Analysis of functional aberration of some important beta hemoglobinopathies (hemoglobin C, D, E, and S) from

Viroj Wiwanitkit1

  • 1Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. wviroj@pioneer.netserv.chula.ac.th <wviroj@pioneer.netserv.chula.ac.th>

Hemoglobinopathy comprises a group of inherited hemoglobin disorders in which hemoglobin (Hb) was improperly formed, but the cause is not depletion of the globin gene. Typically, when the basic pathogenesis is a single substitution disorder, only one aberration presents in the secondary structure. However, the manifested or functional aberration resulting from the structural aberration usually varies. It is sometimes difficult to compare the degree of functional aberration among such hemoglobin disorders. A functional analysis was performed on 4 important beta hemoglobinopathies (hemoglobin C, D, E, and S) using PolyPhen, a novel bioinformatic tool. The mutations Hb C (beta 6, Glu --> Lys), Hb D (beta 121, Glu --> Gln), Hb E (beta 26, Glu --> Lys), and Hb S (beta 6, Glu --> Val) were selected for further study. According to the in silico mutation study, the functional change in the studied hemoglobinopathies was variable. The position-specific independent counts (PSIC) difference score ranged from 1.362 (Hb D) to 2.986 (Hb S). Regarding the degree of damage, all had probable damage. This analysis demonstrated that the functional aberration in the hemoglobinopathy was based on complex pathogenesis. Identifying only the structural aberration in a hemoglobinopathy is not sufficient; additional functional analysis is recommended. The functional analysis presented here may be a good model for further research.

Related Concept Videos

Globular and Fibrous Proteins02:21

Globular and Fibrous Proteins

Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Gene Families01:57

Gene Families

Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Hemoglobin01:24

Hemoglobin

Hemoglobin is a globular protein made up of four subunits. Two of these subunits are alpha chains, and the other two are beta chains. Each subunit contains a molecule of heme, which has an iron atom and can bind to oxygen. When an oxygen molecule binds to one heme group, it changes the shape of hemoglobin, making it easier for the other heme groups to bind oxygen as well.
When all four heme groups are bound to oxygen, the resulting molecule is called oxyhemoglobin. As a result, arterial blood...
Protein and Protein Structure02:15

Protein and Protein Structure

Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
Multiple Allele Traits01:49

Multiple Allele Traits

The Concept of Multiple Allelism
Structure and Function of Erythrocytes01:29

Structure and Function of Erythrocytes

There are between 4.2 and 6 million erythrocytes, also known as red blood cells, in every microliter of blood. These cells are small, flattened biconcave discs with centers that are depressed.
The erythrocyte plasma membrane is associated with proteins such as spectrin, which forms a flexible cytoplasmic meshwork. This meshwork allows erythrocytes to twist, turn, become cup-shaped, and regain their biconcave shape as they pass through narrow capillaries. Additionally, erythrocytes can form...