Week 1: Introduction to medical genetics Flashcards
Types of non-coding DNA
1) Satellite DNA
2) Telomeres
3) Introns
4) Non-coding RNA genes
5) Gene regulatory sequences
Satellite DNA
Tandemly repeating sequences of DNA, a structural component of heterochromatin and centromeres that are conmmonly used for DNA profiling
Telomeres
Regions of repeting DNA at the end of a chromosome to protect against chromosomal deterioration during replication + acts as an anti-cancer mechansim
Introns
Non-coding sequences within genes and are removed during the RNA splicing process prior to the formation of mRNA
Non-coding RNA genes
Codes for RNA molecules that are not translated into protein ie genes that code for tRNA
Gene regulatory sequences
Sequences that are involved in the process of transcription including promoters, enhancers + silencers
What is gene expression and why is it important?
- Gene regulation moderates gene expression, determiong what is expressed + what isn’t
- Regulation of gene expression is important as it would be a waste of energy if everything was expressed all at once
How do defects in genes cause disease?
- Mutation = Defective genetic material = defective protein product
- Types of mutations:
+ Insertion
+ Deletion
+ Substitution - Not all mutations are bad, in fact most are neutral
Pleiotropy
Where a gene mutation that may affect 2 or more seemingly unrelated traits ie sickle cell disease where blood cells are mishaped but people possessing this trait seem to be resistant to malaria
Types of genetic disorders
- Monogenic disorders
- Polygenic/multifactorial disorders
- Chromosomal abnormalities
- Mitochondrial disorders
Monogenic disorders
- Subject to Mendelian inheritance
- DIsorders caused by errors in a single gene
- Several patterns of inheritance can result depending on the chromosome affected + whether 2 or 1 copy of the gene is defective
X-linked recessive disorders
- Mutation in the gene located on the X chromosome
- Affects more men compared to gemales as females have an extra X chromosome to compensate
- Mother passes the mutant allele to 50% of the daughters and 50% of the sons
- Affected fathers pass on the mutant allele to 100% of daughters but none of his sons
- Therefore only men related through the female line are affected
- For offspring born to female carrier, there is a 50 % chance that each male will be affected + 50% each female will be a carrier
- Example: Duchenne muscular dystrophy
Autosomal recessive disorders
- Manifests only if both alleles are defective
- Each mutant allele is generally inherited from carrier parents
- If both parents are carries:
+ 50% will be carriers
+ 25% will be homozygous unaffected
+ 25% will be homozygous affected - Males and females are equally affected
- Examples: Sickle cell disease, cystic fibrosis
Autosomal dominant disorders
- Disease only manifests if only a single defective allele is inherited
- The normal or “wild-type” allele does not compensate for the mutant allele
- Affected individuals have a 50% chance of passing on the mutant allele and therefor the disease (if the other partner is unaffected)
- Both males and females are affected + transmit the disorder to sons and daughters
- Example: Familial hypercholesterolemia
Polygenic/multifactorial disorders
- Believed to represent the combined effect of several genes potentially interacting with environmental factors + epigenetic involvement/imprinting
- Often the subject of Genome-Wide Association Studies (GWAS) to identify causal candidate genes
- Examples: Obesity, type-2 diabetes, cardiovascular disease, alzheimers disease + schizophrenia
