Showing papers on "Chromosome 21 published in 1981"

The Insulin Gene Is Located on the Short Arm of Chromosome 11 in Humans

Abstract: The human insulin gene has been previously localized to chromosome 11. We have analyzed the human DNA sequences present in a human-mouse somatic cell hybrid line possessing a translocation involving human chromosomes 11 and X. These data indicate that the human insulin gene is located on the short arm of chromosome 11 in the region p13 leads to pter.

Demonstration, by somatic cell genetics, of coordinate regulation of genes for two enzymes of purine synthesis assigned to human chromosome 21

Abstract: A method for determining coordinate genetic regulation is proposed for mammalian cells. The method involves (i) isolation of a set of mutants defective in the relevant pathway; (ii) complementation analysis of these mutants to determine dominance and to categorize the mutants into various different complementation groups; (iii) determination of the biochemical blocks in the mutants; (iv) identification of individual mutants that fail to complement the members of at least two distinct complementation groups that complement each other, such mutants being said to show coordinate regulation of the affected functions; (v) biochemical and reversion analysis of the relevant cell types to confirm the basis for the observed coordinate regulation; (vi) assignment of the individual genes to particular human chromosomes; (vii) mapping of the genes to determine contiguity on the genome; and (viii) examination of the structure of the relevant gene products. This method has allowed the demonstration of coordinate regulation between the gene coding for phosphoribosylglycineamide synthetase [5-phosphoribosylamine:glycine ligase (ADP-forming), EC 6.3.4.13], defective in our Ade-C mutants, and the gene coding for phoshoribosylaminoimidazole synthetase [5'-phosphoribosylformylglycinamidine cyclo-ligase (ADP-forming), EC 6.3.3.1], defective in our Ade-G mutants. Moreover, both genes can be assigned to human chromosome 21. Because at least two genes for purine biosynthesis have now been assigned to chromosome 21, and because patients with trisomy 21 (Down syndrome) show increased levels of serum purines, it may be that cells of these patients overproduce purines and that this overproduction may be relevant to the pathology of the syndrome.

Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody

Abstract: Human 6-phosphofructokinase (PFK; ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) is under the control of structural loci that code for muscle (M), liver (L), and platelet (P) subunits, which are variably expressed in different tissues; human diploid fibroblasts and leukocytes express all three genes. Random tetramerization of these subunits produces various isozymes, which can be distinguished from one another by ion exchange chromatography or by subunit-specific monoclonal antibodies. We have examined 17 somatic cell hybrids established between Chinese hamster cells and human diploid fibroblasts or leukocytes for the expression of L-type subunits of human PFK. As electrophoresis does not distinguish between Chinese hamster PFKs and human PFKs, we used an anti-human L-subunit-specific monoclonal antibody, which does not react with chinese hamster PFKs. The expression of human L subunits in the hybrids was detected by the enzyme-immunoprecipitation technique using staphylococci bearing protein A as an immunoadsorbent. Twelve out of 17 hybrids expressed human L subunits and retained chromosome 21, as determined by chromosome and isozyme marker analysis, whereas 5 did not express human PFKL and lacked chromosome 21. The mean erythrocyte PFK of seven individuals with trisomy 21 was found to be elevated (147% of normal). A specific increase in L subunits in trisomic erythrocytes was evident chromatographically by a striking increase in L4 species (50%; normal 10%) and immunologically by decreased precipitation with anti-M monoclonal antibody (50%; normal 80%). We conclude from these data that PFKL is located on chromosome 21 and that the previously noted elevation of erythrocyte PFK activity in individuals with trisomy 21 is due to a gene-dosage effect.

Genetic Characterization of the Region between 86f1,2 and 87b15 on Chromosome 3 of DROSOPHILA MELANOGASTER

Abstract: The region between 86F1,2 and 87B15 on chromosome 3 of Drosophila melanogaster, which contains about 27 polytene chromosome bands including the 87A7 heat-shock locus, has been screened for EMS-induced visible and lethal mutations. We have recovered 268 lethal mutations that fall into 25 complementation groups. Cytogenetic localization of the complementation groups by deficiency mapping is consistent with the notion that each band encodes a single genetic function. We have also screened for mutations at the 87A7 heat shock locus, using a chromosome that has only one copy of the gene encoding the 70,000 dalton heat-shock protein (hsp70). No lethal or visible mutations at 87A7 were identified from 10,719 mutagenized chromosomes, and no female-sterile mutations at 87A7 were recovered from the 1,520 chromosomes whose progeny were tested for female fertility. We found no evidence that a functional hsp70 gene is required for development under laboratory conditions.

B Chromosome Nondisjunction in Corn: Control by Factors near the Centromere.

Abstract: B chromosomes of corn are stable at all mitotic and meiotic divisions of the plant except the second pollen mitosis. In the latter division, B chromosomes undego mitotic nondisjunction at rates as high as 98%. Studies by several workers on B-A translocation chromosomes have provided evidence for the existence of four factors on the B chromosome that control nondisjunction and are separable from the centromere. Two of these factors, referred to here as factors 3 and 4, flank the B chromosome centromere. Factor 3 is the centromere-adjacent heterochromatin in the long arm of the B chromosome; factor 4 is located in the minute short arm. Evidence is presented here supporting the existence of factors 3 and 4. Deficiencies that include each factor were identified following centromeric misdivision events, with breaks at or near the centromere of a B-translocation chromosome. B chromosomes lacking factors 3 or 4 show much less nondisjunction than do chromosomes containing them. The possible function of factor 4 in nondisjuntion is also discussed.

Murine alpha-fetoprotein and albumin: two evolutionarily linked proteins encoded on the same mouse chromosome.

Abstract: Several lines of evidence suggest a close functional relationship and a common evolutionary origin for alpha-fetoprotein and albumin. In the mouse, breeding studies have previously allowed the assignment of the albumin gene to chromosome 5. To test the possible linkage of alpha-fetoprotein and albumin, five somatic cell hybrids containing various combinations of mouse chromosomes, together with a constant set of hamster chromosomes, were tested for the presence of both genes using DNA restriction mapping techniques. Two of the five hybrids possessed both genes, and the other three lacked both. The only mouse chromosome present in the positive lines and absent from the negative ones was number 5, allowing the assignment of both genes to this chromosome.

Prenatal detection of an accessory chromosome identified as an inversion duplication (15).

Abstract: A small accessory chromosome was detected in amniocytes and maternal lymphocytes and identified as an inversion duplication of the short arms of two chromosomes 15. This is the first time that complete identification of this extra chromosome has been possible prenatally. The variant chromosome was not associated with clinical abnormalities.

Functional Implications of Gene Dosage Effects in Trisomy 21

Abstract: Despite the clinical importance of trisomy 21 and other chromosomal abnormalities, very little is known about the mechanisms by which chromosome imbalance results in specific and often highly deleterious phenotypic effects. Gene dosage effects, with direct proportionality be-tween the concentrations of gene products and the number of genes present, have been demonstrated for several loci in both man and mouse. Among these is superoxide dismutase-1 (SOD-1), which is carried by chromosome 21. However, the existence of these primary gene dosage effects does not in itself explain the deleterious outcome of the aneuploid state, and it is therefore necessary to consider the secondary functional consequences of quantitative alterations in the synthesis of gene products. Two general and not necessarily exclusive mechanisms for such secondary effects can be visualized. The first is that aneuploidy interferes indirectly with the delicate regulatory balance among the several chromosomes of a cell and thereby results in a widespread disturbance in the expression of genes on many chromosomes. We have tested this possibility by examining the synthesis of a large number of polypeptides by cultured normal and trisomy 21 fibroblasts and have not been able to detect any generalized disturbance in gene expression.

Robertsonian polymorphism in chromosomes of Oryzomys subflavus(Rodentia, Cricetidae)

Abstract: Eighty-four specimens of Oryzomys subflavus, collected in the State of Pernambuco, Brazil, were studied. A Robertsonian chromosome polymorphism, characterized by a varying diploid number of 50, 49, 48, and 46, was found. All the specimens showed a chromosome arm number of 56. G-banding patterns in somatic cells allowed identification of the chromosome pairs (2, 3, 5, and 7) involved in centric fusion. C-banding revealed the presence of constitutive heterochromatin near the centromere the X chromosome and those of the autosomes. The Y chromosome presented a large heterochromatic block in the distal portion of its long arm.

Chromosome segregation is frequently associated with the expression of recessive mutations in mouse cells.

Abstract: The genes coding for adenosine kinase (ADK; ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20) and esterase-10 (ES-10; carboxylesterase, carboxylic-ester hydrolase, EC 3.1.1.1) are both located on chromosome 14 in the mouse. The near-diploid mouse cell line CAK is heterozygous for two electrophoretic variants of ES-10. Recessive Adk- mutants of CAK have been isolated and analyzed for Es-10 phenotype and karyotypic abnormalities. Two classes of mutants were found with approximatley equal frequencies: those that remained heterozygous in the expression of Es-10 and those that expressed only one Es-10 allele. Of the mutants that lacked one form of ES-10, approximately half were missing most or all of one copy of chromosome 14; the other contained two copies of 14, frequently in the form of an isochromosome. There were no abnormalities of this chromosome found among the mutants that were Es-10 heterozygotes. These results suggest that the expression of an autosomal recessive mutation in near-diploid mouse cells is frequently associated with events that result in the segregation of a physically linked marker and part or all of a chromosome.

Homodicentric chromosomes: a distinctive type of dicentric chromosome.

Abstract: This report describes two patients with a distinctive type of dicentric autosomal chromosome formed by breakage and union between homologous chromosomes. These stable chromosomes possess two C bands, implying the presence of two centromeric regions. The first child, evaluated for dysmorphic features was shown to have an abnormal chromosome 16, designated as 46, XX, -16, + dic (16) (pter leads to cen leads to q22::p11 leads to qter). The second case is a child with the typical features of trisomy 18 whose karyotype is designated as 46, XX, -18, + dic (18) (qter leads to p11.1 :: p11.3 leads to cen leads to qter). The stability of these chromosomes is presumably in result of centromere suppression and associated premature centromere division of the suppressed centromere. The possible mechanism of formation of these homodicentric chromosomes is presented, and a comparison is made between them and three patients with dicentric X chromosomes.

Analysis of banding patterns in a case of ring chromosome 21.

Abstract: An infant with psychomotor retardation, hypertonia, microphthalmia, buphthalmos, cleft palate, nail dysplasia, and hypospadias had the karyotype 46,XY, r(21)/45,XY,-21 Cytogenetic analysis of prophase and prometaphase chromosomes showed the breakpoints of chromosome 21 were at p12 and q222

SOD-A and chromosome 21. Conflicting findings in a familial translocation (9p24;21q214).

Abstract: A balanced maternal chromosome translocation (9p24;21q214) resulted in two offspring with unbalanced karyotypes. One of these, a girl trisomic for both segment 9pter→9p24 and segment 21pter→21q214, was found to have a SOD-A activity not significantly different from those found in a group of five cases with trisomy 21. However, clinical evaluation of this girl revealed no symptoms of the Down syndrome. These findings suggest that, providing the gene dosage theory is correct, the gene for SOD-A is probably localized on chromosome 21 proximal to, or in, band q21.

Duplication 15q22 to 15qter and its phenotypic expression.

Abstract: Two infants with dysmorphism and aortic stenosis were trisomic for the distal part of 15q. Similar to seven other published cases, the facial dysmorphism was characteristic: prominent nose, narrow palpebral fissures, slight anti-mongoloid slant, low-set ears, long upper lip, and a pronounced philtrum. Laboratory studies failed to demonstrate a gene-dose effect for the enzymes coded by chromosome 15 (PK 3 and MPI) and chromosome 21 (SOD 1).

Male-sterilizing interactions between duplications and deficiencies for proximal x-chromosome material in drosophila melanogaster

Abstract: The genetic limits of sixty-four deficiencies in the vicinity of the euchromatic-heterochromatic junction of the X chromosome were mapped with respect to a number of proximal recessive lethal mutations. They were also tested for male fertility in combination with three Y chromosomes carrying different amounts of proximal X -chromosome-derived material ( B S Yy + , y + Ymal 126 and y + Ymal + ). All deficiencies that did not include the locus of bb and a few that did were male-fertile in all male-viable Df(1)/Dp(1;Y) combinations. Nineteen bb deficiencies fell into six different classes by virtue of their male-fertility phenotypes when combined with the duplicated Y chromosomes. The six categories of deficiencies are consistent with a formalism that invokes three factors or regions at the base of the X , one distal and two proximal to bb , which bind a substance critical for precocious inactivation of the X chromosome in the primary spermatocyte. Free duplications carrying these regions or factors compete for the substance in such a way that, in the presence of such duplications, proximally deficient X chromosomes are unable to command sufficient substance for proper control of X -chromosome gene activity preparatory to spermatogenesis. We conclude that there is no single factor at the base of the X that is required for the fertility of males whose genotype is otherwise normal.

Trisomy 10p produced by recombination involving maternal inversion inv(10)(pllq26).

Abstract: An infant with features of trisomy 10p syndrome was found to have an abnormal chromosome 10: 46, XY, rec(10), dup p, inv(10) (p11q26) mat. The infant's mother was heterozygous for a pericentric inversion involving chromosome 10 (46, XX, inv (10) (p11q26). The infant's derivative chromosome was apparently produced by meiotic recombination between the inversion chromosome and its normal homologue.

Structural variation of chromosome 21 and symptoms of Down's syndrome.

Abstract: The analysis of the fine structure of the chromatids permits the identification of different regions on the long arm of chromosome 21. The preponderant role of the distal third of the long arm in the syndrome of trisomy 21 is now well established. Thus, trisomy of only band 21q22 results in a state identical to that caused by complete trisomy 21. If the trisomy involves only a part of band 21q22, the intensity of the symptoms is diminished, but the appearance of the patient is still reminiscent of Down’s syndrome.

Transposition of yeast mating type genes from two translocations of the left arm of chromosome III.

Abstract: In the yeast Saccharomyces cerevisiae, the HIS4C gene lies on the left arm of chromosome III. We analyzed two chromosomal rearrangements that have HIS4C translocated either to chromosome XII or to a new translocation chromosome. Using the cmt mutation that allows expression of the normally silent copies of mating type genes, we found that both of these translocations also carried HML alpha, more than 30 map units distal to HIS4C which normally lies on chromosome III. In the case of the translocation chromosome (designated T3), we also found an exchange event between HML alpha on the translocation chromosome and HMLa on chromosome III. In diploids containing two T3 chromosomes (one carrying HML alpha and the carrying HMLa), we found that HML was 32 centimorgans from HIS4C, which was 10 centimorgans from an unknown centromere. In homothallic strains carrying HMLa MATa HMRa on chromosome III, switching from MATa to MAT alpha could occur by using the HML alpha on the translocation as the sole donor of alpha information. Transposition from HML alpha on chromosome T3 was about 20 to 40% as efficient as transposition from intact chromosome III. In contrast, transposition from the HML alpha inserted into chromosome XII was reduced about 100-fold. This reduced efficiency did not appear to be caused by an alteration in the sequences immediately surrounding HML alpha in the translocation. The translocated HML alpha sequence was located in the same size (29-kilobase) SalI fragment as was found in chromosome III, and the same EcoRI, HindIII, and BglII restriction sites were also found. Furthermore, HML alpha was still under the control of the CMT gene, which maintains HML as a silent copy of mating type information. These results suggested that the position of the HML alpha sequence plays an important role in the efficiency of mating type switching.

Characterization of a new aberration of the human Y chromosome by banding methods and DNA restriction endonuclease analysis.

Abstract: Comparative cytogenetic analyses were performed with ten different banding methods on a previously undescribed, inherited structural aberration of a Y chromosome, and the results compared with those of normal Y chromosomes occurring in the same family The value of the individual staining techniques in investigations of Y chromosomal aberrations is emphasized The aberrant Y chromosome analyzed can be formally derived from an isodicentric Y chromosome for the short arm with a very terminal long-arm breakpoint, in which the centromere, an entire short arm, and the proximal region on one long arm was lost This interpretation was confirmed by determining the amount of the two Y-specific DNA sequences (21 and 34 kb in length) by means of HaeIII restriction endonuclease analysis The karyotype-phenotype correlations in the men with this aberrant Y chromosome, especially the fertility dysfunctions (oligoasthenoteratozoospermia, cryptozoospermia), are discussed The possibility of the existence of fertility factors involved in the control of spermatogenesis within the quinacrine-bright heterochromatic region of the Y long arm is presented

Chromosome structure and DNA sequence alterations associated with mutation of transformed genes.

Abstract: We have constructed a series of tk+ cell lines by DNA-mediated gene transfer to correlate chromosomal behavior and DNA sequence alterations associated with reversion to the tk- phenotype. Tk- revertants were selected from each of four well-characterized transformed cell lines containing the viral tk gene and multiple human growth hormone genes (HGH). Tk- colonies were analyzed for the presence of tk and HGH sequences by blot hybridization to restriction endonuclease cleaved DNA. Revertants were further characterized by detailed karyotype analysis and hybridization in situ. Blot hybridization of forty tk- revertants indicates that over half of the revertants delete all of the transforming DNA from the recipient chromosome. In fifteen additional revertants, significant deletion has occurred, although transforming DNA is retained. The analysis of chromosomes by Giemsa banding together with hybridization in situ reveals that the deletion of transforming DNA is never associated with loss of an entire chromosome. Reversion to the tk- phenotype, therefore, seems to involve discrete deletions of transforming DNA without apparent chromosome loss. In this restricted set of mutants, it thus seems crucial to maintain the diploid chromosomal complement.

Classification of chromosomal eye syndromes.

Abstract: Human chromosome disease arises from a change in the number or structure of one or more chromosomes. The multiple genes represented in the duplicated or deleted chromosomes are not usually defective and any systemic abnormalities can be attributed to a change in gene dosage. Banding techniques are now commonly used to identify each chromosome and the specific chromosome duplication and deletion and structural rearrangements can now be identified unambiguously.

Terminal chromosome attachments.

Abstract: Descriptions are presented of four cases of attachment of chromosome material at the ends of normal chromosomes in Drosophila. Since no material appears to be missing from the polytene chromosomes and there are no ill effects to the organism in morphology, viability, or fertility when the chromosome is made homozygous, it is argued that the attachment occurred without the loss of any essential genetic material and that, in all probability, the break at the end of the chromosome occurred within the telomere of the chromosome. These cases may serve as a parallel to cases of apparent terminal breakage and reunion in certain rearrangements in man.

Study of two cases of ring 13 chromosome using high-resolution banding.

Abstract: The chromosomes of two patients with ring 13 (r13) were studied using high-resolution RBG banding of prometaphase cells. The rings of the two patients differ slightly in breakpoints. Cell with multiple single, double-sized rings, quadruple-sized rings, rod- and ring-shaped fragments, and fragments showing varied states of condensation were seen, as were cells monosomic for chromosome 13. The evolution of these cell lines as a result of sister chromatid exchange, nondisjunction, ring breakage, and premature chromosome condensation is discussed. Clinical features of these patients reflect the heterogeneity of phenotype for r13 patients. Each case includes a feature of trisomy 13. The significance of mosaicism of cell lines in patients bearing ring chromosomes is considered with respect to variation in clinical findings.

Translocation dicentric chromosomes in prostaglandin E2 induced abortuses and possible aneusomy through asynchronous centromeric divisions.

Abstract: The literature shows reports of whole chromosome or chromosome arm trans-locations in both normal and abnormal liveborns. Often the abnormal phenotypes cannot be explained by the genetic defeats of the specific chromosome findings. It is hypothesized that the developmental disturbances occur as epigenetic effects mediated by genetically imbalanced cells produced by the cells with the whole chromosome translocations. 168 abortuses induced by midtrimester PG (prostaglandin) E2 administration were examined at the Kandang Kerbau Maternity Hospital the Alexandria Hospital and the Toa Payoh Hospital in Singapore. 20 cases (11.9%) of mainly euploid aberration were found among the abortuses. 1 case was a numerical aberration 12 were genetically balanced chromosome rearrangements 2 were deletions of short arms of acrocentric chromosomes which should have no obvious phenotypic effects and 5 were only minor delections of chromosome arms. The cells karyotyped were usually from 1-week-old cultures of the kidneys of the abortuses. More detailed information is provided for 4 cases of whole chromosome translocations among these 20. Chromosomal diagrams illustrate the discussion. Even a small proportion of genetically abnormal cells of poor viability could have profound effects. It is possible that PG induces chromosomal abnormalities.

Interferon as a model lymphokine.

Abstract: Examples of our work concerning the production, action, and genetic control of response to interferon are reviewed. We have shown that human immune interferon is a product of mitogen stimulated T lymphocyte subsets T mu, T gamma, and T phi, and have investigated some of interferon's antiviral, antiproliferative, and antidifferentiational (or antimaturational) effects. We also have refined the genetic locus that controls response to interferon to the distal segment of the long arm of chromosome 21 in the human, and have mapped it for the first time to chromosome 16 in the mouse. We have demonstrated that imbalance of this locus in the human, as in trisomy 21, results in enhanced sensitivity of cells to interferon which, because of its immunoregulatory effects, may be involved in the abnormalities of the immune response in such patients.

Translocations involving chromosome 12. I. A report of a 12,21 translocation in a woman with recurrent abortions, and a study of the breakpoints and modes of ascertainment of translocations involving chromosome 12.

Abstract: A translocation t(12;21)(q24.1;q21.5) is described in a woman with a history of recurrent spontaneous abortions. The break points of this translocation are compared with those of 30 other translocations described in the literature, and the following conclusions are drawn: 1) An excess of breaks occurs in the p arm of chromosome 12. 2) The distributions of breaks in the bands of chromosome 12 is significantly different from that expected on a random basis. 3) Translocations of chromosome 12 occur more often with chromosome 21 than any other chromosome, but these rearrangements do not involve a specific region of chromosome 12. 4) Most of the translocations were ascertained through their unbalanced meiotic products but seven translocations were "balanced". Of these "balanced" translocations, three individuals were abnormal and two were recurrent aborters. The concept that phenotypic outcome may be related to the gross structural characteristics of the translocation site is not supported in this study.

Cytological and Cytogenetic Studies on the Transposition of Centromere and the Karyotype Differentiation in Haplopappus gracilis

Abstract: 1. In the inbred line of Haplopappus gracilis KH-1 (2n=4), a new-shaped chromosome was found. The length of this chromosome was similar to chromosome 1 and this is J-shaped chromosome having centromere at the subterminal position.2. From the distribution of the early condensing regions at mitotic prophase and the meiotic chromosome behaviour of the heterozygotes of J-shaped and V-shaped chromosome, it was suggested that the J-shaped chromosome was derived from the V-shaped chromosome by the appearance of a new centromere in the subterminal position and by the disappearance of the centromere in the median position.3. The cause of the appearance of the new centromere in this chromosome was presumed to be an actuation of the suppressed centromere in the subterminal position and a suppression of the median centromere.

Perspectives in chromosome manipulation

Abstract: Three categories of chromosome manipulation are discussed, with examples from hexaploid wheat. First, uncontrolled events, such as intergeneric translocations induced by mutagenic agents, have been frequently isolated but have been infrequently incorporated into widely grown varieties. A method proposed by K. W. Shepherd is designed to select an accommodating genetic background for these interchanges and thereby overcome this deficiency. This relies on selection for yield among many selections that are homozygous for a translocation but segregating for many other genetic components. The second category involves manipulations associated with the distinctive genetic activity of chromosome 5B. ph mutants are expected to play an important role in the transfer of genetic material from other genera to wheat. A method described by E. R. Sears is designed to isolate a small intercalated alien segment. This relies on crossing-over in an alien segment that is common to two distinct types of homoeologous-exchange chromosomes. The third category involves manipulations associated with a male-sterility mutation on chromosome 4A and the distinctive genetic activities of this chromosome. A method, described by the author, is designed to produce hybrid wheat with an induced male-sterility mutation on this chromosome. Fertility restoration is being attempted with four chromosomes, a restriction on which is that they must not pair with the other chromosomes of the wheat complement. These are a modified 4A -2R translocation chromosome, part of the cereal rye genome, chromosome 4 of barley, and chromosome 4 of diploid wheat. It appears that chromosome 4A originated elsewhere than from diploid wheat; thus the A genome of common wheat arose from at least two species. As detected by M. A. Hossain and the author, part of the genetic material for male fertility on 4A has a counterpart on rye chromosome 2R. An exchange between the chromosomes of homoeologous groups 2 and 4 appears to have occurred, perhaps at the diploid level.