Genetics Flashcards
When does DNA replication occur?
During S - Synthesis phase
Mutation?
May or may not cause a disease
What is an acrocentric chromosome?
A chromosome in which the centromere is located quite near one end. They are number 13, 14, 15, 21 and 22
Aneuploidy vs Translocation
Aneuploidy is an extra or missing chromosome
Translocation is rearrangement of chromosome
What causes Down Syndrome
Extra chromosome 21, acrocentric chromosome
What is Robertsonian translocation?
Two acrocentric chromosomes stuck end to end
Edwards Syndrome
Trisomy 18
Small head, clenched fist, cleft lip or palate, toes may be clubbed or fused
Causes of the following -
Turners Syndrome
Triple X
Klinefelter Syndrome
Turners Syndrome - 45 X
Triple X - 47 XXX
Klinefelter Syndrome - 47 XXY
Which translocations have no effect on phenotype
Balanced translocations
What can large unbalanced dislocations result in?
Miscarriage
What is FISH used for
FISH - Florescent in Situ Hybridisation is used to detect and localize the presence or absence of specific DNA sequences on chromosomes
Microarray CGH
Array Comparative Genomic Hybridisation (aCGH)
Detects missing or duplicated chromosomes
However, many changes seen might be polymorphisms
What is mosaicism
Different individual cells have different genetic constitution
Polymerase Chain Reaction
Allows us to select one small piece of human genome and amplify it
Example of an enzyme used in PCR
Heat - resistant Taq Polymerase
What is missense mutation?
Type of point mutation in which a single nucleotide change results in a codon that codes for a different amino acid
What is post zygotic mutation
Mutation that occurs in the embryo
What is penetrance
The likelihood of having a disease if you have a genetic mutation
What is Achondroplasia caused by?
Achondroplasia is caused by a mutation in Fibroblast Growth Factor Receptor 3 (FGFR3)
Salient feature of autosomal dominant
Every generation is affected, 50% risk for children
Salient feature of autosomal recessive
Only one generation affected, 25% chance
X linked recessive inheritance
Carrier father, female offspring always carrier
Passes from female carrier to affected male to female
No male to male transmission
What are copy number variants
Sections of the genome are repeated and the number of repeats in the genome varies
What is the common disease - common variant hypothesis
Thecommon disease-common varianthypothesis predicts that common disease-causingalleles, orvariants, will be found in all human populations which manifest a given disease. However these traits are neutral because many genes influence a trait
How do we know there is a genetic contribution to disease
If the disease is more prevalent or higher risk in first degree relatives
Which parents passes on mitochondrial DNA
Mother
What is heteroplasmy
A cell can have some mutation in mitochondrial DNA and some that do not
Weinberg hallmarks of cancer
Evade apoptosis Self-sufficiency in growth signals Insensitivity to anti-growth signals Tissue invasion and metastasis Limitless replicative potential Sustained angiongenesis
What are driver mutations
Mutations that drive carcinogenesis
What are passenger mutations
Incidental mutations that happen because tumour is unstable
What determines cancer characteristics, driver mutation or tissue of origin
Driver mutation
All cancer cells have the same genetic makeup
False, most cancer cells are genomically unstable and have different genetic makeup
What can be used for treatment of late stage melanoma
Vemurafenib
Significance of HER2
Human epidermal growth factor receptor play an important role in development and progression of certain types of breast cancer. HER2 protein is an important biomarker and target of therapy
Monoclonal antibody used to treat breast cancer
Trastuzumab (Herceptin), especially HER2 receptor positive
What is the Philadelphia chromosome or Philadelphia translocation
Translocation of genetic material between chromosome 9 and 22. ABL-1 gene of 9 onto BRC gene of 22 coding for a tyrosine kinase causing the cell to divide uncontrollably.
What can be used to treat leukemia that are Philadelphia chromosome positive and certain GI stromal tumours
Imatinib (Glivec)
What is a mutator gene
A gene that increases the rate of mutation of one or more genes
What are mismatch repair genes (MMR)
Genes that code for proteins capable of mechanisms to repair errors in repeat units of microsatellites. Errors in these can lead to genomic instability causing mutations
How many % of women get breast cancer
Around 10%
What can mutation in BRCA 1 lead to
Familial breast cancer
What is symptomatic testing
Always test a symptomatic person first. If we identify a mutation in the parent we can offer the offspring a pre-symptomatic test
Estimate the risk for daughter if mother with breast cancer at 70
Low risk
Estimate the risk for daughter if mother and sister with breast cancer at 45
Medium risk
Estimate the risk for daughter with BRCA-1 mutation
Low risk
Drug used to treat pre and post menopausal women
Tamoxifen
Screening for breast cancer
Mammography, breast examination
Surgical intervention for breast cancer
Mastectomy and Oophorectomy
Common disease - Common variant hypothesis
States common disease causing alleles or variants will be found in most of the population. Some of these variants lead to susceptibility to polygenic disease as each variant at each gene influences a disease by having additive effects on the disease phenotype. However, many genes influence a trait and these variants are neutral in part
Common features of Mendelian disorders
Scary family history, young age, more people affected. These need to be identified whereas common disorders need to have risk estimated.
How does symptomatic testing work
Genetic test the diseased family member. If mutation is found, we can confirm our diagnosis. Can also test other family members as part of presymptomatic testing. If no mutation found, treat on clinical parameters
What is presymptomatic testing
Testing a patient who has a relative with a known mutation. If mutation is found, confirms patient will develop the disease.
What is the Wolf-Hirschhorn Syndrome
Partial deletion of short arm of chromosome 4. Results in characteristic facial appearance, delayed growth, intellectual disability and seizures
Huntington’s disease cause
CAG repeat encoding Poly-Glutamine. This has toxic effect on cells, neuronal loss
The more CAG repeats you have, higher chances of developing Huntington’s early on
True
How can genetic testing affect families negatively
Real implication for other family members, family/social issues, adoptions, family feuds
