This page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.

Introduction

                                                               Alcoholism

Alcoholism, or alcohol dependence, is a chronic disease affecting people worldwide (MFMER, 2008; WHO, 2009). In the United States, approximately 17.6 million people, or about 1 in every 12 adults, suffers from the condition (NIAAA, 2007). Primarily due to an imbalance in the neurotransmitters gamma-aminobutyric acid (GABA), glutamate, and dopamine, alcoholism causes a person not only to crave alcohol, but to be unable to control how much alcohol he or she consumes once the person begins drinking (MFMER, 2008). Additionally, the person experiences withdrawl symptoms when cravings for alcohol go unsatisfied (MFMER, 2008). Left untreated, the disease usually leads to damaged relationships, financial problems, and unemployment, as well as severe health problems, including liver disorders, gastrointestinal problems, cardiovascular problems, diabetes complications, birth defects, bone loss, neurological complications, and increased risk of cancer (MFMER, 2008). Alcoholism is acquired gradually over time as a result of excessive, long term drinking; however, factors such as sex, age, genetics, and emotional state, as well as social and cultural influences, can make certain people particularly prone to developing the disease (MFMER, 2008). For example, males have higher rates of alcohol dependence than females (MFMER, 2008). Additionally, Native Americans are almost twice as likely as the general population to be dependent on alcohol (Grant, et al., 2004). An important genetic factor affecting susceptibility to alcoholism is the GRM7 gene (OMIM, 2008).


GRM7

The 880,291 base pair sequence of GRM7, located on the distal portion of the short arm of chromosome 3,  encodes a 915-amino acid long glutamate receptor protein  (OMIM, 2008). This protein, part of a family of the G-protein coupled metabotropic glutamate receptors, is one of the major regulators of glutamate transmission in the central nervous system (Okamoto, et al., 1994). GRM7 was first linked to alcoholism after the finding that mice carrying a GRM7 allele that caused lowered expression of the gene in the brain had increased alcohol consumption (OMIM, 2008). It is interesting to note that the regions of the brain vulnerable to alcohol related abnormalities, as shown in the figure to the right, include the hippocampal region, cerebral cortex and cerebellum (Oscar-Berman and Marinkovic, 2003). While GRM7 is expressed throughout the central nervous system, these structures show the highest levels of GRM7 expression (Makoff, et al., 1996). GRM7 has not yet been directly linked to alcoholism in humans; however, comparison of rat GRM7 to that of human GRM7 shows 92% sequence identity between the genes of the two species and 99% protein identity (Makoff, et al., 1996). Though an in-depth, genomic and bioinformatic investigation of the GRM7 gene,  this website will focus on analysis of the sequence, structure, function, and evolutionary relationships of GRM7 gene and its encoded protein in an effort to evaluate the role of GRM7 in the etiology of alcoholism in humans.


Literature on Alcoholism

Popular Press Review
Scientific Article Review
Popular Press vs. Scientific Article Critque

Videos on Alcoholism

Check out these videos on "Alcohol - The Facts" and  "Defining Alcoholism" to learn more about how alcohol intake affects the body as well as what symptoms an alcoholic may experience:
  Alcohol - The Facts: http://www.videojug.com/film/alcohol-the-facts
  Defining Alcoholism:
http://medindia.healthology.com/hybrid/hybrid-autodetect.aspx?content_id=2710&focus_handle=drug-abuse&brand_name=medindia


Recent visitors to this site:

References

Grant, B.F., Dawson, D.A., Stinson, F.S., Chou, S.P., Dufour, M.C., and Pickering, R.P. (2004, June 11). The 12 month prevalence and trends in DSM-IV alcohol abuse and dependence: United States, 1991-1992 and 2001-2002. Drug and Alcholo Dependence, 74(3), 223. doi: 10.1016/j.drugalcdep.2004.02.004

Makoff, A.; Pilling, C.; Harrington, K.; Emson, P. (1996, August). Human metabotropic glutamate receptor type 7: molecular cloning and mRNA distribution in the CNS. [Abstract]. Brain research. Molecular brain research 40(1), 165. Retrieved on February 2, 2009, from http://www.ncbi.nlm.nih.gov/pubmed/8840028?dopt=Abstract


Mayo Foundation for Medical Education and Research (MFMER). (2008, May 8). Alcoholism. Retrieved February 2, 2009, from http://www.mayoclinic.com/print/alcoholism/DS00340/METHOD=print&DSECTION=all

National Institute on Alcohol Abuse and Alcoholism (NIAAA). (2007, February). FAQs for the general public. Retrieved February 2, 2009, from http://www.niaaa.nih.gov/FAQs/General-English/default.htm#whatis

Okamoto, N., Hori, S., Akazawa, C., Hayashi, Y., Shigemoto, R., Mizuno, M., and Nakanishi, S. (1994, January 14). Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibatory cyclic AMP signal transduction. [Abstract]. The Journal of Biological Chemistry, 269(2), 1231. Retrieved February 2, 2009, from http://www.ncbi.nlm.nih.gov/pubmed/8288585?dopt=Abstract

Online Mendelian Inheritance in Man (OMIM). (2008, January 14). Glutamate receptor, metabotropic, 7; GRM7. Retrieved February 2, 2009, from http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604101

Oscar-Berman, M. and Marinkovic, K. (2003). Alcoholism and the brain: An overview. Alcohol Research and Health, 27(2), 125. Retrieved February 2, 2009, from: http://web.ebscohost.com.ezproxy.library.wisc.edu/ehost/detail?vid=1&hid=7&sid=07de3f40-7d7a-4f64-ad4a-fb9e6825d1ad%40sessionmgr2&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=rzh&AN=2004159543

World Health Organization (WHO). (2009). Alcohol. Retrieved February 2, 2009, from http://www.who.int/substance_abuse/facts/alcohol/en/index.html

Jennifer Wagner
wagner4@wisc.edu
Updated April 25, 2009
http://www.gen677.weebly.com