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Alcohol Dependence and Genes Encoding α2 and γ1 GABAA Receptor Subunits: Insights from Humans and Mice.

Borghese CM, Harris RA - Alcohol Res (2012)

Bottom Line: One approach to identifying the causes of alcoholism, particularly without crossing ethical boundaries in human subjects, is to look at the person's genome (and particularly at the variations that naturally arise in the DNA) to identify those variations that seem to be found more commonly in people with the disease.Some of these analyses have focused on the genes that encode subunits of the receptor for the brain chemical (i.e., neurotransmitter) γ-aminobutyric acid (GABA).Different epidemiological genetic studies have provided evidence that variations in certain GABAA receptor (GABAA-R) subunits, particularly subunits α2 and γ1, are correlated with alcohol dependence.

View Article: PubMed Central - PubMed

Affiliation: Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, Texas.

ABSTRACT
One approach to identifying the causes of alcoholism, particularly without crossing ethical boundaries in human subjects, is to look at the person's genome (and particularly at the variations that naturally arise in the DNA) to identify those variations that seem to be found more commonly in people with the disease. Some of these analyses have focused on the genes that encode subunits of the receptor for the brain chemical (i.e., neurotransmitter) γ-aminobutyric acid (GABA). Different epidemiological genetic studies have provided evidence that variations in certain GABAA receptor (GABAA-R) subunits, particularly subunits α2 and γ1, are correlated with alcohol dependence. Manipulations of these genes and their expression in mice and rats also are offering clues as to the role of specific GABAA-Rs in the molecular mechanisms underlying alcoholism and suggest possibilities for new therapeutic approaches.

No MeSH data available.


Related in: MedlinePlus

Segment of a single strand of DNA representing a fragment of the coding region from the GABRA2 gene from two different people. There are two SNPs in this gene region—one in which both variants of the DNA encode the same amino acid (i.e., a silent mutation) and one in which the two variants of the DNA encode different amino acids (i.e., a missense mutation).
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f2-arcr-34-3-345: Segment of a single strand of DNA representing a fragment of the coding region from the GABRA2 gene from two different people. There are two SNPs in this gene region—one in which both variants of the DNA encode the same amino acid (i.e., a silent mutation) and one in which the two variants of the DNA encode different amino acids (i.e., a missense mutation).

Mentions: Single-nucleotide polymorphisms (SNPs, pronounced “snips”) are spontaneous mutations of single building blocks (i.e., nucleotides) in the genomic DNA. They can occur randomly, in any region of the DNA, including within those regions of the gene that actually encode parts of the resulting protein (i.e., coding sequences), within “silent” regions of a gene that ultimately do not encode parts of the resulting protein (i.e., non-coding regions), or in the regions between genes (i.e., intergenic regions). When a SNP occurs within a coding sequence, it may or may not change the amino acid sequence of the encoded protein. Each amino acid is represented by a three-nucleotide block of DNA (i.e., a codon). Because there are four different nucleotides (represented as A, C, G, and T), 64 possible codons exist; however, these encode only 20 amino acids. As a result, the genetic code is degenerate—that is, several codons may encode the same amino acid (e.g., both ACT and ACC encode threonine). A SNP in which both the original codon and the mutant codon produce the same protein sequence is called a synonymous polymorphism or silent mutation. If a different polypeptide sequence is produced, it is called a replacement polymorphism. This can result either in the introduction of a different amino acid, which is called a missense mutation, or in a premature stop of the protein, which is called a nonsense mutation (see the figure). Even if the SNP occurs in a noncoding region of the gene, it still may affect regulatory processes that could result, for instance, in altered protein levels.


Alcohol Dependence and Genes Encoding α2 and γ1 GABAA Receptor Subunits: Insights from Humans and Mice.

Borghese CM, Harris RA - Alcohol Res (2012)

Segment of a single strand of DNA representing a fragment of the coding region from the GABRA2 gene from two different people. There are two SNPs in this gene region—one in which both variants of the DNA encode the same amino acid (i.e., a silent mutation) and one in which the two variants of the DNA encode different amino acids (i.e., a missense mutation).
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860398&req=5

f2-arcr-34-3-345: Segment of a single strand of DNA representing a fragment of the coding region from the GABRA2 gene from two different people. There are two SNPs in this gene region—one in which both variants of the DNA encode the same amino acid (i.e., a silent mutation) and one in which the two variants of the DNA encode different amino acids (i.e., a missense mutation).
Mentions: Single-nucleotide polymorphisms (SNPs, pronounced “snips”) are spontaneous mutations of single building blocks (i.e., nucleotides) in the genomic DNA. They can occur randomly, in any region of the DNA, including within those regions of the gene that actually encode parts of the resulting protein (i.e., coding sequences), within “silent” regions of a gene that ultimately do not encode parts of the resulting protein (i.e., non-coding regions), or in the regions between genes (i.e., intergenic regions). When a SNP occurs within a coding sequence, it may or may not change the amino acid sequence of the encoded protein. Each amino acid is represented by a three-nucleotide block of DNA (i.e., a codon). Because there are four different nucleotides (represented as A, C, G, and T), 64 possible codons exist; however, these encode only 20 amino acids. As a result, the genetic code is degenerate—that is, several codons may encode the same amino acid (e.g., both ACT and ACC encode threonine). A SNP in which both the original codon and the mutant codon produce the same protein sequence is called a synonymous polymorphism or silent mutation. If a different polypeptide sequence is produced, it is called a replacement polymorphism. This can result either in the introduction of a different amino acid, which is called a missense mutation, or in a premature stop of the protein, which is called a nonsense mutation (see the figure). Even if the SNP occurs in a noncoding region of the gene, it still may affect regulatory processes that could result, for instance, in altered protein levels.

Bottom Line: One approach to identifying the causes of alcoholism, particularly without crossing ethical boundaries in human subjects, is to look at the person's genome (and particularly at the variations that naturally arise in the DNA) to identify those variations that seem to be found more commonly in people with the disease.Some of these analyses have focused on the genes that encode subunits of the receptor for the brain chemical (i.e., neurotransmitter) γ-aminobutyric acid (GABA).Different epidemiological genetic studies have provided evidence that variations in certain GABAA receptor (GABAA-R) subunits, particularly subunits α2 and γ1, are correlated with alcohol dependence.

View Article: PubMed Central - PubMed

Affiliation: Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, Texas.

ABSTRACT
One approach to identifying the causes of alcoholism, particularly without crossing ethical boundaries in human subjects, is to look at the person's genome (and particularly at the variations that naturally arise in the DNA) to identify those variations that seem to be found more commonly in people with the disease. Some of these analyses have focused on the genes that encode subunits of the receptor for the brain chemical (i.e., neurotransmitter) γ-aminobutyric acid (GABA). Different epidemiological genetic studies have provided evidence that variations in certain GABAA receptor (GABAA-R) subunits, particularly subunits α2 and γ1, are correlated with alcohol dependence. Manipulations of these genes and their expression in mice and rats also are offering clues as to the role of specific GABAA-Rs in the molecular mechanisms underlying alcoholism and suggest possibilities for new therapeutic approaches.

No MeSH data available.


Related in: MedlinePlus