Download Inheritance - West East University

INHERITANCE…1
Albinism and Sickle Cell Anaemia
• Recap…Single factor inheritance with
respect to
– Homozygous dominant/recessive
– Heterozygous genotype
• Classifying genetic disorders
– Autosomal – Chromosome 1 - 22
– Sex-linked – Chromosome 23 (X, Y)
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
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
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)
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
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
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
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 betaglobin
• 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)
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
INHERITANCE 2
ABO Blood Group; Rhesus Factor (Rh)/
Incompatibility
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
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
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)