Download Genetic disease

Genetic diseases
Marin Vargas, Sergio Paul
2013
Genetic disease
A genetic disease (genetic disorder or
Mendelian disease) is an illness caused
by one or more abnormalities in the
genome, especially a condition that is
present from birth (congenital).
Most genetic disorders are quite rare and
affect one person in every several
thousands or millions.
Genetic disorders are heritable, and are
passed down from the parents' genes.
Other defects may be caused by new
mutations or changes to the DNA. In
such cases, the defect will only be
heritable if it occurs in the germ line.
The same disease, such as some forms
of cancer, may be caused by an inherited
genetic condition in some people, by new
mutations in other people, and by non
genetic causes in still other people.
Genetic disorder classification
1. Single gene disorder
1.1. Autosomal dominant
1.2. Autosomal recessive
1.3. X-linked dominant
1.4. X-linked recessive
1.5. Y-linked
1.6. Mitochondrial
2. Multifactorial and polygenic (complex) disorders
SNV might cause a genetic disorder
SNV: Single Nucleotide Variant
At least 1% of population SNP (Single Nucleotide Polimorfism)
Otherwise
Mutation
Here is part of the genome from two people who are both smokers and drinkers, but only
one of them gets cancer. The zoom into the chromosomes of these two men shows just
a sampling of the differences in variation that are responsible for their individual cancer
risk. The variations themselves do not cause cancer. They only affect each person's
susceptibility to tobacco smoke and alcohol after exposure.
Protein folding
The protein function depends on the
3D structure that depends on the
sequence
Amino acids
Variations causing no changes
Silent mutation or synonymous mutation
When a SNP occurs within a coding region, it is possible that there is no effect. For
example, when the DNA sequence GAC becomes GAG, the codon in the mRNA
changes from CUG to CUC. Since both codons stand for the same amino acid leucine,
there is no change in the protein. The change in the DNA is called a silent change.
(Very high frequency mutation)
Variations causing harmless changes
Non synonymous harmless mutation
There are also SNPs within coding regions that lead to very subtle changes in proteins.
For example, if a SNP causes the codon GAU to change to GAG, the amino acid
changes from aspartic acid to glutamic acid. These amino acids have very similar
chemical properties, but glutamic acid is just a little bigger. If the SNP causes a change
in a part of the protein that is not important to its function, the result may be very subtle
or totally harmless. The cell continues to function normally.
(High frequency mutation)
Variations causing harmful changes
Non synonymous harmful mutation
There are also SNPs within coding regions that lead to very important changes in
proteins. For example, the sequence GUA becomes GUU, and the amino acid called
aspartic acid changes to valine in the protein. These two amino acids have very different
chemical properties. The substitution of one for the other may, or may not, severely alter
how the protein folds and functions, depending on where the change occurs in the
protein. When the change in the protein does lead to disease symptoms in the patient,
the SNP is harmful and is called a mutation. (Rare mutation
low frequency)
Gene expression and genetic disease
Gene expression is the process by which information from a gene is used in the
synthesis of a functional gene product.
These products are often proteins, but in non-protein coding genes such as
ribosomal RNA (rRNA), transfer RNA (tRNA) or small nuclear RNA (snRNA) genes,
the product is a functional RNA.
The process of gene expression is used by all known life to generate the
macromolecular machinery for life.
Conservation genetics
Since sequence information is normally transmitted from
parents to progeny by genes, a conserved sequence implies
that there is a conserved gene.
Highly conserved DNA sequences are thought to have
functional value.
A base preserved, most likely, indicates a region important for
the protein structure, thus important for the protein functionality.
Researcher goal
Identification of pathogenic DNA sequence alterations in
patients with inherited diseases.
Understanding how a mutation affects the protein functionality,
that is, whether the mutation is or not causative directly or
indirectly of the genetic disorder (deleterious).
Predict whether an amino acid substitution affects protein function
The aim is to introduce single nucleotide variant found, into the
protein’s structure and to predict the possible structural and
functional consequences due to that variant.