cloning cows

dna is not static.

it does change, for some problems, it only takes one basepair, ie pha or th and countless other defects, obviously many more are more mysterious.

an interesting experiment would be to grab the 10 eggs of a cow at say one year, sequence them in a haploid state, then say 10 years later, sequence to more and compare.

telomeres, the ends of chromosomes erode over time.  errors occur as well otherwise there wouldn't be a need for error correction.

perhaps some of the confusion of change is crossover events during meiosis generating change.

spontaneous events occur as well like PHA.  also, duplications occur as do deletions during replication and if in the germ line or donor line, things will change.  granted, these occur during meiosis.  also, it's widely known that all kinds of mutations occur from external events such as radiation, cancer,gamma rays who knows what else.  one only needs a reference and a time line to track them over time.

since sequencing is so cheap now, it would be useful to sequence both heat wave and say 10 clones.

if dna didn't change, we wouldn't have speciation.

one or two clones of smart little lena had monkey mouth.  would be useful to figure that out.

Knabe- are the changes in DNA over time considered significant.  Are the changes always considered negative or have they been shown to have measurable effects on phenotype in the lab?

chambero said:

Knabe- are the changes in DNA over time considered significant.  Are the changes always considered negative or have they been shown to have measurable effects on phenotype in the lab?

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spontaneous effects are significant, probably what pha and th were.  if we were allowed to see the sequence of pha, the two dirty bulls supposedly have the same point mutation, but one allele is supposedly older than the other one.  th has two different mutations.  the concept of time can fool us as we are lulled into safety.  obviously when a point mutation occurs one can use stats the other way to make it look like they happen all the time.  looking at lots of sequencing, it's pretty apparent that point mutations or something is occurring.

a good place to look is stickleback fish.  as fish moved from the ocean to the rivers, a mutation surfaced that caused them to swim differently and reduce their predation.  lots of other mutations occurred or surfaced under selection.  this has all occurred in under 10,000 years from the last significant ice age as some of these fish became land locked.

changes are neither positive or negative, they just are.  take sickle cell anemia, it is both positive and negative, ie resistance to malaria, but has other problems.  one could even argue that pha and th are positive mutations if they have a survival benefit in the heterozygous state other than winning in the ring, kind of like the big heart gene in horses which may be why horses "bleed".  i think we don't know enough about what is happening to definitively state that rate of change is not that big of a deal.  when it does occur, and it's impact is high to that time window, it's important.  yes i agree about your time observation, it can be a perception issue like how people die, we get all excited about the rare events, yet think nothing of the common events and have no concept of looking at occurrences in order and structuring behavior based on rank instead of emotion.

http://kingsley.stanford.edu/publications.html

http://articles.sfgate.com/2004-04-15/news/17420335_1_fins-threespine-sticklebacks/2

http://www.eurekalert.org/pub_releases/2004-04/sumc-srs041204.php

yes, the lab that bred these was in the same building as me and we sequenced them.

"Graduate student and co-first author Melissa Marks and former postdoctoral scholar Katie Peichel, PhD, found that the presence of hind fins seemed to correlate with changes at one particular location of the fish chromosomes. A few other chromosome regions had smaller effects on the length and shape of pelvic features, but most of the major evolutionary change could be attributed to a single region. Mike Shapiro, PhD, a postdoctoral scholar and co-first author, found that a gene located at that region is the stickleback version of a gene in mice called Pitx1 that, when mutated, causes mice to have greatly reduced hind limbs. These mice often have asymmetric limb and pelvic reductions, much like the sticklebacks.

These experiments helped explain how mutations at Pitx1 could nudge one population of fish toward losing hind limbs, but they don't hint at whether these mutations were a one-time solution or a widely used strategy.

The researchers addressed this larger evolutionary question using a second population of freshwater sticklebacks discovered by co-author Bjarni Jonsson from the Institute of Freshwater Fisheries in Iceland. The Icelandic fish also lack hind fins, but evolved thousand of miles away from the Vancouver fish. Marks bred the two freshwater sticklebacks and produced an aquarium full of fish lacking hind fins.

Breeding the Icelandic sticklebacks to a four-finned saltwater fish once again generated offspring with hind fins. Together, these experiments suggest that the same set of genes was responsible for the loss of hind fins in two widely separated geographic locations.

"It looks like evolution is using this gene repeatedly," Kingsley said.

The work fits into a growing pattern in evolutionary biology. Although animals look dramatically different, in some cases only a few gene changes account for the differences. "It looks like a small number of genes can have large effects," said Shapiro.

The work also addressed how a few gene changes cause large evolutionary shifts. Most genes have many roles in an animal, so mutations kill the animal rather than altering its shape. Mice with mutated Pitx1, for example, die soon after birth. In the sticklebacks, however, the group found alterations in the location of the Pitx1 gene activity. Although the Pitx1 protein doesn't show up in the developing pelvic region of the fish lacking hind fins, the gene still does its normal job in other regions such as in the thymus and olfactory bulbs."

Do not mutations like that occur during the combination of DNA from two parents or does it occur inside one animal after its conception?

On any one animal, what % of genes have changed by the end of its life relative to what iy started out with?  Guessing fractions of a percent.

chambero said:

Do not mutations like that occur during the combination of DNA from two parents or does it occur inside one animal after its conception?

On any one animal, what % of genes have changed by the end of its life relative to what iy started out with?  Guessing fractions of a percent.

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eggs are supposedly more susceptible to mutation as all of them are already made while sperm is continually being made.  eggs can accumulate point mutation as there is less or no repair mechanism for unreplicating dna, hence early eggs are more faithful representation than later ones.

if only one point mutation is necessary for lethality, ie pha, and no test breeding on clones to sibs is done to measure fractions of a percent, arguing about what percent is necessary for impact is somewhat  of an unknowable and making projections of impact is somewhat pointless without data and is essentially a bet.

mutations occur to gametes, during meitosis, ie duplications, deletions, there are lots of types of mutations.  i dont' think we know how much they occur as we don't have a cheap and fast way to measure it yet.

I was just curious how far studies had gotten with these kinds of questions.  More fodder for future dissertations.

stkrdge said:

CAB said:

Do you have a cellline on Hazel?

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Yes we have a cell line on Hazel and am considering having her cloned.I would like some input to see how a cloned cow reproduces.

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I think you should do it, just look what she has produced!! Amazing!
The steer in my Avatar is out of a Hazel son!

so that is why my old # 14 cow didn't have a good calf till she was 7, that is when her mitochondria was finally in line with the planets.  maybe should ear-punch every jan 1 then when we dispurse we would have lot 14a: 2010 cell line,  14b: 2011 cell line, 14c 2012 etc etc

While DNA does change some overtime, I dont think the change is significant to cloning.  And I dont think mutation is always the issue when it comes to clones not be phenotypic replicas of the animals they were cloned to match.  While clones will be genetically the same, their environment plays, even in the uterus, plays a big part in how they develop.  Which I feel plays a bigger role in why the clones are not all phenotypically exact.
The Smart Liittle Lena clones were all cloned from the same cell line, so if environment didnt play a roll then they would all be exactly the same, and your right, the 2 that sold low were both parrot mouthed, but I think that is more an issue with development in utero than with the genetic line!
Now people are free to disagree here, I have spent a LOT of time in Science and Genetics classrooms myself, but I am far from an expert on this, as I think many are, there is still lots of research that needs to be done before we know exactly how all of this works!