Complex Disorders

Question 1

Describe mutation and inheritance pattern of achondroplasia

Answer 1

• autosomal dominant, most new mutations

- FGFR3 (fibroblast growth factor 3)

Question 2

Define phenocopy

Answer 2

• mimic of a phenotype that is usually determined by a spec genotype
• is actually produced by an env cause or env interaction w/ diff genotype

Question 3

2 examples of phenocopies?

Answer 3

1. Retinoic acid embryopathy

2. DiGeorge seq

Question 4

What are modifying genes?

Answer 4

• many genes of small effect can modify phenotype of a single major gene

Question 5

Define pleiotrophy

Answer 5

• a single locus produces an effect on several traits

Question 6

2 key characteristics of polygenic inheritance?

Answer 6

1. several genetic loci make equal contribution

2. several loci make additive contribution

Question 7

Describe Threshold model of Multifactorial Inheritance

Answer 7

• dist of liability for a trait/disease determined by genes and env @ a certain threshold
• person affected @ that threshold

Question 8

Criteria for Multifactorial Inheritance? (4)

Answer 8

1. Corr b/w relatives is prop to genes in common
2. Recurrence risk is higher when more than one family member affect OR disorder more severe in expression
3. Occurrence may differ based on sex
4. Consanguinity increases recurrence risk

Question 9

Define uniparental disomy

Answer 9

Both chromosomes of a pair come from 1 parents and none from other parent

Question 10

Define isodisomy

Answer 10

Both chromosomes from 1 parent are identical

Question 11

Define heterodisomy

Answer 11

Both chromosomes from 1 parent are diff

Question 12

Define genetic imprinting

Answer 12

Modification (methylation) of genetic material that occurs dep on whether genetic infor derived from mother or father

Question 13

Examples of genetic imprinting? (2)

Answer 13

1. Prader Willie syndrome

2. Angelman syndrome

Question 14

Sources of Prader Willie?

Answer 14

1. Deletion in paternally derived gene OR

2. Uniparental disomy of maternal genes

Question 15

Sources of Angelman’s

Answer 15

1. Deletion in maternally derived gene OR

2. Uniparental disomy of paternal genes

Question 16

Describe anticipation and correlative factor

Answer 16

• increase in severity or decrease in age of onset of a disorder in successive generations
• often due to increase in no. of tri-nt repeats

Question 17

2 examples of anticipation + genomic imprinting?

Answer 17

1. Huntington’s disease: tri-nt repeats increased and earlier age of onset if transmitted thru male
2. Myotonic dystrophy: more likely to get expansion if transmitted thru female

Question 18

Describe copy no. variants (de novo changes) and implicated disorders

Answer 18

• segments of DNA that are 1 kn or larger and present @ a variable copy no. compared to reference genome
• these are mutations
• devp’mental delay, autism, schizo