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SUMMARY:Haplogroup context is a key element to deciding if an mtDNA varian
 t is a mutation or population polymorphism\, complete study of mitochondri
 al tRNA’s across multiple taxa - Dr Joanna Elson | Wellcome Centre for M
 itochondrial Research\, Newcastle University
DTSTART:20190320T150000Z
DTEND:20190320T160000Z
UID:TALK118621@talks.cam.ac.uk
CONTACT:Hannah Burns
DESCRIPTION:Hannah O'Keefe1\,2 \, Rachel Queen3\, Phillip Lord2\, Joanna L
 . Elson1\,4*\n\n \n\n1.      Institute of Genetic Medicine\, Newcastle Uni
 versity\, Newcastle-upon-Tyne\, NE1 3BZ\,\n\nUnited Kingdom\n\n2.      Sch
 ool of Computing\, Newcastle University\, Newcastle-upon-Tyne\, NE4 5TG\, 
 United Kingdom\n\n3.      Bioinformatics Core Facility\, Newcastle Univers
 ity\, United Kingdom\n\n4.      Centre for Human Metabonomics\, North-West
  University\, Potchefstroom\, South Africa\n\n \nMitochondrial disorders a
 re heterogeneous\, showing variable presentation and penetrance. Over the 
 last three decades\, our ability to recognize mitochondrial patients and d
 iagnose these mutations\, linking genotype to phenotype\, has greatly impr
 oved. However\, it has become increasingly clear that these strides in dia
 gnostics have not benefited all population groups. Recent studies have dem
 onstrated that patients from genetically under-studied populations\, in pa
 rticular those of black African heritage\, are less likely to receive a di
 agnosis of mtDNA disease. It has been suggested that haplogroup context mi
 ght influence the presentation and penetrance of mtDNA disease\; thus the 
 spectrum of mutations that are associated with disease in different popula
 tions. However\, to date there is only one well established example of suc
 h an effect: the increased penetrance of two Leber's hereditary optic neur
 opathy mutations on a haplogroup J background. This paper conducted the mo
 st extensive investigation to date into the importance of haplogroup conte
 xt on the pathogenicity of mtDNA mutations. We searched for proven human p
 oint mutations across 726 multiple sequence alignments derived from 33 non
 -human species absent of disease. 58 pathogenic point mutations arise in t
 he sequences of these species. We assessed the sequence context and found 
 evidence of population variants that could modulate the phenotypic express
 ion of these point mutations masking the pathogenic effects seen in humans
 . This supports the theory that sequence context is influential in the pre
 sentation of mtDNA disease and has implications for diagnostic practices. 
 We have shown that our current understanding of the pathogenicity of mtDNA
  point mutations\, primarily built on studies of individuals with haplogro
 ups HVUKTJ\, will not present a complete picture. This will have the effec
 t of creating a diagnostic inequality\, whereby individuals who do not bel
 ong to these lineages are less likely to receive a genetic diagnosis.  
LOCATION:Sackler Lecture Theatre (Level 7) Wellcome Trust/MRC Building\, C
 ambridge Biomedical Campus
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