Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n

Journal Article · Fri Jun 21 00:00:00 EDT 1991 · Science (Washington, D.C.); (United States)

DOI:https://doi.org/10.1126/science.1675488· OSTI ID:5821658

Kremer, E J; Pritchard, M; Lynch, M; Yu, S; Holman, K; Baker, E; Sutherland, G R; Richards, R I ^[1]; Warren, S T ^[2]; Schlessinger, D ^[3]

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1. Adelaide Children's Hospital (Australia)
2. Emory Univ., Atlanta, GA (United States)
3. Washington Univ., St. Louis, MO (United States)

The sequence of a Pst I restriction fragment was determined that demonstrates 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 sites 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.

• OSTI ID: 5821658
• Journal Information: Science (Washington, D.C.); (United States), Vol. 252:5013; ISSN 0036-8075
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HUMAN X CHROMOSOME
GENETIC MAPPING
DNA SEQUENCING
DNA-CLONING
GENE AMPLIFICATION
NUCLEOTIDES
POLYMERASES
CHROMOSOMES
CLONING
DNA HYBRIDIZATION
ENZYMES
HETEROCHROMOSOMES
HUMAN CHROMOSOMES
HYBRIDIZATION
MAPPING
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES
X CHROMOSOME
550400* - Genetics