GENETICS IN CLINICAL PRACTICE
The proportion of carriers who manifest phenotypic signs of their condition - not all inheritors of a dominant disease mutation necessarily show signs of the condition.
eg. Cherubism occurs with 100% penetrance in males and 50-70% penetrance in females, with 2:1 male predominance.
LINES OF BLASCHKO
Represent territories of clonal cell populations: some using normal X chromosome, some using mutated X chromosome.
Can be manifested in X linked dominant disorders such as incontinentia pigment and Goltz Focal dermal hypoplasia.
TYPES OF GENETIC TESTS
Standard Chromosome analysis
Fluorescent in citu hybridisation FISH
Comparative genomic hybridisation array Array CGH
Single gene testing
Next generation sequencing NGS
CHROMOSOME REARRANGEMENTS - FISH
Aneuploidies: chromosome number not divisible by 23 (Downs, Patau, Edwards, Turner)
Polyploidies: multiple sets of 23 chromosomes
Balanced (translocations 1/500)
Unbalanced (deletions, duplications, inversions, translocations)
Good at detecting Chromosome rearrangements
COMPARATIVE GENOMIC HYBRIDISATION ARRAY aCGH
Identifies very small genomic imbalances: autism spectrum disorder, psychiatric disease, congenital abnormalities
SINGLE GENE TESTING
For diagnosis/confirmation of genetic disorders, reproductive options such as prenatal diagnosis and pre-implantation genetic diagnosis.
NEXT GENERATION SEQUENCING
Determines the actual order of nucleotides in DNA.
A simple model that explains gene frequencies in a population and is therefore useful for calculating the risks of autosomal recessive disorders. lets say dominant is p and recessive is q.
Then we have, AA:p^2, Aa:pq, aa:q^2
We also know that p+q=1
and that p^2+2pq+q^2=1
So if we have cystic fibrosis, incidence 1:2500
we know that q^2=1/2500, so q must be 1/50, and then carrier frequency is 2pq