Week 1 GID Flashcards
Is stroke genetic or enviromental cause or both.
multifactorial with environment and polygenic factors. Sometimes can be caused by a single gene influence (Cadasil)
The traits of a genetic disorder
Rare, Genetics simple, Unifactorial, High recurrence rate: high chance of others to have disorder
The traits of enviromental disorder
Common, Genetically complex, multifactorial, low recurrence rate,
What does multifatorial mean
The combination of multiple gene inheritance and the affect of the enviroment
What is single gene mutation
mutation in a single gene
Chromosomal mutation
imbalance or rearrangement in chromosome structure eg aneuploidy, deletion, translocation
Mitochondrial
mutation in mitochondrial DNA
Somatic mutation
Mutation that occur in the general genes and can cause cancer
Does AD inhertiance run between generation and does it affect males or females more?
runs between generations and affects males and females equally
% chance of inheritance of AD disease
50% chance of inhertiance for new born
Give examples of AD inhertiance disease
Myotonic dystrophy
Marfan Syndrome
Huntington disease
What does penetrance mean?
The frequency with which a specific genotype is expressed by those individuals that possess it, usually given as a percentage.
What is incomplete inheritance and give example of mutation of this type?
not all relatives who inherit the mutation develop the disorder – eg BRCA1 mutations 80% life time chance of developing breast cancer
What type of inheritance is AD
incomplete inheritance
What does expressivity mean?
variation in expression - the extent to which a heritable trait is manifested by an individual. how the disease shows itself
What does Anticipation mean and give example
the symptoms of a genetic disorder become apparent at an earlier age as it is passed from one generation to the next. In most cases there is an increase in the severity of symptoms too. Example is Huntington’s disease
New mutation/ De novo
a new mutation that has occurred during gametogenesis or in early embryonic development. The parents do not have it
Is Ar disease passed on between generations and equal between genders
Usually only seen in one generation and equal in affect
Is Ar inheritance gene mutation or chromosomal deletion
gene mutation
What is the chance of inheriting a Ar disease
1/4
Risk of the unbrone child being a carrier of Ar diseae
2/3rds
Give examples of Ar diseases
- Cystic fibrosis
- Many of the metabolic disorders
- Haemachromatosis
- Sickle cell disease
In X linked disease is the male or female affected
Male are affected but females can be mildly affected ranging to severe symtpoms
Can or cant a male transmit the XL disease and why?
It cannot because males only give the Y chromsome and therefore only transmit from the female
give examples of XL diseases
o Duchenne Muscular dystrophy,
o Fragile X syndrome
o Red / green colour-blindness
o Haemophilia
What are the probablities for the child if the mother is a carrier
o 1/4 (25%) normal girl + 1/4 (25%) carrier girl
o 1/4 (25%) normal boy + 1/4 (25%) affected boy
Probablity if the father is affected
o All daughters are carriers
o All sons are unaffected (no male to male transmission
The two main factors that affect the expression of the phenotype of XL disease in females is
X inactivation
XL dominant vs XL recessive inheritance
Can you predict the phenotype of a female who havea XL disease with prenatal testing?
NO
What is X inactivation
It is when the gamete has two X chromosomes and one of the X chrosome is randomly switched off. Occurs in embryogensis
Examples of Xl dominant disease
o Rett syndrome (lethal in males, phenotype only in females)
o Fragile X syndrome – females:- asymptomatic to fully symptomatic ( due to X-inactivation pattern)
Examples of Xl recessive disease
o Red-green colour blindness
o Haemophilia
o Duchene Muscular dystrophy
o Carrier girls usually unaffected BUT can have significant symptoms because of X-inactivation (switches off normal X)
o Girls fully affected if inherit mutation from mum and dad
Is mitchondrial inheritance maternal or paternal inherited and why?
It is maternally inherited because the sperm has no mitochondria so all comes from the mother
how many genes within the mitchondrial DNA
27
Give exampes of non genetic testing
Blood testing –> enzyme assasys
Haemotology–> thalasemia
X Rays
Examples of genetic testing
o Genomic architecture –> Cytogenetics
o Sequencing –> OLA assays + MLPA tests
What does Pharmacogenomics mean?
Analysing entire genomes, across groups of individuals, to identify the genetic factors influencing responses to a drug.
What does Pharmacogenetics mean?
Studying an individual’s genetic make up in order to predict responses to a drug and guide prescription
What is Chronic myeloid leukemia ?
It is the translocation of a part of chromosome 9 with 22. Causing the over production of WBC
What is the name of the chromsome that caries the BCR/abl gene of CML
Philadelphia chromosome
What treatment is given to treat CML
Glevec
what test do you do if you already know the identity of the mutation?
simple and cheap analytical methods –> robust assay
What tests do you do if you don’t know the identity of the mutation?
You do clonal sequencing and discovery methods ( Sanger DNA sequences)
What enzyme is used to add nucleotides in DNA replication/sequencing
DNA polymerase
Go through the process of PCR
Heat too 97 degrees to denature and sepearte the DNA strand.
Then cool down to 50 degrees for annealing and allow the adding of primers
Then heat slightly too 72 degrees for the addition of nucleotides –> DNA poylmerization can occur
Give examples of what PCR can be used for?
Identifity genetic finger prints
DNA sequences
Isolation of specific DNA strands
Why do DNA move through the gel electrophersis
Because they are negatively charged due to the phosphate backbone
What is the factor that causes the different movement of DNA strands
The size of teh DNA strand
What is allele specific PCR used for
For the absense or presence of product
What is the common mutation in CF
3 base pair deletion –> elimination of a single aa
what is the most common inherited cause of deafiness
connexin 26
What is connexin 26
1 base pari deletion –> nucleotide 35
what is Allele specific mutation detection ?
Process by distinguishing from two different alleles that may only have a single diference in one base
What information does the CF genotype assay is used for?
carrier screening in adults in reporductive age
aind in new born screeing
used in testing new borns and children
What is Cf genotype assay not used in?
Pre implantation testing and fetal diagnostic
Why might the tempalte be unsuitable for PCR
To big for the PCr
Fragile X syndrome FMR1 gene has repetitive tract of (CGG)n sequence
Have to many GC rich regions
What technique is used for unsuitable templates for PCr
Southern blotting
what technique do you use for identifying unknown mutation and what is the pros
DNA sequence –> find the exact postion of the mutation and what type of mutation it is
For DNA sequencing what do you need for the addition of nucleotides
Free hydroxl group on the 3 end
What direction is DNA sequencing ?
5 to 3 direction
What DNA is sequenced by clonal sequencing?
Exome panels –> only exons of the gene
Why do DNA testing
confirm or refute clinical diagnosis, prenatal testing, assess carrier status and for predicting testing
