Genetics: modes of inheritance Flashcards
What is human genetic material encoded on?
chromosomes
How many chromosomes do humans have?
46
23 pairs
22 autosomal pairs + sex chromosomes (XX or XY)
What other DNA do we inherit other than chromosomal?
mitochondrial DNA
16500 bp, encodes 15 proteins, rRNA and some tRNAs
most mitochondrial proteins are encoded by cell genome
Where is the mitochondrial DNA derived from?
the mother
Homozygous for a gene?
contains 2 identical copies of an allele
Heterozygous for a gene?
contains 2 different alleles
What is a locus?
the position of the gene on a chromosome?
What are single gene disorders?
affect all body systems
(most common)
cause a large health burden
What are chromosomal disorders?
occur when the chromosome are damaged during the formation of the sperm or egg or during early development of the embryo
What are complex disorders?
result from a combination of genetic and environmental factors interacting
eg. obesity, type II diabetes
What is autosomal dominant?
A characteristic is dominant if it manifests in a heterozygote (ie two different alleles at a locus)
What are we referring to when talking about dominance?
phenotype
What gene is responsible for eye colour?
OCA-2
active OCA-2 –> melanocytes full of melanin (brown)
inactive OCA-2 –> melanocytes no melanin (blue)
Dominant autosomal disease?
single gene/allele
How is an autosomal dominant disease passed down?
Each child of an affected person has a 1 in 2 chance of being affected
Males and females are equally affected and equally likely to pass on the condition
What pedigree diagram represents the autosomal dominant disease?
Vertical pedigree pattern
What is huntingtons disease?
Symptoms usually start 30-50 years of age
Difficulty concentrating, depression, stumbling, involuntary jerking, problems swallowing
Abnormal intracellular Huntington protein aggregate gains a pathological function and is toxic to neurons resulting in cell death
What is brittle bone disease?
Osteogenesis imperfecta
Bones break easily
Weakening connective tissue particularly bone
What is the “gain of function” dominant autosomal disorder?
gene now makes a protein with a new function
eg longer lifespan/new location thus increasing their effect
What is the “dominant negative effect” dominant autosomal disorder?
the mutated form interferes with the activity of proteins it binds
eg dimers or multimers which reduces activity
What is the “Insufficient” dominant autosomal disorder?
mutant in one gene results in ½ the amount of a protein that is not enough for normal function (rare)
What are autosomal recessive disorders?
two copies of the abnormal (non-working) gene must be present in order for the disease or trait to develop
Tend to be ‘loss of function’ mutations (eg deletions)
Who are “carriers” of autosomal recessive diseases?
They have lost a single copy of a gene but the normal one is sufficient to maintain normal function
What pedigree chart is used for an autosomal recessive disease?
A horizontal pedigree pattern
What pedigree chart is used for an autosomal recessive disease?
A horizontal pedigree pattern
What is Cystic Fibrosis?
Defective chloride ion channel
Results in impaired airway defense
Prone to respiratory infections
Digestive issues eg meconium ileus
What mutations give rise to cystic fibrosis?
Various mutation in gene encoding chloride ion channel (CFTR gene on chromosome 7)
What are the sex chromosomes?
Consist of an X and a Y chromosome
Determine the sex
How many genes do the X and Y chromosomes contain?
- X-chromomsome 1000- 1300 genes (~850 protein coding)
- Y-chromosome 150 genes (50-70 protein coding)
What are X-linked recessive disorders?
- Affects mainly males – effectively dominant
- Females can be carriers
- Females who are homozygous for the mutation (two copies) have the disorder
What are the chances of being affected by having an unaffected father and carrier mother?
boys- 1/2
girls- 1/2 of being a carrier
What is an example of an x-linked recessive disorder?
Haemophilia
- In some cases female carriers exhibit subtle signs of the disease
What are X-linked dominant disorders?
- Similar to autosomal dominant pattern
- all daughters and no sons of an affected father are affected
(Condition often milder and more variable in females than in males)
What is an example of an X-linked dominant disorder?
hypophosphatemia
Results in vitamin D-resistance rickets
What are Y-linked disorders?
- Affects only males
- All sons of an affected father
very few- bc only a few genes are encoded on Y chromosome
What is an example of a Y-linked disorder?
Retinitis Pigmentosa
Cells of retina produce a defective protein
What pedigree chart is used for a Y-linked disease?
vertical pedigree
What are mitochondrial inherited disorders?
caused by mutations in Mitochondrial DNA
How are mitochondrial disorders inherited?
Are maternally inherited
- All children of an affected woman may be affected
- Children of affected men are never affected
Mitochondrial disease variability
- Mitochondria have multiple copies genome some normal some mutant (heteroplasmy)
- Only express disease effects above a threashold
How else are mitochondrial diseases caused?
by mutations in cell genome and have mendalian or sex chromosome linked inheritance
How does a mitochondrial disease develop?
- Random segregation
- Number of affected mitochondria
- Symptoms develop once threshold reached
- Cells different number mutant mitochondria
can change with time
When do mitochondrial diseases develop?
with age due to accumulation of mutant mitochondria
What is an example of mitochondrial disease?
Motor and nerve function commonly affected
Leber’s hereditary optic neuropathy (Visual loss in young adulthood)
