Missense mutations are
the second most common cause of severe hemophilia A
(HA)
3
(http://www.eahad-db.org/; http://factorviii-db.org/) and the most frequent cause of the rare coagulation factor deficiencies,
4
,
5
as well as of other human diseases, and are known to impair several properties of mutated proteins.
What type of mutation is haemophilia A?
Hemophilia A (HA) is an X-linked inherited disorder that results in impaired blood clotting with subsequent bleeding. The disorder is a consequence of a
mutation in the Factor VIII gene (F8; MIM# 300841)
that leads to reduced production or inadequate function of Factor VIII (FVIII), a protein necessary for clotting.
What is an example of missense mutation?
A missense mutation occurs when there is a mistake in the DNA code and one of the DNA base pairs is changed, for example,
A is swapped for C
. This single change means that the DNA now encodes for a different amino acid, known as a substitution.
Is haemophilia A deletion mutation?
Gene deletions
lead to factor VIII deficiency, and large gene deletions result in severe hemophilia, with no detectable factor VIII antigen; such patients are more susceptible to inhibitor development. Insertions are apparently uncommon in the factor VIII gene, but they usually lead to severe hemophilia A.
What are the 4 types of mutation?
- Germline mutations occur in gametes. Somatic mutations occur in other body cells.
- Chromosomal alterations are mutations that change chromosome structure.
- Point mutations change a single nucleotide.
- Frameshift mutations are additions or deletions of nucleotides that cause a shift in the reading frame.
What occurs in a deletion mutation?
A deletion mutation occurs when
a wrinkle forms on the DNA template strand and subsequently causes a nucleotide to be omitted from the replicated strand
(Figure 3). Figure 3: In a deletion mutation, a wrinkle forms on the DNA template strand, which causes a nucleotide to be omitted from the replicated strand.
What is the life expectancy of someone with hemophilia?
Hemophilia can result in: Bleeding within joints that can lead to
chronic joint disease
and pain. Bleeding in the head and sometimes in the brain which can cause long term problems, such as seizures and paralysis. Death can occur if the bleeding cannot be stopped or if it occurs in a vital organ such as the brain.
Which type of hemophilia is more severe?
Hemophilia A
affects 1 in 5,000 to 10,000 males. Hemophilia B
What genotypes would the parents have to be to have a child with hemophilia?
The father only passes half of his sex chromosomes to the baby, either the X or the Y. If the baby gets the Y chromosome from the father it will be a boy. The son can get from the mother either her
X chromosome
with the hemophilia gene or her X chromosome with the normal blood clotting gene.
How do you identify DNA mutations?
Single base pair mutations can be identified by any of the following methods:
Direct sequencing
, which involves identifying each individual base pair, in sequence, and comparing the sequence to that of the normal gene.
What happens if mutations are not corrected?
Most mistakes are corrected, but if they are not, they
may result in a mutation defined as a permanent change in the DNA sequence
. Mutations can be of many types, such as substitution, deletion, insertion, and translocation. Mutations in repair genes may lead to serious consequences such as cancer.
What is the difference between a silent mutation and a neutral mutation?
silent or synonymous mutation – does not change the amino acid sequence encoded by a particular gene. A
neutral mutation is neither adaptive nor deleterious
.
How do you detect deletion mutation?
Amplification refractory mutation system (ARMS) PCR
: Allele-specific amplification (AS-PCR) or ARMS-PCR is a general technique for the detection of any point mutation or small deletion.
What causes transversion mutation?
Transversion, in molecular biology, refers to a point mutation in DNA in which a single (two ring) purine (A or G) is changed for a (one ring) pyrimidine (T or C), or vice versa. A transversion can be spontaneous, or it can be caused by
ionizing radiation or alkylating agents
.
How do mutations occur?
A mutation is a change in a DNA sequence. Mutations can result from
DNA copying mistakes made during cell division
, exposure to ionizing radiation, exposure to chemicals called mutagens, or infection by viruses.
Does hemophilia shorten life expectancy?
Many patients still die before adulthood due to inadequate treatment. With proper treatment, life expectancy is only about
10 years less than healthy men
. Overall, the death rate for people with hemophilia is about twice that of the rate for healthy men. For severe hemophilia, the rate is four to six times higher.
