{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:13:03Z","timestamp":1779930783339,"version":"3.53.1"},"reference-count":30,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5167","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1994,6,24]]},"abstract":"<jats:p>\n            Fragile sites are chemically induced nonstaining gaps in chromosomes. Different fragile sites vary in frequency in the population and in the chemistry of their induction. DNA sequences encompassing and including the rare, autosomal, folate-sensitive fragile site,\n            <jats:italic>FRA16A<\/jats:italic>\n            , were isolated by positional cloning. The molecular basis of\n            <jats:italic>FRA16A<\/jats:italic>\n            was found to be expansion of a normally polymorphic p(CCG)\n            <jats:sub>\n              <jats:italic>n<\/jats:italic>\n            <\/jats:sub>\n            repeat. This repeat was adjacent to a CpG island that was methylated in fragile site-expressing individuals. The\n            <jats:italic>FRA16A<\/jats:italic>\n            locus in individuals who do not express the fragile site is not a site of DNA methylation (imprinting), which suggests that the methylation associated with fragile sites may be a consequence and not a cause of their genesis.\n          <\/jats:p>","DOI":"10.1126\/science.8009225","type":"journal-article","created":{"date-parts":[[2006,10,6]],"date-time":"2006-10-06T00:01:25Z","timestamp":1160092885000},"page":"1938-1941","source":"Crossref","is-referenced-by-count":111,"title":["Implications of\n            <i>FRA16A<\/i>\n            Structure for the Mechanism of Chromosomal Fragile Site Genesis"],"prefix":"10.1126","volume":"264","author":[{"given":"J. K.","family":"Nancarrow","sequence":"first","affiliation":[{"name":"Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Kremer","sequence":"additional","affiliation":[{"name":"Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Holman","sequence":"additional","affiliation":[{"name":"Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Eyre","sequence":"additional","affiliation":[{"name":"Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. A.","family":"Doggett","sequence":"additional","affiliation":[{"name":"Center for Human Genome Studies and Life Sciences Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Le Paslier","sequence":"additional","affiliation":[{"name":"Centre d'Etude du Polymorphisme Humain, F-7501 01, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. F.","family":"Callen","sequence":"additional","affiliation":[{"name":"Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. R.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. I.","family":"Richards","sequence":"additional","affiliation":[{"name":"Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","first-page":"414","volume":"54","year":"1994","unstructured":"ASHIZAWA, T, CHARACTERISTICS OF INTERGENERATIONAL CONTRACTIONS OF THE CTG REPEAT IN MYOTONIC-DYSTROPHY, AMERICAN JOURNAL OF HUMAN GENETICS 54: 414 (1994).","journal-title":"AMERICAN JOURNAL OF HUMAN GENETICS"},{"key":"e_1_2_1_2_1","first-page":"1016","volume":"53","year":"1993","unstructured":"BRUNNER, H.G., INFLUENCE OF SEX OF THE TRANSMITTING PARENT AS WELL AS OF PARENTAL ALLELE SIZE ON THE CTG EXPANSION IN MYOTONIC-DYSTROPHY (DM), AMERICAN JOURNAL OF HUMAN GENETICS 53: 1016 (1993).","journal-title":"AMERICAN JOURNAL OF HUMAN GENETICS"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(92)90035-Q"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/ng0893-387","volume":"4","year":"1993","unstructured":"DUYAO, M, TRINUCLEOTIDE REPEAT LENGTH INSTABILITY AND AGE-OF-ONSET IN HUNTINGTONS-DISEASE, NATURE GENETICS 4: 387 (1993).","journal-title":"NATURE GENETICS"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90283-5"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/ng1093-174","volume":"5","year":"1993","unstructured":"GOLDBERG, Y.P., MOLECULAR ANALYSIS OF NEW MUTATIONS FOR HUNTINGTONS-DISEASE - INTERMEDIATE ALLELES AND SEX OF ORIGIN EFFECTS, NATURE GENETICS 5: 174 (1993).","journal-title":"NATURE GENETICS"},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/0092-8674(93)90365-W","volume":"73","year":"1993","unstructured":"HANSEN, R.S., ASSOCIATION OF FRAGILE-X SYNDROME WITH DELAYED REPLICATION OF THE FMR1 GENE, CELL 73: 1403 (1993).","journal-title":"CELL"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1093\/hmg\/1.8.571","volume":"1","year":"1992","unstructured":"HANSEN, R.S., HUM MOL GENET 1: 571 (1992).","journal-title":"HUM MOL GENET"},{"key":"e_1_2_1_9_1","first-page":"1164","volume":"52","year":"1993","unstructured":"HARLEY, H.G., SIZE OF THE UNSTABLE CTG REPEAT SEQUENCE IN RELATION TO PHENOTYPE AND PARENTAL TRANSMISSION IN MYOTONIC-DYSTROPHY, AMERICAN JOURNAL OF HUMAN GENETICS 52: 1164 (1993).","journal-title":"AMERICAN JOURNAL OF HUMAN GENETICS"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1093\/hmg\/2.8.1221","volume":"2","year":"1993","unstructured":"JANSEN, G, NO IMPRINTING INVOLVED IN THE EXPRESSION OF DM-KINASE MESSENGER-RNAS IN MOUSE AND HUMAN TISSUES, HUMAN MOLECULAR GENETICS 2: 1221 (1993).","journal-title":"HUMAN MOLECULAR GENETICS"},{"key":"e_1_2_1_11_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0092-8674(93)90300-F","volume":"74","year":"1993","unstructured":"Knight, S. J. L., Cell 74: 127 (1993).","journal-title":"Cell"},{"key":"e_1_2_1_12_1","first-page":"229","volume":"11","year":"1992","unstructured":"KOZMAN, H, GENET LIFE SCI ADV 11: 229 (1992).","journal-title":"GENET LIFE SCI ADV"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1675488"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/0168-9525(87)90268-X","volume":"3","year":"1987","unstructured":"LAIRD, C, TRENDS IN GENETICS 3: 274 (1987).","journal-title":"TRENDS IN GENETICS"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1093\/genetics\/117.3.587","volume":"117","year":"1987","unstructured":"LAIRD, C.D., PROPOSED MECHANISM OF INHERITANCE AND EXPRESSION OF THE HUMAN FRAGILE-X SYNDROME OF MENTAL-RETARDATION, GENETICS 117: 587 (1987).","journal-title":"GENETICS"},{"key":"e_1_2_1_16_1","first-page":"875","volume":"52","year":"1993","unstructured":"LAVEDAN, C, MYOTONIC-DYSTROPHY - SIZE-DEPENDENT AND SEX-DEPENDENT DYNAMICS OF CTG MEIOTIC INSTABILITY, AND SOMATIC MOSAICISM, AMERICAN JOURNAL OF HUMAN GENETICS 52: 875 (1993).","journal-title":"AMERICAN JOURNAL OF HUMAN GENETICS"},{"key":"e_1_2_1_17_1","unstructured":"NANCARROW J unpublished data."},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.252.5009.1097"},{"key":"e_1_2_1_19_1","first-page":"122","volume":"268","year":"1993","unstructured":"Rennie, J., Scientific American 268:122 (1993).","journal-title":"Scientific American"},{"key":"e_1_2_1_20_1","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1093\/hmg\/2.9.1429","volume":"2","year":"1993","unstructured":"RICHARDS, R.I., FRAGILE-X SYNDROME UNSTABLE ELEMENT, P(CCG)N, AND OTHER SIMPLE TANDEM REPEAT SEQUENCES ARE BINDING-SITES FOR SPECIFIC NUCLEAR PROTEINS, HUMAN MOLECULAR GENETICS 2: 1429 (1993).","journal-title":"HUMAN MOLECULAR GENETICS"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1136\/jmg.28.12.856","volume":"28","year":"1991","unstructured":"RICHARDS, R.I., DETERMINATION OF DUCHENNE MUSCULAR-DYSTROPHY CARRIER STATUS BY SINGLE-STRAND CONFORMATION POLYMORPHISM ANALYSIS OF DELETED REGIONS OF THE DYSTROPHIN LOCUS, JOURNAL OF MEDICAL GENETICS 28: 856 (1991).","journal-title":"JOURNAL OF MEDICAL GENETICS"},{"key":"e_1_2_1_22_1","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1056\/NEJM199112123252401","volume":"325","year":"1991","unstructured":"ROUSSEAU, F, DIRECT DIAGNOSIS BY DNA ANALYSIS OF THE FRAGILE X-SYNDROME OF MENTAL-RETARDATION, NEW ENGLAND JOURNAL OF MEDICINE 325: 1673 (1991).","journal-title":"NEW ENGLAND JOURNAL OF MEDICINE"},{"key":"e_1_2_1_23_1","first-page":"123","volume":"72","year":"1986","unstructured":"SHERMAN, S.L., SEGREGATION ANALYSIS OF RARE AUTOSOMAL FRAGILE SITES, HUMAN GENETICS 72: 123 (1986).","journal-title":"HUMAN GENETICS"},{"key":"e_1_2_1_24_1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/ng0893-393","volume":"4","year":"1993","unstructured":"SNELL, R.G., RELATIONSHIP BETWEEN TRINUCLEOTIDE REPEAT EXPANSION AND PHENOTYPIC VARIATION IN HUNTINGTONS-DISEASE, NATURE GENETICS 4: 393 (1993).","journal-title":"NATURE GENETICS"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/hmg\/1.6.397","volume":"1","year":"1992","unstructured":"SUTCLIFFE, J.S., HUM MOL GENET 1: 397 (1992).","journal-title":"HUM MOL GENET"},{"key":"e_1_2_1_26_1","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1136\/jmg.30.12.978","volume":"30","year":"1993","unstructured":"SUTHERLAND, G.R., DYNAMIC MUTATIONS ON THE MOVE, JOURNAL OF MEDICAL GENETICS 30: 978 (1993).","journal-title":"JOURNAL OF MEDICAL GENETICS"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1093\/hmg\/2.10.1535","volume":"2","year":"1993","unstructured":"TELENIUS, H, MOLECULAR ANALYSIS OF JUVENILE HUNTINGTON DISEASE - THE MAJOR INFLUENCE ON (CAG)(N) REPEAT LENGTH IS THE SEX OF THE AFFECTED PARENT, HUMAN MOLECULAR GENETICS 2: 1535 (1993).","journal-title":"HUMAN MOLECULAR GENETICS"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90397-H"},{"key":"e_1_2_1_29_1","first-page":"968","volume":"50","year":"1992","unstructured":"YU, S, FRAGILE-X SYNDROME - UNIQUE GENETICS OF THE HERITABLE UNSTABLE ELEMENT, AMERICAN JOURNAL OF HUMAN GENETICS 50: 968 (1992).","journal-title":"AMERICAN JOURNAL OF HUMAN GENETICS"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.252.5009.1179"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.8009225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T05:34:42Z","timestamp":1705296882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.8009225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,6,24]]},"references-count":30,"journal-issue":{"issue":"5167","published-print":{"date-parts":[[1994,6,24]]}},"alternative-id":["10.1126\/science.8009225"],"URL":"https:\/\/doi.org\/10.1126\/science.8009225","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,6,24]]}}}