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Nucleotide sequence analysis of the apolipoprotein B 3' VNTR
D L Ellsworth1, M D Shriver, E Boerwinkle
1Human Genetics Center, University of Texas Health Science Center, Houston 77225, USA.
Human Molecular Genetics
|May 1, 1995
Summary
Apolipoprotein B (Apo B) 3' VNTR instability is driven by intra-allelic mutation, not unequal recombination. Secondary structures, not just repeat copy number, influence variability.
Area of Science:
- Genetics
- Molecular Biology
- Population Genetics
Background:
- Variable number of tandem repeat (VNTR) loci are prone to mutations, making them valuable for studying sequence instability.
- The apolipoprotein B (Apo B) 3' VNTR is a minisatellite locus with known length variation.
Purpose of the Study:
- To elucidate the internal structure and mutational mechanisms of the Apo B 3' VNTR.
- To investigate the relationship between repeat structure, secondary structure formation, and mutation patterns.
Main Methods:
- Nucleotide sequencing of same- and different-sized Apo B 3' VNTR alleles.
- Analysis of linkage disequilibrium between VNTR alleles and flanking polymorphisms.
- Prediction and analysis of secondary structures for VNTR dimeric repeats.
Main Results:
- Linkage disequilibrium suggests intra-allelic mutation (replication slippage/sister chromatid exchange) predominates over unequal recombination.
- Allele length diversity is polarized, with variation concentrated in a specific repeat sequence.
- VNTR variability correlates with the potential for self-complementary secondary structure formation.
Conclusions:
- The Apo B 3' VNTR mutational mechanism is primarily intra-allelic.
- Secondary structure formation, influenced by repeat location and base composition, plays a significant role in VNTR instability.
- Polarized variability may arise independently of the primary mutation process, possibly via secondary structure formation.