Types of Mutation-Deletions and Insertions-Structural Effects of Mutations on the Protein-Non-synonymous mutation

Types of Mutation

•Mutations can range from single base substitutions, through insertions and deletions of single or multiple bases to loss or gain of entire chromosomes. Base substitutions are most prevalent.

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•A substitution is the replacement of a single nucleotide by another. These are the most common type of mutation.

•If the substitution involves replacement by the same type of nucleotide—a pyrimidine for a pyrimidine (C for T or vice versa) or a purine for a purine (A for G or vice versa); this is termed a transition.

•Substitution of a pyrimidine by a purine or vice versa is termed a transversion.

•Transitions occur more frequently than transversionsDeletions and Insertions

•A Deletion involves the loss of one or more nucleotides.

•An Insertion involves the addition of one or more nucleotides into a gene.

•Frameshift mutation: If deletion or insertion  occurs in coding sequences and involves one, two, or more nucleotides that are not a multiple of three, the reading frame will be disrupted. 

•Larger deletions or insertions may result in partial or whole gene deletions and may arise through unequal crossover between repeat sequences.

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•Structural Effects of Mutations on the Protein

•Mutations can also be subdivided into two main groups according to the effect on the polypeptide sequence of the encoded protein, being either:

• Synonymous or silent mutation: If a mutation does not alter the polypeptide product of the gene. A single base-pair substitution, particularly if it occurs in the third position of a codon because of the degeneracy of the genetic code, will often result in another triplet that codes for the same amino acid with no alteration in the properties of the resulting protein.

•Non-synonymous mutation: If a mutation leads to an alteration in the encoded polypeptide. The alteration of the amino acid sequence of the protein product of a gene is likely to result in abnormal function, which is usually associated with disease, or lethality, which has an obvious selective disadvantage.

•Non-synonymous mutations can occur in one of three main ways:

–Missense

–None-sense

–Framshift

Chromosomes-Heterozygous -Variation or change in the genetic material-

Chromosomes

•Chromosomes are the means by which the genes are transmitted from generation to generation.

• The exact location of a gene on a chromosome is known as its locus, and the array of loci constitutes the human gene map.  

•Homologous copies of a gene are termed alleles.

•If alleles are truly identical, their coding sequences and the number of copies do not vary, so the individual is homozygous at that specific locus.

•However, if the DNA is analyzed using either restriction enzyme examination or nucleotide sequencing, then, despite having the same functional identity, the alleles would be viewed as different and the individual would be heterozygous for that locus.  (not to differences in the protein products).Heterozygous 

•A heterozygous individual or genotype frequently results when different alleles are inherited from the egg and the sperm, but it may also occur as a consequence of spontaneous alteration in nucleotide sequence that results in a mutationVariation or change in the genetic material 

•The variation or change in the genetic material (Mutation) could occur at the gene level  or at the chromosome level.

•At the gene level it is called mutation or gene mutation

• at the chromosome level it is called chromosomal Aberration (Chromosome mutations) and involving whole chromosomes or parts of chromosomes

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Great Saphenous Vein Cutdown-The Great Saphenous Vein in Coronary Bypass Surgery

Great Saphenous Vein Cutdown

Exposure of the great saphenous vein through a skin incision (a“cutdown”) is usually performed at the ankle. This site has the disadvantage that phlebitis (inflammation of the vein wall) is a potential complication. The great saphenous vein also can be entered at the groin in the femoral triangle, where phlebitis is relatively rare; the larger diameter of the vein at this site permits the use of large-diameter catheters and the rapid infusion of large volumes of fluids

Anatomy of Ankle Vein Cutdown

The procedure is as follows:

1. The sensory nerve supply to the skin immediately in front of the medial malleolus of the tibia is from branches of the saphenous nerve, a branch of the femoral nerve.

The saphenous nerve branches are blocked with local anesthetic.

2. A transverse incision is made through the skin and subcutaneous tissue across the long axis of the vein just anterior and superior to the medial malleolus. Although the vein may not be visible through the skin, it is constantly found at this site.

3. The vein is easily identified, and the saphenous nerve should be recognized; the nerve usually lies just anterior to the vein

Anatomy of Groin Vein Cutdown

1. The area of thigh skin below and lateral to the scrotum or labium majus is supplied by branches of the ilioinguinal nerve and the intermediate cutaneous nerve of the thigh. The branches of these nerves are blocked with local anesthetic.

2. A transverse incision is made through the skin and subcutaneous tissue centered on a point about 1.5 in. (4 cm) below and lateral to the pubic tubercle . If the femoral pulse can be felt (may be absent in patients with severe shock), the incision is carried medially just medial to the pulse.

3. The great saphenous vein lies in the subcutaneous fat and passes posteriorly through the saphenous opening in the deep fascia to join the femoral vein about 1.5 in. (4 cm), or two fingerbreadths below and lateral to the pubic tubercle. It is important to understand that the great saphenous vein passes through the saphenous opening to gain entrance to the femoral vein. However, the size and shape of the opening are subject to variation.

The Great Saphenous Vein in Coronary Bypass Surgery

In patients with occlusive coronary disease caused by atherosclerosis, the diseased arterial segment can be bypassed by inserting a graft consisting of a portion of the great saphenous vein. The venous segment is reversed so that its valves do not obstruct the arterial flow. Following removal of the great saphenous vein at the donor site, the superficial venous blood ascends the lower limb by passing through perforating veins and entering the deep veins.

The great saphenous vein can also be used to bypass obstructions of the brachial or femoral arteries.

Venous Pump of the Lower Limb-Varicose Veins

Venous Pump of the Lower Limb

Within the closed fascial compartments of the lower limb, the thinwalled, valved venae comitantes are subjected to intermittent pressure at rest and during exercise. The pulsations of the adjacent arteries help move the blood up the limb. However, the contractions of the large muscles within the compartments during exercise compress these deeply placed veins and force the blood up the limb.

The superficial saphenous veins, except near their termination, lie within the superficial fascia and are not subject to these compression forces. The valves in the perforating veins prevent the high-pressure venous blood from being forced outward into the low-pressure superficial veins. Moreover, as the muscles within the closed fascial compartments relax, venous blood is sucked from the superficial into the deep veins.

Varicose Veins

A varicosed vein is one that has a larger diameter than normal and is elongated and tortuous. Varicosity of the esophageal and rectal veins is described elsewhere.

This condition commonly occurs in the superficial veins of the lower limb and, although not life threatening, is responsible for considerable discomfort and pain.

Varicosed veins have many causes, including hereditary weakness of the vein walls and incompetent valves; elevated intraabdominal pressure as a result of multiple pregnancies or abdominal tumors; and thrombophlebitis of the deep veins, which results in the superficial veins becoming the main venous pathway for the lower limb. It is easy to understand how this condition can be produced by incompetence of a valve in a perforating vein. Every time the patient exercises, high-pressure venous blood escapes from the deep veins into the superficial veins and produces a varicosity, which might be localized to begin with but becomes more extensive later. The successful operative treatment of varicosed veins depends on the ligation and division of all the main tributaries of the great or small saphenous veins, to prevent a collateral venous circulation from developing, and the ligation and division of all the perforating veins responsible for the leakage of highpressure blood from the deep to the superficial veins. It is now common practice to remove or strip the superficial veins in addition.

Needless to say, it is imperative to ascertain that the deep veins are patent before operative measures are taken.

Arteries of the Gluteal Region-Superior Gluteal Artery-Inferior Gluteal Artery-The- Trochanteric Anastomosis

Arteries of the Gluteal Region

Superior Gluteal Artery

The superior gluteal artery is a branch from the internal iliac artery and enters the gluteal region through the upper part of the greater sciatic foramen above the piriformis. It divides into branches that are distributed throughout the gluteal region.

 

Inferior Gluteal Artery

The inferior gluteal artery is a branch of the internal iliac artery and enters the gluteal region through the lower part of the greater sciatic foramen, below the piriformis. It divides into numerous branches that are distributed throughout the gluteal region.

The Trochanteric Anastomosis

The trochanteric anastomosis provides the main blood supply to the head of the femur. The nutrient arteries pass along the femoral neck beneath the capsule. The following arteries take part in the anastomosis: the superior gluteal artery, the inferior gluteal artery, the medial femoral circumflex artery, and the lateral femoral circumflex artery.

The Cruciate Anastomosis

The cruciate anastomosis is situated at the level of the lesser trochanter of the femur and, together with the trochanteric anastomosis, provides a connection between the internal iliac and the femoral arteries. The following arteries take part in the anastomosis: the inferior gluteal artery, the medial femoral circumflex artery, the lateral femoral circumflex artery, and the first perforating artery, a branch of the profunda artery.

Veins of the Lower Limb

The veins of the lower limb can be divided into three groups: superficial, deep, and perforating. The superficial veins consist of the great and small saphenous veins and their tributaries, which are situated beneath the skin in the superficial fascia.

The constant position of the great saphenous vein in front of the medial malleolus should be remembered for patients requiring emergency blood transfusion. The deep veins are the venae comitantes to the anterior and posterior tibial arteries, the popliteal vein, and the femoral veins and their tributaries. The perforating veins are communicating vessels that run between the superficial and deep veins. Many of these veins are found particularly in the region of the ankle and the medial side of the lower part of the leg. They possess valves that are arranged to prevent the flow of blood from the deep to the superficial veins.