Mapping of Mendelian disease

Question 1

Why is recombination important?

Answer 1

Genetic recombination is responsible for genetic diversity in a species or population. Recombination or crossing over allows alleles (segments of DNA) on chromosomes to change position from one homologous chromosome to another.
Therefore, recombination is really important because it creates variety.

Question 2

How do we study genetic disease?

Answer 2

On image

Question 3

Define Mendelian / Monogenic disease

Answer 3

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

Question 4

Define Non-Mendelian / Polygenic disease

Answer 4

Non-Mendelian / Polygenic: 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)

Question 5

Define Multifactorial disease

Answer 5

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

Question 6

How do we study genetic disease?

Answer 6

1)	Gene identification by gene mapping
•	Homozygosity mapping
•	Linkage analysis
•	GWAS
2)	How do we find disease-causing mutations?
•	Sequencing
3)	How do we prove they cause disease?
•	Using in silico, in vitro and in vivo tools

Question 7

How can we use information about linked alleles to identify disease causing genes?

Answer 7

• If the alleles and the disease locus are linked (e.g. M3 – M4), all the affected individuals in a family are more likely to inherit this haplotype block.
• If the alleles and the disease locus are unlinked (e.g. M5 – M8) to the disease locus, the affected individuals in a family are less likely to inherit the same marker alleles.

Question 8

How would we find genomic region(s) linked to disease?

Answer 8

1. First take a pedigree 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 (e.g. Merlin or PLINK)
   e. g NPL – nonparametric linkage testing gives you a plot for each chromosome. Each plot if for each pair of chromosomes. No rules imposed in NPL – inheritance pattern is not taken into consideration

e.g Parametric analysis – imposes rules about inheritance and disease frequency
If you have a pedigree showing autosomal recessive inheritance you apply a rule for affected family members to be homozygous for the mutant allele, e.g. the disease-causing allele could be ‘AA’
If you have a pedigree showing autosomal dominant inheritance you apply a rule for affected family members to be heterozygous, e.g. their disease-causing allele could be ‘AB’

Question 9

What do Parametric tests highlight?

Answer 9

• all affected are equal, but different to unaffected

* and the genotypes follow the imposed inheritance pattern