[ensembl-dev] why would a snp have multiple consequences in the same transcript

[Robert Bradbury]

Andreas,

Looking at your last (extensive) response, it generates some more questions.

1) I assume NMD means "Named", e.g. a genomic area named in the Gene Names
database (which I think includes RNA which is non-coding).  Is this correct?

2) How many actual completely sequenced genomes are being used to provide
these statistics?  Or is the data simply derived from the current human SNP
database (which could easily be lacking with respect to complex indels).

3) Is there documentation on how to download the human database from which
the mysql results are derived and set it up locally?  Also documentation on
the table format(s)?

As the accumulation of indels in single cells (due to corruptive repair of
DNA double strand breaks by WRN & DCLRE1C) is likely to be a primary cause
of aging (IMO) [1].  Is there any attempt to determine at what point the
noise level in sequences is suggestive of indels indicates "aged" cells (or
a possibly pre-aged genome if the indels happened during early
embryongenesis) are present? [2]  The problem is that if indels are taking
place in cells individually they may be impossible to detect in gross
multi-cell genome sequencing or SNP studies.  The only way they might be
detected is through unusual noise levels indicating that some fraction of
the cells have damaged genomes.  My assumption here may be that indel
mutations are somewhat more obvious than SNP mutations but this may depend
on the methods used.

Thanks,
Robert

1) Indels accumulate over ones lifespan in cells and a fraction of which
cause frameshift mutations.  These potentially activate the ER and
mitochondrial unfolded protein responses causing a cellular protein
synthesis shutdown and/or apoptosis.  Those which do not do this may
contribute to cellular stress which activates the cellular senescence
program which has other negative consequences.
2) Of course it may be possible that most of the genomes used to produce
current human genomic databases are from relatively young individuals.  Only
that of James Watson would in my book qualify as an "aged" genome.
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