This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison
A comparison between the primary source's discovery of FMR-1 and a popular press article about Fragile-X Syndrome
In the May 1991 article in the journal Cell, Annemieke, J. M. H. et al presented their research on a gene expressed in the brain termed FMR-1, or Fragile-x Mental Retardation-1, the hypothesized gene for Fragile-X Syndrome. This group of scientists used two main DNA sources, one being a hybrid combination between rodent and the human Fragile-X chromosme and the other being two yeast artificial chromosomes (YAC) which, as the paper states, are located near the mutation responsible for the Fragile-X clinical phenotype [1]. It was then determined that there was a CpG island that could be hyper-methylated. They linked this idea to their Southern Blot Analysis of Fragile-X – Associated Translocation Breakpoints, determining the sizes of the rodent-human hybrids after they were digested with EcoRI. The true Fragile-X DNA lane had a thick band at 7.4 kb while the hybrids had bands at 4.8 kb and 3.8kb showing the large increase and expansion in the DNA. It was determined in the paper that a phenotypically normal FMR-1 gene had 5.1 kb while all of the other Fragile-X patients exhibiting much larger sized gene, near 7.4 kb.
To determine that FMR-1 was expressed in the brain, thereby being a possible cause for the mental retardation seen in Fragile-X patients a Northern Blot was run to see where the mRNA was being expressed in phenotypically normal humans. They ran hybridizations sampled from the brain, placenta, liver fetal lung, fetal kidney and lymphocytes and found that FMR-1 RNA was expressed in the brain, placenta and lymphocytes. FMR-1 showing expression in the brain with the breakpoint cluster region that has major expansions in Fragile-X patients proved that Annemieke J. M. H et al correctly identified their gene for Fragile-X Syndrome.
According the New York Times this discovery of FMR-1 not only brought about the discovery for the gene behind Fragile-X Syndrome but also will bring us insight to understanding human intelligence [2], a gross claim given the scientific paper focused on locating the DNA and showing the mRNA is expressed in the brain. The article goes on to talk about how the protein has a very interesting structure, however I think that it would have been more interesting for the paper to discuss the DNA responsible for the protein. The DNA promotes or prevents the transcription, and in the case of FMR-1 the large expansions of CGG prevent transcription of the mRNA.
As one of the major newspapers breaking this story The New York Times did a very nice job in introducing Fragile-X Syndrome to the general public especially in comparing it to a disease they probably knew more about at the time, Down syndrome. The article states that unlike Down syndrome, which is a spontaneous defect in the egg, Fragile-X Syndrome is heritable. They state that it is similar to a dominate pattern of inheritance, which makes it sound like it is dominantly inherited from generation to the next. However given that the mutation is on the X chromosome and females with one good and one bad X chromosome can retain a normal phenotype it might be more correct to say it is a recessive X-linked disease, rather than just comparing it to a dominate disease trait.
As the article looks toward the future with medical diagnostics in families with a predisposition to Fragile-X Syndrome it states that the families will be able to test their unborn children for the disease and be able to go from there. I have no doubt that this happens now as there is information on how to test for Fragile-X for genetic counselors at the Fragile-X foundations site [3]. Even more so just published on February 1st 2010 at msnbc.com is an article regarding a new clinical trial on a drug that looks to block overactive synapses in the brain [4]. Starting May 1991 the discovery of FMR-1 as the gene of Fragile-X Syndrome has not only created more awareness on the disease but also is answering more questions.
To determine that FMR-1 was expressed in the brain, thereby being a possible cause for the mental retardation seen in Fragile-X patients a Northern Blot was run to see where the mRNA was being expressed in phenotypically normal humans. They ran hybridizations sampled from the brain, placenta, liver fetal lung, fetal kidney and lymphocytes and found that FMR-1 RNA was expressed in the brain, placenta and lymphocytes. FMR-1 showing expression in the brain with the breakpoint cluster region that has major expansions in Fragile-X patients proved that Annemieke J. M. H et al correctly identified their gene for Fragile-X Syndrome.
According the New York Times this discovery of FMR-1 not only brought about the discovery for the gene behind Fragile-X Syndrome but also will bring us insight to understanding human intelligence [2], a gross claim given the scientific paper focused on locating the DNA and showing the mRNA is expressed in the brain. The article goes on to talk about how the protein has a very interesting structure, however I think that it would have been more interesting for the paper to discuss the DNA responsible for the protein. The DNA promotes or prevents the transcription, and in the case of FMR-1 the large expansions of CGG prevent transcription of the mRNA.
As one of the major newspapers breaking this story The New York Times did a very nice job in introducing Fragile-X Syndrome to the general public especially in comparing it to a disease they probably knew more about at the time, Down syndrome. The article states that unlike Down syndrome, which is a spontaneous defect in the egg, Fragile-X Syndrome is heritable. They state that it is similar to a dominate pattern of inheritance, which makes it sound like it is dominantly inherited from generation to the next. However given that the mutation is on the X chromosome and females with one good and one bad X chromosome can retain a normal phenotype it might be more correct to say it is a recessive X-linked disease, rather than just comparing it to a dominate disease trait.
As the article looks toward the future with medical diagnostics in families with a predisposition to Fragile-X Syndrome it states that the families will be able to test their unborn children for the disease and be able to go from there. I have no doubt that this happens now as there is information on how to test for Fragile-X for genetic counselors at the Fragile-X foundations site [3]. Even more so just published on February 1st 2010 at msnbc.com is an article regarding a new clinical trial on a drug that looks to block overactive synapses in the brain [4]. Starting May 1991 the discovery of FMR-1 as the gene of Fragile-X Syndrome has not only created more awareness on the disease but also is answering more questions.
Scientific primary source
Identification of a Gene (FMR-1) Containing a CGG Repeat Coincident with a Breakpoint Cluster Region Exhibiting Length Variation in Fragile X Syndrome | |
File Size: | 2238 kb |
File Type: |
From the Journal Cell
Popular press source
References
1] Verkerk, A. J. M. H., Pieretti, M., Sutcliffe, J. S., Fu, Y., Kuhl, D. P. A., Pizzuti, A. et al. (1991). Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell, 65(5), 905-914.
[2] Angier, N. (1991, Gene causing common type of retardation is discovered. New York Times pp. A1. http://www.nytimes.com/1991/05/30/us/gene-causing-common-type-of-retardation-is-discovered.html?pagewanted=all
[3] http://www.nfxf.org/html/genetic_counselor.htm
[4] AP. (2010, Fragile X syndrome could be eased by a pill; researchers work to develop first treatment for genetic learning disorder. http://www.msnbc.msn.com/id/35185356/
[2] Angier, N. (1991, Gene causing common type of retardation is discovered. New York Times pp. A1. http://www.nytimes.com/1991/05/30/us/gene-causing-common-type-of-retardation-is-discovered.html?pagewanted=all
[3] http://www.nfxf.org/html/genetic_counselor.htm
[4] AP. (2010, Fragile X syndrome could be eased by a pill; researchers work to develop first treatment for genetic learning disorder. http://www.msnbc.msn.com/id/35185356/
Aime Agather
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Last Updated 03/02/2010
Genetics 677
[email protected]
Last Updated 03/02/2010
Genetics 677