Isolation of Sequences That Span the Fragile X and Identification of a Fragile X-Related CpG Island

• Published in: Science (American Association for the Advancement of Science) 1991-03, Vol.251 (4998), p.1236-1239
• Main Authors: Heitz, D., Rousseau, F., Devys, D., Saccone, S., Abderrahim, H., Le Paslier, D., Cohen, D., Vincent, A., Toniolo, D., Della Valle, G., Johnson, S., Schlessinger, D., Oberle, I., Mandel, J. L.
• Format: Article
• Language: English
• Subjects: Base Sequence; Biological and medical sciences; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); Chromosome mapping; Chromosomes; Chromosomes, Fungal; Cloning, Molecular; Dinucleoside Phosphates; DNA; DNA Probes; Fragile X syndrome; Fragile X Syndrome - genetics; Genetic mutation; Genetics; Humans; Intellectual disability; Life Sciences; Male; Medical genetics; Medical sciences; Metaphase; Molecular Sequence Data; Mutation; Nucleic Acid Hybridization; Oligonucleotide Probes; Polymerase Chain Reaction; Reference Values; Restriction Mapping; Saccharomyces cerevisiae - genetics; Sex chromosomes; X Chromosome
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2006411

Yeast artificial chromosomes (YACs) were obtained from a 550-kilobase region that contains three probes previously mapped as very close to the locus of the fragile X syndrome. These YACs spanned the fragile site in Xq27.3 as shown by fluorescent in situ hybridization. An internal 200-kilobase segment contained four chromosomal breakpoints generated by induction of fragile X expression. A single CpG island was identified in the cloned region between markers DXS463 and DXS465 that appears methylated in mentally retarded fragile X males, but not in nonexpressing male carriers of the mutation nor in normal males. This CpG island may indicate the presence of a gene involved in the clinical phenotype of the syndrome.