Understanding patterns of
inheritance
This presentation builds on session 1
exploring patterns of inheritance
Patterns of inheritance
The objectives of this presentation are to:
• Understand how genes are inherited
• Understand the differences between the inheritance patterns
associated with Autosomal dominant, Autosomal recessive, Xlinked recessive and chromosomal abnormalities
• Understand that the environment can impact on some
common complex conditions
So how are genes passed on from parent to
child?
Gene
• Genes in the cell nucleus are
physically located on 23 pairs
of chromosomes
• One set of 23 chromosomes is
inherited from each parent
• Therefore, of each pair of
genes, one is inherited from a
person’s mother, and one
from their father
Chromosome
Diagram showing just one pair
of the 23 pairs of
chromosomes in the cell
nucleus. The location of one
of the genes on this
chromosome is shown.
Classification of genetic disorders
Single Gene Disorders
Alterations in single genes
Male
Multifactorial diseases
Variants in genes
+ environment
Chromosome disorders
Chromosomal imbalance
Single gene disorders
Some medical conditions are caused by a change
in just one or both copies of a particular pair of
genes. These are called “single gene disorders”.
The three common types of single gene disorders are called:
•Autosomal dominant
•Autosomal recessive
•X-linked
Dominant
These individuals are called Heterozygotes with one
copy of the altered gene they are affected
Recessive
Homozygotes must have two copies of the altered gene to
be affected
X-linked recessive
Males with an altered gene on the Xchromosome are always affected
Male
Autosomal dominant inheritance
Examples of Autosomal Dominant Conditions
•
•
•
•
•
•
Huntington disease
Neurofibromatosis type 1
Marfan syndrome
Familial hypercholesterolemia
Familial Adenomatous Polyposis (FAP)
Prader-willi
Autosomal dominant inheritance
Marfan syndrome
(a) Arachnodactyly (long fingers). (b ) Dislocated lens.
Fig. 3.2 ©Scion Publishing Ltd
Autosomal dominant inheritance
Parents
Gametes
Autosomal dominant inheritance
Parents
Gametes
At
conception
Affected
Affected
Unaffected
Autosomal recessive inheritance
Examples of Autosomal recessive conditions
• Sickle Cell disease
• Cystic fibrosis
• Batten Disease
• Congenital deafness
• Phenylketonuria (PKU)
• Spinal muscular atrophy
• Recessive blindness
• Maple syrup urine disease
Cystic fibrosis
(a) The outlook for cystic fibrosis patients has improved over the years but they still need
frequent hospital admissions, physiotherapy and constant medications. (b) Chest X-ray of
lungs of cystic fibrosis patient. © Erect abdominal film of newborn with meconium ileus
showing multiple fluid levels. Photos (a) and (b) courtesy of Dr Tim David, Royal Manchester
Children’s Hospital.
Fig. 1.2 ©Scion Publishing Ltd
Photos (a) and (b) courtesy of Dr Tim David
Sickle cell disease.
(a) Blood film showing a sickled cell, marked poikilocytosis (abnormally shaped red cells)
and a nucleated red cell. (b and c) Bony infarcations in the phalanges and metacarpals can
result in unequal finger length.
Fig. 4.1 ©Scion Publishing Ltd
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Parent who are carriers for the same
autosomal recessive condition have one
copy of the usual form of the gene and
one copy of an altered gene of the
particular pair
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Sperm/Eggs
A parent who is
a carrier passes
on either the
usual gene
The other parent who is also a
or the altered
gene into the eggs carrier for the same condition
passes on either the usual
or sperm
gene or the altered gene into
his/her eggs or sperm
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Sperm/Eggs
Unaffected
Unaffected
(carrier)
Unaffected
(carrier)
Affected
X-Linked recessive inheritance
Examples of X-Linked Recessive Conditions
•
•
•
•
•
•
•
•
•
Fragile X syndrome
Haemophilia
Duchenne muscular dystrophy (DMD) (Becker BMD)
Fabry disease
Retinitis pigmentosa
Alport syndrome
Hunter syndrome
Ocular albinism
Adrenoleucodystrophy.
Effects of haemophilia
(a) Bleeding around elbow. (b) A retinal bleed. (c) Repeated bleeds into joints produce severe
arthritis.
Fig. 4.2 ©Scion Publishing Ltd
Photos courtesy of Medical Illustration, Manchester Royal Infirmary (a and c), and Andrew Will (b)
X-linked recessive inheritance
Male
X
Female
Y
One copy of an altered gene on
the X chromosome causes the
disease in a male.
X
X
An altered copy on one of the X
chromosome pair causes
carrier status in a female.
X-linked inheritance where the mother is a carrier
Father
Parents
Gametes
Mother
(Unaffected)
X
Y
(Carrier)
X
X
At
conception
Daughter
Daughter (Carrier)
Son
Son (Affected)
Polygeneic Inheritance
• Single gene disorders are quite rare
• Single gene disorders either give risk to a
condition or they don’t
• Most traits are Polygenic’ i.e. 1 trait coded by
a number of altered and unaltered genes
working together
Common Polygenic Disorders
•
•
•
•
Alzheimer's
Diabetes
Cancer
Eczema
Multifactorial inheritance
• Inheritance controlled by many genes plus the
effects of the environment
• Congenital
malformations
Cleft lip/palate
Congenital hip dislocation
Congenital heart defects
Neural tube defects
Pyloric stenosis
Talipes
• Adult onset disorders
Diabetes mellitus
Epilepsy
Glaucoma
Hypertension
Ischaemic heart disease
Manic depression
Schizophrenia
The contributions of genetic and environmental factors to human
diseases
Haemophilia
Osteogenesis imperfecta
Duchenne
muscular dystrophy
100% genetic
Peptic ulcer
Diabetes
Club foot
Pyloric stenosis
Dislocation of hip
GENETIC
Phenylketonuria
Galactosaemia
Rare
Genetics simple
Unifactorial
High recurrence rate
Tuberculosis
100%
Environmental
ENVIRONMENTAL
Spina bifida
Ischaemic heart disease
Ankylosing spondylitis
Common
Genetics complex
Multifactorial
Low recurrence rate
Scurvy
Multifactorial
• Examples include some cases of cleft lip
and palate; neural tube defects; diabetes
and hypertension
• Caused by a combination of genetic
predisposition and environmental
influences
• Pattern – more affected people in family
than expected from incidence in
population but doesn’t fit dominant,
recessive or X-linked inheritance patterns
Chromosomal abnormalities
Some medical conditions are caused abnormalities
in chromosome number or structure.
Chromosome anomalies
• Cause their effects by altering the amounts of products of the
genes involved.
– Three copies of genes (trisomies)
= 1.5 times normal amount.
– One copy of genes (deletions)
= 0.5 times normal amount.
– Altered amounts may cause anomalies directly or may alter the balance of
genes acting in a pathway.
Most frequent numerical anomalies
in liveborn
Autosomes
Down syndrome (trisomy 21: 47,XX,+21)
Edwards syndrome (trisomy 18: 47,XX,+18)
Patau syndrome (trisomy 13: 47,XX+13)
Sex chromosomes
Turner syndrome 45,X
Klinefelter syndrome 47,XXY
All chromosomes
Triploidy (69 chromosomes)