---
_id: '901'
abstract:
- lang: eng
  text: 'Background: Surveying deleterious variation in human populations is crucial
    for our understanding, diagnosis and potential treatment of human genetic pathologies.
    A number of recent genome-wide analyses focused on the prevalence of segregating
    deleterious alleles in the nuclear genome. However, such studies have not been
    conducted for the mitochondrial genome.Results: We present a systematic survey
    of polymorphisms in the human mitochondrial genome, including those predicted
    to be deleterious and those that correspond to known pathogenic mutations. Analyzing
    4458 completely sequenced mitochondrial genomes we characterize the genetic diversity
    of different types of single nucleotide polymorphisms (SNPs) in African (L haplotypes)
    and non-African (M and N haplotypes) populations. We find that the overall level
    of polymorphism is higher in the mitochondrial compared to the nuclear genome,
    although the mitochondrial genome appears to be under stronger selection as indicated
    by proportionally fewer nonsynonymous than synonymous substitutions. The African
    mitochondrial genomes show higher heterozygosity, a greater number of polymorphic
    sites and higher frequencies of polymorphisms for synonymous, benign and damaging
    polymorphism than non-African genomes. However, African genomes carry significantly
    fewer SNPs that have been previously characterized as pathogenic compared to non-African
    genomes.Conclusions: Finding SNPs classified as pathogenic to be the only category
    of polymorphisms that are more abundant in non-African genomes is best explained
    by a systematic ascertainment bias that favours the discovery of pathogenic polymorphisms
    segregating in non-African populations. This further suggests that, contrary to
    the common disease-common variant hypothesis, pathogenic mutations are largely
    population-specific and different SNPs may be associated with the same disease
    in different populations. Therefore, to obtain a comprehensive picture of the
    deleterious variability in the human population, as well as to improve the diagnostics
    of individuals carrying African mitochondrial haplotypes, it is necessary to survey
    different populations independently.Reviewers: This article was reviewed by Dr
    Mikhail Gelfand, Dr Vasily Ramensky (nominated by Dr Eugene Koonin) and Dr David
    Rand (nominated by Dr Laurence Hurst).'
acknowledgement: We thank Ivan Adzhubei and Shamil Sunyaev for extensive assistance
  with PolyPhen 2 and insightful discussion. We thank the Spanish Ministry of Science
  and Innovation, Plan Nacional Program grant BFU2009-09271 for funding.
author:
- first_name: Michael
  full_name: Breen, Michael S
  last_name: Breen
- first_name: Fyodor
  full_name: Fyodor Kondrashov
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
citation:
  ama: Breen M, Kondrashov F. Mitochondrial pathogenic mutations are population-specific.
    <i>Biology Direct</i>. 2010;5. doi:<a href="https://doi.org/10.1186/1745-6150-5-68">10.1186/1745-6150-5-68</a>
  apa: Breen, M., &#38; Kondrashov, F. (2010). Mitochondrial pathogenic mutations
    are population-specific. <i>Biology Direct</i>. BioMed Central. <a href="https://doi.org/10.1186/1745-6150-5-68">https://doi.org/10.1186/1745-6150-5-68</a>
  chicago: Breen, Michael, and Fyodor Kondrashov. “Mitochondrial Pathogenic Mutations
    Are Population-Specific.” <i>Biology Direct</i>. BioMed Central, 2010. <a href="https://doi.org/10.1186/1745-6150-5-68">https://doi.org/10.1186/1745-6150-5-68</a>.
  ieee: M. Breen and F. Kondrashov, “Mitochondrial pathogenic mutations are population-specific,”
    <i>Biology Direct</i>, vol. 5. BioMed Central, 2010.
  ista: Breen M, Kondrashov F. 2010. Mitochondrial pathogenic mutations are population-specific.
    Biology Direct. 5.
  mla: Breen, Michael, and Fyodor Kondrashov. “Mitochondrial Pathogenic Mutations
    Are Population-Specific.” <i>Biology Direct</i>, vol. 5, BioMed Central, 2010,
    doi:<a href="https://doi.org/10.1186/1745-6150-5-68">10.1186/1745-6150-5-68</a>.
  short: M. Breen, F. Kondrashov, Biology Direct 5 (2010).
date_created: 2018-12-11T11:49:06Z
date_published: 2010-12-31T00:00:00Z
date_updated: 2021-01-12T08:21:46Z
day: '31'
doi: 10.1186/1745-6150-5-68
extern: 1
intvolume: '         5'
license: https://creativecommons.org/licenses/by/4.0/
month: '12'
publication: Biology Direct
publication_status: published
publisher: BioMed Central
publist_id: '6749'
quality_controlled: 0
status: public
title: Mitochondrial pathogenic mutations are population-specific
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
volume: 5
year: '2010'
...