Genomics and Epigenomics Flashcards
What is rare disease
It affects less than 1 in 2000 people
Typically single gene - can be monogenic, syndromes, or the genetic cause unknown
Give examples of monogenic rare diseases
Cystic fibrosis, phenylketonuria and sickle-cell disease
Give examples of syndromic rare diseases
Down syndrome – trisomy 21
Turner syndrome – monosomy X
DiGeorge syndrome – 22q11 deletion
What is common disease
Affects are more than one in 2000 people
Typically they are complex genetic diseases involving genetic and environmental factors
Come on non-genetic diseases such as bacteria infection may still involve genetics such as in susceptibility and resistance e.g. Covid 19 and ABO locus
Give examples of common non-infectious paediatric diseases
Obesity
Allergic disorders such as hayfever eczema asthma food allergies
Mental health disorders such as anxiety, eating, ADHD, schizophrenia
Learning disabilities
What are some examples of genome variations
SNP Microsatellite Minisatellites Copy number variation Structural variation Chromosomal variants
Describe chromosomal rearrangements
These can be insertions, deletions, inversions and translocations
Unbalanced – localised gene dosage changes
Balance – gene dosage is unaffected but can cause gene disruption or fusion products
An example of this is the chronic myeloid leukaemia BCR-ABL gene located on the Philadelphia chromosome
How are chromosomal rearrangements detected
INSERT ANS
What is are balanced and unbalanced translocations
Unbalanced - localised gene dosage changes
Balanced - gene dosage unaffected but fusion products can occur or it can fall under a different promoter
Example: in chronic myeloid leukaemia, a Philadelphia chromosome contains a BCR-ABL fusion gene, causing constant expression of ABL(a tyrosine kinase gene) causing increased unnecessary thus harmful cellular signalling pathways
What is penetrance and expressivity
Penetrance is when an individual has the disease genotype but do not express symptoms thus does not express a phenotype
Many diseases show age dependent penetrance
Expressivity is the severity of the symptoms and how they can differ person-to-person
What is pleiotropy
A mutation that affects multiple body systems
This is usually seen when the gene affected is involved in early development
What is sex-influence or limited inheritance
This is when there is over representation of a disease in one sex not due to the gene but due to other factors related to sex such as hormones or presence of womb/prostate etc.
What may be a complication caused by presence of de novo mutations when sequencing DNA for genetic diagnosis
De novo mutation may be discarded as the mutation is not found in the parents and may seem like an artefact
Analysis is performed after Mendelian inheritance is investigated
Give an example of a single gene that is associated with multiple disorders
The LMNA gene produces lamin A and C
These are nuclear lamin protein which form the fibrillar network
These are involved in many different disorders including muscular dystrophies
What is heritability
Heritability is the proportion of phenotypic variation due to genotypic variation
What are two ways of measuring heritability
GWAS
Twin studies
What is missing heritability
It is when GWAS results differ from twin studies
What are the possible reasons for missing heritability
GWAS may measure many infrequent or rare SNPs
Each SNP may have variable effect sizes
There may be copy number or structural variations
Epigenomic influence
Or maybe the measurements and investigations were conducted wrong
