Genes and disease 2 Flashcards
Diagnosis of genetic disorders often involves what? (3)
1- A physical examination
- Examine dysmorphic features
- Distinctive facial features, head circumference, distance between the eyes, length of arms and legs, neurological etc
2- Detailed medical family history
Occurrence of the same condition in more than one family member can indicate a genetic disorder
3- Genetic Testing
Molecular, chromosomal, and biochemical testing are used to diagnose genetic disorders
What is cytogenetics?
-
Examination of whole chromosomes for abnormalities
> Chromosome abnormalities can be numerical (wrong number of complete sets of chromosomes)
> Or structural when one or more chromosomes contain the wrong DNA.
1- What is the significance of chromosomal abnormalities?
2- Give an example of a mechanism behind chromosomal abnormalities.
1- Large-scale changes in chromosomes mean several genes can be affected
2- Chromosomes break or fail to segregate during meiosis or mitosis
What is karyotyping? How is it done? What does it allow geneticists to do?
- Examination of whole chromosomes for numerical abnormalities or structural abnormalities.
- Needs mitotic cells eg WBCs
- Stain metaphase chromosomes with eg Giemsa
- Giemsa dye stains heterochromatic regions dark and euchromatic regions as light bands.
- Characteristic pattern of bands to ID each chromosome
What are structural abnormalities can be seen? (3)
What numerical abnormalities can be seen? (3)
- Aneuploid: Incorrect total number of chromosomes
Anything other than 22+XX or 22+XY - Monosomy: only one of a pair, one homolog is missing
- Trisomy: three copies of one chromosome
Why are numerical sex chromosome abnormalities less problematic?
- The Y chromosome carries few genes
- An X chromosome can be inactivated (reduces the effect if have an extra X chromosome)
Many genetic disorders are caused by mutations affecting a single base or small part of a gene.
These changes cannot be detected by karyotyping and requires DNA based molecular genetic tests.
- What is molecular genetic testing?
> Name + explain an example.
- Looking for a specific gene, a certain mutation within a specific gene or any mutation on a specific gene .
> Fluorescencein situhybridization (FISH)
Complementary DNA sequences hybridise
Synthesise a probe to region of interest - labelled with fluorescent
Allow probe to hybridise to DNA of patient
If patient DNA has mutation hybridisation is prevented
What is amplification based- gene testing?
- Amplify the gene of interest-PCR
- Sequence the gene to look for DNA changes
> Enables genomes to be sequenced very rapidly
DIFFERENT TYPES OF GENETIC TESTING:
- What is the difference between the following:
1- Diagnostic testing
2- Predictive + pre-symptomatic genetic tests
3- Carrier testing
1- To confirm a diagnosis when a disease is suspected
Patients may already experience symptoms
Involve chromosome analysis, biochemical analysis and molecular testing
Provide choices in management/treatment
2- A predictive test can provide information about whether or not a person will develop or is likely to develop a specific condition, usually at a later stage in life
Done if the condition can be prevented or symptoms can be treated
Also the information may be useful in decisions about lifestyle and important life decisions
3- To identify whether a healthy unaffected individual is a carrier of a genetic condition
A carrier status has implications for future offspring
Offered to individuals with a family history of certain
1-What does pre-natal testing include?
1- Screens and diagnostic tests
- Identify the risk of developing a genetic disease or condition e.g. Combined test for Down’s syndrome uses ultrasound scans to measure the nuchal translucency (LESS THAN 3.5MM IS NORMAL) and a blood test to measure the levels of PAPP-A (LOW LEVELS ASSOCIATED WITH DOWNS SYNDROME) and hCG ( HIGH LEVELS ASSOCIATED WITH DOWNS SYNDROME)
> If results indicate the risk to be more than 1 in 150 then diagnostic tests are offered
Pre-natal testing:
- Explain the following diagnostic tests:
1- Chorionic villus sampling
2- Amniocentesis
1- Done between 11 to 14 weeks of pregnancy
Cells are taken from the chorionic villi using a needle
Cells are analysed for chromosomal abnormalities
2- Done between 15 to 20 weeks of pregnancy
Cells are taken from the amniotic fluid and analysed for chromosomal abnormalities
What is Non-invasive prenatal testing?
- Blood test taken from the mother in pregnancy, that uses DNA sequencing technology to evaluate whether a baby has a high chance of a certain chromosomal condition.
Where can patient’s get specialist genetic advice?
- Regional Genetic Centres
What 4 groups of people require referral to a specialist genetic centre?
1- Those with a known / suspected genetic disorder
2- Children with dysmorphic features / learning difficulties
3- Couples with a history of miscarriage
4- Those with a history of cancer
What is Crispr/Cas9?
- Clustered Regularly Interspaced Short Palindromic Repeats in bacterial genomes
- Cas9 is a bacterial protein that degrades foreign DNA (using CRISPR sequences to target)
In gene editing
Template RNA (sgRNA) and Cas9 introduced to a cell
sgRNA targets a gene
Cas9 cleaves the DNA which is then repaired
If a repair template is present, an edited gene can be inserted
If not NHEJ pathway is used
