Genetic studies

Question 1

Gene mapping

Answer 1

refers to any strategy that permits finding the chromosomal location of one or more genes, often related to a disease

Question 2

Pairwise concordance rate

Answer 2

estimated as a number of twin pairs who both have the disorder divided by the total number of pairs

Question 3

Probandwise concordance rate

Answer 3

number of affected twins divided by the total number of co-twins

Question 4

Family history method

Answer 4

• simple but unreliable
• psychiatric history is taken from the probands himself/herself
• comparison is then made as to how many relatives are affected in one group compared to another
• many false negatives

Question 5

Family study method

Answer 5

• time consuming
• all available relatives are directly interviewed
• expensive

Question 6

Complete case ascertainment

Answer 6

• identification of all affected individuals in a given population
• rarely possible

Question 7

Adoption studies

Answer 7

• used to differentiate between genes and environemnt
• however, higher rates of psychiatric difficulties due to difficult social circumstances
• adoptive parents are more likely than not to resemble biological parents as social agencies attempt to match the families of origin to the families of adoption

Question 8

Linkage analysis

Answer 8

• alleles of loci that are close together on the same chromosome are likely to be inherited together
• these are said to be linked
• distance between two loci can be inferred by estimating the frequency with which cross-overs occur among them
• the lesser the cross over the closer the lcoi
• this is done by looking at recombination in families and this is called recombination frequency
• cross over event in meiosis- recombination

Question 9

LOD scores

Answer 9

• estimate the likelihood that two loci are truly linked with a specific recombination frequency
• LOD=log10 (probability that recombination frequency is the observed value)/ probability that the recombination frequency is 50%)
• LOD score of greater than 3 is usually interpreted as statistical evidence of linkage
• LOD score of -2 or less is taken as evidence that two loci are not linked

Question 10

Candidate genes

Answer 10

• approach to linkage study

- protein is suspected to be involved, then the gene is traced from this pathogenetic knowledge

Question 11

Positional cloning

Answer 11

• approach to linkage studies
• genes are identified through their positions in the genome rather than functions
• supported by human genome project

Question 12

Linkage studies

Answer 12

• uses families
• detectable over large distances > 10cM
• Can usually only detect large effects

Question 13

Association studies

Answer 13

• uses cases and controls or families with ‘internal controls’
• detectable only over small distances
• capable of detecting small effects

Question 14

Transgenic studies

Answer 14

• transgenesis is a term that describes the transfer of a gene from one species to another but in this case refers to the insertion of a modified mouse gene into the mouse genome to study gene function
• direct and powerful

Question 15

Epigenetics

Answer 15

• Waddington
• descibes modification that occurs to what is translated from the DNA
• being researched in mental illness

Question 16

Position effects

Answer 16

• gene activity can be dependent on the precise chromosomal location of the gene and its neighbourhood
• such genes show altered activity during translocation, even if the gene itself is not disrupted by chromosomal breakage