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Tiny Genetic Differences Have Huge Consequences

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PhysOrg.com, January 19, 2008

A study led by McGill University researchers has demonstrated that small differences between individuals at the DNA level can lead to dramatic differences in the way genes produce proteins. These, in turn, are responsible for the vast array of differences in physical characteristics between individuals.

The study, part of the Genome Regulators in Disease (GRID) Project funded by Genome Canada and Genome Quebec, was led by Dr. Jacek Majewski of McGill University’s Department of Human Genetics and the McGill University and Genome Quebec Innovation Centre, and first-authored by his research associate Dr. Tony Kwan. It was published January 13 in the journal Nature Genetics.

{snip}

This study solves in part the mystery of how a relatively small number of differences within DNA protein coding sequences could be responsible for the enormous variety of phenotypic differences between individuals. It had previously been shown that individual differences reside in simple, relatively small variations in the DNA sequence called single nucleotide polymorphisms (SNPs, often pronounced “snips”), which exist primarily in the “junk code” of the DNA not previously known to have any profound genetic effect.

“There are many SNPs,” explained Dr. Majewski. “If you add them all together, you’d expect that two individuals would differ at more than a million of those positions. So we have a million or more small differences that distinguish you and me, and yet it would be very hard to explain all the phenotypic differences in the way we look, grow, and behave just by the handful of these protein coding differences.”

Majewski and his colleagues have demonstrated that the natural processing of messenger RNA (mRNA), via a process called splicing, is genetically controlled by these SNPs. The SNPs in certain individuals lead to changes in splicing and result in the production of drastically altered forms of the protein. These out-of-proportion consequences may lead to the development of genetic diseases such as cystic fibrosis and Type 1 diabetes.

{snip}

[Editor’s Note: “Genome-Wide Analysis Of Transcript Isoform Variation In Humans, Majewski, et al.” can be purchased or downloaded here. The abstract appears below.]

Original article

(Posted on January 22, 2008)


Abstract: Genome-Wide Analysis Of Transcript Isoform Variation In Humans

Jacek Majewski, et al., Nature Genetics, January 13, 2008

Tony Kwan1,2, David Benovoy1,2, Christel Dias1, Scott Gurd2, Cathy Provencher2, Patrick Beaulieu3, Thomas J Hudson1,2,4, Rob Sladek1,2 & Jacek Majewski1,2

We have performed a genome-wide analysis of common genetic variation controlling differential expression of transcript isoforms in the CEU HapMap population using a comprehensive exon tiling microarray covering 17,897 genes. We detected 324 genes with significant associations between flanking SNPs and transcript levels. Of these, 39% reflected changes in whole gene expression and 55% reflected transcript isoform changes such as splicing variants (exon skipping, alternative splice site use, intron retention), differential 5’ UTR (initiation of transcription) use, and differential 3’ UTR (alternative polyadenylation) use. These results demonstrate that the regulatory effects of genetic variation in a normal human population are far more complex than previously observed. This extra layer of molecular diversity may account for natural phenotypic variation and disease susceptibility.

1. Department of Human Genetics, McGill University, 740 Dr. Penfield, Room 7210, Montréal, Québec H3A 1A4, Canada.

2. McGill University and Génome Québec Innovation Centre, 740 Dr. Penfield, Room 7210, Montréal, Québec H3A 1A4, Canada.

3. Division of Hematology-Oncology, Research Centre, Sainte-Justine Hospital, Montréal, Québec H3T 1C5, Canada.

4. Ontario Institute for Cancer Research, MaRS Centre, South Tower, 101 College Street, Suite 800, Toronto, Ontario M5G 1L7, Canada.

Correspondence to: Jacek Majewski1,2 e-mail: jacek.majewski@mcgill.ca

Original article

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Comments

So they didn’t know everything! The human organism is much more complex than was thought. That should humble the scientists, but I doubt that it will.

Posted by "Sharia-compliant" at 6:07 PM on January 22


I don’t see how this is as new as the authors state, since Holliday at majorityrights.com brought up the fact that “junk” DNA isn’t so junk after all - at least a year ago, probably longer.

Posted by Svigor at 6:31 PM on January 22


Lol….that’s been known for at least ten years (when I studied genetics as part of my doctorate). It’s hardly ground breaking information.

Posted by at 9:49 PM on January 22


“Majewski and his colleagues have demonstrated that the natural processing of messenger RNA (mRNA), via a process called splicing, is genetically controlled by these SNPs. The SNPs in certain individuals lead to changes in splicing and result in the production of drastically altered forms of the protein.”

That was not known “at least ten years ago.” The paper would never have gotten past the peer-review process if it were just repeating known facts. The idea that, perhaps, “junk DNA” has function has been around for as long as “junk DNA” was known to exist. However, most “mainstream” scientists were content to consider the “junk” as junk.”

This paper is actually showing evidence demonstrating the validity of a minority view.

Posted by snp at 5:40 AM on January 23


So ‘junk DNA’ isn’t ‘junk’ after all.

Posted by Kenelm Digby at 6:37 AM on January 23


There is no waste in nature. There is no “junk” in DNA. Nature does not carry about “waste” since it requires energy to do so. To replicate “junk” DNA would take energy from the organism, thus defeating the essence of being the “fittest”. Nature does not, and can not, do that.

Thus, being logical, concludes that there is absolutely NO JUNK DNA just junk science that hasn’t figured out what it is there for.

100% of all the DNA has a purpose or it would not be there.

Posted by LOGIC at 4:24 PM on January 23


According to the 3rd president of the Mormon church, John Taylor, Cain’s curse of a dark skin marks the representatives of the Devil:

“And after the flood we are told that the CURSE that had been pronounced upon Cain was continued through HAM’S WIFE, as he had married a wife of that seed. And why did it pass through the flood? because it was necessary that the DEVIL SHOULD HAVE A REPRESENTATION upon the earth as well as God;…” (Journal of Discourses, Vol. 22, page 304)

Posted by stevepearsonnl at 10:43 PM on January 23


‘Junk DNA’ is now in the same category of ‘useless organs’ like the appendix and tonsils - that category being “Things The ‘Experts’ Pretended They Knew All About.”

Posted by Dark-Star at 3:18 PM on January 24


It has been clear from the very beginning of the genome project that so-called “nonsense” DNA were responsible for important protein synthetic functions. This was made manifest by the fact that some 95 plus % of the genome of mice and humans is the same. Since there are clearly major phenotypic differences between the two, they must be accounted for by something.
There are also major phenotypic differences between different races which can be accounted for by relatively small differences in genomic DNA. The fact that anyone ever doubted this is a sign of just how far many will go in order to maintain the egalitarian illusion.

Posted by at 6:32 PM on January 24


There is massive and inexorable waste and fraud in government, there is very little waste in terms of environmental adaption in nature. This is not a claim that in nature things develop with symmetry in mind when relating to race though.

Ever notice that those who tend to verently push evolution seem to wildly defend it to a certain point…the point where true difference could just even possibly occur within races? That’s out of bounds!

Government tends to attempt to capitalize on our insecurities and ignorance of those little known facts.

Posted by NEONMANIAC at 12:02 AM on January 27



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