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Flashcards in Mapping mandelian disease Deck (25)
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1
Q

Independent assortment

A
  • Chromosomes segregate independently of one another during meiosis
  • Alleles that are located on separate chromosomes get sorted into gametes independently of one another
2
Q

Linkage

A

Two alleles are located on the same chromosomes

3
Q

Linkage equilibrium

A

the frequency of alleles inherited from one parent in a given population have the same value that they would have if the alleles at each locus were combined random

4
Q

Two regions on the same chromosome. Freqiency of allele A is found to be 0.5 and the frequency of allele B is 0.5. Assuming normal linkage equilibrium, what is the expected frequency of AB?

A

0.5 x 0.5 = 0.25

so all genetic variations will be 0.25

5
Q

Frequency of allele A is found to be 0.5 and the frequency of allele B is 0.5. However, the frequency of AB is found to be 0.49 in the same population. What genetic principle most likely explains this finding?

A

AB 49%
ab 49%
Ab 1%
aB 1%

Linkage disequilibrium

6
Q

Mendelian/ monogeic:

A

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

7
Q

Non-Mendelian/ polygenic

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)

8
Q

Multifactorial

A

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

9
Q

Gene identification by gene mapping

A

Homozygosity mapping
Linkage analysis
GWAS

10
Q

How do we find disease-causing mutations?

A

Sequencing

11
Q

How do we prove they cause disease?

A

Using in silico, in vitro and in vivo tools

12
Q

Genetic linkage

A

The tendency for alleles (A1, A2, B1 and B2) at neighbouring loci to segregate together at meiosis
Therefore to be linked, two loci must lie very close together

13
Q

Halotype

A

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

14
Q

Recombination events

A

During meiosis are more likely to occur between loci separated by some distance than those close together

15
Q

Linkage analysis

A
  • Gene mapping tool
  • Using observed loci (alleles) to draw inferences about an unobserved locus (disease gene)
  • Family-based design (from a few large families to many small nuclear or sib-pairs)
16
Q

Steps for linkage analysis

A
  1. First take a pedrigree and get as many DNA samples as possible
  2. Use some kind of tool to observe alleles, i.e. generate genotyping data for your pedigree
  3. Generate a file with your pedigree information plus the genotyping data from the SNP array
  4. Run your file in a linkage programme
17
Q

LOD score >3.0

A

Significant evidence for linkage

18
Q

LOD score below 2

A

Significant non-linkage

19
Q

LOD score between -2 and 3

A

inconclusive

20
Q

Lymphoedema treatment

A
Treatment 
•	Compression socks,
•	Lymphatic drainage 
•	Exercise – aids natural drainage of fluid 
•	Skincare
21
Q

Symptoms of lymphoedema

A
  • Debilitating
  • Embarrassing
  • Stressful
  • Recurrent infections
22
Q

Primary lymphoedema

A
  • Chronic oedema caused by a developmental abnormality of the lymphatic system
  • Often progressive
23
Q

Generalised lymphatic dysplasia (Hennekam syndrome (HS)

A
  • Antenatal hydrops with ascites and pleural effusions
  • Oedematous at birth
  • Intestinal lymphangiectasia
  • Peripheral lymphoedema; arms, legs, face
  • Mild developmental delay
24
Q

4- limb lymphoedema

A
  • Autosomal dominant
  • Pubertal/adult onset
  • Associated with venous incompetence
  • No other abnormalities
25
Q

How do we find disease-causing mutations?

A
•	Traditional Sanger sequencing
	 Candidate gene screen (as seen in the previous example)
•	Next generation sequencing (NGS)
	 Whole genome sequencing (WGS)
	 Whole exome sequencing (WES)