Majid Flashcards
Malformation
A morphological abnormality that arises because of an abnormal development process
E.g. Cleft palate
Dismorphology
The recognition and study of birth defects and related syndromes
Syndrome
A particular set of developmental abnormalities that are known or assumed to be the result of a single aetiology
E.g. Down’s syndrome
The 5 types of genetic components to congenital disorders:
- Single gene (monogenic/Mendelian)
- Multifactorial (polygenic): many loci and environmental factors
- Multifactorial mosaic (different tissue-specific expressivity)
- Mitochondrial
- Chromosomal abnormalities (numerical/structural)
Penetrance
The percentage of individuals expressing the disorder (to any degree)
Age dependent penetrance
Features are not present at birth but are progressive (e.g. Huntingtons)
Incomplete penetrance
Not all carriers will manifest disease in their lifetime
Eg. HNPCC- heredity non-polyposis colorectal carcinoma
Expressivity
The variation in severity between individuals with the same mutation
Anticipation
The worsening of disease severity in successive generations
E.g. Triplet repeat expansion in the paternal germ line in Huntington’s disease
Somatic mosaicism
A new mutation arising at an early stage in embryogenesis can give rise to a partial phenotype
Germline mosaicism
A new mutation arising during oogenesis or spermatogenesis may cause no phenotype in the parent but can be transmitted to offspring
Describe dominant negative mutations
Mutant copy impairs function of WT. In proteins with multiple units (e.g. Haemoglobin) a mutation in one subunit will disrupt the whole complex
Give an example of a gain of function mutation.
FGFR3 mutation allows constitutively active FGF signalling in the absence of a ligand. This inhibits chondrogenesis (development of cartilage).
Main cause of dwarfism
Describe the 3 types of nucleotide substitutions.
Synonymous: does not result in AA change
Missense: results in AA change (not all are pathogenic)
Nonsense: substitution generates a stop codon. Results in truncation (normally pathogenic)
Copy number variation
Phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals
Copy number variation can involve:
- Small genomic regions (coding and non coding)
- Whole genes
- Contiguous stretches of genes (share a common border)
Give 2 examples of genes with multiple copies and the advantage of this.
- Amylase: can have up to 16 copies. Allows faster digestion of starch
- Cytokine: HIV binds to cytokine receptors to infect lymphocytes. People with more cytokine copies are more resistant to HIV as there is more competition for receptors
Haplotype
a group of genes in an organism that are inherited together from a single parent.
SNPs have a minor allele frequency of…
1%
How many differences are there in the SNPs of two random people when their genomes are compared?
3 million
1 SNP in every 1000bp
Give an example of a SNP allele that contributes to disease.
E4 allele of APOE gives individuals a higher risk of developing Alzheimer’s
Give an example of a protective SNP allele.
Deletion with CCR5 makes individuals resistant to HIV
Define linkage peak
The peak in a graph of LOD against genomic position
Association studies look for…
Association between SNPs and a trait/disease
Linkage disequilibrium
Nom-random association of alleles at two or more loci
Haplotype blocks
Regions of high LD separated by recombination hotspots
SNPs can be arranged in haplotype blocks
