Gene Function Can Be Established Biology Essay

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Bioinformatics is the study of information and processes in biotic systems. Due to the wide range of highly accessible internet sources, bioinformatics has been able to progress at an exponential rate. These internet sources can be used to store, sequence and analyse biological information. Websites such as GenBank, based at the National Centre for Biotechnology Information enables the scientific community to freely share data, a condition of publication in reputable scientific journals. There are no restrictions on access and anyone can add sequences.

Gene function can be established through the comparison of a query gene with a similar gene in another organism from which the function of the similar DNA sequence is known.

Identity of the Gene and Host Organism

Firstly, the gene within a particular query sequence needs to be identified. If the host organism is unknown, the Basic Local Alignment Search Tool or BLAST may be used. This identifies the closest match to a particular sequence in a database, by comparing all the genomes in the database at once. BLAST can also be used to identify the gene name, query length and any sequences producing significant alignments. The query sequence is 840 base pairs (bp) in length, and with a query cover of 100%, the most significant alignment was found in the Homo sapien species (Altschul, 1990).

The query sequence is part of the Homo sapiens glycine receptor, alpha 1 (GLRA1) gene, as this matched the query sequence with 100% accuracy.

Using the Blat search function on the UCSC Genome Bioinformatics website enables a search for the query sequence in the now known organism. BLAT on DNA enables the user to find sequences that have a similarity of more than 95% (Kent, 2002). Blat search produces 5 results. The exact chromosomal location of the hit with the highest degree of homology to query sequence is chr5:151,202,468-151,239,521, and is 37,054 bp in length (Kent, 2002).

There are three splice variants, and the genomic size of the largest of the three is 102,324, this contains 449 amino acids.

Ensembl allows you to obtain more information on particular genes. There are 5 transcripts derived from the gene, 3 of which are protein coding. The molecular weight of the protein is 51,692.77 g/mol (Flicek, 2012).

The Predicted Structure, Cellular Localisation and Biological Function of the Encoded Protein

Online resources such as Online Mendelian Inheritance in Man, or OMIM enable the research into all known mendelian disorders and the research into over 12,000 genes. Internet resources such as NCBI can be used collect information with regards to the structure, cellular localisation and biological function of the encoded protein.

The GLRA1 gene contains 9 exons. The gene that this protein encodes is a subunit of an inhibitory glycine receptor acting as a ligand-gated chlorine channel. Glycine binding to the receptor enables an increase in chloride conductance, producing hyperpolarization (The UniProt Consortium, 2012). The glycine receptor, found on the postsynaptic cell membrane acts as an inhibitory receptor mediating postsynaptic inhibition in the central nervous system, notably the spinal cord. The receptor controls inhibitory neurotransmission (Kniffin, 2012).

The query sequence represents only part of the glycine receptor, the alpha-1 subunit. There can be 4 alpha subunits coded for and one beta subunit coded for. These genes are the GLRA1 gene (of which the query sequence is a part of) the GLRA2 gene, the GLRA3 gene and the GLRA4 gene. The beta subunit is encoded by the GLRB gene (Kniffin, 2012). The biological function of the alpha-1 subunit protein is to bind to glycine. As the alpha-1 subunits bind to glycine a conformational change occurs, causing the chloride channels to open.

Human Hereditary Disorders Caused by Alterations in the Coding Sequence of this


In order to find information on human hereditary disorders caused by alterations in the coding sequence, online resources such as OMIM can again be used. OMIM can only be used if the gene name is known. Searching for GLRA1 produces a large quantity of useful information.

Mutations in the coding sequence for the alpha-1 subunit protein result in a decrease in the efficiency of glycine receptors to conduct chloride ions across the postsynaptic membrane. This decrease in efficiency is the cause of a disease named hyperekplexia (HPX). A GLRA1 mutation may cause a glycine protein with a faulty tertiary structure to be coded for, meaning glycine is not able to bind to the glycine receptor, resulting in inefficient transport of calcium ions across the postsynaptic membrane.

This is a human hereditary disorder, found in more than 70 families worldwide and is characterised by an excessive startle response.

There are five genes associated with hyperekplexia. These genes contribute to the production of proteins found in neurones, and affect how neurones respond to glycine. This glycine acts as a neurotransmitter, transmitting signals throughout the nervous system. The mutations that cause hereditary hyperekplexia disrupt the signalling through the spinal cord and brainstem, and are found in the five genes associated with the disorder. Mutations can occur through SLC6A5, GLRB, GPHN and ARHGEF9 genes, the latter being associated with hyperekplexia in one individual, who also had an intellectual disability and epilepsy (Tijssen, 2007). 80% of cases are caused by mutations in the GLRA1 gene.

Hereditary hyperekplexia can be inherited in an autosomal dominant pattern, meaning one copy of the gene in each cell is enough to bring about the disorder, an autosomal recessive pattern, meaning both copies of the gene in each cell cause the disorder, or alternatively and rarely, in an X-linked pattern. This means the gene is located on the X chromosome and notably, fathers cannot pass the disorder on to their son’s through this method (Genetics Home Reference, 2013).

HPX causes an increased muscle tone unexpected stimuli may cause a startle reaction in infants. Following the startle reaction, there can often be a brief period in which individuals are unable to move. Other symptoms can include movement of the arms and legs whilst asleep, twitching muscles and rarely, epilepsy. Symptoms usually fade around the age of 1, but older individuals with HPX may still have a startle reflex, rigidity and limb movement during sleep. Epilepsy can also be associated with some cases of HPX (Genetics Home Reference, 2013). Individuals with HPX can also exhibit an exaggerated head-retraction reflex, brought on by tapping on the nose, and hypersensitivity in the mantle area (Tijssen, 2007).

Spasmodic Oscillator mutant mice that are null for this gene

A mouse is a good model for study of the GLRA1 human mutation due to its genotypic and phenotypic similarities with the equivalent human gene. The mutant phenotype in mice is called spasmodic (spd), the mutant mice (homozygous oscillator mice) are null for the GLRA1 gene.

Mice show a recessive mutant phenotype called 'spasmodic' (spd), which is phenotypically similar to HKP and is inherited as a recessive disorder. The mouse mutant phenotype also includes an altered startle response, as seen in humans with the disorder. The mutant gene is found on chromosome 11 and has been mapped to a seven base pair microdeletion in the GLRA1 gene in mice and this region shows extensive similarities to the human genetic mutation, found on chromosome 5.

In mice, there is a switch from the neonatal Glra2 subunit to the adult Glra1 subunit after the second postnatal week. This means that neuromotor symptoms are produced later in oscillator and spasmodic mice that have mutant Glra1 subunits.


The internet is an ever expanding resource in the analysis of query genes, making it much easier for almost anyone to find the structure, location and biological functions of any proteins, using the many databases available. The query sequence was found to be part of the Homo sapiens glycine receptor, alpha 1 (GLRA1) gene, as this was found to match the query sequence with 100% accuracy.

Hyperekplexia is a potentially fatal but thankfully, rare, neuromotor disorder in which individuals show an exaggerated startle reflex in response to many different stimuli. Hyperekplexia is caused primarily by inherited mutations in the genes encoding the glycine receptor (GlyR) α1 subunit (GLRA1) and the presynaptic glycine transporter GlyT2 (SLC6A5) (Chung, 2010).