Brainscape's Knowledge GenomeTM

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


See full index

Genomics > Mapping Mendelian Disease > Flashcards

Mapping Mendelian Disease Flashcards

1
Q

What is a mendelian / monogenic disease?

A

disease that is caused by a single gene, with little or no impact from the environment (e.g. PKD)

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

What is meant by a non-mendelian / polygenic disease?

A

Diseases or traits caused by the impact of many different genes, each having only a small individual impact on the final condition (e.g. psoriasis)

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

What is a multifactorial disease?

A

Diseases or traits resulting from an interaction between multiple genes and multiple environmental factors (e.g. heart disease)

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

How is gene identifcation carried out with gene mapping?

A

Homozygosity mapping
Linkage analysis
GWAS

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

What methods are used to prove certain genes cause disease?

A

We find disease causing mutations by sequencing

Using in silico, in vitro and in vivo tools we can prove they cause disease

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

What is genetic linkage?

A

The tendency for alleles at neighbouring loci to segregate together at meiosis

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

What causes gene linkage to occur?

A

To be linked, two loci must lie very close together

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

What is a haplotype?

A

A haplotype defines multiple alleles at linked loci. Haplotypes mark chromosomal segments which can be tracked through pedigrees and populations

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

Which loci are more susceptible to crossing over?

A

Cross-overs are more likely to occur between loci separated by some distance than those close together

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

How can we use loci to identify disease genes?

A

If a marker is linked to a disease locus (i.e. M3 and M4), the same marker alleles will be inherited by two affected relatives more often than expected by chance - can use this to identify disease

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

What is the effect of an unmarked loci in gene identification?

A

If the marker and the disease locus are unlinked (e.g. M5 – M8), affected relatives in a family are less likely to inherit the same marker alleles

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

Outline the features of linkage analysis

A

Gene mapping

Family based design (from few large families to many small nuclear or subpairs)

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

How is linkage analysis carried out?

A

Using an observed locus (marker) to draw inferences about an unobserved locus (disease gene)

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

What is the aim of linkage analysis?

A

Find genomic region(s) linked to disease

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

Summarise the method used for linkage analysis

A
  1. Take a pedigree
  2. Use a tool to generate genotyping data for your
    pedigree
    • E.g. Genome-Wide Human SNP Array 6.0
  3. Physical and genetic distribution of markers on a
    genotyping array
  4. Approx. 6000 SNP markers distributed uniformly across
    human genome
  5. Run a linkage programme
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is NPL?

A

Nonparametric Linkage Testing

17
Q

What is the significance of NPL?

A

No rules imposed in NPL –

looks for IBD (identity by descent)

18
Q

How does NPL testing identify genes?

A

Highlights regions (by high LOD scores) where:
all affected are equal, but different to unaffected.
Regardless of what inheritance pattern might be relevant

19
Q

How does parametric analysis differ from NPL?

A

Parametric imposes rules about inheritance and disease frequency

20
Q

How does parametric analysis identify disease genes?

A 
Highlights regions (by high LOD scores) where:
all affected are equal, but different to unaffected
and the genotypes follow the imposed inheritance pattern
21
Q

What is a significant LOD score?

A

LOD scores > 3.0 are taken as significant evidence for linkage

LOD scores below -2.0 show significant non-linkage
LOD scores between -2 and 3 are inconclusive

22
Q

What are the functions of the lymphatic system?

A
  • Fluid homeostasis
  • Immune function
  • Fatty acid transport
23
Q

What is primary lymphoedema?

A

Chronic oedema caused by a developmental abnormality of the lymphatic system

24
Q

How many people are affected by primary lymphoedema?

A

Affects 1 in 6,000

Often progressive

25
Q

What is the generic phenotype of lymphoedema patients?

A

Phenotypes vary:

  • age of onset
  • site
  • inheritance patterns
  • associated features
  • genetic causes
26
Q

Why is research in lymphoedema so significant?

A

Research is significant as lymphoedema is debilitating, causing recurrent infections, embarrassment and stress with no current medical cure

27
Q

What are the current treatments available for lymphoedema?

A

The only treatments available are:

  • Manual Lymph Drain (MLD) massage
  • Bandaging
28
Q

What is Hennekam Syndrome?

A

Generalised Lymphatic Dysplasia

29
Q

What are the effects of Hennekam syndrome?

A
  • Antenatal hydrops with ascites and pleural effusions
  • Oedematous at birth
  • Intestinal lymphangiectasia
  • Peripheral lymphoedema; arms, legs, face
  • Mild developmental delay
30
Q

How would we go about mapping an autosomal recessive disease gene?

A
  1. Generate genotyping data using Genome-Wide Human
    SNP Array 6.0
  2. Run linkage analysis using an autosomal recessive
    model (parametric)
  3. A LOD score > 3 translates to a p-value of approximately
    1. 05

This means the genetic locus is significantly linked to disease

LOD max = 2.0787

Result: Linkage to chromosome 18
(autosomal recessive model)

31
Q

Once you’ve established the significance of the GOIs what is the next step in mapping an autosomal recessive disease?`

A

Finding the disease causing mutation in one of the candidate genes

32
Q

How was the rare autosomal recessive disease identified?

A

100 candidate genes and 2 years later with lots of Sanger sequencing, mutations in CCBE1 was identified

33
Q

What is the final step in identifying the disease causing gene?

A

Proving that mutations in the gene identified are disease causing

34
Q

Outline the inheritance and onset of Limb lymphoedema

A

Autosomal dominant
Pubertal/adult onset
Associated with venous incompetence
No other abnormalities

35
Q

Outline how an autosomal dominant model is used to identify GOI

A
  1. Generate genotyping data e.g. using Genome WIde
    Human SNP Array 6.0
  2. Run linkage analysis on the 2 families using an
    autosomal dominant model

Result: the two families showed linkage to chr. 1 with an accumulative LOD max = 3.347

36
Q

What are the 2 methods used to prove disease-causing mutations?

A

Traditional Sanger sequencing
- Candidate genes

Next generation sequencing (NGS)

  • Whole genome sequencing (WGS)
  • Whole exome sequencing (WES)
37
Q

What is the benefit of NGS?

A

Next Generation Sequencing (NGS) makes us faster!

38
Q

What is the main cause of rare disease?

A

Rare disease is often caused by mutations in a single gene

Genomics (20 decks)

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