Case 1 – Sickle Cell Disease
Genetics
Learning Goals
1. Know the general features of Sickle Cell Disease (SCD) and make distinctions with other,
related haemoglobin diseases
Sickle Cell disease is a disease which is caused by a mutation in the β-subunit of haemoglobin.
The mutation can be caused by many mutations in the HBB gene which lies on the top of
chromosome 11. It is a monogenetic trait. Although all the mutations are autosomal recessive,
SCD can be a compound disease (caused by combinatorial effect of multiple mutant alleles
two alleles with different mutation)
Due to the mutation, an amino acid is replaced by another amino acid, which causes the
haemoglobin to form long strands. Sickle cell disease is thus a qualitative problem.
Another disease which is linked to haemoglobin, is thalassemia. Thalassemia is a qualitative
problem, in which the body destroys the red blood cells due to a different structure of the
haemoglobin. Both the α and the β subunit can be affected.
2. Be able to distinguish the different processes controlling a phenotype (genetics, epigenetics,
developmental noise and environment)
The phenotype is controlled by:
- Genetics
- Epigenetics changes are not caused by changes in DNA sequence. Alterations are made in
the transcription of the DNA; this may be heritable.
- Developmental noise incidental changes during development. Contains all differences
between individuals with same genotype in same environment. Example: fingerprint.
- Environment
3. Know the basic terminology for Mendelian genetics (dominant / recessive, homozygous /
heterozygous, sex linked, incomplete penetrance, incomplete expressivity, proband and
carrier.
- Dominant one allele is expresse over second allele at same locus
- Recessive opposite of dominant
- Co-dominant both alleles are visible in phenotype
- Homozygous individual has same allele on both chromosomes
- Heterozygous individual has two different alleles on chromosomes
- Sex linked the allele is on the X/Y chromosome
- Autosomal not sex-linked allele on one of the other chromosomes
- Incomplete penetrance other genes in the shadow that interact with the gene. Although
the individual has a certain genotype, the phenotype is not expressed. might be explained
by variable expression of one gene in addition to lack of expression to the other
- Incomplete expressivity although the phenotype is expressed, it is milder than expected.
Expressivity quantifies variation in non-binary phenotypes across individuals with same
genotype.
- Proband first “line” in pedigree. Often first family member that searches medical help
with symptoms.
Genetics
Learning Goals
1. Know the general features of Sickle Cell Disease (SCD) and make distinctions with other,
related haemoglobin diseases
Sickle Cell disease is a disease which is caused by a mutation in the β-subunit of haemoglobin.
The mutation can be caused by many mutations in the HBB gene which lies on the top of
chromosome 11. It is a monogenetic trait. Although all the mutations are autosomal recessive,
SCD can be a compound disease (caused by combinatorial effect of multiple mutant alleles
two alleles with different mutation)
Due to the mutation, an amino acid is replaced by another amino acid, which causes the
haemoglobin to form long strands. Sickle cell disease is thus a qualitative problem.
Another disease which is linked to haemoglobin, is thalassemia. Thalassemia is a qualitative
problem, in which the body destroys the red blood cells due to a different structure of the
haemoglobin. Both the α and the β subunit can be affected.
2. Be able to distinguish the different processes controlling a phenotype (genetics, epigenetics,
developmental noise and environment)
The phenotype is controlled by:
- Genetics
- Epigenetics changes are not caused by changes in DNA sequence. Alterations are made in
the transcription of the DNA; this may be heritable.
- Developmental noise incidental changes during development. Contains all differences
between individuals with same genotype in same environment. Example: fingerprint.
- Environment
3. Know the basic terminology for Mendelian genetics (dominant / recessive, homozygous /
heterozygous, sex linked, incomplete penetrance, incomplete expressivity, proband and
carrier.
- Dominant one allele is expresse over second allele at same locus
- Recessive opposite of dominant
- Co-dominant both alleles are visible in phenotype
- Homozygous individual has same allele on both chromosomes
- Heterozygous individual has two different alleles on chromosomes
- Sex linked the allele is on the X/Y chromosome
- Autosomal not sex-linked allele on one of the other chromosomes
- Incomplete penetrance other genes in the shadow that interact with the gene. Although
the individual has a certain genotype, the phenotype is not expressed. might be explained
by variable expression of one gene in addition to lack of expression to the other
- Incomplete expressivity although the phenotype is expressed, it is milder than expected.
Expressivity quantifies variation in non-binary phenotypes across individuals with same
genotype.
- Proband first “line” in pedigree. Often first family member that searches medical help
with symptoms.
