Talk:Variant of uncertain significance/Archive 1

Archive 1

History section

The History section should be subdivided. It should also be more explicitly chronological - there are currently very few dates mentioned in it. Roger (Dodger67) (talk) 17:55, 12 January 2017 (UTC)

Title and first sentence changed

Based on discussion on the Genetics Project talk page, I changed the use of gene to variant in the title and modified the first sentence. Note that there is already a page named variants of unknown significance and it would have been better to have added to that page than start this page, IMHO. DennisPietras (talk) 04:24, 16 January 2017 (UTC)

I'm done with the history section

Let the editing begin! I'm going to take a nap. No sleep last night. DennisPietras (talk) 17:01, 20 January 2017 (UTC)

Is everybody at work or watching the inauguration???? You're missing your chance to edit before I put the "in use" banner up! DennisPietras (talk) 19:53, 20 January 2017 (UTC)

We're leaving it to you. You seem to know what you are doing, but, since you are giving us a chance to edit, I've turned a rhetorical question into a statement. Dbfirs 10:30, 21 January 2017 (UTC)

first attempt at using sandbox left me with...

{{reflist|33em|refs= in my eyes. That is, I wrote the applications section in my sandbox, then copied and pasted it in place of the original section. That resulted in about 10 reference errors. I finally got it down to only having {{reflist|33em|refs= at the top of the reference section. I've already undone my own edits twice, so I'm out of undo's. I hope that somebody knows how to deal with that, and yes, I'm going to be very reluctant to play in te sand again. Thanks, DennisPietras (talk) 04:16, 22 January 2017 (UTC)

I think I've fixed the errors now, and no more broken reflist template. Psiĥedelisto (talk) 13:50, 22 January 2017 (UTC)

When I looked at it there was one reference error, a Vancouver style error caused by a curly quote mark character. I have corrected that, and another curly quote that I tripped over. Curly quotes are referred to in MOS:CURLY, so if you have put any more in the text you ought to change them to straight quote marks. --David Biddulph (talk) 14:04, 22 January 2017 (UTC)

@David Biddulph: I'm not even sure how to type curly quotes so I can assure you it wasn't me. I think it may have been in the reference that I saved from the References section and put in its proper place - thanks for your edit. Psiĥedelisto (talk) 14:07, 22 January 2017 (UTC)

@Psiĥedelisto: As you will see from the indentation, my reply was not to your message, but to the OP, DennisPietras. --David Biddulph (talk) 14:11, 22 January 2017 (UTC)

Oops, sorry Psiĥedelisto (talk) 14:12, 22 January 2017 (UTC)

Thanks all! I had seen the vancouver error and just gave up on it. Who knew there was such a thing as a curly quote???? They were from copying and pasting the original reference info. How long have you folks actually been at this to learn about stuff like curly quotes? No, don't bother to answer that. I don't want to think about how long I've been a biologist... DennisPietras (talk) 15:43, 22 January 2017 (UTC)

Whipping a dead horse and accomodating the visually impaired at the same time.

@Dbfirs, Maunus, Psiĥedelisto, Slashme, and Graham87:I've stalled near the end of my revisions of the VUS article to bring up this issue of acess again.

An insignificant mutation?^{TTS caption: The image shows a beautiful, perfectly formed red tulip in bloom, but about twenty percent of the flower is an equally beautiful yellow. The yellow occurs as a block of color with a straight sharp line dividing yellow from red running vertically up the petal. This is used to visually illustrate the idea that there are mutations, in this case a somatic mutation, that have little or no consequence for the growth or health of the organism. end TTS}

As some of you can see, I've made a revised version of the tulip image. Rather than having a consensus image caption, why not have image captions that are better suited for BOTH normal and visually impaired people at the same time? That is, people with normal vision can see the "cute" pithy "An insignifcant mutation?" in yellow text on red background and the visually impaired can get a better description from their TTS software. People with normal vision can simply ignore anything after "TTS caption", which, for the visually impaired, is composed with the html code tags for really small text, which I assume is not read by your TTS software.

Sequencing costs plunge.^{TTS caption: The image shows a graph that plots the monetary cost per genome sequenced versus the year, and a line showing how the cost would decline if the decline followed Moore's law. The data starts at 2001 with a cost of one hundred million dollars. For about 7 years, the real cost declines nearly coincidentally with Moore's law. Then, there is a dramatic decline in real cost, until it is just sligtly more than one thousand dollars at the end of 2015. That dramatic decline was essentially coincident with the devlopment of massively parallel DNA sequencing technology. end TTS}

A more important example is the sequencing cost image. I inserted it into the article without a caption, because for people with normal vision I don't think a caption is needed. However, that doesn't help the visually impaired at all.

Something I didn't expect is that if you click on the image to expand it, all the text is in the normal large size, which means that people with normal vision have the opportunity to get more information. (What I really didn't expect is that now as I preview this discussion, clicking on the tulip image doesn't work like that. It seems to be calling up the caption from the discussion above. Perhaps when I actually save this, it will behave right. sigh.) Now, I have several questions:

1) I think I invented the term "TTS caption", in analogy with the "CC" for closed captioning. Is there a peexisting universal symbol?

2) Is there an "ultra small" or "nano small" text that can be used for this?

3) Is there a way to completely hide the accomodating text from view? That is, what I envision is some HTML code like <TTS>write tts caption here</TTS> which would visually completely hide the text while allowing TTS programs to voice it. This is of some importance because the pysical size (footprint) of the TTS caption can get quite large, unless there is some "nano" font.

4) Comments? DennisPietras (talk) 16:56, 21 January 2017 (UTC)

Well, now that it is saved NEITHER of the images show the captions when I click them. siiggghh.....DennisPietras (talk) 17:00, 21 January 2017 (UTC)

Thanks for calling us back to continue the discussion! I like what you're doing with the article in general, and to help out, I have made some edits and I have a few comments:

• I have trimmed the background discussion that you wrote there: I think that it had grown beyond what was needed to introduce the topic. I also think that the graph of falling sequencing prices wasn't really relevant enough, so I cut it out, along with the picture of outlines of people with a colourful ATCG background, which I found to be more decorative than instructive.
• If you are motivated to make your images more accessible to our blind readers, I'd recommend that you take a look at Wikipedia:Manual_of_Style/Accessibility#Images. The alt attribute is the right way to achieve this purpose.
• The reason for my opposition to the yellow/red caption was never founded on accessibility. I find it garish and unnecessary, I don't think it adds to the understanding of the topic, and it doesn't fit with the overall Wikipedia style. Maybe it would work at vikidia?

Cheers! --Slashme (talk) 22:57, 21 January 2017 (UTC)

Yes, I was going to mention alt text as well. Graham87 02:33, 22 January 2017 (UTC)

@Slashme and Graham87: Thanks for the tip about alt text. I was amused by, I bet, the first use in recorded human history of the term "garish" in any relationship to a picture of a tulip! DennisPietras (talk) 04:30, 22 January 2017 (UTC)

second Dbfirs 08:11, 22 January 2017 (UTC)

 Oppose as per Dbfirs, Slashme, WP:MOS. The color adds nothing and the more description caption helps more than just the visually impaired. Psiĥedelisto (talk) 13:42, 22 January 2017 (UTC)

To defend myself against possible future accusations of plagiarism by User:Dbfirs's more fanatical acolytes, let me just say that tulips have been described as "garish" since at least the 1870s. --Slashme (talk) 14:06, 22 January 2017 (UTC)

Good catch! No accusations intended. I would point out, however, that we were both describing the caption, and your find describes the tulip itself. The only usage I can find describing a picture of a tulip is here. Dbfirs 16:50, 22 January 2017 (UTC)

A valid point. --Slashme (talk) 18:45, 22 January 2017 (UTC)

suggested revision of history section

Folks, at Central_dogma_of_molecular_biology you'll find:

The central dogma of molecular biology is an explanation of the flow of genetic information within a biological system. It was first stated by Francis Crick in 1958[1]

“ The Central Dogma. This states that once ‘information’ has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein. ”

— Francis Crick, 1956

with the quote in artistic emphasis.

In 2037 or so, I predict that the quote from the 1977 paper: "It is to be noted that the sickle cell mutation at amino acid 6 can be accounted for by a single base transversion of adenosine to uridine." is going to be highlighted in artistic quotes in an article about the dawn of molecular (DNA) analysis of human disease, just as Crick's was above.

I would like to suggest that we do that for the 1977 quote in this article. If not artisticly emphasized, at least having the full quote in the article would be a step in the right direction to acknowledge how fundamental the quote is. DennisPietras (talk) 19:47, 22 January 2017 (UTC)

The quote from Crick is the seminal statement of the Central Dogma, so it's clearly worth emphasising in that article. The quote about the SNP causing sickle-cell disease is kind of the first example of a "variant of certain significance", to coin a term: the opposite of the topic of this article. I'm mildly against highlighting and emphasising that quote, but I won't climb the Reichstag dressed as Spiderman to protest it. --Slashme (talk) 08:12, 23 January 2017 (UTC)

slashme Yet another belly laugher when I read about the real publication deadline! Thank you DennisPietras (talk) 02:15, 24 January 2017 (UTC)

slashme It is now about 2:40AM my time. Over an hour ago, I realized that the sickle cell mutation is still a VUS: Variant of Undisputable Significance. Maybe now that I wrote this I can get to sleep. DennisPietras (talk) 07:45, 24 January 2017 (UTC)

Review of sources

User:DennisPietras has pointed out that this article is supported to a large extent by research articles, which WP:MED considers to be primary sources, and therefore to be used with caution. Let's review them and discuss how to handle them and other weak sources. I've given my opinions below --Slashme (talk) 21:58, 24 January 2017 (UTC)

• Marotta et al. (1977)
  • Keep - not contentious, used for historical reference. --Slashme (talk) 21:47, 24 January 2017 (UTC)
• Grand View Research website
  • Find better source - surely we can find a better source telling us that sequencing is getting cheaper? --Slashme (talk) 21:48, 24 January 2017 (UTC)
  • Number of dollars = not a medical fact. Any basic newspaper/trade magazine article would do. WhatamIdoing (talk) 19:22, 31 January 2017 (UTC)
• Kühnemund et al. (2017)
  • Find better source as per Grand View - this is a cool article, but only tangentially related to the point being made. --Slashme (talk) 21:49, 24 January 2017 (UTC)
• Smemo et al. (2014)
  • Not urgent - this is a great example of how one can be misled by distant effects on the genome. We can look for other examples with non-primary sources, but I don't think it's a big deal, as this source is being used for illustrative purposes only. --Slashme (talk) 21:52, 24 January 2017 (UTC)
  • I agree with User:Slashme: It is not critically important for an illustrative examples to be supported by a top-quality source (although a top-quality source is nice if you have one). It is critical that said illustrative example not contradict the top-quality sources. WhatamIdoing (talk) 19:22, 31 January 2017 (UTC)
• O'Neill et al. (2009); Vos et al. (2012); Eccles et al. (2015)
  • Find better sources or collapse into one statement: Can we find a secondary source that says that vague VUS reports stress patients out and confuse doctors? I would hope so, but otherwise, we can maybe collapse the comments so that we don't deal with the various studies separately, and use the three different studies together to support the conclusion. --Slashme (talk) 21:54, 24 January 2017 (UTC)
• WebMD article
  • Keep: it's being used to support the rather uncontentious fact that many people have heard about the topic due to AJ's diagnosis and treatment. --Slashme (talk) 21:57, 24 January 2017 (UTC)
  • "People heard about this because of a celebrity" = not a medical fact. This source is fine; alternatively, any standard news source or a primary research article should be acceptable. WhatamIdoing (talk) 19:22, 31 January 2017 (UTC)

supplemental viewing section

I added it 1/31/17. I have mixed feelings about the first 2, especially since they come from companies, but I think they are still worth listing. Comments? DennisPietras (talk) 16:51, 31 January 2017 (UTC)

@DennisPietras: I took a look at WP:YT, and we don't have copyright violations, but I found the second video very promotional in tone. I'm also not sure about the first one, but I'm willing to leave it alone for now, because it's very relevant and informative. I did a bit of link formatting, and instead of saying to start at the 23 minute mark, I made the link to the Craig Venter talk skip to the relevant section directly. --Slashme (talk) 19:25, 31 January 2017 (UTC)

Thanks. I found something interesting by following the link you gave. In https://en.wikipedia.org/wiki/Wikipedia:External_links#Linking_to_user-submitted_video_sites section: "Links to be considered" point # 4. "Sites that fail to meet criteria for reliable sources yet still contain information about the subject of the article from knowledgeable sources." I'm thinking that both of the first 2 links fell under that guideline, but, again, I have mixed feelings. DennisPietras (talk) 19:36, 31 January 2017 (UTC)

I think there's an important distinction to be made between reliable sources and promotional sources here. --Slashme (talk) 09:05, 2 February 2017 (UTC)

Lead paragraph

I've rewritten the lead paragraph a bit so that it starts out by clearly defining the terms. I'm not a geneticist, though, so if I have stated anything incorrectly, feel free to hack away at my text. --Slashme (talk) 23:22, 21 January 2017 (UTC)

The term variant of uncertain significance comes out of and is used by clinical geneticists and genetics laboratories. Geneticists studying other organisms do not use this term at present. Therefore, I believe it would make sense to connect it with people. I changed organism to individuals in the lead paragraph. Dpaulbick (talk) 23:31, 21 February 2017 (UTC)

@Dpaulbick:I reverted your removal of "or unknown". Some "real-life" genetic counselors use the term. I'm a relative newbie, and I suspect you are also. Why not start your own user page (assuming you aren't Dpaulbick/TWA/Earth)? Also, it is best to indent new comments, as I did with your comment above. DennisPietras (talk) 02:59, 22 February 2017 (UTC)

@DennisPietras:I I can see why we would leave 'unknown' for now as I do hear it used at meetings from time to time, it is used on various sites, and can be seen in the literature (PMID: 28215547 for example). With time I expect the field will move to the word 'uncertain' as it more accurately describes the situation. Dpaulbick (talk)

The TULIP caption

I'm digging my heels in here, which is especially difficult in a wheelchair. That caption stays the way it is: yellow text on red background, or I'll keep reverting any changes. Remember that the WRONG comparison in the original article was blue/brown eyes, and that I'm retired with nothing but time on my hands to devote to an edit war, and live with it! DennisPietras (talk) 11:26, 20 January 2017 (UTC)

@Slashme:see above DennisPietras (talk) 11:59, 20 January 2017 (UTC)

Digging in your heels is unwise if Wikipedians reach a consensus that the other caption is better - at worst, it could result in you being blocked from editing, which would be a terrible loss to the project.

Unfortunately, my edit, Dodger67's edit and Slashme's edit show that consensus is currently against you. The reason is multifold. First, your caption breaches WP:ACCESS...accessibility is not just for the color-blind, but also for the blind. Graham87 recently talked to me about this in relation to a map I made for Dust Bowl, and showed me that we have blind administrators. If we have blind admins, who knows how many countless blind people read Wikipedia? All a screen reader tells them about the image is, "An insignificant mutation". (I hope that Graham does not take offense for my namedropping of him)

To continue, using color where color is not needed to convey meaning is a MOS:COLOR issue.

Therefore, in light of the above, I propose the following caption as a way to possibly make all parties happy:

This tulip demonstrates an insignificant mutation - one half of one of its petals is yellow instead of red. The function of the petal is, however, unaffected by the mutation.

I really like you Dennis, but you cannot get your way by threatening an edit war. Wikipedia must be edited in a collaborative rather than combative process and reaching WP:CONSENSUS should be the aim.

I invite mentioned users to approve or oppose my above proposal. Psiĥedelisto (talk) 13:02, 20 January 2017 (UTC)

I have to take some blame here because I suggested the compliant colour contrast (but not the increase in font size) to Dennis, but I have to admit that I prefer the detailed description in normal black text. This is an adult encyclopaedia and the shouting colour doesn't add to the appeal of the article in my view. Dbfirs 13:18, 20 January 2017 (UTC)

@Psiĥedelisto: No wrries; the suggested caption sounds fine to me, but I have no opinion on the colour of the detailed description, obviously. Graham87 13:53, 20 January 2017 (UTC)

I support the modified, more descriptive caption. Thank you all for your edits. To support a friendly editing environment, I recommend a virtual gift of Heelys™ for User:DennisPietras, to allow him to dig in his heels and yet be dragged along by consensus :-D --Slashme (talk) 14:00, 20 January 2017 (UTC)

I have spent decades of my life complaining about the gratuitous use of color in educational materials. Publishers, in my experience, routinely use variable background coloring without any benefit, and only harm, to the student's education. If a visually impaired person cannot read the yellow text on red background, they cannot appreciate the two colors of the tulip either, which is a pity, but I can't use heelys, and that's a pity too. 3 words in yellow over a red background explains everything I want to convey with that image. It's not gratuitous. It's not cute. It's effective. You are all wrong, IMHO. But I concede, both on this issue and the apparent fact that concede is the accepted konsensus speling ov a wurd that shud be spelt conceed, dammit. DennisPietras (talk) 14:36, 20 January 2017 (UTC)

Hey DennisPietras. Let me try to explain the policy once more, I think you can agree with us that it makes sense. For a text book or another kind of printed material, it's absolutely true that just making sure that the colors are appropriate for the color blind is enough. But Wikipedia is different: we have to make sure that our images, tables, and layout makes sense on mobile phones, on B&W print outs, on 4K displays, and when read aloud to a person who is completely blind by a screen reader or when displayed on a braille display. Such a person cannot really understand what the image is of if it just says "Irrelevant mutation" or similar; they need a description of the image. That's why, fundamentally it was changed, and that's why WP:COLOR exists. It goes like this: we make our layout accessible to those without sight. Then we make our extra visual cues accessible to the colorblind. Finally we make them visually appealing for the sighted. But our decisions should always be first and foremost towards inclusion of the blind. Psiĥedelisto (talk) 15:31, 20 January 2017 (UTC)

Also, who says this mutation is insignificant? The only arbiter of which mutations are significant is natural selection - if it confers no evolutionary advantages or detriments then yes - but there is no way we can make that judgment ahead of evolutionary time. The only genetic difference that can be said to be apriori insignificant is one in which two different nucleotide sequences produce the exact same protein outcome - if they produce different proteins but with no discernible difference in phenotype there is still the possibility that the difference may be significant and we just can't see or predict how.·maunus · snunɐɯ· 16:28, 20 January 2017 (UTC)

Actually, tulips are waaaaayyyyy removed from natural selection. The only thing that matters for tulips is whether people like them. As an aside, I'm not going to waste my time looking for a reference for this, (and it may well be proprietary) but I believe that the propensity to undergo the somatic mutation that produced the yellow color was actually genetically engineered into the plant. There are transposable elements in plants that can be engineered to jump into/out of "color genes" at high enough frequencies that the sort of color variants shown is actually expected and helps sell plants. And @Psiĥedelisto: relax, I thought with the missspelings at the end of my manifesto you would have realized that I totaly capitulated!

The principle is exactly the same for artificial selection. If people like the yellow variant and decide to breed it then the variant is not insignificant. And we cannot know before hand. So basically either way the image does not illustrate what it claims to illustrate.·maunus · snunɐɯ· 17:10, 20 January 2017 (UTC)

Fortunately, I can simply reply that I didn't write the caption

Plus, in the text I wrote (at least I think I wrote it...) "...the differences have no effect on the growth or health of the..." which is true for the tulip, as far as I know. DennisPietras (talk) 19:51, 20 January 2017 (UTC)

I took the photograph. Interesting to learn that my tulips have been the cause of such debate :) — Preceding unsigned comment added by Dmccabe (talk • contribs) 03:03, 28 February 2018 (UTC)