Basics

Question 1

what can the aetiology of a disease range from

Answer 1

single gene to polygons or to 100% environmental

Question 2

what are the 5 types of genetic disease

Answer 2

single gene disease (rare than environmental disease)
multifactorial / complex disease - interaction of multiple genes in combination with environment such as type 2 diabetes
chromosomal diseases - imbalance or rearrangement in chromosome structure such as deletion or translocation
mitochondrial disease/mutation
somatic mutations - mutation within a gene in a defined population of cells ie breast cancer

Question 3

what are the 4 ways in which single genes may be inherited

Answer 3

autosomal dominant
autosomal recessive
x linked
mitochondrial

Question 4

describe autosomal dominant inheritance

give 3 examples of diseases associated with AD

Answer 4

offspring of affect person has a 50% chance of inheriting the mutation

Myotonic dystrophy
Marfan Syndrome
Huntington disease

Question 5

describe autosomal recessive inheritance

give examples of disorders

Answer 5

affected individuals must be homozygous or compound heterozygous - genes from both parents are affected so no working allele
risk of off spring being infected is 1 in 4

CF
metabolic disorders
hemochromastosis
sickle cell disease

Question 6

what is the risk of offspring being an unaffected carrier

Answer 6

2/3

Question 7

what is X linked inheritance and what is it determined by - who is affected most

Answer 7

disease within the X chromosome, females can be affected but more mildly than males
determined by X inactivation and whether the gene is dominant or recessive

Question 8

what happens with skewed X inactivation

Answer 8

the healthy X chromosome is inactivated instead of the mutated one

Question 9

how does tissue variability affect X linked inheritance

Answer 9

random preference for the X chromosome with the mutation to be active in the crucial tissue group such as muscle in Duchenne Muscular dystrophy (X linked recessive)

Question 10

what are some XL dominant disease and how common are they

Answer 10

rett syndrome - only in females as lethal in males, fragile X syndrome - males full symptomatic and females can be either

these are rare conditions

Question 11

what are some XL recessive diseases

Answer 11

red green colour blindness, haemophilia, Duchenne Muscular Dystrophy

Question 12

describe mitochondrial inheritance

Answer 12

all mitochondria are inherited from the mother, if disease is in the male it can’t be passed on - males and females affected equally
only 27 genes in mitochondrial DNA

Question 13

what is penetrance

Answer 13

the frequency with which specific genotype is expressed by those individuals that posses it - given as a percentage

Question 14

what can affect penetrance

Answer 14

age - older you are the greater the penetrance

Question 15

what is incomplete penetrance - give an example where this occurs

Answer 15

not all relatives who inherit the mutation develop the disorder eg BRCA1 mutations, 80% life time chance of developing breast cancer

Question 16

what is expressivity

Answer 16

variation in expression - the extent to which a heritable trait is manifested by an individual

Question 17

what is “anticipation” with genes

give examples of diseases with anticipation

Answer 17

the symptoms of genetic disorder be one apparent at an earlier age as it is passed from one generation to the next
ie more its passed through generations the more severe and earlier in age the disease is

myotonic dystrophy
huntington

Question 18

define new dominant ore de novo dominant

Answer 18

a new mutation that has occurred during gametogenesis or in early embryonic development

Question 19

what is consanguinity and what are the consequences

Answer 19

couples who are blood relatives
potentially share recessive gene mutations
risk of congenital brith defect (5-6%) if no family history of genetic condition