Genes & HSP

The beginner’s guide to genes, mutations and gene testing

from a presentation by Dr. Marina Kennerson, Principal Hospital Scientist in Genetics, at the 2007 HSPRF Workshop

What is a gene?

A gene is a segment of DNA that codes for the synthesis of a protein. We can think of a gene as a paragraph of three word sentences that tells us information. The paragraph can be broken up into sentences (exons) and the sentences can be broken down into three letter words (codons which tell us the amino acids used). Amino acids are the building blocks of a protein. All genes begin with a start codon and end with a stop codon.

Gene:

The sun was hot. The man did not get his hat. The hat was old.

Start codon Stop codon

We can think of genes being made up of sentences with three letter words (amino acids) that provide information about protein.

Genes contain exons:

The sun was hot. The man did not get his hat. The hat was old.

Each sentence represents an exon:

Exon 1 The sun was hot.

Exon 2 The man did not get his hat.

Exon 3 The hat was old.

What is a Mutation?

An error in the coding sequence of a particular gene results in the gene producing the wrong protein and the error is called a mutation ….. Over 40 HSP genes have been identified, some with a large number of mutations. Gene tests are used to identify the mutation.

What is Gene Testing?

A genetic test is the analysis of human DNA, RNA, protein or certain metabolites in order to detect alterations related to a heritable disorder.

When you have agreed with your doctor to have a gene test the doctor will decide which gene or genes to have tested for the presence of a mutation. The diagnostic laboratory detects and describes the mutation in the gene nominated if a mutation is present.

Types of Testing

Confirmational diagnosis of symptomatic individual

Predictive testing:

Predict possible future illness

Predict carrier state in individuals whose children might be at risk.

What mutations can occur?

Missense Mutation

The sun was hot. The man did not get his gat. The hat was old.

Nonsense Mutation

The sun was hot. The man did not old.

Insertion Mutation

The sun was hot. The man did not not get his hat. The hat was old.

Deletion Mutation

The sun was hot. The did not get his hat. The hat was old.

HSP Gene Testing – Prevalence

Here are the 3 genes for which tests are available via Molecular Medicine Laboratory at Concord Hospital, Sydney. They represent about half of all HSP incidence.

Spastin (16 exons) SPG4

Atlastin (13 exons) SPG3A

NIPA1 (5 exons) SGP6

Mutation Discovery by DNA Scanning

Spastin & Atlastin

o High Resolution Melt (HRM) – Missense, Nonsense, small insertion, small deletion

o MLPA* – Exon Duplication, Exon Deletion

NIPA1