal translocations with human chromosome 8 (8q24) in B-cell neoplasms.

Assignment of first random restriction fragment length polymorphism (RFLP) locus ((D14S1) to a region of human chromosome 14.

Abstract: A locus responsible for a restriction fragment length polymorphism (RFLP) has been identified by hybridization of Eco RI fragments to the random human DNA sequence in recombinant plasmid pAW101. We have examined DNA extracted from 20 human X Chinese hamster somatic cell hybrids for the presence of sequences homologous to the human insert in pAW101. The hybrids were derived from six different human donors, five of whom were heterozygous, producing two bands on Southern transfers. The presence of homologous sequences in the hybrids correlated exclusively with the presence of human chromosome 14. Three hybrids contained chromosome 14 in a frequency of greater than one per cell and were positive for two alleles. Two hybrids contained only the distal half of the long arm of 14 as part of a translocation and were still positive. These results assign the first highly polymorphic random RFPL locus (D14S1) to region q21 leads to qter of chromosome 14.

Multiple sex chromosomes in Drosophila miranda: A system to study the degeneration of a chromosome

Abstract: Drosophila miranda possesses an intriguing sex chromosome constitution. While female metaphase plates have 10 chromosomes (diploid set), in males only 9 chromosomes can be identified. The missing homologue has been translocated to the Y, forming a neo-Y chromosome which is polytenized in the salivary gland cells. This report presents a detailed characterization of DNA, isolated from D. miranda flies. In situ hybridizations, using cRNA transcribed from unfractionated D. miranda DNA, reveal hybridization to the neo-Y with label distributed over the entire chromosome. The original partner of the translocated chromosome, X2, is essentially unlabelled. These results suggest that repetitive DNA sequences “invade” the translocated chromosome. This result is discussed with reference to the hypothesis of “degeneration” of the Y chromosome, formulated by Muller (1918, 1932a).

Sequences on the human Y chromosome homologous to the autosomal gene for argininosuccinate synthetase

Abstract: We have used a probe (pAS-1) to the human urea cycle enzyme argininosuccinate synthetase (AS) to detect individual variation in restriction enzyme digests of human DNA from lymphocytes, fibroblasts and transformed cell lines (including HeLa). pAS-1 is a 1.55 kilobase (kb) sequence of cDNA from poly(A)+ RNA cloned in pBR322; it represents more than 90% of the AS message1. At least 15 genomic fragments are detected with pAS-1 in DNA digested with restriction enzymes recognizing 6-base sequences2. This multiplicity of fragments is explained in part by the observation that AS-like sequences are found on more than seven human chromosomes3. We report here population data and gene dosage experiments demonstrating an AS-like sequence on the human Y chromosome and confirming an AS-like sequence on the human X chromosome.

Selective linkage disruption in human-Chinese hamster cell hybrids: deletion mapping of the leuS, hexB, emtB, and chr genes on human chromosome 5.

Abstract: Chinese hamster-human interspecific hybrid cells, which contain human chromosome 5 and express four genes linked on that chromosome, were subjected to selective conditions requiring them to retain one of the four linked genes, leuS (encoding leucyl-tRNA synthetase), but lose another, either emtB (encoding ribosomal protein S14) or chr. Cytogenetic and biochemical analyses of spontaneous segregants isolated by using these unique selective pressures have enabled us to determine the order and regional location of the leuS, hexB, emtB, and chr genes on human chromosome 5. These segregants arise primarily by terminal deletions of various portions of the long arm of chromosome 5. Our results indicate that the order of at least three of these genes is the same on human chromosome 5 and Chinese hamster chromosome 2. Thus, there appears to be extensive homology between Chinese hamster chromosome 2 and human chromosome 5, which represents an extreme example of the conservation of gene organization between very divergent mammalian species. In addition, these hybrids and selective conditions provide a very simple and quantitative means to assess the potency of various agents suspected of inducing gross chromosomal damage.

Mapping of aminoacylase-1 and beta-galactosidase-A to homologous regions of human chromosome 3 and mouse chromosome 9 suggests location of additional genes.

Abstract: Conserved linkage groups have been found on the X and autosomal chromosomes in several mammalian species. The identification of conserved chromosomal regions has potential for predicting gene location in mammals, particularly in humans. The genes for human aminoacylase-1 (ACY1, N-acylamino acid aminohydrolase, E.C.3.5.1.14), an enzyme in amino acid metabolism, and beta-galactosidase-A (GLB1, E.C.3.2.1.23), deficient in GM1-gangliosidosis, have been assigned to human chromosome 3. Using human-mouse somatic cell hybrids segregating translocations of human chromosome 3, expression of both ACY1 and GLB1 correlated with the presence of the p21 leads to q21 region of chromosome 3. In a previous study, assignment of these genes to mouse chromosome 9 used mouse-Chinese hamster somatic cell hybrids, eliminating mouse chromosomes. To approximate the size of the conserved region in the mouse, experiments were performed with recombinant inbred mouse strains. An electrophoretic variant of ACY-1 in mouse strains was used to map the Acy-1 gene 10.7 map U from the beta-galactosidase locus. These data suggest that there is a region of homology within the p21 leads to q21 region of human chromosome 3 and a segment of mouse chromosome 9. Since the mouse transferrin gene (Trf) is closely linked to the aminoacylase and beta-galactosidase loci, we predict that the human transferrin (TF) gene is on chromosome 3.

Parental trisomy 21 mosaicism.

Abstract: A family with three children with trisomy 21 in which the mother is a phenotypically normal, trisomy 21/normal mosaic was studied. Chromosome 21 fluorescent heteromorphisms were used to document that two of the three number 21's in two of the Down syndrome offspring were of maternal origin. Five cytogenetic surveys in which both parents of a child with trisomy 21 were studied have been reviewed. From these data, it is estimated that 3% of couples producing a child with trisomy 21 can be explained by parental mosaicism. From 17 informative sibships, with one parent mosaic, the segregation ratio was estimated to be 0.43 +/- 0.11.

Non-random chromosomal changes involving chromosomes 6 and 7 in spontaneous rat immunocytomas.

Abstract: G-banding analysis of seven Ig-secreting spontaneous rat immunocytomas showed a consistent translocation of the distal part of the q-arm of chromosome 7 to the telomeric end of chromosome 6. The breakpoints were assigned to q3.3 on chromosome 7 and q3.2 on chromosome 6. Previously, we found a similar translocation pattern in mouse plasmacytomas induced by different agents. The distal part of the q-arm of chromosome 15 was translocated to the telomeric end of chromosome 12, known to carry Igh, the immunoglobulin heavy chain cluster. The banding homologies between the chromosomes involved in the translocation in the two species suggest that a similar mechanism is responsible for plasmacytomagenesis in both. We also predict that the rat Ig heavy chain gene cluster will be located to the terminal segment of chromosome 6.

Inherited partial X chromosome duplication in a mentally retarded male.

Abstract: A mentally retarded male patient with a structurally abnormal X chromosome is reported (karyotype 46, dir dup (X)(p11.2 leads to p21.2)Y). In the normal mother a similar X chromosome duplication was found, which was preferentially inactivated. Xg blood groups were studied in the family. The findings indicated that recombination took place at maternal meiosis, as both karyotypically normal sons and the proband were Xg(a-), the mother being Xg(a+). Functional X chromosome disomy may explain clinical abnormalities in reported patients with X duplication and a normal Y chromosome.

A cytogenetic analysis of X- ray induced male steriles on the Y chromosome of Drosophila melanogaster

Abstract: A total of 1020 B s Yy +chromosomes was screened for the induction of male sterile mutations by X irradiation. The 29 recovered mutations were analyzed by genetic complementation and the metaphase chromosomes stained with Hoechst 33258 and observed with fluorescence microscopy. The cytological and genetic maps derived from this analysis were compared to similar maps of the Y chromosome mutations isolated in an earlier study (Brosseau, 1960). Unlike the previous work we have identified only 6 male fertility loci (2 on the short arm, 4 on the long arm) on the Y chromosome. These loci are distributed along the length of the long arm and are likely to reside at two separate sites on the short arm. There is no apparent clustering of these fertility factors in this heterochromatic chromosome. The deletions obtained in this study were observed to be unstable and the nature of this instability was investigated. The original Y chromosome was marked at both telomeres with normally X-linked genes. The loss of one or the other of these markers was accompanied in many cases by the concomitant loss of large segments of Y chromosome material. The possible mechanism of this loss is discussed.

Polymorphisms of Ag-stained nucleolar organizer regions in man

Abstract: Polymorphisms of the NORs as tested by Ag-staining of metaphase G-banded chromosomes were investigated in cultured blood lymphocytes of karyotypically normal individuals from the Moscow population. The study of cell-to-cell variability in the number of Ag-stained NORs carried out on 14 monozygotic twin pairs showed the phenomenon to have some features of real intercellular variation. In 40 unrelated individuals the individual acrocentric chromosomes were compared by the number of Ag-stained NORs, their degree of staining, and their participation in acrocentric association. Chromosome 21 was found to be significantly more active than four others by all the criteria, and chromosome 15 was less active compared with the others by the size of the Ag deposits and the frequency of participation in NOR associations. The frequency distribution of homozygotes and heterozygotes for Ag-stained NORs in the same group of 40 individuals was in accordance with the Hardy-Weinberg law.

Microcell-Mediated Chromosome Transfer

Abstract: Somatic cell genetics is a field which encompasses a number of parasexual techniques that can be used to transfer genetic information from one mammalian cell to another. These techniques include somatic cell hybridization (Ruddle and Creagan, 1975), microcell-mediated chromosome transfer (Fournier and Ruddle, 1977a), chromosome-mediated gene transfer (McBride and Ozer, 1973), and DNA-mediated gene transfer (Wigler et al., 1978). The distinguishing features of each approach are (a) the form in which donor genetic material is presented to recipient cells, and (b) the fraction of the donor genome ultimately retained by the cells. Microcell-mediated chromosome transfer occupies a unique position in this hierarchy: although only a fraction of the donor genome is transferred to the recipients, the introduced genetic material is retained as intact chromosomes. Thus, karyo-typically simple clones can be constructed which contain only one or a few introduced chromosomes. Since the transferred genetic material can be identified using cytogenetic tests, microcell hybrids constitute powerful gene mapping tools.

Isolation of a human repetitive sequence and its application to regional chromosome mapping

Abstract: Recombinant lambda phage Charon 4A with repetitive human DNA inserts have been constructed by using cellular DNA from a human-Chinese hamster ovary cell hybrid retaining the complete hamster genome and a single human chromosome 12. One recombinant phage, 12-11, contains several repetitive sequences, each with a different repetition pattern in the human genome. A 2.2-kilobase (kb) EcoRI fragment of this phage was subcloned in pBR325. This sequence has fewer than 5,000 copies in the human genome and does not cross-hybridize with Chinese hamster DNA. When the labeled 2.2-kb probe was hybridized to human chromosome 12 DNA digested with EcoRI, there was an intense band at the 2.2-kb position and a series of other discrete bands. The band pattern at positions other than 2.2 kb appears to be distinct for each human chromosome. The 2.2-kb fragment is composed of at least three subregions. The ends of the fragment are repeated more frequently in the genome than is the middle portion. Hybridization of chromosome 12 DNA with probes made to these subregions yielded simpler band patterns. By using a series of cell hybrids containing various deletions of human chromosome 12, five sequences related to the 2.2-kb fragment have been assigned regionally to a specific portion of the short arm of chromosome 12. These results demonstrate that certain repetitive sequences in the human genome can be used as genetic markers and may permit detailed regional mapping of human chromosomes.

Down's syndrome as a model disease.

Abstract: Aneuploid chromosomal disorders may offer insight into the pathogenesis of certain common diseases. The birth defects and mental retardation that characterize Down's syndrome are well recognized. In addition, the altered chromosomal content that occurs in the syndrome apparently affects the prevalence of a variety of disorders, such as malignancy, endocrine dysfunction, infection, atherosclerosis, and premature aging. Because the single distinguishing factor in Down's syndrome is the presence of an excess of a part of chromosome 21, the genetic information contained in this chromosomal segment seems to be responsible for the disease manifestations. Techniques of somatic cell genetics and molecular biology allow mapping of human genes and study of their expression. With such methods it should be possible to understand Down's syndrome and other aneuploid disorders and to apply these considerations to other areas of medicine. ( Arch Intern Med 1982;142:462-464)

Assigning the polymorphic human insulin gene to the short arm of chromosome 11 by chromosome sorting.

Abstract: We have determined the subchromosomal location of the human insulin gene by analyzing DNA isolated from sorted human metaphase chromosomes. Metaphase chromosome suspensions were sorted into fractions according to relative Hoechst fluorescence intensity by the fluorescence activated chromosome sorter. The chromosomal DNA in each fraction was characterized by restriction endonuclease analysis. Initial sorts indicated that the insulin gene-containing fragment resided in a fraction containing chromosomes 9, 10, 11 and 12. Studies of cell lines that contained chromosome translocations permitted the assignment of the insulin gene to a derivative chromosome that contains portions of the short arm of chromosome 11. Simultaneous sorting of the normal homolog from this small derivative chromosome separated the two different sized insulin gene-containing restriction fragments in this individual. These data indicate that the two restriction fragments represent insulin gene polymorphism and not duplicate gene loci.

Regional mapping of the gene coding for enolase-2 on human chromosome 12

Abstract: Enolase-2 (ENO2), previously termed 14-3-2 protein, is an isozyme of enolase that is enriched in neuronal tissue. The gene coding for ENO2 was previously assigned to human chromosome 12. The present study presents data for a regional mapping of gene ENO2 using cell hybrids containing various deletions of human chromosome 12. These deletions were produced by treatment with chromosome-breaking agents. Cytogenetic analysis has allowed assignment of ENO2 to the short arm of chromosome 12, in the region of pter-p1205. This assignment is consistent with the segregation pattern of the 93 hybrid clones analysed. The segregation pattern has also established the linear order of 6 genes on chromosome 12:pter-TPI-GAPD-LDHB-ENO2-centromere-SHMT-PEPB-qter. Estimation of the relative distances between the 6 genes on chromosome 12 has been made by a statistical mapping analysis of the segregation data of the hybrid clones. A set of deletion hybrids containing various combinations of these 6 markers has been established for a rapid regional mapping of genes in one of these regions on chromosome 12.

Somatic cell genetic approaches to Down's syndrome.

Abstract: Somatic cell genetic analysis of mutants of Chinese hamster ovary cells with deficient purine synthesis and of hybrids between these mutants and human cells is described. Data are presented substantiating that two genes for enzymes of purine synthesis, AdeC and AdeG, can be coordinately regulated in mammalian cells. Analysis of a human-hamster hybrid cell, Ade C/21, which contains a normal complement of hamster chromosomes and human chromosome 21 as its only human genetic component recognizable by electrophoretic and immunogenetic techniques demonstrates that genes associated with the presence of human chromosome 21 and required for the synthesis of specific polypeptides and specific human lethal cell surface antigens can be detected in these hybrids.

Protein Variations Associated with Down's Syndrome, Chromosome 21, and Alzheimer's Disease*

Abstract: N EXTRA COPY of chromosome 21, a small acrocentric chromosome, A or a specific segment of it , is the cause of the disorder known as Down’s syndrome. This syndrome is characterized by mental retardation, moderate growth retardation, epicanthal eye folds, simian palmar crease, muscle hypotonia, an increased incidence of leukemia, and some signs of premature aging. Abnormalities found in Down’s syndrome that are also associated with premature aging include increased susceptibility to neoplasms, diabetes mellitus, increased frequency of cataracts, and dementia with degenerative brain lesions similar to those found in Alzheimer’s disease.’ A search for trait-specific protein markers in Alzheimer’s disease, with the use of high resolution two-dimensional electrophoresis,z is being conducted in our laboratory. Given the brain lesions found in Down’s syndrome, it may be of interest if some of the protein variants found in