Mendelian Inheritance of Human Disease Flashcards
What is a chromosome?
A linear DNA molecule.
What is a gene?
A length of DNA that encodes a specific protein.
What is an allele?
An alternative form of a gene at a specific locus.
How many chromosomes do humans have?
46 chromosomes (23 pairs).
What does homozygous mean?
Having identical alleles at a given locus.
What does heterozygous mean?
Having different alleles at a given locus.
What is a Genetic Disease?
A disease caused by a change in the gene sequence or chromosomal structure.
Types of genetic abnormalities?
- Aneuploidy (extra/missing chromosome)
- Chromosome fragments (extra or missing pieces)
- Base substitutions or indels
- Trinucleotide repeat expansions
Where can mutations occur in the gene structure?
Promoter, intron, exon, splice sites.
Mutation in promoter/splice site effects?
Stops transcription or causes abnormal splicing.
What does a missense mutation do?
Changes the amino acid sequence of a protein.
What is a nonsense mutation?
Introduces a premature stop codon.
What is the effect of indels?
- In-frame indels: insert/delete a multiple of 3 bases (may still produce a functioning protein).
- Out-of-frame indels: disrupt the reading frame, usually resulting in a nonfunctional protein.
What defines Mendelian inheritance?
Diseases caused by a single gene mutation passed in predictable patterns (dominant, recessive, X-linked).
What is required for an autosomal dominant disease to manifest?
One faulty copy of the gene.
Key features of autosomal dominant inheritance?
- Appears in every generation
- Affected individuals have a 50% chance of passing it on
- Both sexes equally affected
- May show variable expression or nonpenetrance
What are some example diseases of autosomal dominant inheritance?
- Marfan’s Syndrome (FBN1 mutation)
- Hereditary Haemorrhagic Telangiectasia (HHT1: Endoglin gene, HHT2: ALK1 gene)
What is allelic heterogeneity?
Different mutations in the same gene cause the same disease.
What is locus heterogeneity?
Different genes can cause the same disease.
What is required for disease to occur in autosomal recessive inheritance?
Two faulty gene copies (one from each parent).
What are they key features of autosomal recessive inheritance?
- Often only one generation affected
- 25% chance of affected child if both parents are carriers
- Common in consanguineous families
Example disease of autosomal recessive inheritance
Sickle Cell Anaemia (Glutamate > Valine mutation due to A>T substitution)
How are X-linked recessive disorders inherited?
- Carrier mothers pass to 50% of sons (affected) and 50% of daughters (carriers)
- Affected males pass the mutation to all daughters (carriers) but no sons
What is an example disease of X- Linked recessive inheritance
Duchenne Muscular Dystrophy
