Behavioural and psychiatric genetics I: L22

Question 1

pedigree map, dominant:

1. dominant traits can’t
2. two unaffected parents can’t

Answer 1

1. skip generations

2. have affected offspring

Question 2

pedigree map, recessive:

1. two affected parents can’t have

Answer 2

1. unaffected offspring

Question 3

X linked, pedigree map:

1. cannot transfer
2. dominant - daughter of affected father
3. recessive - father of affected daughter

Answer 3

1. father to son
2. must be affected
3. must be affected

Question 4

pedigree examples

1. 2 unaffected parents with affected offspring =
2. unaffected father with affected daughter =
3. 2 affected parents with unaffected offspring =
4. affect father with unaffected daughter =
5. affected father with 100% affected daughters, no sons=
6. 2 unaffected parents with only affected sons, no daughters =

Answer 4

1. recessive
2. autosomal recessive
3. dominant
4. autosomal dominant
5. x-linked dominant (clue, cant ever be proved)
6. x-linked recessive (clue, cant ever be proved)

Question 5

monogenic disorders

1. we can trace the origins of monogenic disorders to
2. it results from a …
3. FMR1 is critical for
4. expansion of repeated CGG sequence of bases triggers

Answer 5

1. a single gene
   - > huntington’s disease (single gene = HTT)
   - > fragile x syndrome (FMR1)
2. copy number variant in the 5-untranslated region of the gene FMR1
3. synaptic plasticity
4. methylation
   - constricts x chromosome & causes fragile appearance
   - a methylated promotor region prevents transcription of the gene

Question 6

Polygenic disorders

1. monogenic disorders are the exception to

Answer 6

1. the rule in behavioural and psychiatric genetics

- > there is no single gene for schizo, autism, bipolar, depression or anxiety

Question 7

GWAS (genome-wide association studies)

1. what happens?
2. genome-wide association studies examine
3. how many markers

Answer 7

1. saliva sample collected, extract DNA, goes onto a chip, goes into a machine & list of numbers is produced (for every chromosome)
2. the statistical association between a phenotype and many SNP markers throughout the genome
3. 500,000 - 2, 000 000

Question 8

GWAS

1. we can sample common variation sparsely because
2. in a direct association
3. in an indirect association

Answer 8

1. linkage disequilibrium (LD) allows us to observe indirect associations
   - > many variants in chromosomes are highly correlated
2. phenotype has a functional association with a genotypes SNP
3. phenotype has a functional association with a non-genotypes SNP that is in LD with a genotyped SNP

Question 9

GWAS

1. for quantitative traits, we use (e.g. frequency of alcohol use)
2. for categorical and binary traits (e.g. bipolar disorder) we can use

Answer 9

1. an allelic dosage model

2. an allelic association model

Question 10

GWAS

1. a manhattan plot graphically summarises
2. each point
3. physical location on the genome & within a chromosome
4. transformed p value
   - > lower p values are

Answer 10

1. the results of all of our individual tests of association
2. represents the outcome of a test for one single SNP
3. is on the horizontal axis
4. vertical axis
   - > higher on the axis, emphasising strongest associations

Question 11

GWAS

1. thresholds for significance are stringent because

Answer 11

1. multiple comparisons increase the likelihood of type I error
   - threshold set: a= 5x10 -8 (p < .00000005) (very high)
   - this corresponds to bonferroni correction for ~1 million independant (uncorrelated) tests

Question 12

GWAS

1. prediction of genotypes at non genotyped SNPs is
2. This prediction relies on
3. applies patterns of linkage

Answer 12

1. imputation
2. data from a reference panel of individuals genotypes at high density
3. disequilibrium discovered in the reference panel

Question 13

GWAS

1. genetic distance and recombination rate reflect
   - > this defines
2. the extent to which a sequence is maintained across a species is called
   - > important function preserved during evolution is indicated by

Answer 13

1. the frequency with which two markers are inherited together
   - > the region likely to contain the functional variant
2. conservation
   - > high conservation

Question 14

GWAS

-> ‘skyscrapers’ often observed in manhattan plots could be explained by (2)

Answer 14

-> Multiple SNPs in linkage disequilibrium with a functional SNP
or
-> multiple functional SNPs in the same gene