Classification of Genetic Disorders
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teaching of genetics concepts.
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educational purposes.
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Etiology of diseases.
For any condition the overall balance of genetic and environmental determinants can be represented by a point
somewhere within the triangle.
Fig. 13.3 ©Scion Publishing Ltd
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Classification of genetic disorders
• Multifactorial
+ environment
• Single gene
Male
• Chromosomal
• Mitochondrial
• Somatic mutations (cancer)
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Continuum of penetrance.
There is a continuum of penetrance from fully penetrant conditions, where other genes and environmental
factors have no effect, through to low-penetrance genes that simply play a small part, along with other genetic
and environmental factors, in determining a person’s susceptibility to a disease.
Multiple sclerosis is used as an example of a multifactorial condition where genetic factors play a major part in
determining susceptibility, but current research suggests that each individual factor has a very low penetrance.
Fig. 1.15 ©Scion Publishing Ltd
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Genetic factors
Mutations in single
genes (often causing loss
of function)
Male
Variants in genes causing
alteration of function
Chromosomal imbalance
causes alteration in gene
dosage
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Classification of genetic disorders
Single Gene Disorders
Mutations in single genes
Male
Multifactorial diseases
Variants in genes
+ environment
Chromosome disorders
Chromosomal imbalance
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcare
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Dominant
Heterozygotes with one copy of the altered gene
are affected
Recessive
Homozygotes with two copies of the altered gene are
affected
X-linked recessive
Males with one copy of the altered gene on the
X-chromosome are affected
Male
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Genetic disorders
• Multifactorial (common)
- “Environmental” influences act on a genetic predisposition to produce a liability to
a disease.
- One organ system affected.
- Person affected if liability above a threshold.
• Single gene (1% liveborn)
- Dominant/recessive pedigree patterns (Mendelian inheritance).
- Can affect structural proteins, enzymes, receptors, transcription factors.
• Chromosomal (0.6% liveborn)
- Thousands of genes may be involved.
- Multiple organ systems affected at multiple stages in gestation.
- Usually de novo (trisomies, deletions, duplications) but can be inherited
(translocations).
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
The contributions of genetic and environmental
factors to human diseases
Haemophilia
Osteogenesis imperfecta
Club foot
Pyloric stenosis
Dislocation of hip
Duchenne
muscular dystrophy
GENETIC
Phenylketonuria
Galactosaemia
Rare
Genetics simple
Unifactorial
High recurrence rate
© 2009 NHS National Genetics Education and Development Centre
Peptic ulcer
Diabetes
Tuberculosis
ENVIRONMENTAL
Scurvy
Spina bifida
Ischaemic heart disease
Ankylosing spondylitis
Common
Genetics complex
Multifactorial
Low recurrence rate
Genetics and Genomics for Healthcare
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• Multifactorial
“Environmental” influences act on a genetic predisposition
One organ system affected
• Single gene
Dominant/recessive pedigree patterns
Structural proteins, enzymes, receptors, transcription factors
• Chromosomal
Multiple organ systems affected
Inherited or de novo
• Environmental
Drugs, infections
© 2009 NHS National Genetics Education and Development Centre
Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Single gene disorders
I:1
AA
High risks to relatives
Dominant/recessive pedigree patterns
Some isolated cases due to new dominant mutations
Structural proteins, enzymes, receptors, transcription factors
I:2
AB
I:1
II:1
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AA
II:2
AB
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BB
III:1
?
I:1
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BB
Tom
I:2
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IV:1
II:1
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II:2
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© 2009 NHS National Genetics Education and Development Centre
II:7
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III:6
IV:7
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III:9
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IV:11
II:14
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III:14 III:15
III:16 III:17
IV:13
Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk