GENETICS IN CLINICAL PRACTICE


REDUCED PENETRANCE

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

Methylation analysis

CHROMOSOME REARRANGEMENTS - FISH

NUMBER:

Aneuploidies: chromosome number not divisible by 23 (Downs, Patau, Edwards, Turner)

Polyploidies: multiple sets of 23 chromosomes

STRUCTURE:

Balanced (translocations 1/500)

Unbalanced (deletions, duplications, inversions, translocations)

FISH

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.

HARDY-WEINBERG PRICIPLE

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

#genomics

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