203 L5 Flashcards
Testing genetic disorders
Progress in molecular medicine
First thing that is done is to identify the disease with —— components that are —— and ———.
Preventative medicine
Treatment of —— disease is advanced for disorders in which the underlying ———- phenotype is well characterised
Example: inborn errors of metabolism
Babies that are born and screened for these inborn errors, can actually be treated
Babies with PKU deficiency - dietary intervention by decreasing the intake of ———– prevents symptoms of the disorder
Pharmacogenomics
Personalised ——- based usually on the response to ——–
Commonly used in ——– treatments because different people with different genotypes, ———- different drugs in different ways
Targets the individual based on their ———–.
Gene therapy
———— modification of the patient ——
E.g. transplanting the —— to overcome the deficiency, encouraging the killing of harmful cells, stem cell treatment
First thing that is done is to identify disease with genetic components that are inherited and genes
Preventative medicine
Treatment of gentic disease is advanced for disorders in which the underlying biochemical phenotype is well characterised
Example: inborn errors of metabolism
Babies that are born and screened for these inborn errors, can actually be treated
Babies with PKU deficiency - dietary intervention by decreasing the intake of phenylalanine prevents symptoms of the disorder
Pharmacogenomics
Personalised medicine based usually on the response to drugs
Commonly used in cancer treatments because different people with different genotypes, metabolise different drugs in different ways
Targets the individual based on their genotype.
Gene therapy
Genetic modification of the patient cells
E.g. transplanting the genes to overcome the deficiency, encouraging the killing of harmful cells, stem cell treatment
What is genetic testing
The analysis of human ——, ——-, ————, ——— or certain metabolites in order to detect ————- related to a ——— disorder
Direct testing - looking at the —— and ——– that makes up a gene (looking for mutations)
Cytogenetic testing - examining the ———- (structure and number)
Biochemical testing - assaying certain metabolites
The analysis of human DNA, RNA, chromosomes, proteins or certain metabolites in order to detect alterations related to a genetic disorder
Direct testing - looking at the DNA and RNA that makes up a gene (looking for mutations)
Cytogenetic testing - examining the chromosomes (structure and number)
Biochemical testing - assaying certain metabolites
Genetic services
Are organised to coordinate gene testing, and are typically multidisciplinary teams located at specialist centres
Genetic testing can be arranged, performed and their results can be interpreted and reported back to the patients
Genetic counseling provides ongoing psychosocial support for patients and family members, translation of information from the multidisciplinary team
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Is a genetic test just like any other medical test?
—– because the results don’t ———, it forms a permanent record for the studied individual
Need to be able to accurately convey the results to the patient because it could have an impact on the family as well
No because the results don’t change, it forms a permanent record for the studied individual
Reasons for a referral to a genetics clinic
A child born with several abnormalities - looking for specific mutations
There is a history in the family of a medical condition - Looking for the specific mutation inherited in the family
Women who have a history of several miscarriages - Tested for chromosomal abnormalities
Women over 35 years and pregnant - Tested for chromosomal abnormalities
A family member diagnosed with cancer at a young age
Family history of cancer
Anyone uncertain about their genetic risks and family medical background
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Diagnostic testing
Used to help confirm a specific ——- in a patient who already has ————-.
Pre-symptomatic or predictive testing
Offered to ————- individuals with an increased risk of a family ———- of a ——– disorder
Important if early diagnosis allows interventions which improve health outcomes
Used to help confirm a specific condition in a patient who already has symptoms
Pre-symptomatic or predictive testing
Offered to asymptomatic individuals with an increased risk of a family history of a genetic disorder
Important if early diagnosis allows interventions which improve health outcomes
Genetic testing: some practical issues
Have we got a confirmed phenotype associated with the disease?
- A way to determine which genes are going to be tested for
What is the pattern of inheritance?
- Essential for the interpretation of the data
- Points to how we can cancel to families
Which genes should we test, is the test available?
- Test are often not clinically available but research available (often for rare diseases)
What is the advice to the patient if the test is positive or negative
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Genetic heterogeneity
Locus heterogeneity
Where the —— clinical phenotype can result from mutations at any of the ——-.
Different ——-, many mutations = ——- disease
Example
Retinitis Pigmentosa
Group of eye conditions that leads to an incurable blindness
Extensive locus heterogeneity - 30-35 gens can cause the disease.
Allelic heterogeneity
Where many different ———- within the —– gene can be seen in ———— patients with a —— genetic condition
——- gene, many mutations = disease
Example
Cystic fibrosis
1000 known mutant alleles in single CFTR gene can cause CF
Most common is the F508, (causes an in-frame shift to remove a single amino acid from the protein)
Where the same clinical phenotype can result from mutations at any of the loci.
Different genes, many mutations = same disease
Example
Retinitis Pigmentosa
Group of eye conditions that leads to an incurable blindness
Extensive locus heterogeneity - 30-35 gens can cause the disease.
Allelic heterogeneity
Where many different mutations within the same gene can be seen in different patients with a certain genetic condition
same gene, many mutations = disease
Example
Cystic fibrosis
1000 known mutant alleles in single CFTR gene can cause CF
Most common is the F508, (causes an in-frame shift to remove a single amino acid from the protein)
Penetrance
The probability that a gene will have any phenotypic expression or the percentage of people with a certain genotype who are actually affected
100% penetrance is unusual
Reduced penetrance caused by: Skipping a generation Normal carriers The result of modifying genes Environment factors Causes difficulties in genetic counselling
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Expressivity
Variation in the severity of the problems arising from a particular genetic defect
Manifestation of a phenotype (development of symptoms) differs in people with the same genotype
Even within a family different members show different features of the syndrome
e.g. Waardenbug syndrome
One is deaf, the other has white hair.
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Preimplantation genetic diagnosis
Testing —– of the developing ——- before putting it back into the mothers —–.
Testing cells of the developing embryo before putting it back into the mothers uterus
Prenatal diagnostics
Genetic testing of the ——- (e.g. down syndrome testing)
fetus
Presymptomatic genetic testing
———- screening, done just after ——–, looking for inborn errors of ———–.
Newborn screening, done just after birth, looking for inborn errors of metabolism
Presymptomatic or predictive genetic testing
There are a number of single gene disorders which appear postnatally or have delayed age of onset (things that happen in adulthood but can be tested earlier)
These tests are usually used if there is an intervention that could help so you could alter your lifestyle factors
The results allow you to predict whether a person has inherited the gene before the onset of symptoms or signs
Tests are often offered in early adulthood
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Prenatal Diagnosis
Chromosomal and genetic analysis of a fetus, by the analysis of cultured cells from the amniotic fluid
Important for testing women of late maternal age for an increased risk of down syndrome (trisomy 21)
The ethical issues surrounding prenatal diagnosis and selective termination of pregnancy
Goals of prenatal diagnosis
Not simply to detect abnormalities and terminate pregnancy
All parents to make an informed choice
Provide reassurance and reduce anxiety in high risk groups, who might otherwise forgo pregnancy
To provide couples with an affected child time to prepare for the arrival
To enable prenatal treatment of the affected child
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