FMR1 in global populations

Journal Article · Fri Mar 01 04:00:00 EST 1996 · American Journal of Human Genetics

OSTI ID:381279

Kunst, C B; Zerylnick, C; Karickhoff, L ^[1]

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1. Emory Univ. School of Medicine, Atlanta, GA (United States); and others

Fragile X syndrome, a frequent form of inherited mental retardation, results from the unstable expansion of a cryptic CGG repeat within the 5{prime} UTR region of the FMR1 gene. The CGG repeat is normally polymorphic in length, and the content is frequently interrupted by AGG triplets. These interruptions are believed to stabilize the repeat, and their absence, leading to long tracts of perfect CGG repeats, may give rise to predisposed alleles. In order to examine the stability of normal FMR1 alleles, the repeat length of 345 chromosomes from nine global populations was examined with the content also determined from 114 chromosomes as assessed by automated DNA sequencing. The FMR1 alleles, defined by the CGG repeat, as well as by the haplotypes of nearby polymorphic loci, were very heterogeneous, although the level of variation correlated with the age and/or genetic history of a particular population. Native American alleles, interrupted by three AGG repeats, exhibited marked stability over 7,000 years. However, in older African populations, parsimony analysis predicts the occasional loss of an AGG, leading to more perfect CGG repeats. These data therefore support the suggestion that AGG interruptions enhance the stability of the FMR1 repeat and indicate that the rare loss of these interruptions leads to alleles with longer perfect CGG-repeat tracts. 42 refs., 4 figs., 2 tabs.

• OSTI ID: 381279
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 3 Vol. 58; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
DNA SEQUENCING
DOMINANT MUTATIONS
GENE MUTATIONS
GENES
HEREDITARY DISEASES
HUMAN POPULATIONS
HUMAN X CHROMOSOME
MENTAL DISORDERS
NUCLEOTIDES