Mapping Mendelian Disease

Question 1

What is the definition of Mendelian disease?

Answer 1

→ A disease caused by a single gene with little or no impact from the environment

Question 2

What is an example of mendelian disease?

Answer 2

→ PKD

Question 3

What is the definition of non mendelian disease?

Answer 3

→ Diseases or traits caused by the impact of many different genes each having only a small individual impact on the final condition

Question 4

What is an example of a non mendelian disease?

Answer 4

→ Psoriasis

Question 5

What is the definition of a multifactorial disease?

Answer 5

→ Diseases or traits resulting from an interaction between multiple genes and often multiple environmental factors

Question 6

What is an example of a multifactorial disease?

Answer 6

→ heart disease

Question 7

What are the 3 ways of identifying a gene by mapping?

Answer 7

→ Homozygosity mapping
→ Linkage analysis
→ GWAS

Question 8

How do you find disease causing mutations?

Answer 8

→ Sequencing

Question 9

How do you prove genes cause disease?

Answer 9

→ In silico, in vitro and in vivo tools

Question 10

What is genetic linkage?

Answer 10

→ The tendency for alleles at neighbouring loci to be segregated together at meiosis

Question 11

When are crossovers more likely to occur?

Answer 11

→ between loci separated by some distance than those close together

Question 12

If a marker and a disease locus are unlinked what does this mean?

Answer 12

→ The affected individuals in the family are less likely to inherit the same marker alleles

Question 13

If a marker and a disease locus are linked what does this mean?

Answer 13

→ Affected individuals are more likely to inherit this haplotype block

Question 14

What are the steps for the linkage analysis method?

Answer 14

1) a pedigree is taken
2) genotyping data is generated like a GWAS SNP array
3) Physical and genetic distribution of markers on genotypic array
4) a file is generated with pedigree information and genotyping data from microarray
5) linkage programme is run

Question 15

What is non parametric linkage testing?

Answer 15

→ Not having assumptions about linkage data

Question 16

What does non parametric linkage testing look for?

Answer 16

→ All affected regions are equal but different to unaffected regardless of inheritance pattern
→ Any LOD score above 3

Question 17

What does parametric analysis look for?

Answer 17

→ All affected are equal but different to unaffected

→ AND genotypes follow the imposed inheritance pattern

Question 18

What does a LOD score of -2 mean?

Answer 18

→ significant non linkage

Question 19

What does a LOD score of -2 to 3 mean?

Answer 19

→ Inconclusive

Question 20

Where is a gene likely to be located if the LOD score is ?> 3?

Answer 20

→ between the two markers defining the linkage peak

Question 21

What are the symptoms of generalised lymphatic dysplasia?

Answer 21

→ Antenatal hydrops
→ Oedematous at birth
→ intestinal lymphangiectasia 
→ peripheral lymphoedema 
→ mild developmental delay

Question 22

What kind of a disease is 4 limb lymphoedema?

Answer 22

→ autosomal dominant

Question 23

What are the two methods of finding disease causing mutations?

Answer 23

→ Traditional Sanger sequencing
→ Next generation sequencing
- whole genome
- whole exome