1. Understanding patterns of inheritance
This presentation builds on session 1 exploring patterns of inheritance

2. 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, X-linked recessive and chromosomal abnormalities
Understand that the environment can impact on some common complex conditions

3. So how are genes passed on from parent to child?
Chromosome
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
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.

4. Classification of genetic disorders
Single Gene Disorders
Male
Mutations in single genes
Multifactorial diseases
+ environment
Variants in genes
Chromosome disorders
Chromosomal imbalance

5. 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

6. Heterozygotes with one copy of the altered gene are affected
Dominant
Heterozygotes with one copy of the altered gene are affected
Recessive
Homozygotes with two copies of the altered gene are affected
Male
X-linked recessive
Males with one copy of the altered gene on the X-chromosome are affected

7. Examples of Autosomal Dominant Conditions
Autosomal dominant inheritance
Examples of Autosomal Dominant Conditions
Huntington disease
Neurofibromatosis type 1
Marfan syndrome
Familial hypercholesterolemia
Familial Adenomatous Polyposis (FAP)

8. Fig. 3.2 ©Scion Publishing Ltd
Autosomal dominant inheritance
Marfan syndrome
(a) Arachnodactyly (long fingers). (b ) Dislocated lens.
Fig. 3.2 ©Scion Publishing Ltd

9. Autosomal dominant inheritance
Parents
Gametes

10. Autosomal dominant inheritance
Parents
Gametes At
conception
Unaffected
Affected
Affected

11. Examples of Autosomal Recessive Conditions
Autosomal Recessive inheritance
Examples of Autosomal Recessive Conditions
Sickle Cell disease
Cystic fibrosis
Recessive mental retardation
Congenital deafness
Phenylketonuria (PKU)
Spinal muscular atrophy
Recessive blindness

12. 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

13. Fig. 4.1 ©Scion Publishing Ltd
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

14. 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

15. 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 carrier for the same condition passes on either the usual gene or the altered gene into his/her eggs or sperm
or the altered gene into the eggs or sperm

16. AUTOSOMAL RECESSIVE INHERITANCE
Parents
Sperm/Eggs
Unaffected (carrier)
Unaffected (carrier)
Unaffected
Affected

17. Examples of X-Linked Recessive Conditions
X-Linked Recessive inheritance
Examples of X-Linked Recessive Conditions
Fragile X syndrome
Haemophilia
Duchenne muscular dystrophy (DMD)
Becker muscular dystrophy (BMD)
Fabry disease
Retinitis pigmentosa
Alport syndrome
Hunter syndrome
Ocular albinism
Adrenoleucodystrophy.

18. 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)

19. X-linked Recessive Inheritance
Male
Female X Y X X
One copy of an altered gene on the X chromosome causes the disease in a male.
An altered copy on one of the X chromosome pair causes carrier status in a female.

20. Y X Parents Gametes X X (Unaffected) (Carrier) Father Mother
X-linked inheritance where the mother is a carrier
Father
Mother Y X
Parents
(Unaffected)
(Carrier)
Gametes X X At
conception
Daughter
Daughter (Carrier)
Son (Affected)
Son

21. Multifactorial inheritance
Inheritance controlled by many genes plus the effects of the environment
Clinical clue: One organ system affected
Adult onset disorders Diabetes mellitus Epilepsy Glaucoma Hypertension Ischaemic heart disease Manic depression Schizophrenia
Congenital malformations Cleft lip/palate Congenital hip dislocation Congenital heart defects Neural tube defects Pyloric stenosis Talipes

22. Rare Genetics simple Unifactorial High recurrence rate
The contributions of genetic and environmental factors to human diseases
GENETIC ENVIRONMENTAL
Duchenne
muscular dystrophy
Haemophilia
Osteogenesis imperfecta
Club foot Pyloric stenosis Dislocation of hip
Peptic ulcer Diabetes
Tuberculosis
Phenylketonuria Galactosaemia
Spina bifida Ischaemic heart disease Ankylosing spondylitis
Scurvy
Rare Genetics simple Unifactorial High recurrence rate
Common Genetics complex Multifactorial Low recurrence rate

23. 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
Other patterns of Inheritance
Cleft lip and palate is an example of a condition which may have a genetic factor but can also have environmental causes. For example, certain drugs used to treat epilepsy are associated with an increased incidence of cleft lip
Genetic factors underlie many common diseases such as cancer, heart disease and diabetes
When there is significant family history, monitoring and preventative regimens can be offered. Genetic testing is currently very limited but much research is underway

24. Chromosomal abnormalities
Some medical conditions are caused abnormalities in chromosome number or structure.
Chromosome abnormalities was covered in “DNA, genes and chromosomes” presentation in lesson 1. This section provides a refresher of the previous lesson.

25. 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.

26. 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)

27. Summary of Chromosome Anomalies
Change in number
e.g. trisomy 21 Down syndrome; Edwards’ syndrome; Turner syndrome.
Usually an isolated occurrence.
Change in structure
e.g. deletions
May be inherited.
Down’s Syndrome
An example of a chromosomal abnormality which causes learning difficulties
The karyotype shows a case of Down’s syndrome (trisomy 21)
For more information about Down’s syndrome, visit:
[NOTES FOR TRAINING FACILITATORS IN CASE OF QUESTIONS ONLY
In total, there are normally 23 pairs of chromosomes, but in a trisomy there is an extra chromosome (tri somy = three bodies)
A normal karyotype is written 46,XY or 46,XX
The karyotype, or complement of chromosomes, seen in a regular trisomy 21 is written as 47,XX +21 if female or 47, XY +21 if male
Note that Down’s syndrome can be inherited, although this is rare. These cases are due to a change in chromosome structure (a translocation)]
Trisomy 21