1. Inheritance…1
Albinism and Sickle Cell Anaemia

2. Recap…Single factor inheritance with respect to
Homozygous dominant/recessive
Heterozygous genotype
Classifying genetic disorders
Autosomal – Chromosome
Sex-linked – Chromosome 23 (X, Y)

3. Autosomal recessive disorders
An affected person usually has unaffected parents, each carrying a single copy of the mutated gene i.e. carriers (heterozygotes)
Two mutated copies of the gene are present in each cell when a person has an autosomal recessive disorder
A mutation is a change to the structure of a gene
It occurs when a gene is damaged or changed, altering the genetic information carried by that gene
Autosomal récessive disorders are typically not seen in every generation of an affected family
Example: Albinism, Sickle-cell Anaemia, Cystic Fibrosis

5. Albinism Albinos; homozygous recessive (aa) individuals
Recognized by partial or complete lack of pigment
Heterozygotes have normal pigmentation (Aa)
Gametes produced: A or a
Offspring: 1/4 would be albinos
Carriers of the gene for albinism have a 25% chance that one of their offspring will be born with albinism
Two albinos will not automatically produce an albino child
Though the risks are several times higher compared to normal individuals
Albinism is a recessive genetic disorder, which means both parents must have the defective chromosome in order for their child's genes to be affected

7. Types of Albinism
The National Organization for Albinism and Hypo-pigmentation (NOAH) of the USA classifies albinism into two
1. Oculocutaneous albinism types 1 – 4 (OCA):
affects the eyes, hair and skin, producing the pale skin and eyes typically affiliated with albinism
the four types have varying levels of genetic defects of the enzyme tyrosinase
2. Ocular albinism (OA):
affects the eyes only and does not generally cause the lack of pigment associated with OCA
individuals with OA appear more pale compared to other members of their family
Alternative classification: Amelanosis (amelanism) and hypomelanosis 9hypomelanism)
OA is less common than OCA
Albinism is associated with vision defects such as
photophobia (unusual sensitivity to light),
nystagmus (involuntary eye movement and/or reduced or limited vision) and astigmatism (aberrations of focussing)
Further classifications of albinism depend on the extent to which the individual lacks melanin. Complete lack of melanin is called amelanosis (or amelanism), while partial lack of pigment is called hypomelanosis (or hypomelanism).

8. Occurrence of Albinism Genes
OCA appears on both X and Y chromosomes
OCA autosomal as well
The gene won't allow the information to be created correctly
The X chromosome only carries the OA defect
Almost all people with OA are male because of its location on the X chromosome
OA appears on the GPR143 gene, which controls the pigments of the eye only

9. Causes of Albinism Several mutations may cause albinism:
1. lack of one or another enzyme along the melanin-producing pathway, or
2. inability of the enzyme tyrosinase to enter the melanocytes and convert tyrosine into melanin
Tyrosinase assists in the conversion of tyrosine, an amino acid, into pigment in melanocytes

10. Sickle-cell Anaemia
Sickle cell disease is a group of disorders that affects haemoglogin
Haemoglogin (in RBCs) delivers oxygen to cells throughout the body
People with this disorder have abnormal haemoglogin called haemoglogin S
HbS distorts red blood cells into a sickle, or crescent shape
Features of the disorder include
low number of red blood cells (anaemia)
repeated infections and
periodic episodes of pain
Symptoms vary from individual to individual
Others have mild symptoms, while some are frequently hospitalized for more serious complications
Abnormal versions of beta-globin can distort red blood cells into a sickle shape. The sickle-shaped red blood cells die prematurely, which can lead to anemia. Sometimes the inflexible, sickle-shaped cells get stuck in small blood vessels and can cause serious medical complications.

12. Causes of Sickle-cell Anaemia
Mutations in the HBB gene (haemoglogin, beta; located on chromosome 11 ) cause sickle cell disease
The HBB gene provides instructions for making beta-globin
Haemoglogin consists of four protein subunits:
two subunits called alpha-globin, and
two subunits called beta-globin
Various versions of beta-globin result from different mutations in the HBB gene, causing different types of sickle cell disease
One HBB gene mutation produces an abnormal version of beta-globin known as haemoglogin S (HbS)
Other mutations in the HBB gene lead to additional abnormal versions of beta-globin such as haemoglogin C (HbC) and haemoglogin E (HbE)
Sickle-cell anaemia is the commonest form of sickle-cell disease. This is because the mutation to the HBB gene which produces haemoglogin S (HbS) is the commonest.

13. Expression of Sickle-cell Disease
In sickle cell disease, at least one of the beta-globin subunits in haemoglogin is replaced with haemoglogin S
In sickle cell anaemia, the commonest form of sickle cell disease, hemoglobin S replaces both beta-globin subunits in haemoglogin
In other types of sickle cell disease, just one beta-globin subunit in haemoglogin is replaced with haemoglogin S
The other beta-globin subunit is replaced with a different abnormal variant, such as hemoglobin C
For example, individuals with sickle-haemoglobin C (HbSC) disease have haemoglogin molecules with haemoglogin S and haemoglogin C instead of beta-globin

14. Inheritance 2
ABO Blood Group; Rhesus Factor (Rh)/ Incompatibility

15. Multiple alleles…1
Multiple allelism is the phenomenon in which a gene has three or more alternative forms
multiple allelic series
Characteristics
Multiple alleles of a series always occupy the same locus on a chromosome
No crossing over occurs with multiple alleles of the same series
they occupy the same locus
Multiple alleles always influence the same trait e.g. ABO blood group

16. Multiple alleles…2
The normal (wild type) allele is almost always dominant
The other alleles in the series (mutant types) may show dominance or there may have intermediate phenotypic effect
When any two mutant multiple alleles are crossed, the phenotype is always mutant type, not the wild type
Remember
Multiple allelism is the phenomenon in which the same gene has more than two alternative forms
In normal Mendelian inheritance, a gene has only two alleles
These alleles combine in pairs to form the genotypes

17. The ABO blood group
Erythrocytes have surface markers (antigens) which come in three or more varieties
Three alleles: A, B and O
Six possible genotypes: AA, AB, AO, BB, BO, and OO
The ABO blood group exhibits the following phenomena:
recessive alleles (IO)
dominant alleles (IA and IB)
co-dominance (IA and IB)
multiple alleles (A, B and O)