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Hello, my name is Evan Eichler.
I'm a Professor in the
Department of Genome Sciences
at the University of Washington.
Title of my lecture today
is The Future
of Copy Number Variation:
Sequence Based Resolution
and Links to Human Disease.
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For many years,
it's been appreciated
that there's a wide spectrum
of human genetic variation,
ranging on one hand
from single base-pair changes
such as point mutations,
which can be detected
at the level of sequence,
the very large
chromosomal variations
that can be detected
through a light microscope
such as translocations,
inversions, and fusions.
What I want to focus on today
is really an intermediate
form of variation,
large scale genomic variation
typically defined
as greater
than 1 kilobase in length,
which includes
large-scale deletions, inversions,
as well as segmental duplications.
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Collectively,
this type of variation
is known as
genome structural variation
and it can be thought of as really
being of two different flavors
that which varies
in terms of copy number
within a genome,
such as insertions and deletions
where an individual
may have one copy
more or less of a given sequence
with respect to another
or balanced structural
variation events,
such as translocations
and inversions
in which there is no difference
in copy number
but there's a difference
in the structure
and organization of the sequence.
Over the last few years,
there's been a number
of different approaches
that have been used
to actually characterize
the pattern
of normal structural variation.
A normal structural variation
refers to variation
that's found in individuals
who are not thought to suffer
from obvious frank disease
but in fact maybe risk factors
for that disease.
The various approaches
can be divided
into three different groups,
those dependent upon microarrays,
so these are DNA molecules
that have been affixed to slides
and measuring the relative
hybridization intensity of a test
and reference DNA sample
to assess copy number.
There are genomics-based approaches
which often compare
the sequence of one genome
against the human
reference sequence.
And population
genetic-based approaches
which look for failures
in genotyping
or evidence
of "Non-Mendelian transmission
to detect potential sites
of copy number variation."
So I'll be focusing mainly
in this talk
on genomic-based approaches
to detect copy number variation
with exquisite sequence resolution.
