Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Genetics > 6. Complex genetic disorders > Flashcards

6. Complex genetic disorders Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

Diabetes

A

chronic hyperglycaemic state
characterised by beta cell dysfunction and/or insulin resistance
polygenic or monogenic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Type 1 Diabetes

A

Autoimmune system destroys pancreatic beta cells
Diminished/absent endogenous beta cell function, no/ little production of insulin
Presents at any age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Treatment of Type 1 diabetes

A

Insulin replacement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Type 2 Diabetes

A

resistance to insulin action leads to increased production and ultimately pancreatic exhaustion
Presents at middle/old age, increasing in youth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Treatment of type 2 diabetes

A

Diet
Exercise
Oral hypoglycaemic agents
Eventually insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Monogenic diabetes

A

Single gene defect:
Maturity onset diabetes of the young (MODY)
Permanent neonatal diabetes (PND)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Maturity onset diabetes of the young (MODY)

A

Collection of autosomal dominant monogenic disorders affecting genes involved in beta-cell glucose sensing and insulin secretion.
Often mutation of HNF1-α or Glucokinase
Different from Type 1 & Type 2 diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Heritability

A

Study of genetic contribution to increased risk of a disease

Difficult to disentangle genetic from non-genetic factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Percentage of diabetes that is monogenic and polygenic

A

monogenic: 5%, born with it
polygenic: 95%, may develop it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Proportion of T1DM and T2DM that are polygenic

A

T1DM: 5%
T2DM: 95%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Monogenic diabetes

A

100% risk of developing diabetes
No environmental factors
100% heritable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Polygenic diabetes

A

T1/2
Not born with it but can have genetic predisposition
Compilation of genetic changes that increase predisposition
Not 100% risk
Affected by environment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the difference between monogenic and polygenic diabetes?

A

In polygenic there has to be a 2nd hit to develop diabetes:
Environmental
Lifestyle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are genome wide association studies (GWAS)?

A

Hypothesis free approach to find common variants in common disease
Looking to identify SNPs statistically associated with disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Genomic Copy Number Variation (CNVs)

A

Deletions/duplications/insertions in genome
Range from few base pairs to > 1Mb
Can increase risk of polygenic disease
Common in obesity
Most risk appears to be conferred through single nucleotide changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What did GWAS show for Type 2 diabetes?

A

SNPs account for 6%

Shows environment is heavily influential

17
Q

What is Hepatic nuclear factor 1-alpha (HNF1-alpha)?

A

Transcription factor that stimulates insulin production

18
Q

What is the consequence of absence/ mutation of HNF-1 alpha?

A

Insulin production reduced

Only manifests in adulthood when beta- cell function starts to naturally decline

19
Q

How are HNF1-alpha mutations best managed?

A

With sulphonylureas

20
Q

What are those with HNF1-alpha mutations at risk of?

A

Micro- and microvascular complications

21
Q

Clinical features of HNF1-alpha mutations

A 
Hypoglycaemic response to low dose sulphonylureas
Young onset
Generational family history
Non- insulin requiring
Atypical for T1/T2
22
Q

What is glucokinase?

A

Enzyme that converts glucose to glucose-6-phosphate

Triggered at certain beta-cell glucose levels

23
Q

What do glucokinase mutations result in?

A

Higher set-point at which insulin secretion is triggered

24
Q

What defect characterises MODY 2?

A

Glucokinase mutation

25
Q

Features of MODY 2

A

High fasting and low post-prandial plasma glucose
Stable, mild hyperglycaemia
Often misdiagnosed as T2DM, IFG or GDM

26
Q

Why are there not often complications to MODY 2?

A

Isolated risk factor
Hyperglycaemia is mild and under homeostatic regulation
Similar insulin resistance and obesity as general population
‘Normal’ lipid profile

27
Q

Name 2 rarer types of HNF mutation

A

HNF-4 alpha

HNF-1 beta

28
Q

Describe HNF-4 alpha mutation

A 
Clinically similar to HNF-1 alpha but rarer
Older age of onset
Low renal glucose threshold
Macrosomia
Transient neonatal hypoglycaemia
29
Q

What characterises HNF-1 beta mutation (RCAD)?

A

Renal cysts and diabetes

Genital tract mutations

30
Q

What are the barriers to diagnosing monogenic diabetes?

A

Incomplete understanding regarding benefits of diagnosis
Clinical challenge: need to think of it to make diagnosis
Access to genetic testing and robust interpretation
Interpreting variants of unknown significance
Needle in haystack

31
Q

Mitochondrial diabetes

A

Maternally inherited diabetes and deafness (MIDD)

Associated with MELAS

32
Q

Features of MIDD

A 
Diabetes
Young-onset sensorineural deafness
Lactate
Muscle aches
Short stature
33
Q

Permanent neonatal diabetes features

A

Monogenic
Diabetes in 1st 6 months of life
Genetic defect resulting from mutations in
KCNJ11, ABCC8 and INS

34
Q

Precision diabetes allows accurate diagnosis and treatment

A

SNPs predict metformin side effects

Use sulphonylureas in HNF1a MODY and PND

Genetics (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions