Human brain contains high levels of heteroplasmy in the noncoding regions of mitochondrial DNA.

Abstract:

:We have analyzed the level of intraindividual sequence variability (heteroplasmy) of mtDNA in human brain by denaturing gradient gel electrophoresis and sequencing. Single base substitutions, as well as insertions or deletions of single bases, were numerous in the noncoding control region (D-loop), and 35-45% of the molecules from a single tissue showed sequence differences. By contrast, heteroplasmy in coding regions was not detected. The lower level of heteroplasmy in the coding regions is indicative of selection against deleterious mutations. Similar levels of heteroplasmy were found in two brain regions from the same individual, while no heteroplasmy was detected in blood. Thus, heteroplasmy seems to be more frequent in nonmitotic tissues. We observed a 7.7-fold increase in the frequency of deletions/insertions and a 2.2-fold increase in the overall frequency of heteroplasmic mutations in two individuals aged 96 and 99, relative to an individual aged 28. Our results show that intraindividual sequence variability occurs at a high frequency in the noncoding regions of normal human brain and indicate that small insertions and deletions might accumulate with age at a lower rate than large rearrangements.

authors

Jazin EE,Cavelier L,Eriksson I,Oreland L,Gyllensten U

doi

10.1073/pnas.93.22.12382

subject

Has Abstract

pub_date

1996-10-29 00:00:00

pages

12382-7

issue

22

eissn

0027-8424

issn

1091-6490

journal_volume

93

pub_type

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