Inheritance Patterns

Question 1

Variable expressively example

Answer 1

Digeorge

Brca

Question 2

X linked recessive example

Answer 2

Dmd

Bmd

Question 3

X linked dominant example

Answer 3

X linked alports
Intercontinental pigmentia
Rett

Question 4

Autosomal recessive example

Answer 4

Cf
Breakage syndromes
Sma

Question 5

Example of anticipation and definition

Answer 5

Frax

Increased/earlier with each generation

Question 6

What is genetic linkage

Answer 6

The tendency of alleles located close together on Chr to be inherited together during meiosis. Genes that are physically closer are less likely to be separated onto diff chromatids at crossover
Use large pedigrees. Identify a genetic marker that is always inherited by those family members with disease but not by those who don’t have disease.

Question 7

What are gwas?

Answer 7

Hypothesis free approach. Useful When several genes make small contributions to eitiology. Use markers across entire genome to find an association. Powerful in detecting markers with high or moderate effect, not so good for weaker effect (esp recessive)

Question 8

What is lod score?

Answer 8

Logarithm of the odds. A measure for likelihood of linkage

Question 9

What lod score indicates linkage

Answer 9

> 3

Question 10

What lod score indicates no linkage

Answer 10

Less than -2

Question 11

What assumption does lod score analysis require

Answer 11

Precise genetic models, inc penetrance, disease gene freq, clear classification of individuals as affected or unaffected. Misdiagnosis or presence of phenocopies can affect lod score greatly

Question 12

What are diseases with differing phenotypes but that map to same gene locus called? I’d caused by diff mutations in same gene

Answer 12

Allelic

Question 13

What is linkage disequilibrium

Answer 13

The non random association of alleles at 2 or more loci with freq greater than that expected by chance

Question 14

What does LD D=0 mean?

Answer 14

No association between alleles and the distribution of alleles

Question 15

What does LD score of 1 mean?

Answer 15

Represent alleles in complete LD

Question 16

What factors affect LD

Answer 16

Recombination: will gradually reduce LD, gene conversion: markers either side of a gene conversion may still show LD, selection: a selective advantage for 2 alleles to coexist will increase chance of LD being maintained (negative selection pressure can remove LD), new mutation: high new mutation rate at locus will make it difficult to detect LD

Question 17

Why are SNPs used to measure LD

Answer 17

Frequent occurrence, relatively low mutation rate, easy to genotype large scale

Question 18

What is transmission/disequilibrium test TDT

Answer 18

Test for linkage between complex disease and genetic marker

Question 19

In the TDT transmission/disequilibrium test, what does a deviation from a ratio of 50:50 mean?

Answer 19

An association is determined

Question 20

4 explanations for positive associations found by gwas

Answer 20

1. Found by chance, 2. Due tips limitations of the study method (not the true disease causing variant but is situated close on the dna), 3. Population stratification- vary frequencies of genetic variants independent of the freq of disease, 4. It is important in disease causation

Question 21

Which type of linkage study is better for multi factorial disease

Answer 21

Gwas

Question 22

Which technique is used for most gwas

Answer 22

Chip based SNP genotyping snp arrays

Question 23

What does p value of 0.05 mean.?

Answer 23

It is the significance - a 5% chance of a false result. P needs to be very low for gwas due to large number of SNPs tested at once

Question 24

How can the power of a gwas study be increased

Answer 24

Increase sample size and use carefully matched cases and controls

Question 25

Factors that affect gwas power

Answer 25

Freq of allele in population, relative risk conferred by disease allele, LD between genotyped marker and true risk allele, sample size, genetic heterogeneity of sample popn

Question 26

Example of variable penetrance

Answer 26

16q11.2del/dup

Question 27

Example variable expressivity

Answer 27

DGS, Brca

Question 28

Definition of pleiotrophy and example

Answer 28

1 gene influence 2 or more unrelated traits. PKU, RET,PMP22

Question 29

Antagonistic pleiotrophy definition and example

Answer 29

One gene with competing effects (good and bad) P53

Question 30

What is amorphic mutation

Answer 30

Complete lof

Question 31

Example of hypomorphic mutation

Answer 31

Friedrichs. Partial lof.

Question 32

Antimorphic mutation defn

Answer 32

Dom-neg. act in opposition to normal function

Question 33

Example of X linked dominant

Answer 33

Rett

Question 34

Example X linked recessive

Answer 34

DMD/BMD

Question 35

Example autosomal dominant microdel

Answer 35

DGS, CDC, whs, pw/as - haploinsufficiency

Question 36

Examples of autosomal dominant Gof mutations

Answer 36

HD, MD, achondroplasia, bcr-Abl - increased gene exp or create new product

Question 37

Example autosomal dominant with dominant negative mutations

Answer 37

Marfan. OI. Tp53. Osteopetrosis. Impair normal function- more severe in heterozygous

Question 38

Example autosomal recessive

Answer 38

Cf, breakage syndromes and sma