Genetic variation and evolutionary stability of the FMR1 CGG repeat in six closed human populations

Journal Article · Fri Jul 12 04:00:00 EDT 1996 · American Journal of Medical Genetics

DOI:https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<220::AID-AJMG40>3.0.CO;2-M· OSTI ID:476937

Eichler, E E; Nelson, D L ^[1]

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1. Baylor College of Medicine, Houston, TX (United States)

In an attempt to understand the allelic diversity and mutability of the human FMR1 CGG repeat, we have analyzed the AGG substructure of this locus within six genetically-closed populations (Mbuti pygmy, Baka pygmy, R. surui, Karitiana, Mayan, and Hutterite). Most alleles (61/92 or 66%) possessed two AGG interspersions occurring with a periodicity of one AGG every nine or ten CGG repeats, indicating that this pattern is highly conserved in all human populations. Significant differences in allele distribution were observed among the populations for rare variants possessing fewer or more AGG interruptions than the canonical FMR1 CGG repeat sequence. Comparisons of expected heterozygosity of the FMR1 CGG repeat locus with 30 other microsatellite loci, demonstrated remarkably similar levels of polymorphism within each population, suggesting that most FMR1 CGG repeat alleles mutate at rates indistinguishable from other microsatellite loci. A single allele (1 out of 92) was identified with a large uninterrupted tract of pure repeats (42 pure CGG triplets). Retrospective pedigree analysis indicated that this allele had been transmitted unstably. Although such alleles mutate rapidly and likely represent evolving premutations, our analysis suggests that in spite of the estimated frequency of their occurrence, these unstable alleles do not significantly alter the expected heterozygosity of the FMR1 CGG repeat in the human population. 45 refs., 1 fig., 2 tabs.

• OSTI ID: 476937
• Journal Information: American Journal of Medical Genetics, Journal Name: American Journal of Medical Genetics Journal Issue: 1 Vol. 64; ISSN 0148-7299; ISSN AJMGDA
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL EVOLUTION
BIOLOGICAL MARKERS
CHROMOSOMAL ABERRATIONS
DISEASE INCIDENCE
DNA SEQUENCING
GENE MUTATIONS
GENES
GENETIC VARIABILITY
GENETICS
HEREDITARY DISEASES
HUMAN POPULATIONS
HUMAN X CHROMOSOME
MENTAL DISORDERS
METHYLATION
MUTATION FREQUENCY
MUTATIONS
NUCLEOTIDES
POPULATION DYNAMICS
STATISTICS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION