Document Detail

Persistent heteroplasmy of a mutation in the human mtDNA control region: hypermutation as an apparent consequence of simple-repeat expansion/contraction.
MedLine Citation:
PMID:  10762545     Owner:  NLM     Status:  MEDLINE    
In the genealogical and phylogenetic analyses that are reported here, we obtained evidence for an unusual pattern of mutation/reversion in the human mitochondrial genome. The cumulative results indicate that, when there is a T-->C polymorphism at nt 16189 and a C-->T substitution at nt 16192, there is an extremely high rate of reversion (hypermutation) at the latter site. The apparent reversion rate is sufficiently high that there is persistent heteroplasmy at nt 16192 in maternal lineages and at the phylogenetic level, a situation that is similar to that observed for the rapid expansion/contraction of simple repeats within the control region. This is the first specific instance in which the mutation frequency at one site in the D-loop is markedly influenced by the local sequence "context." The 16189 T-->C polymorphism lengthens a (C:G)n simple repeat, which then undergoes expansion and contraction, probably through replication slippage. This proclivity toward expansion/contraction is more pronounced when there is a C residue, rather than a T, at nt 16192. The high T-->C reversion frequency at nt 16192 apparently is the result of polymerase misincorporation or slippage during replication, the same mechanism that also causes the expansion/contraction of this simple-repeat sequence. In addition to the first analysis of this mitochondrial hypermutation process, these results also yield mechanistic insights into the expansion/contraction of simple-repeat sequences in mtDNA.
N Howell; C B Smejkal
Related Documents :
6201325 - Molecular and genetic studies on the euchromatin-heterochromatin transition region of t...
16905325 - No evidence of association between bdnf gene variants and age-at-onset of huntington's ...
18481795 - Genomewide linkage scan reveals novel loci modifying age of onset of huntington's disea...
18795115 - Cross chromosomal similarity for dna sequence compression.
10521305 - Identification of a new locus for generalized epilepsy with febrile seizures plus (gefs...
11417905 - Preimplantation genetic diagnosis and embryo research--human developmental biology in c...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2000-04-10
Journal Detail:
Title:  American journal of human genetics     Volume:  66     ISSN:  0002-9297     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-06-28     Completed Date:  2000-06-28     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1589-98     Citation Subset:  IM    
Biology Division 0656, Department of Radiation Oncology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Base Sequence
Cells, Cultured
Cloning, Molecular
Cytoplasm / genetics*
DNA Replication / genetics
DNA, Mitochondrial / genetics*
Gene Frequency / genetics
Haplotypes / genetics
Models, Genetic
Mutagenesis / genetics
Mutation / genetics*
Optic Atrophies, Hereditary / blood,  genetics,  pathology
Polymorphism, Genetic / genetics
Regulatory Sequences, Nucleic Acid / genetics*
Trinucleotide Repeat Expansion / genetics*
Reg. No./Substance:
0/DNA, Mitochondrial

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

Previous Document:  Characteristics and frequency of germline mutations at microsatellite loci from the human Y chromoso...
Next Document:  Equivalence of single- and multilocus markers: power to detect linkage with composite markers derive...