{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:36:44Z","timestamp":1791056204652,"version":"4.1.0"},"reference-count":37,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"4813","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1987,7,24]]},"abstract":"<jats:p>Fragile X syndrome is a common form of mental retardation associated with a fragile site on the human X chromosome. Although fragility at this site is usually evident as a nonstaining chromatid gap, it remains unclear whether or not actual chromosomal breakage occurs. By means of somatic cell hybrids containing either a normal human X or a fragile X chromosome and utilizing two genes that flank the fragile site as markers of chromosome integrity, segregation of these markers was shown to be more frequent if they encompass the fragile site under appropriate culture conditions. Hybrid cells that reveal marker segregation were found to contain rearranged X chromosomes involving the region at or near the fragile site, thus demonstrating true chromosomal breakage within this area. Two independent translocation chromosomes were identified involving a rodent chromosome joined to the human X at the location of the fragile site. DNA analysis of closely linked, flanking loci was consistent with the position of the breakpoint being at or very near the fragile X site. Fragility at the translocation junctions was observed in both hybrids, but at significantly lower frequencies than that seen in the intact X of the parental hybrid. This observation suggests that the human portion of the junctional DNA may contain part of a repeated fragility sequence. Since the translocation junctions join heterologous DNA, the molecular cloning of the fragile X sequence should now be possible.<\/jats:p>","DOI":"10.1126\/science.3603029","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T20:28:58Z","timestamp":1160080138000},"page":"420-423","source":"Crossref","is-referenced-by-count":89,"title":["The Fragile X Site in Somatic Cell Hybrids: An Approach for Molecular Cloning of Fragile Sites"],"prefix":"10.1126","volume":"237","author":[{"given":"Stephen T.","family":"Warren","sequence":"first","affiliation":[{"name":"Departments of Biochemistry and Pediatrics, Division of Medical Genetics, Emory University School of Medicine, Atlanta, GA 30322."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Pediatrics, Division of Medical Genetics, Emory University School of Medicine, Atlanta, GA 30322."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg R.","family":"Licameli","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Pediatrics, Division of Medical Genetics, Emory University School of Medicine, Atlanta, GA 30322."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne F.","family":"Peters","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Pediatrics, Division of Medical Genetics, Emory University School of Medicine, Atlanta, GA 30322."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/BF00295659","volume":"71","year":"1985","unstructured":"BROWN, W.T., GENETIC-LINKAGE HETEROGENEITY IN THE FRAGILE X-SYNDROME, HUMAN GENETICS 71: 11 (1985).","journal-title":"HUMAN GENETICS"},{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/BF00489751","volume":"81","year":"1984","unstructured":"BUYS, CHCM, THE GIEMSA-11 TECHNIQUE FOR SPECIES-SPECIFIC CHROMOSOME DIFFERENTIATION - A SIMPLE STAIN MODIFICATION LEADING TO DEPENDABLE DIRECT AND SEQUENTIAL STAINING PROCEDURES, HISTOCHEMISTRY 81: 465 (1984).","journal-title":"HISTOCHEMISTRY"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3952500"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1126\/science.2950591","volume":"235","year":"1987","unstructured":"COLLINS, F.S., CONSTRUCTION OF A GENERAL HUMAN-CHROMOSOME JUMPING LIBRARY, WITH APPLICATION TO CYSTIC-FIBROSIS, SCIENCE 235: 1046 (1987).","journal-title":"SCIENCE"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/BF01538680","volume":"8","year":"1982","unstructured":"DANA, S, LINKAGE OF THE LEUS, EMTB, AND CHR GENES ON CHROMOSOME-5 IN HUMANS AND EXPRESSION OF HUMAN GENES ENCODING PROTEIN SYNTHETIC COMPONENTS IN HUMAN CHINESE-HAMSTER HYBRIDS, SOMATIC CELL GENETICS 8: 245 (1982).","journal-title":"SOMATIC CELL GENETICS"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(84)90381-6"},{"key":"e_1_2_1_7_1","first-page":"512","volume":"26","year":"1974","unstructured":"FRANCKE, U, LINKAGE RELATIONSHIPS OF X-LINKED ENZYMES GLUCOSE-6-PHOSPHATE-DEHYDROGENASE AND HYPOXANTHINE GUANINE PHOSPHORIBOSYLTRANSFERASE - RECOMBINATION IN FEMALE OFFSPRING OF COMPOUND HETEROZYGOTES, AMERICAN JOURNAL OF HUMAN GENETICS 26: 512 (1974).","journal-title":"AMERICAN JOURNAL OF HUMAN GENETICS"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1159\/000132178","volume":"40","year":"1985","unstructured":"GOODFELLOW, P.N., REPORT OF THE COMMITTEE ON THE GENETIC CONSTITUTION OF THE X-CHROMOSOMES AND Y-CHROMOSOMES, CYTOGENETICS AND CELL GENETICS 40: 296 (1985).","journal-title":"CYTOGENETICS AND CELL GENETICS"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0165-4608(84)90132-8","volume":"12","year":"1984","unstructured":"HECHT, F, FRAGILE SITES AND CANCER BREAKPOINTS, CANCER GENETICS AND CYTOGENETICS 12: 179 (1984).","journal-title":"CANCER GENETICS AND CYTOGENETICS"},{"key":"e_1_2_1_10_1","first-page":"312","volume":"40","year":"1987","unstructured":"HOFKER, M.H., EFFICIENT ISOLATION OF X-CHROMOSOME SPECIFIC SINGLE-COPY PROBES FROM A COSMID LIBRARY OF A HUMAN-X HAMSTER HYBRID-CELL LINE - MAPPING OF NEW PROBES CLOSE TO THE LOCUS FOR X-LINKED MENTAL-RETARDATION, AMERICAN JOURNAL OF HUMAN GENETICS 40: 312 (1987).","journal-title":"AMERICAN JOURNAL OF HUMAN GENETICS"},{"key":"e_1_2_1_11_1","first-page":"552","volume":"34","year":"1982","unstructured":"JACOBS, P.A., EXPRESSION OF THE MARKER(X)(Q28) IN LYMPHOBLASTOID CELL-LINES, AMERICAN JOURNAL OF HUMAN GENETICS 34: 552 (1982).","journal-title":"AMERICAN JOURNAL OF HUMAN GENETICS"},{"key":"e_1_2_1_12_1","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/308607a0","volume":"308","year":"1984","unstructured":"LEBEAU, M.M., HERITABLE FRAGILE SITES IN CANCER, NATURE 308: 607 (1984).","journal-title":"NATURE"},{"key":"e_1_2_1_13_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/ajmg.1320230136","volume":"23","year":"1986","unstructured":"LEDBETTER, D.H., CAFFEINE ENHANCES FRAGILE-(X) EXPRESSION IN SOMATIC-CELL HYBRIDS, AMERICAN JOURNAL OF MEDICAL GENETICS 23: 445 (1986).","journal-title":"AMERICAN JOURNAL OF MEDICAL GENETICS"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/324161a0","volume":"324","year":"1986","unstructured":"LEDBETTER, D.H., IMPLICATIONS OF FRAGILE-X EXPRESSION IN NORMAL MALES FOR THE NATURE OF THE MUTATION, NATURE 324: 161 (1986).","journal-title":"NATURE"},{"key":"e_1_2_1_15_1","unstructured":"MCKUSICK V.A. MENDELIAN INHERITANC (1986)."},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(84)90808-X"},{"key":"e_1_2_1_17_1","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1056\/NEJM198610303151806","volume":"315","year":"1986","unstructured":"NISEN, P, THE MOLECULAR-BASIS OF SEVERE HEMOPHILIA-B IN A GIRL, NEW ENGLAND JOURNAL OF MEDICINE 315: 1139 (1986).","journal-title":"NEW ENGLAND JOURNAL OF MEDICINE"},{"key":"e_1_2_1_18_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1146\/annurev.ge.20.120186.000545","volume":"20","year":"1986","unstructured":"NUSSBAUM, R.L., FRAGILE-X SYNDROME - A UNIQUE MUTATION IN MAN, ANNUAL REVIEW OF GENETICS 20: 109 (1986).","journal-title":"ANNUAL REVIEW OF GENETICS"},{"key":"e_1_2_1_19_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/BF00327113","volume":"64","year":"1983","unstructured":"NUSSBAUM, R.L., EXPRESSION OF THE FRAGILE (X)CHROMOSOME IN AN INTERSPECIFIC SOMATIC-CELL HYBRID, HUMAN GENETICS 64: 148 (1983).","journal-title":"HUMAN GENETICS"},{"key":"e_1_2_1_20_1","first-page":"1016","volume":"83","year":"1986","unstructured":"OBERLE, I, GENETIC-ANALYSIS OF THE FRAGILE-X MENTAL-RETARDATION SYNDROME WITH 2 FLANKING POLYMORPHIC DNA MARKERS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83: 1016 (1986).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/0168-9525(86)90219-2","volume":"2","year":"1986","unstructured":"POUSTKA, A, JUMPING LIBRARIES AND LINKING LIBRARIES - THE NEXT GENERATION OF MOLECULAR TOOLS IN MAMMALIAN GENETICS, TRENDS IN GENETICS 2: 174 (1986).","journal-title":"TRENDS IN GENETICS"},{"key":"e_1_2_1_22_1","first-page":"493","volume":"72","year":"1975","unstructured":"ROSENSTRAUS, M, ISOLATION OF MAMMALIAN-CELL MUTANTS DEFICIENT IN GLUCOSE-6-PHOSPHATE-DEHYDROGENASE ACTIVITY - LINKAGE TO HYPOXANTHINE PHOSPHORIBOSYL TRANSFERASE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 72: 493 (1975).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(84)90301-5"},{"key":"e_1_2_1_24_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1469-1809.1984.tb00830.x","volume":"48","year":"1984","unstructured":"SHERMAN, S.L., THE MARKER (X) SYNDROME - A CYTOGENETIC AND GENETIC-ANALYSIS, ANNALS OF HUMAN GENETICS 48: 21 (1984).","journal-title":"ANNALS OF HUMAN GENETICS"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/BF00291644","volume":"69","year":"1985","unstructured":"SHERMAN, S.L., FURTHER SEGREGATION ANALYSIS OF THE FRAGILE-X SYNDROME WITH SPECIAL REFERENCE TO TRANSMITTING MALES, HUMAN GENETICS 69: 289 (1985).","journal-title":"HUMAN GENETICS"},{"key":"e_1_2_1_26_1","first-page":"793","volume":"62","year":"1969","unstructured":"SINISCALCO, M, EVIDENCE FOR INTERGENIC COMPLEMENTATION IN HYBRID CELLS DERIVED FROM 2 HUMAN DIPLOID STRAINS EACH CARRYING AN X-LINKED MUTATION, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 62: 793 (1969).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(75)80083-0"},{"key":"e_1_2_1_28_1","unstructured":"SUTHERLAND G.R. FRAGILE SITES HUMAN (1985)."},{"key":"e_1_2_1_29_1","first-page":"107","volume":"81","year":"1983","unstructured":"SUTHERLAND, G.R., THE FRAGILE X-CHROMOSOME, INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY 81: 107 (1983).","journal-title":"INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY"},{"key":"e_1_2_1_30_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/0168-9525(85)90042-3","volume":"1","year":"1985","unstructured":"SUTHERLAND, G.R., THE ENIGMA OF THE FRAGILE-X CHROMOSOME, TRENDS IN GENETICS 1: 108 (1985).","journal-title":"TRENDS IN GENETICS"},{"key":"e_1_2_1_31_1","first-page":"7855","volume":"81","year":"1984","unstructured":"SZABO, P, CYTOLOGICAL MAPPING OF THE HUMAN GLUCOSE-6-PHOSPHATE-DEHYDROGENASE GENE DISTAL TO THE FRAGILE-X SITE SUGGESTS A HIGH-RATE OF MEIOTIC RECOMBINATION ACROSS THIS SITE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 81: 7855 (1984).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES"},{"key":"e_1_2_1_32_1","first-page":"83","volume":"13","year":"1983","unstructured":"TURNER, G, MARKER(X)-LINKED MENTAL-RETARDATION, ADVANCES IN HUMAN GENETICS 13: 83 (1983).","journal-title":"ADVANCES IN HUMAN GENETICS"},{"key":"e_1_2_1_33_1","first-page":"3683","volume":"76","year":"1979","unstructured":"WAHL, G.M., EFFICIENT TRANSFER OF LARGE DNA FRAGMENTS FROM AGAROSE GELS TO DIAZOBENZYLOXYMETHYL-PAPER AND RAPID HYBRIDIZATION BY USING DEXTRAN SULFATE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 76: 3683 (1979).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_34_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/BF00295528","volume":"69","year":"1985","unstructured":"WARREN, S.T., LINKAGE AND RECOMBINATION BETWEEN FRAGILE X-LINKED MENTAL-RETARDATION AND THE FACTOR-IX GENE, HUMAN GENETICS 69: 44 (1985).","journal-title":"HUMAN GENETICS"},{"key":"e_1_2_1_35_1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/BF01535636","volume":"10","year":"1984","unstructured":"WARREN, S.T., EXPRESSION OF FRAGILE X-CHROMOSOME IN HUMAN RODENT SOMATIC-CELL HYBRIDS, SOMATIC CELL AND MOLECULAR GENETICS 10: 409 (1984).","journal-title":"SOMATIC CELL AND MOLECULAR GENETICS"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6336310"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6239375"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.3603029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T10:31:46Z","timestamp":1705228306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.3603029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1987,7,24]]},"references-count":37,"journal-issue":{"issue":"4813","published-print":{"date-parts":[[1987,7,24]]}},"alternative-id":["10.1126\/science.3603029"],"URL":"https:\/\/doi.org\/10.1126\/science.3603029","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1987,7,24]]}}}