Modes of Inheritance Flashcards
dominant autosomal disorders?
a single gene/allele disease which is passed to offspring with multiple generations affected
each affected person usually has one affected parent
why are brown eyes dominant?
OCA-2 controls amount of melanin in melanocytes
active OCA-2 –> melanocyte –> brown eyes
inactive OCA-2 –> no melanocyte –> blue eyes
chromosomes?
46 in 23 pairs
22 are autosomal, then a pair of sex chromosomes
what other DNA do we have?
mitochondrial DNA
inherited from mother
gene locus meaning?
position of gene on a chromosome
single gene disorders?
most common gene disorder
affect all body systems
can cause a large health burden
definition of dominant?
if a condition manifests in a heterozygote
refers to phenotype, not the gene
pedigree for autosomal dominant conditions?
vertical pedigree pattern
males and females equally affected
3 types of changes that cause a dominant condition?
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
example of dominant genetic mutation?
osteogenesis imperfecta = brittle bone disease
osteogenesis imperfecta?
=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
carriers?
individuals who have lost a single copy of the gene but the normal one is sufficient to maintain normal function
recessive disorders?
2 copies of abnormal gene must be present in order for disease to develop
tend to be loss of function mutations
pedigree for autosomal recessive?
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
risk factor for autosomal recessive conditions?
consanguineous marriages
cystic fibrosis?
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)
type of mutation in cystic fibrosis?
loss of function mutation
how many genes on X chromosome
1000-1300 genes
no. of genes on Y chromosome?
150 genes
X-linked recessive disorder
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
pedigree for X-linked recessive?
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
example of X-linked recessive?
haemophilia
can female carriers exhibit subtle signs of the disease?
yes e.g. in Fabry’s disease
X-linked dominant disorder?
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
example of X-linked dominant disorder?
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
Y-linked disorders?
only affects males
ALL SONS OF AN AFFECTED FATHER ARE AFFECTED
example of Y-linked disorder?
Retinitis Pigmentosa
mutation in RPY gene
cells of retina produce defective protein
why are mitochondria special?
specialised organelle of eukaryotic cells and share past with bacteria
HAVE THEIR OWN DNA
how does mitochondrial disease affect different genders?
ALL MITOCHONDRIA INHERITED FROM MOTHER
all children of affected mother may be affected
children of affected men never affected
pedigree pattern for mitochondrial disease?
vertical pattern
heteroplasmy?
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)
how do mitochondria replicate?
via binary fission, this means they can lose or gain mutated genes
variability of mitochondrial disease?
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
presentation of mitochondrial disease
unrelated multi-system symptoms
motor and nerve function commonly affected
KEY IS THAT THESE CONDITIONS ARE EXTREMELY VARIABLE (EVEN WITHIN THE SAME FAMILY)
example of mitochondrial disease?
LHON
vision loss in adulthood, degeneration of optic nerve and retina
typically in males
