This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison
Introduction to Fragile X Syndrome
Fragile X syndrome is the most commonly inherited mental disability worldwide [2]. According to The Fragile X Association of Australia 1 in 3,600 boys and about 1 in 4,000-6,000 girls each year are born with the full mutation of FMR1, the gene of Fragile X syndrome. A normal and unaffected FMR1 gene contains anywhere from 6-45 CGG repeats in the promoter portion of the gene compared with the full mutation, which contains 200 or more CGG repeats [2].
Fragile X syndrome boys can be characterized by their physically long faces and their prominent foreheads and ears [2]. Behaviorally both boys and girls with fragile x-syndrome may have attention deficit hyperactivity disorder (ADHD) or attention deficit disorder (ADD) [2]. These children also can have high levels of anxiety especially regarding events that are out of routine. People with Fragile X syndrome often are socially shy and have a hard time making eye contact. This means children and adults affected by Fragile X syndrome often are placed along the spectrum of autistic disorders [5].
Fragile X syndrome boys can be characterized by their physically long faces and their prominent foreheads and ears [2]. Behaviorally both boys and girls with fragile x-syndrome may have attention deficit hyperactivity disorder (ADHD) or attention deficit disorder (ADD) [2]. These children also can have high levels of anxiety especially regarding events that are out of routine. People with Fragile X syndrome often are socially shy and have a hard time making eye contact. This means children and adults affected by Fragile X syndrome often are placed along the spectrum of autistic disorders [5].
Sequence repeats and the FMR1 gene
Sequence repeats appear as dangling threads
Until the discovery of the sequence repeats expansions of FMR1 it wasn’t believed that anticipation, how a disease becomes more severe through generations, existed; however Fragile X, with increasing deleterious CGG repeats each generation, proved a link for anticipation and genetic disease. It is assumed that these repeats abolish transcription of FMR1 through the methylation of the promoter [7].
Below is an example of how the FMR1 gene can still be transcribed even at a premutation of 96 CGG repeats. Expression stops at high levels of repeats and here with 720 repeats there is no longer any expression. A male with a full mutation in the FMR1 gene will not have any protein expressed, where as a female with a full mutation in one X chromosome might still have lower FMR1 expression depending on which X chromosome is inactivated.
Below is an example of how the FMR1 gene can still be transcribed even at a premutation of 96 CGG repeats. Expression stops at high levels of repeats and here with 720 repeats there is no longer any expression. A male with a full mutation in the FMR1 gene will not have any protein expressed, where as a female with a full mutation in one X chromosome might still have lower FMR1 expression depending on which X chromosome is inactivated.
The purpose of this website will be to delve into the genomics and proteomics of FMR 1, the associated Fragile X syndrome and the gene’s homolog in a model organism.
References
[1] Header photo: Jeff Miller, UW-Madison
[2] http://www.nfxf.org/html/genetic_counselor.htm
[3] www.fragilex.org.au
[4] Photo: http://www.cafamily.org.uk/medicalinformation/conditions/azlistings/f33_6.htm
[5] Moss,J. (2009) Autism spectrum disorders in genetic syndromes: implications for diagnosis, intervention and understanding the wider autism spectrum disorder population Journal of Intellectual Disability Research, 53(10), 852-873.
[6] Photo: http://www.citris-uc.org/publications/articles/serious_play_using_games_screen_fragile_x
[7] Strachan, Tom; Read, Andrew P. Human Molecular Genetics. 3rd ed. Garland Science. New York, 2004.
[8] Warren, S. T., & Nelson, D. L. (1994). Advances in molecular analysis of fragile X syndrome. JAMA, 271(7), 536-542.
[1] Header photo: Jeff Miller, UW-Madison
[2] http://www.nfxf.org/html/genetic_counselor.htm
[3] www.fragilex.org.au
[4] Photo: http://www.cafamily.org.uk/medicalinformation/conditions/azlistings/f33_6.htm
[5] Moss,J. (2009) Autism spectrum disorders in genetic syndromes: implications for diagnosis, intervention and understanding the wider autism spectrum disorder population Journal of Intellectual Disability Research, 53(10), 852-873.
[6] Photo: http://www.citris-uc.org/publications/articles/serious_play_using_games_screen_fragile_x
[7] Strachan, Tom; Read, Andrew P. Human Molecular Genetics. 3rd ed. Garland Science. New York, 2004.
[8] Warren, S. T., & Nelson, D. L. (1994). Advances in molecular analysis of fragile X syndrome. JAMA, 271(7), 536-542.
Aime Agather
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Last Updated 11/08/2011
Genetics 677
[email protected]
Last Updated 11/08/2011
Genetics 677