28 June 2006
anonymous – at 02:41
anonymous – at 03:13
posts from the flutrackers-thread:
Mingus-----
Ok, back on data.
It’s true theses 14 mutation suddently apearing in others gene than
polymerases clearly point out to recombination by dual infection.
It seem a recombination in real-time example to me.
From your analysys method Dr.Niman, is there an obvious parental strain
in the databases for theses changes appearing in this cluster ?
BTW, I like the playing card analogy, well done.
-----niman-----
Here is more on the analysis. The 14 changes
probably represent both recombination and reassortment. The only
hard evidence for recombination is in HA. The father had the C29T
polymorphism found in the second H5N1 collection from his son.
The other 8 changes could have come from the second H5N1. That
distribution would only require a single crossover somewhere between
position 29 and 150, the location of the next novel polymorphism.
The remainder of HA probably matched the second H5N1. Similarly,
all of NA and M could have come from the second parent. PB2,
PB1, PA, NP, and NS matched the son.
Thus, the data can be
easily explained by a dual infection by the son’s H5N1 and a separate
H5N1. The new info in the H5N1 from the father would come from
the parent via recombination in HA and reassortment of NA and M.
therefore, only one new gene needed to be created. HA was
the only gene with a marker fro the son and 8 new markers. The
other changes could have been acquired via acquisition of the
entire gene.
Thus, the gene pool may not have dramatically
changed, but the genes in the cluster changed via a second infection.
Infection of the father by two separate sources would be a
major worry, indicating H5N1 was widespread and other family members
may have been infected with a milder version. There was a ninth
family member hospitalized, but released after testing negative
and thee were media reports of others hospitalized and under observation,
but those reports were not confirmed.
Since a reporter noticed
the symptoms in the father and the family did not trust the WHO
investigators, it is not all that clear on who was infected and
who was not. The dual infection in the father may have been a
signal of infections in more family members or neighbors.
-----mingus-----
Theses 8 new polymorphisms in this cluster…are they
present on others knowns indo-chicken strain or swine strain?
-----JJackson -----
If I understand you correctly you think a homologous recombination
event took place on HA somewhere between loci 29 & 150 and Mingus
is asking, what I would also like to know, is there a candidate
donor with these changes in the released sequence data? If so
is it known to be circulating in Indonesia?
-----niman-----
The new sequences in the
father are largely traceable tyo other H5′s and some have links
to Indonesia. Two of the polymorphisms are in Qinghai strains
http://www.recombinomics.com/News/06…ghai_Karo.html
Others trace back to the 1997 outbreak in Hong Kong.
-----Racter-----
I’m curious about how common
“common” is. I realize it would be difficult to attach meaningful
numbers to that, but if you were inclined to hazard a guess as
to what percentage of the total number of cases were likely to
represent dual infections, I think a lot of us would be interested
to hear it.
I’m also wondering about how strictly “dual infection”
is defined. I mean, if homologous recombination often involves
two strains so similar that the changes are easily mistaken for
random mutation, where is the point at which they are so similar
that we can no longer consider it “dual infection”?
-----rodin33-----
Dr Niman,
The father of the nephew with the 14 changes, isn’t he also the
patient that left (escaped?) the hospital? The fact that he left
the hospital and my understanding is that he hid out in various
places, seems to me that the oportunity for dual infection increased
dramatically. I have no medical or science background qualifying
me to give an educated opinion, however it seems to me that the
proof, sometimes is found in the pudding.
-----niman-----
Dual infections of H5N1 are
common in birds or pigs. In humans it is pretty rare. The changes
accumulate gradually and create opportunity for more recombination
as regions of identity grow. That is why the acquisition of mammalian
polymorphisms. The more mammalian the easier it is to recombine
and acquire more mammalian polymorphisms.
It is like a chain
reaction and when critical mass is achieved, it explodes.
-----niman-----
I believe the “escaping” brother is the sole survivor, not
the brother infected by his son. There were two brothers and one
sister of the index case who were infected. The brother with 14
changes became symptomatic after his son died (and also died).
However, he was moving about when symptomatic and his symptoms
were reported by a reporter, not whoever was supposed to be monitoring
him.
23 July 2006
pandemicflu – at 15:37
looking again at the phylogenetic tree and the mutations:
The closest avian sequence is A/Chicken/Dairi/BPPVI/2005,
and this one is available.
The father differs from the son in 9 positions
and from these nine, the father has 5 in common with the
Dairi-chicken and the son only 4, if I made no mistake.
So, how can the father be so much closer to the
chicken in the picture ?
24 July 2006
pandemicflu – at 00:52
the father is the first green sequence in the picture. The son is the sequence below. The Dairi chicken is the sequence above.
10 October 2006
Closed - Bronco Bill – at 20:18
Closed to maintain Forum speed.