Molecular Genetics 2 Flashcards by Yazan Halasa

Function of G72?

Oxidize serine - an activator of glutamate transmission via modulatory site on NMDA receptor.

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How does G72 lead to schizophrenia?

Inadequate DAOA function may lead to problems in modulating glutamate signal in areas of brain like prefrontal cortex.
G72 my be involved in maintaining neural structure.

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What do antidepressants do to BDNF?

Increased central BDNF in animals

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Which chromosome is DISC1 (disrupted in schizophrenia 1) found?

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What is DISC1 associated with?

Microtubules

Mice: abnormal neuronal migration and dendritic organization in delevoping cerebral cortex.

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How does DISC1 play a role in mood regulation?

Ineracts with phosphodiesterase 4B

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Which three genes are associated with other behavioural phenotypes, which interact with environment to increase risk of major depression?

5HTT

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Which three genes are associated with other behavioural phenotypes, which interact with environment to increase risk of major antisocial personality disorder?

MAOA

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Which three genes are associated with other behavioural phenotypes, which interact with environment to increase risk of schizophrenia?

COMT

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What is dysbindin involved in?

Formation of synaptic structures

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What is neuregulin involved in?

Neuronal migration and genesis of glial cells and subsequent myelination of neurons by these cells

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What is GRK3 involved in?

Only animal studies

Down-regulation of G-protein coupled receptors - associated with bipolar

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Mutations leading to Alzheimers?

Amyloid precursor protein and presenilin 1 and 2 for as much as 50% of familiar alzheimers before 60 years og age.

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Where is amyloid precursor protein?

Chr 21

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Where is presenilin 1?

Chr 14

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Where is presenilin 2?

Crr 1

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Which genetic factor has highest attributable risk for Alzheimers?

Apolipoprotein E

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Where is apolipoprotein E?

Chromosome 19q with 3 codominant alleles, differing by single base substitutions in coding region.

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Which alleles are over and under-represented in apolipoprotein E?

Ancestral allele, 3, is over represented

Allele 2 is under-represnted

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Mean age of onset of Alzheimers in those with allele 4 apolipoprotein E homozygous?

2 decades earlier
Also increases risk in nonwhite populations
More in females

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Which protein is associated with both Downs and Alzheimers?

Chr 21 - mutant amyloid precursor protein

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Risk of Alzheimers in first degree relatives and controls

15-19%

5% (controls)

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DZ concordance rates of Alzheimers

40%

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MZ concordance rates for Alzheimers

84%

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What are the three different syndromes of frontotemporal lobar degenaration?

Frontotemporal dementia Progressive non-fluent aphasia Semantic dementia

Genes in frontotemporal lobar degeneration

Some patients show tau protein | Familial cases - MAPT on chromosome 17q21

Which gene has been located in tau-negative patients with frontotemporal lobar degenaration?

Progranulin gene on chromosome 17q21

What is progranulin?

Growth factor involved in round repair and inflammation by activating signalling cascades in cell cycle. Tumrigenesis.

How are Lewy bodies formed?

Synucleinopathies - synuclein molecules aggregate in presynaptic terminals

Gene position of PARk 1 and 4

5Q21 gene

Protein made from PARK 1 and 4

Alpha-synuclein

Features of PARK 1, 4 inheritance in Parkinsons

Onset in 40s

Inheritance of PARk 1 and 4

Dominant inheritance

Pathology in PARK 1 and 4 Parkinsons

Nigral degenaration with Lewy bodies

Position of gene in PARk 2

6q25

Protein made by PARK 2

Parkin gene

Inheritance of PARK 2

Recessive

Pathology of PARk 2

Nigral degeneration w/o Lewy Bodies

Onset of PARK 2 Parkinsons

40-60

Position of gene of PARK 8

12 cen (pericentromeric) LRRK2 gene

Inheritance of PARK 8

Dominant

Onset of PARK 8 Parkinsons

Pathology of PARk 8 Parkinsons

Variable alpha-synuclein and tau pathology

Location of gene of PARk 6

1p35-37 -PTEN-Induced | Kinase (PINK1) in mitochonrdia

Inheritance of PARk 6

Autosomal recessive

Onset of Parkinsons in PARk 6

30-40

Location of gene of PARk 7

1p38 DJ-1

Inheritance of PARK 7

Autosomal recessive

Onset of Parkinsons in PARk 7

Autosomal recessive

What is alpha-synuclein?

Protein expressed in brain, role in learning, synaptic plasticity, vesicle dynamics and dopamine synthesis

Recurrence rate in siblings of austic children

2-8%

MZ twin concordance rate of autism

60%

DZ twin concordance rate for autism?

Heritability of autism?

90%

Which chromosomes are implicated in autism?

2 7 15

Possible inheritance patterns of autism?

AR | Sex-specific modifications

Which gene disorder is associated with autism?

Fragile X - 16% of males are autistic

Risk to first degree relatives of ADHD

15-60%

Heritability of ADHD

70-80%

Risk of ADHD in terms of gender?

Higher in males

Largest factor for personality disorder?

Nearly 50%: | Nonshared, person-specific environmental variation

Which PD has the highest heritability?

Antisocial - 60-70%

Which feature has high heritability in BPD?

Emotional dysregulation

Lifetime prevalence of panic disorder?

4.7%

Heritability of panic disorder

0.43

Which type of social phobia does not show familial transmission

Non-generalised, discrete social phobia

Which phobias are 3-4 times more common in first degree relatives?

Specific phobias

What do twin studies show re phobias?

Individual-specific environmental influences more important for simple phobies

Risk of alcoholism in families

4-6x general population

Genetic factors for alcohlism

Variants in GABRA2 on chromosome 4p - also related to impulse control ADH4 - associated with earlier onset of drinking A1 allele of DRD2

Which enzyme breaks down EtOH?

Alcohol dehydrogenase

What is EtOH broken down into?

Acetaldehyde and then aldehyde dehydrogenase.

What increases genetic risk of OCD?

Increased severity and chronicity

Risk of OCD to first degree relatives if onset <18?

10-35%

MZ Twin concordance of OCD?

53-87%

DZ twin concordance of OCD?

22-47%

Tests for genetic testing?

Direct Gene tracking Prenatal identification

What is direct testing?

Sample is tested for a certain genotype. | Only one person is tested.

What is gene tracking?

Family members are tested to discover if suspected patient has inherited high risk chromosome from heterozygous parent.

What does gene tracking look for?

Segregation of chromosome within a family.

What is prenatal identification?

Test of fetus to identify suspected genotype.