Single Gene Disorders Flashcards

(50 cards)

1
Q

What are the classifications of genetic disorders

A

Single gene disorders
Multi factorial diseases
Chromosome disorders
Mitochondrial disorders
Somatic mutations

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2
Q

What are single gene mutations

A

Mutations in single genes often causing loss in function
Leads directly to disease

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3
Q

Types of single gene disorders

A

Dominant - heterozygotes with one copy of the altered genes

Recessive - homozygotes wit two copies of altered gene

X linked recessive - males with one copy of altered gene on X chromosome

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4
Q

Exceptions to Mendels rules in autosomal dominant inheritance

A

Variance in expression
Penetrance
New mutations
Anticipation

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5
Q

What do majority of mutations in autosomal dominant disorders cause?

A

Loss of function of the allele

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6
Q

Dominant disorders cause cell to cope with half of the amount of gene product. Examples of this:

A

50% Structural protein/ receptor clinical effect
50% enzyme - body can cope so no clinical effect

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7
Q

What is Marfans syndrome?

A

Autosomal dominant condition
Affects skeletal system, heart and eyes
Caused by fibrillins gene on chromosome 15

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8
Q

How can there be diagnosis using DNA

A

Allows determination of sequence/ copy number variant
Determines whether normal variant or pathogenic (harmful)

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9
Q

What is genotype-phenotype analysis

A

Sequencing of affected family member to confirm the mutation

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10
Q

What is polymorphism

A

the presence of two or more variant forms of a specific DNA sequence that can occur among different individuals or populations

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11
Q

How to determine whether a mutation is cause of disease in a family and not just polymorphism

A

Segregation studies - see whether family members that are clinically affected have same mutation

Genetic testing - see if member with mutation will develop disease

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12
Q

Clinical effects of neurofibromatosis

A

Skin cafe au last patches
Multiple neurofibroma

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13
Q

Example of a disease with variation of expression

A

Neurofibromatosis type 1
Exception of Mendels rules of autosomal dominance
Family members have different signs of the same disease
Cant predict severity of the disease

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14
Q

What disease demonstrates age related penetrance

A

Huntingtons disease
Breast cancer BRCA1

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15
Q

Is NF1 completely penetrant

A

Yes
If individual has affected gene NF1 always expressed

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16
Q

What is Huntington’s disease

A

Progressive neurological disorder
Involuntary movements
Dementia
Psychiatric disturbance

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17
Q

What is age dependant penetrance

A

Delay in onset of a genetic disease
The older they are without signs the less likely they are to develop disease

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18
Q

What is incomplete penetrance

A

Not everyone who has gene will develop disease e.g. some cancers

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19
Q

What is Achondroplasia

A

New mutation that causes the disorder in 80% patients

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20
Q

Which disease are new mutations increase with paternal age

A

Marfan
Achondroplasia

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21
Q

How does a chance of new mutation increase with paternal age

A

Higher mutation rates in males are likely to be related to greater number of germ cell divisions

22
Q

What is myotonic dystrophy

A

Autosomal dominant
Muscle weakness
Impaired muscle contraction after relaxation (myotonia)
Usual age of onset 20s-30s

23
Q

What is anticipation

A
  • In successive generations age of onset is reduced and/ or severity of the phenotype is increased
  • Unstable & expanding trinucleotide repeat mutation
  • Severity/ age of onset may correlate with number of repeats
24
Q

What is an example of anticipation

A

Myotonic dystrophy
Huntingtons

(Disorders of the nervous system)

25
Examples of intragenic triplet repeats causing dominant disease
Myotonic dystrophy - CTG Huntington disease - CAG
26
What is an intragenic triplet repeat disorders
Number of triplet repeats above the upper normal limit cause the disease
27
What is the usual gene repeats for huntingtons disease?
11-34 CAG repeats = 11-34 glutamine residues in protein Above 34 glutamine residues causes progressive cell death
28
Anticipation in Huntingtons disease:
Runs of more than 34 CAG repeats in HD gene expand further (during male meiosis) causing earlier age of onset in children of men with HD allele
29
What is mosaicism?
Mutation after fertilisation Present in somatic/ germline cells
30
What is osteogenesis imperfecta
Brittle bone disease Severe cond. not inherited because baby dies
31
What causes osteogenesis imperfecta
Father has mutation in gonads Patch of Gonadal stem cells with gene mutuion arisen from error in cell while gonad was being populated Gamete has effected genes
32
How to recognise autosomal recessive disease from pedigree
Cant follow disease through pedigree See siblings affected - horizontal transmission Equal incidence of males and females May be evidence of consanguinity (parents have common ancestor)
33
What is consanguinity?
Parents have shared common ancestor Doesn’t cause genetic condition but increases likelihood of parents being carriers of autosomal recessive condition in family
34
What is X linked recessive inheritance
One copy of an altered gene on the X chromosome Causes disease in males Cause females to be carriers
35
The results for offspring if mother is a carrier of X linked and father unaffected
Unaffected daughter Carrier daughter Unaffected son Affected son
36
Available options for mother who is carrier of x linked disease
Postpone pregnancy No further pregnancies - adoption Further pregnancies - accept risk, prenatal diagnosis if available, egg donation, preimplantation diagnosis if available
37
What is an example of x linked disease
Duchenne muscular dystrophy Progressive muscle weakness (cardiac and respiratory) Decreases life span
38
How may female carriers of X linked disease be affected
Can show mild symptoms of X linked disease - mild muscle aches and pain - myalgia - cardiac muscle abnormalities
39
What causes females to show X linked recessive traits
Skewed X inactivation Turner syndrome Homozygous for a recessive trait - carry X linked mutation on both X chromosomes X autosome translocations
40
What is skewed X inactivation
Random X inactivation in female embryo Should be equal paternal and maternal X But data can become skewed and more mutated X present which causes mild symptoms
41
Results for offspring if father is affected with X linked recessive inheritance but mother unaffected
All daughters Unaffected carriers All sons Unaffected
42
What does the pedigree for X linked dominant disease look like
Similar to autosomal dominance But excess of affected females No male to male transmission (sons inherit X from mother) Uncommon diseases
43
How many DNA bases and genes in mitochondria
16,600 DNA bases 37 genes
44
What is mitochondrial inheritance
Exclusively maternal inheritance
45
Description of maternal pedigree
May think its autosomal dominance All offspring of affected mother will have condition Males don’t pass on condition - sperm don’t mass on mitochondrial genes
46
The number of mitochondria in egg cells
100,000
47
The number of mitochondria in sperm cells
100
48
The number of genes and DNA bases in nucleus
3,200 million DNA bases 24 chromosomes
49
Examples of mitochondrial DNA disorders
Kearns-Sayre syndrome MELAS
50
Mode of Inheritance of haemophilia
X linked recessive