Talk:Human genetic resistance to malaria

Statement

The malaria article is already at the upper limit of length and I would suggest the bulk of the genetic resistance material in Malaria go into the new Genetic resistance to malaria page. I think this subject deserves a page on its own: it is a biological subject of fundamental importance with common elements that nevertheless cross a number of fields. The mechanisms by which sickle cell disease and thalassaemia (to include just two examples from many) protect against malaria have been subject to investigation for several decades and remain unclear in several key aspects. A summary can be provided on the malaria page Scientist2 (talk) 00:07, 1 December 2009 (UTC)

Agree Doc James (talk · contribs · email) 11:02, 20 December 2010 (UTC)

Pictures and information

added some images and informations Hempelmann (talk) 06:37, 16 March 2010 (UTC)

Capitals

The many capitals in the headings of the sections need to be fixed.Doc James (talk · contribs · email) 18:29, 2 May 2010 (UTC)

GA Review

This review is transcluded from Talk:Genetic resistance to malaria/GA1. The edit link for this section can be used to add comments to the review.

Reviewer: Xtzou (Talk) 15:41, 3 May 2010 (UTC)

GA review (see here for criteria)

1. It is reasonably well written.

   a (prose): The prose is filled with unexplained jargon. Examples:

   • "Evidence has accumulated that the first line of defense against malaria is provided by genetically-controlled innate resistance, mainly exerted by abnormal hemoglobins and glucose-6-phosphate dehydrogenase deficiency."
   • "Pauling postulated that the hemoglobin (Hb) in sickle-cell disease is abnormal; when deoxygenated it polymerizes into long, thin, helical rods that distort the red cell into a sickle shape. In his laboratory electrophoretic studies showed that sickle-cell Hb (S) is indeed abnormal, having at physiological pH a lower negative charge than normal adult human Hb (A).[3] In sickle-cell trait carriers there is a nearly equal amount of HbA and HbS, whereas in persons with sickle-cell disease nearly all the Hb is of the S type, apart from a small amount of fetal Hb."
   • Such sentences need explanation of jargon. Articles as much as possible should be accessible to the general reader. Further, almost all the section are one huge block of text that are uninviting and intimidating to the reader.

   b (MoS): Examples:

   The article does not comply with WP:LEAD which states that the lead should be a concise introduction to the article and summary of the article's sections; everything in the lead must appear in the article. Most of the article is not summarized in the lead.

   It also does not comply with WP:LAYOUT which states, among other guidelines, that the TOC should hierarchical, whereas in this article all the heading are on the same level. The section titles violate the guidelines on section headings which says that heading should be written with care, for example, very long heading are distracting.

2. It is factually accurate and verifiable.

   a (references): Examples:

   "Malaria has placed the strongest known selective pressure on the human genome since the origination of agriculture within the past 10,000 years." - Is this true?

   Malaria is the strongest known force for evolutionary selection in recent history. It is estimated that at least 15% of the world’s population are carrier for one or other of the Red Blood Cell disorders that have been maintained in areas where malaria is endemic. (Kwiatkowski DP.How Malaria Has Affected the Human Genome and What Human Genetics Can Teach Us about Malaria. Am J Hum Genet 2005; 77: 171–192) Hempelmann (talk) 10:18, 4 May 2010 (UTC)

   Some sections such as "The Natural History of Malaria Infections" and "The Sickle-Cell Gene" have only a few references in the middle of the section.

3. "b (citations to reliable sources): } c (OR):

   I suspect there may be too great a reliance on primary sources rather than surveys, per WP:MEDRS, but I did not evaluate this aspect.

4. It is broad in its coverage.

   a (major aspects): b (focused):

   I have a feeling that this article contains very good information, but it is inaccessible to the general reader.

5. It follows the neutral point of view policy.

   Fair representation without bias:

6. It is stable.

   No edit wars, etc.:

7. It is illustrated by images, where possible and appropriate.

   a (images are tagged and non-free images have fair use rationales): } b (appropriate use with suitable captions): }

8. Overall:

   Pass/Fail:

• I will put this article on hold for seven days, and I am willing to help to the degree I can. I suggest ordering the article with hierarchical headings and presenting the information in an organized way so the reader can see the structure of the article. The article also needs a major copy edit by an editor familiar with the guidelines and policies of WP:MoS. This article has great potential.

If you disagree with this assessment, you may renominate the article for GA again, or ask for Wikipedia:Good article reassessment . Regards, Xtzou (Talk) 16:23, 3 May 2010 (UTC)

• Addendum. I'm going to ask for a second opinion from another reviewer, as I'm not confident in my ability to give an informative and useful review of this article. Xtzou (Talk) 16:29, 3 May 2010 (UTC)

Second opinion

I agree with Xtzou assessment.

• There are significant issues with none compliance to WP:MOS. The extensive use of caps still requires improvement.
• The language is too technical and complicated terms are not linked like DARC and G6PD deficiency.

DARC and G6PD deficiency are linked Hempelmann (talk) 16:54, 4 May 2010 (UTC)

• The article does not have an easy to recognize order to it.

Subarticles rearranged Hempelmann (talk) 16:39, 4 May 2010 (UTC)

• "inherited variants in erythrocytes" in the lead should be hemoglobin not erythrocytes

Inherited variants in erythrocytes are not only hemoglobin variants but also membrane modifications (ovalocytosis etc) and abnormally low levels of glucose-6-phosphate dehydrogenase Hempelmann (talk) 13:16, 4 May 2010 (UTC)

• This page is a sub page of one of the topic areas of the main malaria article and should have a name similar to this subsection.

Adjusted the name of the subsection of the main malaria article Hempelmann (talk) 13:10, 4 May 2010 (UTC)

Doc James (talk · contribs · email) 12:40, 4 May 2010 (UTC)

Further comments The article is much improved by the addition of subsections. However, serious problems remain, including:

• The article still does not comply with WP:LEAD nor with the WP:MOS rules regarding section headings.
• I think the article should start out with some introduction to the disease of malaria. It says it is caused by a parasite, but it says little else about the disease process. Likewise, much of the other information in the article needs a prologue or introduction to set it in context.

Malaria is caused by an unicellular parasite that lives in the blood and is transmitted by mosquitoes, link to the Malaria article is made. Our entry is not only about malaria, but describes the first example of natural selection in human populations, as well as the first example of innate immunity to an infectious disease. Both of these are major contributions to biomedical science which are widely taught in school and university courses. Hempelmann (talk) 15:33, 5 May 2010 (UTC)

• The passive voice, such as "It was found to be caused by" is consider to be {{weasel}}, that is, the attribution is indirect while wikipedia requires direct attribution. "So-and-so found that...."

In 1927 Vernon Hahn and Elizabeth Biermann Gillespie showed that sickling of the red cells was related to low oxygen, reference is added. Hempelmann (talk) 15:28, 5 May 2010 (UTC)

• Most sections are still monolithic blocks of text. This is not considered reader friendly.

More images have been included Hempelmann (talk) 06:38, 5 May 2010 (UTC)

• The possible use of primary sources, rather that secondary sources or survey articles as set forth by WP:MEDRS.

We have given a comprehensive account of the main contributions in the field. Hempelmann (talk) 19:47, 4 May 2010 (UTC)

Wikipedia is a encyclopedia. It is not for original ideas, but for ideas cited in a secondary sources per WP:MEDRS. Xtzou (Talk) 20:11, 4 May 2010 (UTC)

Recent reviews have been included Hempelmann (talk) 05:23, 5 May 2010 (UTC)

Xtzou (Talk) 17:20, 4 May 2010 (UTC)

More comments

• Please read the MOS and fix headings accordingly, among other problems. (For example, heading must comply with Article titles, headings, and sections) It is necessary to comply with the MOS. The "blocks of text" do not refer to a lack of images but to the way the text is laid out in paragraphs. Please read WP:LEAD for what should go into the lead. And WP:LAYOUT, WP:summary style (avoiding unnecessary detail) and WP:JARGON. Also, necessary is to comply with Wikipedia:NOR, which means an editor may not compile information from sources in a novel or original way in a Wikipedia article. That is why reliable, secondary sources are necessary to show that the article is not original. It is necessary to comply with all of these guidelines in order to pass as a GA. This article should be accessible to the general reader with no expertise in the field. Xtzou (Talk) 12:13, 6 May 2010 (UTC)

• I am going to fail the article, as the problems outlined above have not been addressed. I urge you to renominate the article when you feel it is ready. Meanwhile, you may get significant help at Peer review. If you feel this assessment is is error, you may appeal it at Good article reassessment. Thank you for your hard work. The article contains important material and, when the problems are addressed, will be worthy of GA. Best wishes, Xtzou (Talk) 16:23, 10 May 2010 (UTC)

Content from main article which needs to be added here

Sickle-cell disease

Frequency of malaria cases in 1996.

The most-studied influence of the malaria parasite upon the human genome is a hereditary blood disease, sickle-cell disease. The sickle-cell trait on both genes causes disease, but those only partially affected (carrying only one gene with the trait) by sickle-cell have substantial protection against malaria.

In sickle-cell disease, there is a mutation in the HBB gene, which encodes the beta-globin subunit of haemoglobin. The normal allele encodes a glutamate at position six of the beta-globin protein, whereas the sickle-cell allele encodes a valine. This change from a hydrophilic to a hydrophobic amino acid encourages binding between haemoglobin molecules, with polymerization of haemoglobin deforming red blood cells into a "sickle" shape. Such deformed cells are cleared rapidly from the blood, mainly in the spleen, for destruction and recycling.

In the merozoite stage of its life cycle, the malaria parasite lives inside red blood cells, and its metabolism changes the internal chemistry of the red blood cell. Infected cells normally survive until the parasite reproduces, but, if the red cell contains a mixture of sickle and normal haemoglobin, it is likely to become deformed and be destroyed before the daughter parasites emerge. Thus, individuals heterozygous for the mutated allele, known as sickle-cell trait, may have a low and usually unimportant level of anaemia, but also have a greatly reduced chance of serious malaria infection. This is a classic example of heterozygote advantage.

Individuals homozygous for the mutation have full sickle-cell disease and in traditional societies rarely live beyond adolescence. However, in populations where malaria is endemic, the frequency of sickle-cell genes is around 10%. The existence of four haplotypes of sickle-type hemoglobin suggests that this mutation has emerged independently at least four times in malaria-endemic areas, further demonstrating its evolutionary advantage in such affected regions. There are also other mutations of the HBB gene that produce haemoglobin molecules capable of conferring similar resistance to malaria infection. These mutations produce haemoglobin types HbE and HbC, which are common in Southeast Asia and Western Africa, respectively.

Thalassaemias

Another well-documented set of mutations found in the human genome associated with malaria are those involved in causing blood disorders known as thalassaemias. Studies in Sardinia and Papua New Guinea have found that the gene frequency of β-thalassaemias is related to the level of malarial endemicity in a given population. A study on more than 500 children in Liberia found that those with β-thalassaemia had a 50% decreased chance of getting clinical malaria. Similar studies have found links between gene frequency and malaria endemicity in the α+ form of α-thalassaemia. Presumably these genes have also been selected in the course of human evolution.

Duffy antigens

The Duffy antigens are antigens expressed on red blood cells and other cells in the body acting as a chemokine receptor. The expression of Duffy antigens on blood cells is encoded by Fy genes (Fya, Fyb, Fyc etc.). Plasmodium vivax malaria uses the Duffy antigen to enter blood cells. However, it is possible to express no Duffy antigen on red blood cells (Fy-/Fy-). This genotype confers complete resistance to P. vivax infection. The genotype is very rare in European, Asian and American populations, but is found in almost all of the indigenous population of West and Central Africa. This is thought to be due to very high exposure to P. vivax in Africa in the last few thousand years.

G6PD

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that normally protects from the effects of oxidative stress in red blood cells. However, a genetic deficiency in this enzyme results in increased protection against severe malaria.

HLA and interleukin-4

HLA-B53 is associated with low risk of severe malaria. This MHC class I molecule presents liver stage and sporozoite antigens to T-Cells. Interleukin-4, encoded by IL4, is produced by activated T cells and promotes proliferation and differentiation of antibody-producing B cells. A study of the Fulani of Burkina Faso, who have both fewer malaria attacks and higher levels of antimalarial antibodies than do neighboring ethnic groups, found that the IL4-524 T allele was associated with elevated antibody levels against malaria antigens, which raises the possibility that this might be a factor in increased resistance to malaria.

Resistance in South Asia

The lowest Himalayan Foothills and Inner Terai or Doon Valleys of Nepal and India are highly malarial due to a warm climate and marshes sustained during the dry season by groundwater percolating down from the higher hills. Malarial forests were intentionally maintained by the rulers of Nepal as a defensive measure. Humans attempting to live in this zone suffered much higher mortality than at higher elevations or below on the drier Gangetic Plain.

However, the Tharu people had lived in this zone long enough to evolve resistance via multiple genes. Medical studies among the Tharu and non-Tharu population of the Terai yielded the evidence that the prevalence of cases of residual malaria is nearly seven times lower among Tharus. The basis for their resistance to malaria is most likely a genetic factor. Endogamy along caste and ethnic lines appear to have confined these to the Tharu community. Otherwise these genes probably would have become nearly universal in South Asia and beyond because of their considerable survival value and the apparent lack of negative effects comparable to Sickle Cell Anemia.

Doc James (talk · contribs · email) 11:02, 20 December 2010 (UTC)

 Done Hempelmann (talk) 16:09, 28 December 2010 (UTC)

References

accessibility to the general reader

There is an overarching consideration, which is a synthesis of remarks in the GA review, which I amplify. This article is not understandable to the general reader. Starting with the word 'erythrocyte' in the second sentence of the intro: even erudite readers (I'm post-grad myself), likely won't know that word. It gets worse from there. A majority of Americans do not subscribe to the theory of Darwinian evolution, and do not have a college education. Some are very young (like me, when I received my first set of Encyclopedia Britannica at age 6 or 7). Is the article accessible to them? I am aware now, though I wasn't only a few years ago, that certain races, ethnicities, or regional populations are inherently immune to particular diseases. I had given no thought to how, historically, in biological time, that might have happened; I just dismissed it as somehow "natural". It is indeed, natural, though an understanding of the specific way that comes about is essential to understanding the article, and that mechanism has nothing to do with malaria. And understanding that, one needs to have a specific understanding of how malaria acts upon the blood, liver and other tissues of the body during its lifecycle, before entering upon the topic of the article. It is essential to cover those things, in an accessible way, in some kind of prelude to the article. Maybe a pair of sidebar boxes, one covering the lifecycle of malaria, and the other the origin of genetic immunity to disease.

Keep on mind also, that a fair number of persons will have no knowledge of parasitism, don't know what a protozoan is, don't understand the components of a cell, or know that malaria isn't caused by what's generally called a "germ", or that it isn't infectious in the familiar way (i.e. passes from person to person directly by contact or through the air). Contrast with pneumonic plague, which is also acquired from an insect vector, but passes readily from person to person. That is, that the infectivity of malaria is of a different kind, and gives rise to unique problems and opportunities.

I suggest that the article needs to be re-drafted to confine technical jargon to footnotes and greatly expand general explanatory text, at a high-school level, on cellular biology, infectivity and transmissibility of disease, biological mechanisms of resistance, and epidemiological phenomena,

I'm willing to help in this effort, but we need to acknowledge accurately where we are, and define where it is we wish to go.

Sbalfour (talk) 21:21, 16 March 2014 (UTC)

An Activist wrote this?

Is it just me, or does this article written by some kind of human rights activist or someone who lost a relative to malaria or something. . .? It just appears so. . .so. . .biased! This article violates Wikipedia's neutrality policies and guidelines. Does it even talk about its name?--Mr. Guye (talk) 04:20, 27 March 2014 (UTC)

There's no doubt this article needs some help. I sort of inherited it :-| I haven't added or changed much, mostly some basic structuring. Tagging the head of the article isn't specific enough, and adds baggage that the article doesn't need to carry. Let's work the issues. Can you suggest what statements need to be modified? (Subsections, paragraphs, etc.). Are any statements actually FALSE?Sbalfour (talk) 04:35, 27 March 2014 (UTC)

reorganization, and spurious sections

I've significantly reorganized the article and retitled sections to bring related topics together. Now we have two substantial sections whose topics are not properly part of this article: Genetic resistance to malaria#Sickle-cell history and Genetic resistance to malaria#Adaptive immunity. I've proposed merging them into appropriate main articles. That done, the Genetic resistance to malaria#Sickle cell section will be left nearly void. It was suggested in the original GA review that a portion of the main article be merged here, but it appears that only a summary (and barely that) was transliterated. The genetics of sickle cell are highly relevant here, and that certainly needs to be expanded, so I've tagged the section.Sbalfour (talk) 04:21, 27 March 2014 (UTC)

moving article maintenance tags to talk page for discussion

[8 disruptive closely related maintenance tags previously moved from article page deleted; 2 original maintenance tags restored to article]Sbalfour (talk) 17:58, 28 March 2014 (UTC)

I've moved the article maintenance tags here for discussion and to focus work on the article by consensus. I wish I knew what to do with these. Eight of these ten tags were inserted by a single editor in a set of sequential edits. I think the wikipedia policies WP:TAGBOMBING and WP:OVERTAGGING need to be reviewed with regard to these. Previous to this, there were only two tags. The article doesn't need to carry this baggage - it certainly doesn't help editors to focus on the one or two most important issues. Which are what, exactly? Four of these tags essentially deal with the lead being non-neutral or biased, and four others with the article being non-neutral or biased (the two outtake tags are [technical] and [off-topic table]). I propose that these eight tags be combined into one, with appropriate explanation added with a 'text=' or 'for=' parameter. Let us deal with the issues here, and reach consensus - so far, only one editor, who placed the tags, has opined - then fix the article as we go, rather than tag the article.Sbalfour (talk) 18:18, 27 March 2014 (UTC)

After consulting a senior editor and administrator on what should be done in cases of disruptive editing like this, I was informed that 5% of all edits (that seems like a lot - I don't see nearly that much) are vandalism or disruptive, but that disruptive editors usually don't repeat on the same article. So the advice was to simply undo or delete the disruptive edits, or request reversion by an administrator or reverter to the last edit not by the disruptive editor. It's too late for reversion - there've been several dozen intervening edits - so I'm manually undoing the disruptive edits by restoring the original maintenance tags to the article, and deleting the disruptive tags I'd previously collected in this section of the talk page.

There is the possiblity that in spit of his inappropriate way of proceeding, the editor raised a valid issue of WP:NPOV. I've reviewed the whole article for context, and my assessment is that the article is blandly factual, 95% cited, and the sources are nearly all scholarly studies; spot checking the sources indicate article text closely follows the sources. If there are specific statements in question, an editor can tag them inline, or list them here, and I'll check them against other available sources to see if they can stand. I don't at this time see any such perjorative or prejudicial statements.

Sbalfour (talk) 17:58, 28 March 2014 (UTC)

section Duffy antigen receptor ([copyedit] tagged)

In a single paragraph appears these three phrases: "P. vivax variants can develop, using receptors other than Duffy to enter red cells"; "this parasite is able to use receptors other than Duffy to invade erythrocytes", and "P. vivax are being transmitted to humans who are not expressing DARC on their red cells". It only needs to be said once: either an opening phrase like "The following are reported examples of P. vivax infecting Duffy-negative populations..." or a summary phrase like, "The foregoing studies provide evidence that P. vivax can infect Duffy-negative erythrocytes...". Along with deleting or summarizing supporting text, the paragraph should shrink quite a bit, and increase readability and understandability. Maybe the whole paragraph can replaced by a single summary sentence like: While the Duffy antigen still appears to be a major receptor for human transmission of P. vivax, there is significant evidence in sub-Saharan Africa and elsewhere that this parasite is able to use receptors other than Duffy to invade erythrocytes [1][2][3][4],etc.Sbalfour (talk) 18:48, 28 March 2014 (UTC)

I've copy-edited (fixed) this and removed the copy-edit tag; however, two large paragraphs (about 3/4 of the text in the section), are devoted to describing why Duffy-negativity is not relevant to P. vivax infectivity. This whole phenomenon shoould perhaps be moved into a footnote or sidebar; the topic of the section is how Duffy-negativity inhibits infectivity of P. vivax (and possibly P. malariae?), and we give it short-shrift.Sbalfour (talk) 19:20, 28 March 2014 (UTC)

I've further merged everything about Duffy-negative infectivity of P. vivax into a single paragraph, and moved animal studies into a footnote. That leaves a paragraph that's still too much about too little. P. vivax infectivity of Duffy-negative samples is either asymptomatic, or exhibits clinical disease in less than 5% of persons. It appears that Duffy-negativity is PGP (Pretty Good Protection :-) ).Sbalfour (talk) 19:53, 28 March 2014 (UTC)

what this article is NOT about

I've added an opening sentence to the lead, describing what this article is about. In pursuance thereof, I've deleted most of several sections, subsections and paragraphs of things this article is not about. This article is not about *Adaptive resistance, *History of sickle cell, *non-human malaria or genetic adaptations of other species, *genetic adaptations to other microorganisms like virii and fungi. The article is a lot smaller now. This looks like how wikipedia ia evolving; with a plethora of articles covering a topic in everywhichway, each needs to remain strictly focussed. Any section or subsection that gets "too big" splits off into its own article, or merges into another main article. I've stayed true to form.

In place of deleted off-topic things, I've added relevant sections on PK deficiency, HLA polymorphisms, Gerbich antigen negativity, Elliptocytosis, and other rare (but clinically notable) erythrocyte mutations. These sections are skeletons which need to be fleshed out. The section on Sickle cell, formerly about 90% history (moved to other main article), is now also threadbare.

The lead will also need to be restructured, once the reorg of the article stabilizes.

Sbalfour (talk) 23:44, 28 March 2014 (UTC)

autosomal/sex-linked; dominant/recessive; heterozygous/homozygous

None of these attributes in relation to inherited resistance to malaria is directly discussed (though one or another of the words is used occasionally). In terms of effective resistance, these are critical concepts. Some traits MUST be homozygous to be effeective, for example; others are deadly if homozygous. This part of the topic is worth a book; it certainly needs a subsection or even a whole section to characterize the polymorphisms.Sbalfour (talk) 03:09, 29 March 2014 (UTC)

lexicon with regard to technical maintenance tag

This article has been tagged as [technical], meaning not accessible to the general reader. That may mean a whole hierarchy of concepts from simple to complex, is embedded in the article, which renders it inaccessible. The bottom level, the simplest one, is vocabulary. There are a lot of words in this article I don't know, and I'm post-grad, though not in the medical field. While it's true that these can be wikilinked, the wiki-linked to articles are themselves inaccessible, sometimes more so than this one. Wikilinking primarily is for more information on the term. The article should be basically understandable without following the wikilinks. Here's a lexicon of technical terms that either need to be defined in the article, or replaced with vernacular. I ask the question, can this article be read with facility and comprehensively understood by a literate 18-year highschool graduate? If not, it's a tough sell for GA. Here's the lexicon, quite long.

• actin
• allele
• alpha-chain
• alveolar
• amino acid
• anabolic
• anaerobic
• anion (transporter)
• ankrin
• antigenic
• ATP
• beta-chain
• catabolic
• chemokines
• codon
• corpuscles
• cytoadherence
• cytoplasmic
• diathesis
• DNA
• Drosophila
• endocytic
• endogamy
• endothelial
• enzyme
• epidemiological
• erythroctye
• erythroid
• fitness (genetic)
• genome
• genotyping
• glycolysis
• glycophorin
• haplotype
• Hb (Hb A, Hb C, Hb E, Hb S)
• hematopoietic
• heme
• heme oxygenase (HO-1)
• hemoglobin
• hemolytic
• heterozygotes
• homozygotes
• hypotonic
• in vitro
• in vivo
• leucocyte
• ligand
• locus (chromosome or gene)
• macrophage
• major histocompatibility complex
• micro-RNA
• microvasculature
• mitochondria
• mutation
• natural selection
• nucleotide
• (oxygen)radical
• pathogenesis
• PCR
• phenotype
• Plasmodium
• polymerize
• polymorphism
• polypeptide
• reducing (chem. reaction)
• RNA
• sequestration (biochem.)
• sex-linked
• spectrin
• sporozoa
• TCA (cyle)
• translocation
• transmembrane
• venous
• vesicles
• virulence (factor)

Terms to be replaced with vernacular, or deleted from the text:

• (DARC)46 T->C
• association mapping
• β26Glu → Lys
• β6Glu → Lys
• band 3 (protein)
• band 4.1 (protein)
• CD36 (protein)
• disequilibrium linkage
• DRB1*13OZ*DQB1*0501
• GWA
• Hardy-Weinberg (equation)
• hGATA1
• HLA Bw53
• HBB (gene)
• MHC class I
• MHC class II
• pattern recognition (receptor)
• pentose phosphate pathway
• PfMP-1 (protein)
• phosphatidylserine
• promoter activity
• SDS-page
• silverstained
• Toll-like receptor
• transcription factor

Further, understanding the words doesn't mean understanding the concepts. I know Drosophila is come kind of fly, but why is that fly genetically significant? Most adults don't have a basic understanding of cellular biology, don't subscribe to Darwinian evolution, and don't understand the processes of infection, replication, systemia and toxicosis that characterize disease. This article has a ways to go.Sbalfour (talk) 17:53, 29 March 2014 (UTC)

I think this list ought to be divided: one sublist is those terms that contribute little to understanding the article (like DRB1*13OZ*DQB1*0501 - we don't need to know the name, since we don't go into specifics about it); the other sublist is those terms whose understanding is essential to the article, and without which, we can hardly write the article (hemoglobin and heterozygosity, for example). Items on the former list should be replaced with vernacular, or that aspect of hematology elided to keep this article comprehensible. The items on the second list are good candidates for a glossary appendix. That glossary would be the kind of definitions that might be found in a student desk dictionary, with particular relevance to the context of the article, rather than medical dictionary-type definitions.

Ok, I've split the list and added a glossary. Only about 20% of the list isn't in the glossary, so it substantially reduces the amount of work to do on the article text to define or replace the terms not in the glossary.Sbalfour (talk) 01:26, 4 April 2014 (UTC)

The glossary could be contained with a collapsible box [default closed], so it doesn't clutter up the article. I've seen this frequently in books and occasionally magazine articles, but not in wikipedia. There's wictionary, of course, but the problem with extensive cross-linking is those on dial-up connections; also, the convention in wikipedia is to wikilink only the first occurrence of each term, and that means in order to follow the link, one may have to scan backwards through a long article to locate the one and only wikilink. That's unacceptable here. Many readers will be looking up a word every sentence, or even multiple words in a sentence. Alternatively, I like the idea of mousing over a word, and getting a one-line type definition, with an embedded link to follow for [more], like some of the wiki-templates work. I've seen that idea on other medical-wiki websites, and it's very convenient.Sbalfour (talk) 16:38, 30 March 2014 (UTC)

move sidebar on Nature of Malaria to talk page

It is somewhat off topic, and not very helpful. Store here, for later use (or other article use).Sbalfour (talk) 19:02, 29 March 2014 (UTC)

The nature of malaria Malaria is a serious and potentially lethal human and animal disease characterized by cyclic high fevers transmitted exclusively by the bite of an infected mosquito. It is caused by a microscopic single celled organism called a protozoan, similar to an amoeba, which infects human red blood cells. A handful of different protozoans in the genus Plasmodium cause different varieties of the dieease. The Plasmodia are parasites which cannot exist or reproduce outside their human hosts and insect vectors. Only specific species of mosquito transmit the disease. The lifecycle of Plasmodia responsible for malaria is complex, and consists of several distinct stages, each with a different and characteristic form. Some stages are carried out in the mosquito, and others in humans. The stages are sporozoites injected into the bloodstream migrate to the liver; sporozoites infect liver cells and produce tens of thousands of haploid merozoites per liver cell; merozoites leave the liver and enter the bloodstream, initiating a cycle of invasion of red blood cells, asexual replication, and release, resulting in the characteristic cyclical fevers of malaria; some merozoites develop into sexual forms called (male and female) gametocytes that circulate in the blood; mosquito ingests red blood cells infected with gametocytes; these cells burst in the mosquito gut, releasing the gametocytes which mature into male and female gametes; male and female gametes fuse into zygotes (analogous to a fertilized human egg) which develop into mobile ookinetes that attach to the mosquito midgut wall and grow into oocysts; growth and division of the oocyst produces thousands of sporozoites; after a week or two, the oocyst bursts, releasing the sporozoites into the bloodstream of the mosquito where they migrate to the salivary glands. The cycle starts over when the mosquito bites its host and injects the sporozoites with its saliva into the host.

Hb C and Hb E; heterozygous AC, SC, etc genotypes

The text includes a bullet point for the distribution of Hb C and Hb E, but there is no description of what these are, what if any protection against malaria they afford, and what if any disease is associated with them (probably need to break this down by homozygous and heterozygous varieties). There's also an opaque section on fitness of genotypes, but no description of what kind of protection against malaria the heterozygous genotypes offer, or what if any disease is associated with these genotypes.Sbalfour (talk) 23:07, 29 March 2014 (UTC)

a note on article topic organization

While reading an excellent professional review article that was spot-on to the content of our wikipedia article, I deduced what should probably be discussed in each section. A section nominally represents an indivivual polymorphism of hemoglobin or something else. Each such section should discuss at least the following:

• the Mendelian genetics of the polymorphism: such things as dominant/recessive, heterozygous/homozygous; autosomal/sex-linked
• the molecular chemistry of the polymorphism - for example if it's a mutant form of hemoglobin, how are the subunit chains affected?
• the effective protection provided
• the extent of disease it causes
• the geographic distribution of the polymorphism
• the cellular biochemistry of the protective mechanism (if known) - how does it interfere with infection or replication of Plasmodia?
• which of the five (or six) species of Plasmodia (falcipaum, vivax, ovale(2), knowlesii, malariae) does the polymorphism affect?

The hemoglobin polymorphism geographic distributions are collected into a unified section, but not the erythrocyte protein polymorphism distributions. The structure should be one way or the other for consistency. The protective mechanisms are also (mostly) collected into a unified section, but only mechanisms for a few polymorphisms are discussed (maybe we don't know a whole lot here?). We don't discuss polymorphism effects on P. knowlesii, P. ovale or P. malariae at all. We also don't discuss what is probably a mutation of P. falciparum itself in response to human genomic mutations, wherein it has acquired variant antigenic pathways of invasion via Glyphorin A, Glycophorin B, and Glyphorin C.

Some new subsections on combination heterozygous polymorphisms like HbE/beta-thalassemia probably need to be added, parallel to the existing level 4 subsections. I just discovered there's also a HbH and HbF, as well as Hb Constant Spring that are relevant here.

I don't want to add another maintenance tag for {{missing information|see talk page}} to the article, but this issue would fail the broad coverage qualification for GA. The article needs to be fleshed out. I've added the interesting review to the references. Though it's not directly cited in the article, I'm borrowing ideas as well as bits and pieces from it.Sbalfour (talk) 02:58, 1 April 2014 (UTC)

Advice

Although the article isn't specifically about adaptive immunity, I think there should be some sort of explanation given for how and/why the writer seems to think that the innate immunity acquired at birth (genetic resistance) to malaria could somehow lead to adaptive immunity. Moreover, I think there should be a section on how and/or why the 'plasmodium' parasite and for that matter malaria started to exert a significant selective pressure on the populations with high prevalence of malaria.

Kyeremateng.1 (talk)   — Preceding undated comment added 16:03, 3 October 2014 (UTC) 

The significance of malaria needs to be given a little bit more focus

The world even today is still suffering from the effects of the malaria pandemic, due to the very significant problem of drug resistance of Plasmodium malaria parasites (Evans & Willems, 2002). According to Evans and Willems, the ineffectiveness of insecticides against mosquitoes due to the adaptation of mosquitoes to life above the height of DDT spraying has acted to suppress the measures that were put in place to curtail the spread of the parasites some fifty years ago even though it produced very hopeful results in the beginning. Also the initially impressive results garnered by the use of the antimalarial drug chloroquine in the 1950's, were negated very soon by the appearance and then quick spread of mutated, chloroquine resistant plasmodium strains (Evans and Willems, 2002) Kyeremateng.1 (talk)

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