Direct detection of novel expanded trinucleotide repeats in the human genome.
Expansion of trinucleotide repeats can give rise to genetic disease. We have developed a technique, repeat expansion detection (RED), that can identify potentially pathological repeat expansion without prior knowledge of chromosomal location. Human genomic DNA is used as a template for a two-step cycling process that generates oligonucleotide multimers when expanded trinucleotide sequences are present at the level found in myotonic dystrophy and fragile-X patients. We have identified at least one new locus exhibiting trinucleotide expansion. Analysis of three families transmitting a long CTG repeat shows that the allele in these families corresponds to a locus on chromosome 18. RED constitutes a powerful tool to identify other diseases caused by this mechanism, particularly diseases associated with anticipation.
Schalling
M
M
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Hudson
T J
TJ
Buetow
K H
KH
Housman
D E
DE
D002887:Chromosomes, Human, Pair 18; D011088:DNA Ligases; D004252:DNA Mutational Analysis / Q000379:methods*; D005600:Fragile X Syndrome / Q000235:genetics; D005784:Gene Amplification; D005820:Genetic Testing; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D009223:Myotonic Dystrophy / Q000235:genetics; D009691:Nucleic Acid Denaturation; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid; D013698:Templates, Genetic
D009841:Oligonucleotides; D011088:DNA Ligases