Document Detail


Fragile X gene instability: anchoring AGGs and linked microsatellites.
MedLine Citation:
PMID:  7668261     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interspersed AGGs within the FMR1 gene CGG repeat region may anchor the sequence and prevent slippage during replication. In order to detect the AGG position variations, we developed a method employing partial MnlI restriction analysis and analyzed X chromosomes from 187 males, including 133 normal controls (117 with 20-34 and 16 with 35-52 repeats), plus 54 fragile X premutations with 56-180 repeats. Among controls, the interspersed AGG positions were highly polymorphic, with a heterozygosity of 91%. Among the control samples, 1.5% had no AGG positions, 25% had one, 71% had two, and 3% had three. Among the fragile X premutation samples, 63% had no AGG, while 37% had only one AGG. Analysis of premutation samples within fragile X families showed that variation occurred only within the 3' end of the region. Thus, the instability was polar. Controls with > or = 15 pure CGG repeats were associated with the longest alleles of two nearby microsatellites, FRAXAC1 with 20-21 repeats and DXS548 with 202-206 bp and with increased microsatellite heterozygosity. The association of long pure CGG regions, as with fragile X chromosomes, with the longer and more heterozygous microsatellite alleles suggests they may be related mechanistically. Further, our results do not support a recent suggestion that the frequency of fragile X alleles may be increasing. Finally, analysis of a set of nonhuman primate samples showed that long pure CGG tracks are variable in size and are located within the 3' region, which suggests that polar instability within FMR1 is evolutionarily quite old.
Authors:
N Zhong; W Yang; C Dobkin; W T Brown
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of human genetics     Volume:  57     ISSN:  0002-9297     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-10-12     Completed Date:  1995-10-12     Revised Date:  2013-04-15    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  351-61     Citation Subset:  IM    
Affiliation:
Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
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MeSH Terms
Descriptor/Qualifier:
Alleles
Base Sequence
DNA, Satellite / genetics*
Fragile X Syndrome / genetics*
Genetic Linkage*
Haplotypes
Humans
Male
Molecular Sequence Data
Polymerase Chain Reaction
Repetitive Sequences, Nucleic Acid*
Grant Support
ID/Acronym/Agency:
HD29407/HD/NICHD NIH HHS; MCJ360587//PHS HHS
Chemical
Reg. No./Substance:
0/DNA, Satellite
Comments/Corrections
Comment In:
Am J Hum Genet. 1996 Jul;59(1):252-3   [PMID:  8659532 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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