Modes of Inheritance

Question 1

dominant autosomal disorders?

Answer 1

a single gene/allele disease which is passed to offspring with multiple generations affected
each affected person usually has one affected parent

Question 2

why are brown eyes dominant?

Answer 2

OCA-2 controls amount of melanin in melanocytes
active OCA-2 –> melanocyte –> brown eyes
inactive OCA-2 –> no melanocyte –> blue eyes

Question 3

chromosomes?

Answer 3

46 in 23 pairs
22 are autosomal, then a pair of sex chromosomes

Question 4

what other DNA do we have?

Answer 4

mitochondrial DNA
inherited from mother

Question 5

gene locus meaning?

Answer 5

position of gene on a chromosome

Question 6

single gene disorders?

Answer 6

most common gene disorder
affect all body systems
can cause a large health burden

Question 7

definition of dominant?

Answer 7

if a condition manifests in a heterozygote
refers to phenotype, not the gene

Question 8

pedigree for autosomal dominant conditions?

Answer 8

vertical pedigree pattern
males and females equally affected

Question 9

3 types of changes that cause a dominant condition?

Answer 9

gain of function - gene now makes protein with a new function
dominant negative effect - mutated form interferes with activity of proteins it binds; this reduces activity
insufficient - mutant in one gene results in 1/2 the amount of a protein that’s not enough for normal function

Question 10

example of dominant genetic mutation?

Answer 10

osteogenesis imperfecta = brittle bone disease

Question 11

osteogenesis imperfecta?

Answer 11

=brittle bone disease
bones break easily
hearing loss, breathing problems, short height

caused by:
mutations in Type I - IV collagen
this results in abnormal protein with an altered structure which interferes with the function of the normal protein

Question 12

carriers?

Answer 12

individuals who have lost a single copy of the gene but the normal one is sufficient to maintain normal function

Question 13

recessive disorders?

Answer 13

2 copies of abnormal gene must be present in order for disease to develop
tend to be loss of function mutations

Question 14

pedigree for autosomal recessive?

Answer 14

parents and children of affected people normally unaffected but are carriers
one or more siblings affected
each subsequent sibling of an affected child has 1 in 4 chance of being affected
males and females equally affected
=HORIZONTAL PEDIGREE PATTERN

Question 15

risk factor for autosomal recessive conditions?

Answer 15

consanguineous marriages

Question 16

cystic fibrosis?

Answer 16

recessive genetic mutation
defective chloride ion channels result in mucus build-up and impaired airway defence, these individuals are prone to respiratory infections

mutations are in gene encoding chloride ion channels

single copy of normal gene is sufficient to prevent mucus build up (because condition is recessive)

Question 17

type of mutation in cystic fibrosis?

Answer 17

loss of function mutation

Question 18

how many genes on X chromosome

Answer 18

1000-1300 genes

Question 19

no. of genes on Y chromosome?

Answer 19

150 genes

Question 20

X-linked recessive disorder

Answer 20

affects mainly males because effectively dominant for them as they only have one copy of the X chromosome

females can be carriers and affected males linked through females
although females homozygous for condition will have the condition
parents and children of those affected are most commonly unaffected

Question 21

pedigree for X-linked recessive?

Answer 21

brothers of affected son have 1/2 chance of having disorder
sister 1/2 chance of being carrier
all daughters of a man with condition will be carriers as males only have one copy of X chromosome
all sons healthy, as they inherit Y from father

Question 22

example of X-linked recessive?

Answer 22

haemophilia

Question 23

can female carriers exhibit subtle signs of the disease?

Answer 23

yes e.g. in Fabry’s disease

Question 24

X-linked dominant disorder?

Answer 24

similar to autosomal dominant
ALL DAUGHTERS AND NO SONS OF AFFECTED FATHER ARE AFFECTED
if mother is affected, both sons and daughters could be affected
condition often milder and more variable in females than males

Question 25

example of X-linked dominant disorder?

Answer 25

X-linked hypophosphatemia
PHEX gene mutation = overproduction of FGF21
FGF21 inhibits kidney phosphate reabsorption
kidneys cannot retain phosphate
=low levels of blood phosphate
- vitD resistant rickets

Question 26

Y-linked disorders?

Answer 26

only affects males
ALL SONS OF AN AFFECTED FATHER ARE AFFECTED

Question 27

example of Y-linked disorder?

Answer 27

Retinitis Pigmentosa
mutation in RPY gene
cells of retina produce defective protein

Question 28

why are mitochondria special?

Answer 28

specialised organelle of eukaryotic cells and share past with bacteria
HAVE THEIR OWN DNA

Question 29

how does mitochondrial disease affect different genders?

Answer 29

ALL MITOCHONDRIA INHERITED FROM MOTHER
all children of affected mother may be affected
children of affected men never affected

Question 30

pedigree pattern for mitochondrial disease?

Answer 30

vertical pattern

Question 31

heteroplasmy?

Answer 31

mitochondria have multiple copies of gene, some are normal and some are mutant
disease affects are only expressed above a threshold (certain number of mutant gene copies required)

Question 32

how do mitochondria replicate?

Answer 32

via binary fission, this means they can lose or gain mutated genes

Question 33

variability of mitochondrial disease?

Answer 33

random segregation
severity of symptoms vary with:
number of affected mitochondria
symptoms develop once threshold reached
each cell has many mitochondria that segregate randomly during cell division
this means disease develops with age due to accumulation of mutant mitochondria

Question 34

presentation of mitochondrial disease

Answer 34

unrelated multi-system symptoms
motor and nerve function commonly affected
KEY IS THAT THESE CONDITIONS ARE EXTREMELY VARIABLE (EVEN WITHIN THE SAME FAMILY)

Question 35

example of mitochondrial disease?

Answer 35

LHON
vision loss in adulthood, degeneration of optic nerve and retina
typically in males