User:Z3389343

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)


--Mark Hill 10:04, 3 August 2011 (EST) Where are your answers to first lab assessment? Need to be completed before Lab 2.

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: http://nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html

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

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080369/

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. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441939/


  • 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?
  • What animal model helped elucidate the neural crest origin and migration of cells?
  • What abnormality results from neural crest not migrating into the cardiac outflow tract?

Group Project References

Current research: [1]

Mapping of frataxin gene: [2]

Genetics: [3]

[4]

[5]

[6]

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 precise location to chromosome 9p22-CEN was identified for the first time by Chamberlain et al (1988) [7], using a linkage study for the mapping.

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[8] [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. [8]

Evolution

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

Consequences of the repeat expansion

Glossary

codon - A triplet of nucleotides that specifies an amino acid or a start or stop signal in the genetic code.

intron - DNA sequence that lies between coding regions of a gene. Introns are transcribed but are spliced out of the primary RNA product and thus do not contribute to the polypeptide encoded by the gene.

missense mutation - A mutation that alters a codon to that of another amino acid and thus leads to an alteration in the resulting polypeptide.

nonsense mutation - A mutation that creates a stop codon, thus leading to the halt of translation and a shortened gene product.

point mutation - A mutation affecting a single nucleotide.

triplet repeat (trinucleotide repeat) - A tandemly repeated cluster of three nucleotides, such as GAA in FRDA, within or near a gene.

Founder event - A form of genetic drift. The establishment of a population by a small number of indivduals whose genotypes carry only a fraction of the different kinds of alleles in the parental population.

Heterozygous - Possessing two different variants of a gene.

Homozygous - Possessing two identical variants of a gene.


triplet repeat expansion


Inheritance

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 [8]. Nevertheless, some cell specificity, such as primary sensory neurons, still remains unexplained.

Developmental expression has been investigated in mouse embroys [10], 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.



Notes:

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

References

  1. http://www.future-science.com/doi/abs/10.4155/cli.11.93?journalCode=cli
  2. http://www.nature.com/nature/journal/v334/n6179/abs/334248a0.html
  3. http://www.nejm.org/doi/full/10.1056/NEJM199610173351601#t=articleBackground
  4. <pubmed>8596916</pubmed>
  5. <pubmed>11351269</pubmed>
  6. <pubmed>11269509</pubmed>
  7. <pubmed>2899844</pubmed>
  8. 8.0 8.1 8.2 <pubmed>2899844</pubmed> Cite error: Invalid <ref> tag; name 'PMID21827895' defined multiple times with different content
  9. 9.0 9.1 9.2 <pubmed>9207112</pubmed>
  10. <pubmed>9331900</pubmed>