0130 explanation slides classification of genetic disorders (1)

8/12/2019 0130 Explanation Slides Classification of Genetic Disorders (1)

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2009 NHS National Genetics Education and Development Centre Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk

Classification of Genetic Disorders

This PowerPoint file contains a number of slides that may be useful forteaching of genetics concepts.

You may use these slides and their contents for non-commercial

educational purposes.


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Fig. 13.3Scion Publishing Ltd

Etiology of diseases.For any condition the overall balance of genetic and environmental determinants can be represented by a pointsomewhere within the triangle.


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Classification of genetic disorders

Multifactorial

Single gene

Chromosomal

Mitochondrial

Somatic mutations (cancer)

Male

+ environment


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Fig. 1.15Scion Publishing Ltd

Continuum of penetrance.

There is a continuum of penetrance from fully penetrant conditions, where other genes and environmentalfactors have no effect, through to low-penetrance genes that simply play a small part, along with other geneticand 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 indetermining susceptibility, but current research suggests that each individual factor has a very low penetrance.


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Genetic factors

Male

Mutations in singlegenes (often causing loss

of function)

Variants in genes causingalterationof function

Chromosomal imbalancecauses alteration ingene

dosage


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Classification of genetic disorders

Male

Mutations in single genes

Variants in genes

Chromosomal imbalance

Single Gene Disorders

Multifactorial diseases

Chromosome disorders

+ environment


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Recessive

Homozygotes with two copiesof the altered gene areaffected

Dominant

Heterozygotes with one copyof the altered geneare affected

X-linked recessive

Males with one copyof the altered gene on theX-chromosome are affected

Male


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Genetic disorders Multifactorial (common)

- Environmental influences act on a genetic predisposition to produce a liability toa 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).


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GENETIC ENVIRONMENTAL

Duchennemuscular dystrophy

HaemophiliaOsteogenesis imperfecta

Club footPyloric stenosisDislocation of hip

Peptic ulcerDiabetes

Tuberculosis

Phenylketonuria

Galactosaemia

Spina bifidaIschaemic heart disease

Ankylosing spondylitis

Scurvy

The contributions of genetic and environmentalfactors to human diseases

RareGenetics simple

UnifactorialHigh recurrence rate

CommonGenetics complexMultifactorialLow recurrence rate


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Multifactorial

Environmental influences act on a genetic predispositionOne organ system affected

Single geneDominant/recessive pedigree patternsStructural proteins, enzymes, receptors, transcription factors

ChromosomalMultiple organ systems affectedInherited or de novo

EnvironmentalDrugs, infections


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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

I:1AA

I:2AB

II:1AA

II:2AB

II:3BB

?

III:1BB

Tom

I:2I:1 I:3

II:1 II:2 II:3 II:4 II:5 II:6 II:7 II:8 II:9 II:10 II:11 II:12 II:13 II:14 II:15

III:1 III:2 III:3

IV:1 IV:2 IV:3 IV:4

III:4 III:5

IV:5 IV:6 IV:7

III:6 III:7

IV:8 IV:9 IV:10

III:8 III:9 III:10 III:11 III:12 III:14III:13 III:15 III:16 III:17

IV:11 IV:12 IV:13

I:1 I:2

II:1 II:2 II:3 II:5 II:6 II:8

III:1 III:2

IV:1

0130 explanation slides classification of genetic disorders (1)

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