Lec 3 - SAQ Genetics Quiz

Homozygous AA - Group A BB - Group B OO - Group O Heterozygous AO - Group A BO - Group B AB - Group AB (co-dominant expression)

Carry O2

23

Both paternal and maternal alleles are expressed (αβ)2 (Haemoglobin A)

Hb F (α2γ2) - Foetal Haemoglobin (HbFF)

320-350g/L of cytoplasm

Haemoglobinopathies and Thalassaemias

Mutation in β globin gene sequence

Codominance is when two alleles of the same gene which code for proteins with different specific functions are co-expressed in heterozygote individuals.

The H antigen is responsible for the synthesis of a sequence of monomers on the surface of red blood cells.

The H locus is located on chromosome 19.

The ABO locus on chromosome 9 determines the ABO blood group.

Codominance is when both alleles are expressed completely, while incomplete dominance is a blending of traits.

The AB blood group is an example of codominance.

Hemoglobin biosynthesis is the process of producing hemoglobin and it changes during development and is regulated.

Mutations that disrupt the balanced biosynthesis of globin production lead to thalassemias.

HBB

2

Chromosome 11

Minor and Major

Minor: heterozygous mutation, one defective gene copy. Major: homozygous/compound heterozygous mutations, both gene copies defective

Transcription (promoter), Processing of mRNA, Translation of mature mRNA, Post translation integrity of β globin

β/β0 or β/β+

β0/β0, β+/β+, or β0/β+

Clinically asymptomatic or mild symptoms (mild microcytic anaemia)

Antimorph (dominant negative)

Neomorph

Chorionic Villous Sampling (9-10 weeks) PCR Amplify Fragment of β-globin Gene Oligonucleotide Probe Hybridization/Sequencing

Not specified in the text

16%

4%

Not specified in the text

Deletions, Insertions, Substitutions, Frameshifts, Dynamic mutation (tandem repeats e.g. HD)

Loss of function (inactivating) and Gain-of-function (activating)

It refers to the coexistence of two or more alleles in a population, maintained at a relatively stable frequency due to selective advantage

Sickle cell trait refers to individuals who inherit one copy of the sickle cell gene and do not usually experience symptoms, while sickle cell anaemia occurs in individuals who inherit two copies of the sickle cell gene and experience severe symptoms

Mutations distant from structural genes can affect gene regulation and disrupt normal protein production, leading to disease. An example is thalassaemia

DNA Transcription Pre mRNA Splicing mRNA Translation peptide Post –Translation Folding Protein Then multimer assembly

A permanent heritable change in the nucleotide sequence of a gene or chromosome

Guanine is replaced by Adenine

Balanced polymorphism refers to the persistence of multiple alleles in a stable equilibrium in a population, with one allele being disadvantageous in the homozygous state.

The sickle cell allele is particularly associated with populations that originated from areas with a high incidence of malaria. Natural selection favors the HbAS sickle cell trait as it provides protection against malaria.

Sickle cell anaemia (HbSS) is a recessive inherited disorder characterized by a clinically manifest phenotype, while sickle cell trait (HbAS) is a dominant inherited trait with a cryptic phenotype.

Sickle cell anaemia (HbSS) follows an autosomal recessive pattern of inheritance.

Thalassaemias are inherited disorders of balanced haemoglobin biosynthesis, characterized by an imbalance in the production of structurally normal globin chains.

In β-thalassaemias, the regulation of gene expression is critical to function. Mutations in the β-globin gene promoter, such as the A to G mutation at position -34, can disrupt binding of the transcription machinery and result in reduced or no transcription of the gene.

First, the blood of both parents should be checked by Hb electrophoresis. If both parents have the β-thalassaemia trait, more invasive tests such as chorionic villus sampling (CVS) or amniocentesis can be performed to obtain fetal DNA for PCR/sequencing analysis.

The abnormal shape of the face in β-thalassaemia is related to the physiological response to compensate for the physiological deficit associated with the inherited mutation. Hypoxia leads to increased production of erythropoietin (EPO), which causes bone marrow hyperplasia and distorts the bones.

Sickle cell anaemia is mainly seen in people of African descent and is characterized by an autosomal recessive pattern of disease. It is caused by the presence of abnormal haemoglobin (HbS) that distorts red blood cells into a sickle shape, leading to various complications such as pain crises, organ damage, and increased susceptibility to infections.