New Zealand Next Generation Sequencing Conference - Innovative ...

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Speaker Biographies and Abstracts
Listed in the order they appear in the Programme
Session 1
Earthquake induced stress cardiomyopathy: is it a Mendelian condition
Martin Kennedy
Department of Pathology, University of Otago, Christchurch
Biography
Martin Kennedy obtained his PhD in bacterial
genetics at the University of Auckland, and carried
out postdoc research in leukaemia genetics at the
Laboratory of Molecular Biology, Cambridge (UK)
before returning to Christchurch, New Zealand in
1991. His current research interests include the
genetics of complex disease, gene by environment
interactions, and pharmacogenomics. He also
holds a Marsden grant to examine the role of G-
quadruplex structures in DNA and their relevance
to genomic imprinting
Abstract
The major earthquakes of 4th September 2010 and
22nd February 2011 both triggered case clusters of
a rare condition called stress cardiomyopathy (also
known as broken heart syndrome or Takotsubo
cardiomyopathy). Many of these patients received
critical care in the coronary care unit of
Christchurch Hospital, and some required intensive
care with ventilatory support, but ultimately all
survived. The resulting very well characterised,
tightly homogenous cohort of 30 patients is
unprecedented. Almost all patients presenting with
the condition were post-menopausal females,
consistent with other reports. This provides a
unique opportunity to study the underlying causes
and presentation of this perplexing disorder. The
exact aetiology of stress cardiomyopathy remains
unknown with catecholamine induced myocardial
stunning a proposed pathway. Many forms of
cardiomyopathy have genetic origins, and it is
reasonable to propose that this syndrome arises
from a very rare underlying genetic predisposition
that is exposed in times of major, acute stress. We
hypothesised that stress cardiomyopathy is a rare
Mendelian predisposition that is exposed with
acute major stress. The rarity of the underlying
mutation requires that large numbers of people
must be exposed to the stressor, which only
happens in times of natural disaster such as major
earthquakes. This is rather speculative, although
two prior reports describe occurrence of the
syndrome in relatives. Exome sequencing provides
a method to test this hypothesis. We obtained
exome data on 12 of the Christchurch earthquake
stress cardiomyopathy patients using Illumina
TruSeq exome enrichment and the Illumina HiSeq
platform (New Zealand Genomics Ltd). The data
have been processed through the GATK pipeline,
and we are examining candidate variants that
occur in patient samples with a higher than
expected distribution based on 1000 Genomes
Project data. This presentation will describe these
preliminary analyses and some of the pitfalls
encountered so far.
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