From Embryology

Lab 4 Online Assessment

  1. The allantois, identified in the placental cord, is continuous with what anatomical structure?
  2. Identify the 3 vascular shunts, and their location, in the embryonic circulation.
  3. Identify the Group project sub-section that you will be researching. (Add to project page and your individual assessment page)

--Z3389343 12:56, 28 July 2011 (EST)

Lab Attendance

--Z3389343 12:56, 28 July 2011 (EST)

--z3389343 12:53, 4 August 2011 (EST)

--z3389343 12:34, 11 August 2011 (EST)

--z3389343 11:09, 18 August 2011 (EST)

--z3389343 11:42, 25 August 2011 (EST)

--z3389343 11:41, 1 September 2011 (EST)

--z3389343 11:18, 15 September 2011 (EST)

--z3389343 11:09, 22 September 2011 (EST)

--z3389343 11:15, 29 September 2011 (EST)

--z3389343 11:12, 6 October 2011 (EST)

--z3389343 11:06, 13 October 2011 (EST)

--z3389343 11:05, 20 October 2011 (EST)

Lab Assesments

Lab 1 Assessment

1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique.

In Vitro Fertilization was developed by Robert Edwards, for which he won the Nobel Prize in 2010. He started research on the biology of fertilization in the 1950s, and soon realized fertilization outside the body was a possible treatment for infertility. This had previously been proven successful in rabbits, therefore Edwards tried to use the same process in humans. He identified the processes related to the maturation of human eggs and when they could be fertilized. He further identified how sperm is activated. With collaboration of gynecologist Patrick Steptoe, they developed IVF for medical practice. Source:

2. Identify a recent paper on fertilisation and describe its key findings.

Pandian, Z., Bhattacharya, S., Ozturk, O., Serour, G., & Templeton, A. (2009). Number of embryos for transfer following in-vitro fertilization or intra-cytoplasmic sperm injection. Chochrane Database of Systematic Reviews, 15. IVF pregnancies often result in multiple pregnancies due to multiple embryo transfers, which in turn can cause maternal and perinatal morbidity. In order to reduce this, single embryo transfers are considered and their pregnancy success rates are compared to multiple embryo transfers (MET). The researchers found that for a single fresh IVF cycle, single embryo transfer is associated with lower life birth rates (LBR) than dual embryo transfer, however statistically, there is no significant difference. There were not enough data to compare single embryo transfers to three or four embryo transfer policies.

3. Identify 2 congenital anomalies.

Polydactyly is a dysmelia; a limb defect, caracterised by the presence of additional fingers or toes. The atrial septal defect is an example of a heart congenital anomaly in which the blood can flow between the left and right atria via the interatrial septum. This is usually closed, forming a barrier between the two atria.

--z3389343 12:53, 4 August 2011 (EST)

Lab 2 Assessment

1. Identify the ZP protein that spermatozoa binds and how is this changed (altered) after fertilisation.

In humans, there are three ZP proteins, ZP1, ZP3 and ZP4, that are known to bind to the capacitated spermatozoa and play a role in the induction of the acrosome reaction. (The ZP protein ZP2 has been found to only bind to acrosome-reacted spermatozoa.) After fertilisation, ZP protein ZP3 is known to undergo a conformational change, leading to the hardening of the zona pellucida, thus playing part in the prevention of polyspermy.

2. Journal Articles:

--z3389343 21:12, 9 August 2011 (EST)

--z3389343 12:34, 11 August 2011 (EST)

Differentially expressed RefSeq genes in human trisomy 21.jpg

Differentially expressed RefSeq genes in human trisomy 21.jpg

Figure 6 Differentially expressed RefSeq genes in human trisomy 21. (A) Standard MA-plot of the normalized global observed counts per each RefSeq gene. (B) shows the percentage of RefSeq genes classified as strong, good, acceptable evidence of DE with respect to those not showing any statistical evidence.

Copyright Costa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Lab 3 Assessment

  • 1. What is the maternal dietary requirement for late neural development?

Choline is critical critical for the development of the hippocampus and memory function. It influences stem cell proliferation and apoptosis, thus shaping brain development and function as well as neural tube development.

  • 2. Upload a picture relating to you group project. Add to both the Group discussion and your online assessment page. Image must be renamed appropriately, citation on "Summary" window with link to original paper and copyright information. As outlined in the Practical class tutorial.
File:Frataxin mRNA levels and histone modifications on chromatin in the first intron of the frataxin gene in KIKI and WT mice.png
Frataxin mRNA levels and histone modifications on chromatin in the first intron of the frataxin gene in KIKI and WT mice

--z3389343 11:09, 18 August 2011 (EST)

Lab 4 Online Assessment

  • 1. The allantois, identified in the placental cord, is continuous with what anatomical structure?

It is continuous with the developing hindgut.

  • 2. Identify the 3 vascular shunts, and their location, in the embryonic circulation.

Two of these vascular shunts are involved in shunting the pulmonary circulation: the foramen ovale shunts the blood from the right atrium to the left atrium, and the ductus arteriosis shunts the blood from the pulmonary artery to the aorta. The third shunt is the ductus venous in the liver, which shunts the blood from the umbilical blood directly to the heart's venous return.

  • 3. Identify the Group project sub-section that you will be researching.

I will be focusing on the genetics, as well as trying to find some information on the cellular and molecular mechanisms involved in the degradation of the neuromuscular junction and other synapses affected by the disease.

--z3389343 11:42, 25 August 2011 (EST)

Lab 5 Assessment

  • Which side (L/R) is most common for diaphragmatic hernia and why?

The left side is the most common side as congenital diaphragmetic hernia is most commonly caused by a failure of the left pleuroperitoneal membrane to completely seal off the left pleural cavity from the peritoneal cavity.

--z3389343 11:41, 1 September 2011 (EST)

Lab 6 Assessment

  • What week of development do the palatal shelves fuse?

This occurs in week 9 of embryonic development.

  • What animal model helped elucidate the neural crest origin and migration of cells?

This was the chick embryo.

  • What abnormality results from neural crest not migrating into the cardiac outflow tract?

This leads to deficient smooth muscle differentiation around aortic arch arteries. [1]

--z3389343 11:18, 15 September 2011 (EST)

Lab 7 Assessment

  • 1. Are satellite cells (a) necessary for muscle hypertrophy and (b) generally involved in hypertrophy?

Satellite cells are not necessary for muscle hypertrophy as this can occur normally without satellite cells. However, satellite cell are normally involved in hypertrophy as satellite cell proliferation is a normal response to hypertrophy.

  • 2. Why does chronic low frequency stimulation cause a fast to slow fibre type shift?

Fast twitch fibres use anaerobic metabolism to create the energy and are particularly good for short and sudden bursts of strength or speed. Slow twitch fibres in contrast use aerobic metabolism to produce slow, continuous muscle contractions. The fibre types are interchangeable (though this is not achieved in a single step but involves a slow shift). In a scenario of chronic low frequency stimulation, it would be the slow fibre types that would be active and most useful during the contraction while fast fibre types wouldn't be needed that much, and thus the fast to slow fibre type shift is an adaptation to the chronic low frequency stimulation to produce a more efficient response, mediated by slow fibre types.

  • Comments on the Trisomy 21 page:
    • The introduction could be a little bit longer, and maybe include a little bit of a historic timeline?
    • Having the recent findings follow the introduction immediately is confusing as the reader hasn't had a chance to learn anything about the condition yet, so can't really relate the recent findings to anything.
    • A broad range of topics is covered which is good, but there doesn't seem to be a logical structure to it - things don't lead on from each other.
    • The links to further external resources are a very good idea, and there are a lot of them, which is good and makes it easy to find out more and get a deeper understanding. Including these links also makes the page itself less crowded and helps keep a good overview.
    • The mere use of bullet points in most parts does keep things simple and clear, but also partly gives an impression of lack of depth. Certain points could be explained in a little bit more detail.
    • The table that is used for Screening Strategies is an efficient way of showing the data, though I don't quite understand what the "maternal age" screening procedure is, and how that can have a detection rate? I assume it relates to the fact that older mothers have a higher risk of bearing Down Syndrome children, but what exactly is the screening procedure?
    • Though the terms are explained in "detection using tandem nucleotide repeats", the section is still too technical. It doesn't explain why this technique allows the detection of the trisomy 21. For somebody who isn't familiar with genetics, it is very hard to understand. I am familiar with genetics, but the sentence "Tandem SNP sequences identified as heterozygous on maternal buccal swab are amplified on maternal plasma by ..." doesn't quite make sense to me - how can the sequences be amplified ON the maternal plasma?
    • Listing the screening by country is a good idea, but then should contain more than just information for 1 country.
    • Generally, there is a curious mix of very well explained terms and sections, and sections that still seem incomplete.

--z3389343 11:09, 22 September 2011 (EST)

Lab 8 Assessment

Peer Assessment

--z3389343 11:15, 29 September 2011 (EST)

--z3389343 11:12, 6 October 2011 (EST)

Lab 10 Assessment

  • Besides fetal alcohol syndrome, identify another environmental teratogen that can lead to hearing loss.

The cytomegalovirus is known to cause hearing loss in a fetus whose mother is newly infected.

  • Identify 3 factors that contribute to poor neonatal drainage of the middle ear.

The fluid normally drains out of the middle ear through the eustachian tubes. In neonates, the eustachian tubes are at a more horizontal level than in the adult, which leads to poorer drainage of the middle ear. Furthermore, the eustachian tubes in a neonate are smaller than in the adult structure, which leads them to be obstructed more easily, which can also obstruct fluid drainage. Another factor that has been associated to poor drainage of the middle ear is a cleft palate.

  • Identify 1 genetic abnormality that affects hearing development and link to the OMIM record. (Your individual abnormality should be different from all other students)

The Axenfeld-Rieger syndrome has been associated with sensorineural hearing loss.

Lab 11 Assessment

  • Name the components that give rise to the interatrial septum and the passages that connect the right and left atria.

The interatrial septum is formed through fusion of the muscular septum primum and the muscular septum secundum. During gestation, this fusion is incomplete and there is a large opening in each septum, allowing right-to-left shunting of the blood, thus bypassing the developing pulmonary system. The two passages that allow this blood flow during gestation, thus connecting right and left atria, are Foramen ovale and Foramen secundum.

  • Identify the cardiac defects that arise through abnormal development of the outflow tract.

Abnormal development of the outflow tract can give rise to an interrupted aortic arch, which leads to the obstruction of the blood flow to the lower body parts; coarctation of the aorta, characterised by a narrowing in the area where the ductus arteriosus inserts; and aortic stenosis, where the aortic valve doesn't open fully and thus restricts blood flow from the heart.

Lab 12 Assessment

  • Give examples of 3 systems that continue to develop postnatally.

Firstly, the nervous system continues to develop postnatally. While most of the wiring of the neurons in the central nervous system has been achieved prenatally, there is extensive remodeling and pruning of the neuronal connections during the early years of life. Secondly, the respiratory system continues to develop postnatally, as the lungs are collapsed and filled with fluid until birth. The liquid is replaced by air through respiratory movements. Thirdly, the cardiovascular system also continues development postnatally to adjust for the altered blood circulation that results after birth when the respiratory blood circulation is not bypassed anymore.

  • Identify the abnormalities detected by the Guthrie Test and link to one abnormality listed in OMIM.
    • Phenylketonuria (OMIM)
    • Cystic Fibrosis
    • Congenital Adrenal Hyperplasia
    • Congenital Hypothyroidism
    • Galactosemia
    • Congenital Toxoplasmosis
    • Biotinidase Deficiency
    • Homocystinuria
    • Maple Syrup Urine Disease
    • Medium-Chain Acyl-CoA Dehydrogenase Deficiency
    • Toxoplasma gondii IgM antibodies

Peer Assessment

Group 1 - Turner Syndrome

  • Introduction: The second paragraph of the introduction partly observes poor sentence structure, and in general needs a little bit more clarification. Also, I wouldn't necessarily include that information in the introduction, but put it under a different heading, etiology maybe? The following paragraph is good, just watch out with this sentence: "Each person who has turner syndrome all vary" - that doesn't quite make sense. Each person varies, or people with TS all vary...
  • Epidemiology: This sentence really doesn't make sense to me: "Whereby, the maternal X is retained in two-thirds of women and the paternal X in the remainder." Furthermore, the whole paragraph needs editing in terms of sentence structure. The content is good, though could do with slightly more explanation.
  • The table with the common abnormalities is good, but in a slightly random place.
  • None of these first sections include links to the glossary. Explaining some of the terms in more detail could easily be achieved by linking them to the glossary.
  • Etiology: Be careful when saying meiosis creates genetic diversity. Yes, meiosis creates diversity by shuffling existing alleles and producing new combinations, but the underlying mechanism, which is the main drive for genetic diversity, is mutation because that is what creates new alleles. (I'm just saying this because my lecturer in genetics was very keen on making us understand this difference!) Other than that, excellent explanation of how the genotype of Turner Syndrome occurs. Considering some of the genetic component was also explained under epidemiology, it would be useful to relate this information to what has already previously been mentionned.
  • Clinical Manifestations: Poor. Referencing not done properly, no explanations, a simple list really tells hardly anything about the manifestations. Linking them to articles is useful, but not doing anything else makes the whole exercise of creating a page dedicated to a disease pointless if there won't actually be any descriptions or explanations.
  • Diagnostic Procedures: Very well explained, good use of diagrams and figures to illustrate the text.
  • Treatment: Links to the glossary would be good. Content is good, but the referencing isn't done properly, and some figures would be nice to illustrate things, it looks a little bit dry as such a long blurb of text.
  • Current research: Looks fine to me
  • Future research: Good idea!
  • Glossary: Could be more extensive, mainly because some sections do not contain any links to the glossary.
  • References: Needs fixing. it appears as though it hasn't been done right a single time... (ie one and the same paper occurs multiple times in the list)
  • General: There are obvious quality differences between the different sections, which is a shame. Parts are done really well, others not so much. The content and subsections would be fine if they all had the same standard as the well-written ones.

Group 2 - DiGeorge Syndrome

  • Introduction: Good in general. Last paragraph needs a slight revision in sentence structure. "The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality" - significant in what way? As in they have a big impact? And also, poor quality of what? Life?
  • Historical Background : Very detailed, which is nice. The layout isn't quite 100% consistent, which should be easily fixed. Some findings could do with further explanations to show how this lead to progress. Also, some terms should be linked to the glossary, or in some cases, a mention that subsequent paragraphs will provide more detail.
  • Epidemiology: Seems fine to me, though a figure would be nice to break up the text.
  • Etiology: Links to glossary needed. This part contains many technical terms that aren't explained. Also, is it known why this region is specially prone to rearrangements?
  • Pathogenesis: Seems to repeat what was said in etiology, but in more detail. Well written and explained.
  • Diagnosis: There's a typo in the title - Dianostic instead of Diagnostic. You might want to split your table into prenatal and postnatal, as otherwise it is a bit confusing to read "ultrasound" as a diagnostic tool. It does become obvious very quickly that it is prenatal, but just for clarity's sake, splitting the table could help, especially as you mix pre- and postnatal tools throughout the table. Also, just be careful about using capitals - in the beginning you say BACS, and later you say BACs. BACs is the plural of BAC, which is what Bacterial Artificial Chromosome stands for, not BACS. Your explanations in this part of the table are quite technical - you might want to explain more terms in the glossary at least.
  • Clinical Manifestations: Very thorough and detailed, which is good. I like the table, but including some more figures might help break up the long bits of text.
  • Treatment: Also quite thorough, well explained.
  • Current and Future Research: Very good and detailed, well explained. Maybe include headings for the different sections, so it's easier to see what each is talking about?
  • Glossary: More terms need explanations.
  • References: Seem fine in general, though there are a few links that probably should be cited differently. Also, some references link to emptiness?
  • General: All the tables are slightly differently formatted, you might want to get that more uniform.

Group 3 - Klinefelter's Syndrome

  • Introduction: Content is good, but it's a bit strange to start the introduction with an explanation about meiosis. Of course you need to include it, but generally one expects a few general sentences about the condition itself first, and then an explanation how problems in meiosis lead to it. Including a figure is good, but maybe put this one under the genetics section, and have a picture of somebody affected by the syndrome here instead?
  • History: It is one very long text, followed by a summary table under timeline. Maybe come up with a mix of the two, and make it one section? Would make keeping an overview easier. Keep the table, but put all the longer explanations you've written out under history into the table, next to the corresponding date? Content is good.
  • Epidemiology: Good, interesting content. The figures nicely break down the text. Well done!
  • Aetiology: Slight contradiction here - previously prevalance was said to be 1 in 500, now 1 in 1000? Also, you refer to Figure 1 which is all the way on top of the page - it would be nice to keep it closer to the text, in the relevant section itself. You might want to mention that MI = meiosis I and MII = meiosis II. I was also slightly surprised that you used the word "synapse" when talking about what happens between the homologous chromosomes - I might just never have come across it before (though I have taken quite a few genetics classes), but maybe double-check that? As far as I know it's called crossing over - that's what forms the chiasmata. In general, your whole explanation is very incomplete, you might wanna revise that. I know what you're trying to get at, but I don't think it's very clear for someone who doesn't have a genetics background. Also, I have a majour problem with Figure 4 - the way you illustrate it, I first thought you were showing two different chromosomes, say chromosome 1 & 2, of which there are two copies present each. Cause this is how it is pictured most of the time. Your explanation under the figure made me realise that it wasn't the case, but a) you need to improve that legend and explain more, and b) I'd strongly suggest you modify your figure so that the chromosomes look more like "X"ses - that'll make it much easier to understand that you're talking about one chromosome type, and are showing the sister chromatids and not separate chromosomes. I hope this makes sense?

The genetics part is good though.

  • Pathogenesis: Why does this section contain the subsection nondysjunction again? Nice, brief explanation of anaphase lagging. The nondysjunction section, unsurprisingly, mainly repeats what has already been said before. Your figures need a legend and more explanations. What are the different colours supposed to depict? Maternal vs paternal chromosomes? You need to point out that it's the size difference that shows chrom 1 vs chrom 2. Cause I thought first the colours mean homologous chromosomes, which then wouldn't be right cause it's the homologous chromosomes that align etc. Also, I'd suggest not talking about cells having three chromosomes instead of two, cause in reality, cells have so many more pairs of chromosomes than 2, instead maybe just say, 1 cell contains both of the homologous chromosomes instead of just one at the end of MI. You seem to be depicting a recombination event in Figure 6 - why? Does it have any relevance to this part? There's no mention of it in the text. Sorry this sounds terribly critical - good effort though!
  • Signs & Symptoms: Maybe explain more, and not just include a list with bullet points?
  • Diagnosis: Put the "featured imagine" right next to where it is mentionned? Otherwise seems fine to me.
  • Management: Looks good.
  • Similar Defects: Maybe rename it Syndromes instead of Defects? I was confused for a second that you were going to talk about further defects that affect KS patients, instead of similar diseases. Otherwise, looking good.
  • Current research: Nice long explanations of the research, though there surely are more than 3 current papers about this out there?
  • Glossary: How do we know which words from the sections can be found in the glossary? More terms could also be included.
  • References: Needs fixing. One and the same reference appears multiple times in the list.

Group 4 - Huntington's Disease

  • Intro: Content is fine, but revise some of your sentences - they are a bit long winded and hard to follow.
  • History: Looks good.
  • Epidemiology: Nice detail.
  • Genetics: Your first sentence doesn't quite make sense. That is not an adequate explanation of autosomal-dominant. Also, in case both parents have the disease, the likelihood of the offspring having the disease is still not 100% - it's 75%.

Also, are you sure there is a mutation that causes the repeat to expand? Repeats in general are susceptible to mutations, especially expansions - that is different from there being another mutation elsewhere in the genome causing the repeat to expand. More terms need to be explained in the glossary. Nice hand-drawn figure though. There's a reasonable amount of information why the disease tends to be inherited in an anticipating pattern, so you could possibly add that information.

  • Molecular Mechanisms & Pathogenesis: Nice detail. Why are some terms in bold and coloured? More terms need to be explained in the glossary.
  • Clinical Manifestations: Good.
  • Diagnostic Tests: Otherwise fine, but you could briefly mention which genetic tests can be used to diagnose the test genetically.
  • Video of Huntington's disease patient: Why is this the main heading for this section? Doesn't quite make sense. Otherwise, the section is good, I like the use of figures to break up the text.
  • Treatment: Nicely comprehensive. Rather few explanations in text form though, maybe expand on this a little bit more?
  • Current/Future Research: Your "Culling out complex traits" figure doesn't have any explanation on the project page. Also, what exactly does it contribute, but a picture? It seems a bit redundant. Otherwise, nice detail.
  • Glossary: Looks good, but some more terms still need explaining.
  • References: Needs fixing, some papers appear multiple times, and some references lead to emptiness.

Group 5 - Fragile X Syndrome

  • Introduction: Concise and to the point.
  • History: 1977... revise this sentence, I don't quite understand it. Generally, the explanations about the different discoveries could be longer and explain more how this lead to progress with regards to FXS.
  • Epidemiology: All of the sudden you talk about "other populations" - which was the population you were initially referring to? Also, when you bullet-point the studies about the different populations, it would be good including a reference to each study.
  • Screening/Population testing: Looks fine.
  • Etiology: Generally well explained, though your last paragraph remains rather technical. You also sometimes use very long sentences - try to break those down, that'll make it easier to follow the argument. None of your terms seem to be explained in the glossary, and I doubt that anyone who hasn't done somewhat advanced genetics will understand the stuff relating to the RICS complex, the dicer enzyme and mRNA and miRNA regulation. Otherwise, nice depth and detail.
  • Development: Well explained, good use of subheadings.
  • Signs and Symptoms: Also well explained, good use of subheadings.
  • Diagnosis: Too short. What about non-genetic diagnosis?
  • Treatment: You jump in with mGluR5 treatment without having previously mentioned that this is affected by the syndrome. Mention it somewhere earlier, so it makes more sense that it needs to be treated?
  • Recent Research: The autism related bit is well explained, but is there no current research looking at other aspects of the disease?
  • Glossary: Too short, more terms need to be explained.
  • References: The links probably need fixing. Also, a few articles seem to appear a couple of times in the list, but in general it looks fine.
  • General: I feel like you mainly focus on the behavioural/cognitive aspects of the disease. Is there nothing more physiologicall to it? Otherwise, well organised, but maybe include a few more figures, as most of the page appears to be text?

Group 6 - Tetralogy of Fallot

  • Intro: What's a tet spell?
  • History: Very good in general. Not sure it makes sense to split it into 2 parts, with surgical being separate? I think it would work just as well combining the two.
  • Edidemiology: Looks fine
  • Signs and Symptoms: Otherwise good, but considering you have a whole subsection entitled clubbing, I'd suggest explaining what it is right there, and not just in the glossary.
  • Genetics/Aetiology: Love the detail and depth, though the more technical terms should be explained in the glossary. Tiny comment: "there is only a single copy of the gene in one allele" - I know what you're trying to say, only one allele is functioning, but saying it like this kinda means, this allele only has one copy of the gene, whereas usually there are multiple copies of a gene in one allele, which is, as far as I know, not the case (that would just be contradictory, as an allele is a copy/varient of a gene).
  • Pathophysiology and Abnormalities: Very good, nice use of figures.
  • Diagnostic Tests: Not sure I like the table. It is just a hell of a lot of text... in a table. It doesn't really help give an overview, maybe just have subheadings, with (once you have an image) a picture on the side? Also, referencing needs fixing.
  • Treatment/Management: Very good, nice amount of detail. Again not sure a table is required. Also, the colour is a bit in your face, but that might just be me. I like the links at the end.
  • Prognosis: Content seems fine. A bit odd there's only one reference?
  • Future directions: Otherwise seems fine, though referencing needs fixing.
  • Glossary: A bit poor. More technical terms need to be explained.
  • General: The last few sections lack some figures, it is just a lot of text. The content in general (as in of the whole project) was really good, so well done!

Group 7 - Angelman Syndrome

  • Introduction: brief and to the point.
  • History: Very well explained, but references have been forgotten? Also, you mention two dates in the summary table, 1980 & 1982, that you don't seem to explain previously.
  • Epidemiology: Looks a little bit bare. If there simply is not much information about it, I wouldn't split it in three sections with each only containing a sentence, but rather write one short paragraph.
  • Aetiology: I assume the UBE3A gene lies within the 15q11.2-q13 region? You might want to specify that. Also, some terms should be linked to the glossary.
  • Pathogenesis: Watch out with your terminology - you say "its function is vague" - its function most likely isn't vague, but it is only vaguely known. Subtle, but important difference. Why do you mention LTP? Is LTP affected in AS? Otherwise, impressive detail in the mechanisms, well explained.

Not quite sure it makes sense to have the "animal models" subheading under pathogenesis. Maybe have a separate section, entitled, animal models used in the study of AS? I'd also suggest having pathophysiology as a brief, but separate section from pathogenesis, and not have it as a subsection.

  • Signs and Symptoms: Not quite sure what the table is for? Having a table combined with text with subheadings seems a bit odd. The text is well explained. (Just correct obesity, not obeseness.)
  • Complications: A bit brief and out of the blue. How does it link in with the rest? Maybe include in under another section instead of have it as its own.
  • Diagnosis: Prenatal diagnosis looks good, very detailed. Just watch out with the chorionic villus sampling, not chronic villus sampling ;)

Postnatal: Revise your first sentence, doesn't quite make sense. Also, it seems a bit brief, maybe add a bit more detail? Differential Looks fine.

  • Related Diseases: Might make sense to combine this with differential diagnosis? Also, considering pretty much exactly the same region is affected in PWS as in AS, you might want to explain more how this still leads to two separate syndromes.
  • Treatment & Management: Needs a bit more detail.
  • Prognosis: The information provided seems a bit random, thus needs a bit more explanations and how it relates to everything else.
  • Genetic counseling: No explanations provided, simple table. How are people supposed to understand this?
  • Current and Future Research: Fine.
  • Glossary: (Your definition of an allele is not quite right.) Otherwise looks good, though some more terms need explanations.
  • References: The links probably need fixing, and some papers appear several times in the list.

Group 9 - Williams Syndrome

  • Intro: More info about the syndrome itself needed. Add a picture if you can? The text alone is a bit dry.
  • History: ... 1952 is really not early. I'd call it a rather new syndrome if that's when it was discovered..? Otherwise, lots of info and references, which is good.
  • Genetic factors and Etiology: Looks good.
  • Diagnosis: Seems fine.
  • Epidemiology: Not sure it makes sense to have management and treatment under epidemiology? Content seems fine, though is very text-heavy, maybe find a figure to break it up?
  • Phenotype: I like the table. Gives an easy overview.
  • Cardiac Conditions: Good content. I assume the "other problems" section is still under construction?
  • Genitourinary Conditions: Content seems fine, but it's very text heavy, this really needs to be broken up somehow. Possibly use a table, or include more figures.
  • Endocrine: Endocrine what? Conditions? That title is a bit odd. Otherwise, looks good. How come the thyroid section doesn't have a reference?
  • Other Associated Medical Conditions: Good content, I like the table.
  • Cognitive, Behavioural and Neurological Phenotype: Very impressive amount of (really interesting) information, which however currently mainly consists of text. Some more figures will help break that down a bit. (Watch out with the spatial cognition part - the title is spelled correctly, but within the text it's all "spacial".) Otherwise, very well done!
  • Structural Differences in the Brain: Not quite sure it makes sense to have this section here - put it before the cognitive phenotype section, instead after? Content is very good.
  • Specialised Facilities and Supportive Associations: Interesting idea. Not quite sure it's needed cause I think we're supposed to focus on the science, but at the same time I don't see why not include it. Though your formatting makes it a very long section - I'd keep it more brief.
  • Current research and developments: A little bit too brief. You could expand a little bit more on what is being done. The links are good, but maybe give a few more examples of recent papers and reviews.
  • Glossary: Poor. MANY more terms need explanations.
  • References: Looks fine in general, though the link might need fixing, and also one reference leads to emptiness?
  • General: From the conditions sections onwards I'm not quite sure the sections and different titles you have chosen make sense, it seems a bit confusing. Maybe rethink that and try and come up with a more clear structure? Also, you need to make your structuring and how you split up a section into subsections more uniform.

Overall though, you cover an impressive spectrum of information. Well done!

Group 10 - Duchenne Muscular Dystrophy

  • Intro: Fine
  • History: Nicely detailed, but missing a timeline.
  • Epidemiology: Seems fine, though you might wanna mention that the daughter of an affected male will automatically become a carrier. Or do males generally not survive til reproductive age?
  • Aetiology - Genetics: Could do with a little bit more detail on the actual genetics/mutations, how they occur, if it is known why they occur, what effect it has.
  • Pathogenesis: Content seems fine, could do with a figure?
  • General Signs and Symptoms of Duchenne’s Muscular Dystrophy: Not sure I'd give this it's own subsection - maybe put it under the next one?
  • Clinical manifestations and complications: Fine
  • Diagnosis: Clinical Diagnosis is a bit short?
  • Treatment: Current and Future Prospects: Poor. Treatment needs expansion. The table doesn't give much detail.
  • Where's the current research section? Surely you could use at least some bits of the future prospects for treatment for this.
  • Glossary: Poor. More terms need explanations.
  • General: The content is rather superficial. It is a very small page? Surely there must be more information available. Also, more figures are needed.

Group 11 - Cleft Palate and Lip

  • Introduction: Too short. Also, how come there are no references? How about starting with a brief anatomical description?
  • History: No reference for the first paragraph? I like the idea of mentioning Plato, but could you then also expand a little bit more on his thoughts? Also, what was the explanation offered by Philippe Frederick Blandin?
  • Timeline: Looks good to me, though some terms should be explained in the glossary.
  • Diagnosis: I'm not sure I'd make this follow on immediately from the Timeline. I would put this section between Types of Cleft Palate/Lip & Pathophysiology, maybe? While you do talk about the technical difficulties just before the Cleft Soft Palate Detection part, but considering you start a new subsection, it's confusing to keep talking as if it was the same paragraph. Maybe say "the technical difficulties mentionned above" instead? An explanation in the glossary of what a cleft soft palate actually is, is definately needed! The Cleft Hard Palate section is very well done.
  • Syndromes and Anomalies associated with cleft: Looks fine.
  • Development: Under construction? or is there meant to be no text, and you're simply splitting this section into the two subsections? If yes, you might want to make that clearer.
  • Aetiology: This part is slightly technical and could do with some more detailed explanations. It doesn't feel like a coherent section.
  • Developmental Staging: Well explained.
  • Types of Cleft Palate/Lip: Looks fine. Though the "algorhythm for repair..." figure seems to be in a slightly random place..? How does it relate to this section (or the next)?
  • Pathophysiology: The cranio-facial development pathway is a very complex process. Since the several points of development at which “Clefting” might occur is based on the condition and the wide range of its phonotypical expression. Make this one sentence? You start talking about neural crest cells quite out of the blue. Has there been any mention of them before? It's quite confusing to have them added into the story without having previously told why. The first two paragraphs under the table lack references? This part repeats what has been partly said before, but adds more physiological detail to it. I'd find it more logical to combine the different aspects to give one, more complete picture.
  • Genetic configuration: Very poor language/sentence structure. Where are the references? Putting womb and external environment together does make sense, but you might want to explain in a sentence why.
  • Neuroembryology and functional anatomy of craniofacial clefts: Excellent explanation, though some terms should be explained in the glossary. Why are some words in bold? Again, this sort of repeats previous information, again with more detail from a different point of view, apparently unrelated to what's been told before, as this section doesn't follow the previous sections?
  • Treatment: Can you explain the different techniques a little bit more, instead of just having bullet points? The figures are really nice, but don't illustrate all of the techniques mentioned.
  • Problems associated with Cleft Palate: Mere list with bullet points isn't enough, more explanations needed.
  • Current and Future Research: Very poor. There must be more than 3 articles?
  • Glossary: Poor. Many more terms need explanations.
  • References: Need fixing. The same article appears lots of times in the list. Watch out with your german references... the fact that you misspell the german makes me wonder whether you could have actually read the papers? In case you're citing a reference cited within the reference you've read, there usually is a special way of doing it.
  • General: Your sections are really random and don't follow logically from one another. There is a lot of repetition of similar content in multiple different places, which is confusing. It is hard to keep an overview. Nevertheless, some of the sections are well done.

Group Project References

Current research: [2]

Mapping of frataxin gene: [3]

Genetics: [4]




check Jiralerspong S, Liu Y, Montermini L et al. (1997). Frataxin shows developmentally regulated tissue-specific expression in the mouse embryo. Neurobiol Dis 4: 103–113. for developmental genetics

Group Project Work

Genetic Component

The frataxin gene is located on the proximal long arm of chromosome 9. Its location on chromosome was identified for the first time by Chamberlain et al (1988) [8], using a linkage study for the mapping. Subsequent studies further refined its location to 9q13-q21 [9].

The most common mutation leading to the FRDA phenotype is an expansion of the GAA triplet repeat in the first intron of the frataxin gene. Repeats up to approximatively 40 are normal, and manifestations of the disease start at 70 repeats. The repeat number can reach up to 1700, and the most common number of repeats in FRDA patients is between 600-900[10] [9]. The mutation is recessive, thus heterozygous carriers of the repeat are clinically normal. Most FRDA patients are homozygous for a repeat expansion, although there are some rare cases of heterozygous patients who have a repeat expansion on one allele and a missense or nonsense point mutation on the other allele. [11]


FRDA is the most common repeat-expansion caused disease, with as many as 1 in 90 carriers in the European population. While repeats up to 40 do not show any clinical manifestations, most normal repeats are smaller, consisting of only 8-9 repeats. In a study investigating the evolution of the repeat expansion, Cossée et al (1997) [9] found that only approximatively 17% of clinically normal repeats consist of repeats of longer than 16. The comparatively high prelevance of FRDA in European populations compared to other populations has been suggested to be the result of a founder event. The presence of long repeat alleles without clinical manifestations served as a pool for further length variations, including transitions to pathological repeat expansions. In same cases, this transition has been achieved within one single generation. [9]

Genetic instability

Several other disorders, including Fragile X Syndrome, Huntington's Disease as well as other ataxias, are caused by repeat expansions, suggesting the possibility of a common underlying mechanism. Indeed, repeat regions, especially trinucleotide repeats, are generally unstable structures and can undergo additions or deletions of the repeated unit [12]. The cause for this instability is replication slippage: during DNA replication, one strand of the DNA template may loop out and become displaced, alternatively, DNA polymerase might slip or stutter. Both of these scenarios lead to either replication of already replicated sequences when the DNA polymerase rebinds to the template, which thus leads to expansions, or alternatively, DNA polymerase might rebind further down the strand, thus failing to replicate part of the sequence, leading to deletions. Replication slippage is a lot more common in repeat regions, and furthermore, the longer the repeat, the more likely slippage is to occur. (For further detail on the mechanisms of replication slippage, see Viguera et al (2001) [12].) This observation explains why a pathological repeat expansion can be achieved within very few generations if the parental alleles are longer variants of the normal repeat length. This further explains the anticipating pattern of inheritance in families with the disease, further discussed in the Inheritance section.

Consequences of the mutation

In a study investigating the consequences of the repeat expansion for DNA transcription, Bidichandani et al (1998) [13] found that splicing of the expanded intron is not affected, and thus is not the cause for abnormal frataxin protein. Instead, they showed that mRNA levels of frataxin are very low in FRDA patients, speaking for ineffective transcription. Indeed, they showed in further experiments that the GAA triplet expansion interferes with transcription. This interference is length dependent, and here a threshold of 79 GAA repeats was found before interference occurs. Furthermore, the interference is orientation specific, it only occurs during the synthesis of the GAA transcript which is the physiological direction of transcription, and not in the complementary strand transcript. The reason for this interference is assumed to be the formation of unusual DNA structures. Both G (guanine) and A (adenine) are purines while T (thymine) and C (cytosine) are pyrimidines. Thus a GAA repeat leads to a strand of pure purines binding to a complementary strand of pure pyrimidines. Such structures have been found to form unusual DNA structures, and it is assumed that this is also the case in the GAA repeat in the frataxin gene. These unusual structures are also present in the shorter GAA repeats which don't lead to transcription interference, and it is thought that a longer repeat stabilises the unusual structure. It is thought that these unusual structures interfere with the transcription, thus making longer repeats more stable and more efficient in the transcription blockage, which leads to gene silencing. This would account for the negative correlation between repeat length and frataxin mRNA levels as well as frataxin levels as such. [13] More recent studies are looking at whether the elongation and/or the initiation of transcription are affected. While it is generally accepted that there are problems with the elongation in repeat expansions, some have found evidence for inhibited initiation, though this is still a matter of debate. [14] [15]

In the rare cases of heterozygous individuals with a repeat expansion and a point mutation, the point mutation most often leads to either a shortened or abnormal frataxin protein, which is unfunctional. [11]

The protein frataxin is a mitochondrial protein that can bind iron and is thought to be involved in the mitochondrial iron metabolism. It is the deficiency in frataxin which leads to the clinical manifestations of FRDA.

Add more about histone modifications



GAA repeat is unstable - leads to anticipating pattern of inheritance of GAA repeat

Genetic Expression

The frataxin gene is expressed in all cells, though the expression levels vary between different tissues and at different times during development.

In adult cells, frataxin levels are highest in the heart, brain and spinal cord, followed by the liver, skeletal muscle and the pancreas. Generally, the frataxin levels are higher in cells that are abundant in mitochondria, such as cardiomyocytes and neurons [10]. Nevertheless, some cell specificity, such as primary sensory neurons, still remains unexplained.

Developmental expression has been investigated in mouse embroys [16], and it was found that frataxin is expressed during embryonic development, though generally at a lower level than postnatally. The highest prenatal level of expression was found in the spinal cord, followed by the periventricular zone, the cortical plates and the heart. This distribution is in concordance with the distribution observed in adults, the only exception being expression in the cerebral cortex, which has not been manifested in adults. Overall, it seems that the tissues expressing frataxin during embryonic development are the ones that become dysfunctional in adults suffering from FRDA.


Cosse´e M, Schmitt M, Campuzano V et al. (1997). Evolution of the Friedreich’s ataxia trinucleotide repeat expansion: founder effect and premutations. Proc Natl Acad Sci U S A 94: 7452–7457.

the longer the repeat - the more susceptible it is to mutations --> repeat instability --> replication slippage from normal long repeat can get to pathological repeat within one single generation

transcriptional consequences of GAA repeat: check The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. and Friedreich Ataxia: Molecular Mechanisms, Redox Considerations, and Therapeutic Opportunities

Rename "consequences of mutation" frataxin gene silencing? put it in somewhere else?

Check Prenatal Diagnosis 1995 for map of markers around the frataxin gene


  1. <pubmed>15226263</pubmed>
  5. <pubmed>8596916</pubmed>
  6. <pubmed>11351269</pubmed>
  7. <pubmed>11269509</pubmed>
  8. <pubmed>2899844</pubmed>
  9. 9.0 9.1 9.2 9.3 <pubmed>9207112</pubmed>
  10. 10.0 10.1 <pubmed>21827895</pubmed>
  11. 11.0 11.1 <pubmed> 20156111 </pubmed>
  12. 12.0 12.1 <pubmed>11350948</pubmed>
  13. 13.0 13.1 <pubmed>9443873</pubmed>
  14. <pubmed>21127046</pubmed>
  15. <pubmed>20373285</pubmed>
  16. <pubmed>9331900</pubmed>