Implications of FRA 16A structure for the mechanism of chromosomal fragile site genesis

Journal Article · Fri Jun 24 00:00:00 EDT 1994 · Science (Washington, D.C.); (United States)

DOI:https://doi.org/10.1126/science.8009225· OSTI ID:6853669

Nancarrow, J K; Kremer, E; Holman, K; Eyre, H; Callen, D F; Sutherland, G R; Richards, R I ^[1]; Doggett, N A ^[2]; Paslier, D Le ^[3]

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1. Centre for Medical Genetics, North Adelaide (Australia)
2. Los Alamos National Lab., NM (United States)
3. Centre d'Etude du Polymorphisme Humain, Paris (France)

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, FRA16A, were isolated by positional cloning. The molecular basis of FRA16A was found to be expansion of a normally polymorphic p(CCG)[sub n] repeat. This repeat was adjacent to a CpG island that was methylated in fragile site-expressing individuals. The FRA16A 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.

• OSTI ID: 6853669
• Journal Information: Science (Washington, D.C.); (United States), Journal Name: Science (Washington, D.C.); (United States) Vol. 264:5167; ISSN SCIEAS; ISSN 0036-8075
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
BIOTECHNOLOGY
CHEMICAL REACTIONS
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
CLONING
DNA
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
GENETIC ENGINEERING
HUMAN CHROMOSOME 16
HUMAN CHROMOSOMES
HYBRIDIZATION
METHYLATION
MUTATIONS
NUCLEIC ACID HYBRIDIZATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
STRUCTURAL CHEMICAL ANALYSIS