2009 NHS National Genetics Education and Development Centre Genetics and Genomics for Healthcare

www.geneticseducation.nhs.uk
Classification of Genetic Disorders
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2009 NHS National Genetics Education and Development Centre Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Fig. 13.3 Scion Publishing Ltd
Etiology of diseases.
For any condition the overall balance of genetic and environmental determinants can be represented by a point
somewhere within the triangle.
2009 NHS National Genetics Education and Development Centre Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Classification of genetic disorders
Multifactorial

Single gene

Chromosomal

Mitochondrial

Somatic mutations (cancer)

Male
+ environment
2009 NHS National Genetics Education and Development Centre Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Fig. 1.15 Scion Publishing Ltd
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 persons 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.
2009 NHS National Genetics Education and Development Centre Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Genetic factors

Male
Mutations in single
genes (often causing loss
of function)
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

Male
Mutations in single genes
Variants in genes
Chromosomal imbalance
Single Gene Disorders
Multifactorial diseases
Chromosome disorders
+ environment
2009 NHS National Genetics Education and Development Centre Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Recessive
Homozygotes with two copies of the altered gene are
affected
Dominant
Heterozygotes with one copy 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
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
The contributions of genetic and environmental
factors to human diseases
Rare
Genetics simple
Unifactorial
High recurrence rate
Common
Genetics complex
Multifactorial
Low recurrence rate
2009 NHS National Genetics Education and Development Centre Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
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
- High risks to relatives
- Dominant/recessive pedigree patterns
- Some isolated cases due to new dominant mutations
- Structural proteins, enzymes, receptors, transcription factors
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III:1 III:2 III:3
IV:1 IV:2 IV:3 IV:4
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