DOI: 10.1126/science.1675488. Mapping of DNA Instability at the Fragile X to a Trinucleotide Repeat Sequence P(CCG) <i>n</i>

Mapping of DNA Instability at the Fragile X to a Trinucleotide Repeat Sequence P(CCG) n

10.1126/science.1675488

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The sequence of a Pst I restriction fragment was determined that demonstrate instability in fragile X syndrome pedigrees. The region of instability was localized to a trinucleotide repeat p(CCG) n . The sequences flanking this repeat were identical in normal and affected individuals. The breakpoints in two somatic cell hybrids constructed to break at the fragile site also mapped to this repeat sequence. The repeat exhibits instability both when cloned in a nonhomologous host and after amplification by the polymerase chain reaction. These results suggest variation in the trinucleotide repeat copy number as the molecular basis for the instability and possibly the fragile site. This would account for the observed properties of this region in vivo and in vitro.

Bibliography

Kremer, E. J., Pritchard, M., Lynch, M., Yu, S., Holman, K., Baker, E., Warren, S. T., Schlessinger, D., Sutherland, G. R., & Richards, R. I. (1991). Mapping of DNA Instability at the Fragile X to a Trinucleotide Repeat Sequence P(CCG) n. Science, 252(5013), 1711â1714.

Authors 10

E. J. Kremer (first)
M. Pritchard (additional)
M. Lynch (additional)
S. Yu (additional)
K. Holman (additional)
E. Baker (additional)
S. T. Warren (additional)
D. Schlessinger (additional)
G. R. Sutherland (additional)
R. I. Richards (additional)

References 13 Referenced 699

BELL, M.V., PHYSICAL MAPPING ACROSS THE FRAGILE-X - HYPERMETHYLATION AND CLINICAL EXPRESSION OF THE FRAGILE-X SYNDROME, CELL 64: 861 (1991). (10.1016/0092-8674(91)90514-Y) / CELL (1991)
10.1126/science.2006411
Kremer , E., American Journal of Human Genetics 49: 656 (1991). / American Journal of Human Genetics (1991)
KREMER E unpublished data.
LINDSAY, S, USE OF RESTRICTION ENZYMES TO DETECT POTENTIAL GENE-SEQUENCES IN MAMMALIAN DNA, NATURE 327: 336 (1987). (10.1038/327336a0) / NATURE (1987)
SUTHERLAND, G.R., EFFECTS OF NUCLEOTIDES ON EXPRESSION OF THE FOLATE SENSITIVE FRAGILE SITES, AMERICAN JOURNAL OF MEDICAL GENETICS 23: 409 (1986). (10.1002/ajmg.1320230133) / AMERICAN JOURNAL OF MEDICAL GENETICS (1986)
Sutherland G. R. Fragile Sites on Human Chromosomes (1985).
SUTHERLAND, G.R., THE ROLE OF NUCLEOTIDES IN HUMAN FRAGILE SITE EXPRESSION, MUTATION RESEARCH 200: 207 (1988). (10.1016/0027-5107(88)90084-X) / MUTATION RESEARCH (1988)
VINCENT, A, ABNORMAL PATTERN DETECTED IN FRAGILE-X PATIENTS BY PULSED-FIELD GEL-ELECTROPHORESIS, NATURE 349: 624 (1991). (10.1038/349624a0) / NATURE (1991)
WARREN, S.T., ISOLATION OF THE HUMAN CHROMOSOMAL BAND XQ28 WITHIN SOMATIC-CELL HYBRIDS BY FRAGILE X-SITE BREAKAGE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 3856 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
WILLIAMSON, R, REPORT OF THE DNA-COMMITTEE AND CATALOGS OF CLONED AND MAPPED GENES AND DNA POLYMORPHISMS, CYTOGENETICS AND CELL GENETICS 55: 457 (1990). (10.1159/000133027) / CYTOGENETICS AND CELL GENETICS (1990)
10.1126/science.252.5009.1179
YU S unpublished data.

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 6:10 p.m.)
Deposited	1 year, 7 months ago (Jan. 11, 2024, 9:01 a.m.)
Indexed	20 minutes ago (Aug. 25, 2025, 2:24 p.m.)
Issued	34 years, 2 months ago (June 21, 1991)
Published	34 years, 2 months ago (June 21, 1991)
Published Print	34 years, 2 months ago (June 21, 1991)

Funders 0

None

BibTeX

@article{Kremer_1991, title={Mapping of DNA Instability at the Fragile X to a Trinucleotide Repeat Sequence P(CCG) n}, volume={252}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1675488}, DOI={10.1126/science.1675488}, number={5013}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Kremer, E. J. and Pritchard, M. and Lynch, M. and Yu, S. and Holman, K. and Baker, E. and Warren, S. T. and Schlessinger, D. and Sutherland, G. R. and Richards, R. I.}, year={1991}, month=jun, pages={1711–1714} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        25
      ]
    ],
    "date-time": "2025-08-25T18:24:28Z",
    "timestamp": 1756146268661
  },
  "reference-count": 13,
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "issue": "5013",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1991,
        6,
        21
      ]
    ]
  },
  "abstract": "<jats:p>\n            The sequence of a Pst I restriction fragment was determined that demonstrate instability in fragile X syndrome pedigrees. The region of instability was localized to a trinucleotide repeat p(CCG)\n            <jats:italic>n</jats:italic>\n            . The sequences flanking this repeat were identical in normal and affected individuals. The breakpoints in two somatic cell hybrids constructed to break at the fragile site also mapped to this repeat sequence. The repeat exhibits instability both when cloned in a nonhomologous host and after amplification by the polymerase chain reaction. These results suggest variation in the trinucleotide repeat copy number as the molecular basis for the instability and possibly the fragile site. This would account for the observed properties of this region in vivo and in vitro.\n          </jats:p>",
  "DOI": "10.1126/science.1675488",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2006,
        10,
        5
      ]
    ],
    "date-time": "2006-10-05T22:10:16Z",
    "timestamp": 1160086216000
  },
  "page": "1711-1714",
  "source": "Crossref",
  "is-referenced-by-count": 699,
  "title": "Mapping of DNA Instability at the Fragile X to a Trinucleotide Repeat Sequence P(CCG)\n            <i>n</i>",
  "prefix": "10.1126",
  "volume": "252",
  "author": [
    {
      "given": "E. J.",
      "family": "Kremer",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, North Adelaide, South Australia, Australia."
        }
      ]
    },
    {
      "given": "M.",
      "family": "Pritchard",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, North Adelaide, South Australia, Australia."
        }
      ]
    },
    {
      "given": "M.",
      "family": "Lynch",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, North Adelaide, South Australia, Australia."
        }
      ]
    },
    {
      "given": "S.",
      "family": "Yu",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, North Adelaide, South Australia, Australia."
        }
      ]
    },
    {
      "given": "K.",
      "family": "Holman",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, North Adelaide, South Australia, Australia."
        }
      ]
    },
    {
      "given": "E.",
      "family": "Baker",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, North Adelaide, South Australia, Australia."
        }
      ]
    },
    {
      "given": "S. T.",
      "family": "Warren",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Departments of Biochemistry and Pediatrics, Emory University School ofMedicine, Atlanta, GA."
        }
      ]
    },
    {
      "given": "D.",
      "family": "Schlessinger",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Genetics in Medicine, Washington University School of Medicine, St. Louis, MO."
        }
      ]
    },
    {
      "given": "G. R.",
      "family": "Sutherland",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, North Adelaide, South Australia, Australia."
        }
      ]
    },
    {
      "given": "R. I.",
      "family": "Richards",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, North Adelaide, South Australia, Australia."
        }
      ]
    }
  ],
  "member": "221",
  "reference": [
    {
      "key": "e_1_2_1_1_1",
      "doi-asserted-by": "crossref",
      "first-page": "861",
      "DOI": "10.1016/0092-8674(91)90514-Y",
      "volume": "64",
      "year": "1991",
      "unstructured": "BELL, M.V., PHYSICAL MAPPING ACROSS THE FRAGILE-X - HYPERMETHYLATION AND CLINICAL EXPRESSION OF THE FRAGILE-X SYNDROME, CELL 64: 861 (1991).",
      "journal-title": "CELL"
    },
    {
      "key": "e_1_2_1_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2006411"
    },
    {
      "key": "e_1_2_1_3_1",
      "first-page": "656",
      "volume": "49",
      "year": "1991",
      "unstructured": "Kremer , E., American Journal of Human Genetics 49: 656 (1991).",
      "journal-title": "American Journal of Human Genetics"
    },
    {
      "key": "e_1_2_1_4_1",
      "unstructured": "KREMER E unpublished data."
    },
    {
      "key": "e_1_2_1_5_1",
      "doi-asserted-by": "crossref",
      "first-page": "336",
      "DOI": "10.1038/327336a0",
      "volume": "327",
      "year": "1987",
      "unstructured": "LINDSAY, S, USE OF RESTRICTION ENZYMES TO DETECT POTENTIAL GENE-SEQUENCES IN MAMMALIAN DNA, NATURE 327: 336 (1987).",
      "journal-title": "NATURE"
    },
    {
      "key": "e_1_2_1_6_1",
      "doi-asserted-by": "crossref",
      "first-page": "409",
      "DOI": "10.1002/ajmg.1320230133",
      "volume": "23",
      "year": "1986",
      "unstructured": "SUTHERLAND, G.R., EFFECTS OF NUCLEOTIDES ON EXPRESSION OF THE FOLATE SENSITIVE FRAGILE SITES, AMERICAN JOURNAL OF MEDICAL GENETICS 23: 409 (1986).",
      "journal-title": "AMERICAN JOURNAL OF MEDICAL GENETICS"
    },
    {
      "key": "e_1_2_1_7_1",
      "unstructured": "Sutherland G. R. Fragile Sites on Human Chromosomes (1985)."
    },
    {
      "key": "e_1_2_1_8_1",
      "doi-asserted-by": "crossref",
      "first-page": "207",
      "DOI": "10.1016/0027-5107(88)90084-X",
      "volume": "200",
      "year": "1988",
      "unstructured": "SUTHERLAND, G.R., THE ROLE OF NUCLEOTIDES IN HUMAN FRAGILE SITE EXPRESSION, MUTATION RESEARCH 200: 207 (1988).",
      "journal-title": "MUTATION RESEARCH"
    },
    {
      "key": "e_1_2_1_9_1",
      "doi-asserted-by": "crossref",
      "first-page": "624",
      "DOI": "10.1038/349624a0",
      "volume": "349",
      "year": "1991",
      "unstructured": "VINCENT, A, ABNORMAL PATTERN DETECTED IN FRAGILE-X PATIENTS BY PULSED-FIELD GEL-ELECTROPHORESIS, NATURE 349: 624 (1991).",
      "journal-title": "NATURE"
    },
    {
      "key": "e_1_2_1_10_1",
      "first-page": "3856",
      "volume": "87",
      "year": "1990",
      "unstructured": "WARREN, S.T., ISOLATION OF THE HUMAN CHROMOSOMAL BAND XQ28 WITHIN SOMATIC-CELL HYBRIDS BY FRAGILE X-SITE BREAKAGE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 3856 (1990).",
      "journal-title": "PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"
    },
    {
      "key": "e_1_2_1_11_1",
      "doi-asserted-by": "crossref",
      "first-page": "457",
      "DOI": "10.1159/000133027",
      "volume": "55",
      "year": "1990",
      "unstructured": "WILLIAMSON, R, REPORT OF THE DNA-COMMITTEE AND CATALOGS OF CLONED AND MAPPED GENES AND DNA POLYMORPHISMS, CYTOGENETICS AND CELL GENETICS 55: 457 (1990).",
      "journal-title": "CYTOGENETICS AND CELL GENETICS"
    },
    {
      "key": "e_1_2_1_12_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.252.5009.1179"
    },
    {
      "key": "e_1_2_1_13_1",
      "unstructured": "YU S unpublished data."
    }
  ],
  "container-title": "Science",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.science.org/doi/pdf/10.1126/science.1675488",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        11
      ]
    ],
    "date-time": "2024-01-11T14:01:53Z",
    "timestamp": 1704981713000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.science.org/doi/10.1126/science.1675488"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1991,
        6,
        21
      ]
    ]
  },
  "references-count": 13,
  "journal-issue": {
    "issue": "5013",
    "published-print": {
      "date-parts": [
        [
          1991,
          6,
          21
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1126/science.1675488"
  ],
  "URL": "http://dx.doi.org/10.1126/science.1675488",
  "relation": {},
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        1991,
        6,
        21
      ]
    ]
  }
}