Stein Lectures Flashcards
What is FISH?
Fluorescence in situ Hyrbidization: it is a cytogenic technique where a specific DNA probe bound to a fluorescent or radioactive isotope is created to hybridize with a samples DNA in order to detmermine if that DNA exists in the host
What are the three basic types of FISH?
- Repeat sequences: usually derived from telomeres or centrosomes
- Single Copy DNA: usually isolated from a cloned DNA of a disease-causing gene or a fragment of DNA of known loction associated with a particular gene
- Chromosome painting: a combination of many unique fragments of DNA along a chromomse so that the entire chromosome fluoresces
What are contiguous Gene Syndromes?
regions in the genome with clusters of closely associated genes (when duplicated or deleted express a specific clinical symptom) whose normal functions are generally unrelated
What is VCFS?
Velocardiofacial syndrome: 2nd most common syndrome known to humans resulting from a 3 MB deletion on chromosome 22. There is a wide variation of effects including: hypotonia, short stature, learning disabilities, cardiac anomolies
What is William’s Syndrome?
It’s caused by a deletion of an Elastin (ELN) gene on chromososome 7, the symptoms include: blue sclera, gifted musical abilities, usually low IQ, Stellate Iris, renal anomalies, terrible math skills
What type of inheritance pattern do mitochondrial genes have?
Matrilineal, none of the mitochondrial genes are given by the father, however, some mitochondrial disorders could be X-linked or autosomal since mitochondria rely on some nuclear genes
What is homoplasmy?
When all of the mitochondria within a cell have the same genome, meaning they’re the same
What is heteroplamy?
When there are two or more different mitochondrial genomes present in a cell.
In order for a cell to display dysfunction there must be about 85% of mutant mitochondria expressed
What region of DNA is frequently used in forensics?
Hyperviable minisatellite regions
Why is mitochondrial DNA espcially resilient to long term degradation?
Because it is circular and their are multiple copies of it within each cell
How is maternal serum alphafetoprotein useful?
MSAFP levels (high/low) have been associated with fetal abnormalities. Alpha fetoprotein is a major plasma protein produced by the yolk sac during fetal development. Several factors need to be calculated before the effect of this measurement is determined
High=Open spina bifida
Low=Down Syndrome
When is ultrasound normally performed?
Around 18 weeks gestation
What can you gather from an ultrasound?
Verify viability
Detect a multiple pregnancy
Determine gestational age
Determine Sex
Identify some abnormalities (clefting, nuchal translucency, neural tube deftects)
What is alpha fetoprotein?
It is an albumin like protein produced by the fetal liver. It can cross the placenta into the maternal blood circulation.
What is the maternal Quad test?
A serum assay measuring four different chemical concentrations of key molecules involved in fetal development
What is cfpDNA?
cell free placental DNA. It is free floating DNA with placental/fetal origin. This can be analyzed to identify specific DNA sequences indicative of disease
What is amniocentesis?
It is an invasive prenatal screening procedure whereby a needle is inserted through the abdomen into the amniotic cavity and amniotic fluid is withdrawn for testing. Risk of fetal loss is 1/200.
usually performed 16-18 weeks
What can confirm an open neural tube defect, when hinted by elevated AFP levels?
The presence of Acetylcholinesterase which is found only in the neural tube
Low AFP and karyotype analysis can confirm which common developmental disorder?
Down Syndrome
What is Chorionic Villus sampling?
an invasive procedure in which the placenta is sampled as opposed to fetal tissue, both placenta and fetus are derived from teh original zygote and , thus, are usually biologically the same, but not always so an abnormal CVS could be a problem with just the placenta (amniocentesis could confirm)
What is the adavantage of using CVS as opposed to Amniocentesis given it’s greater risk to the fetus?
It can be performed earlier 10-12 weeks gestation which can offer the possibility of more rapid and easier termination in the event of a severely affected fetus
Explain clonality
The concept that a mutant cell line can be traced back to an original mutant cell line
What type of tissue is affected in Sarcoma?
Mesenchymal (bone, muscle, fat, cartilage)
What’s the difference between leukemia and lymphoma?
Both affect white blood cells:
Leukemia: bone marrow
Lymphoma: spleen/lymph nodes
What tissue does carcinoma affect?
Epitheloid tissue (specialized immune system tissue)
What’s different about cancers arising from proto-oncogenes vs. tumor suppressor genes?
Proto-Oncogenes:
gain/change of mutation (only 1 mutation required)
Acquired
Tumor Suppressor:
classical recessive (both losses required)
1 mutation may be inherited
effect is an accumulation of errors,
inheritance significantly increases odds of disease
What is CML (Chronic Myelogenous Leukemia)?
A cancer from a translocation between chromosomes 9 and 22, results in a chimeric protein (tyrosine kinase), example of a proto-oncogene
What is acute promyelitic leukemia?
proto-oncogene related disease where a translocation between chromosomes 15 adn 17 results in a defective,
FISH confirmation is required for diagnosis
What are retinoblasts?
They are precursor to retinal cells in the eye,
in retinoblastoma these cells can acquire mutations leading to blindness or dangerous tumors of the eye
Explain what must occur in a somatic tumor gene suppressor mutation?
There must be two mutations of the same gene in the same cell, if this does occur it is typically at a later onset than the inherited disease
What is the disease Li Fraumeni?
A familial cancer syndrome, resulting from a p53 defect,
it causes multiple neoplasia
What are 4 main characteristics of breakage syndromes?
Recessive mutation
Chromosomal Instability
Susceptibility to cancer
Defective DNA repair mechanisms (allows an accumulation of defective genes)
What are microsatellites?
Repeats of 2, 3, or 4 nucleotides
highly polymorphic in population
Often used to detect DNA repair defects
(they are sensitive to slippage)
Indirect test
What is a constitutional karyotype/genotype?
The original DNA and chromosome complement that originated in the zygote.
What is Prader-Willi syndrome?
Common microdeletion syndrome of chromosome 15,
can cause obesity, bad temper, hypergonadism, small feet/hands
It appears the same as Angleman syndrome under karytype analysis
Results from a paternal deletion or maternal upd
What is angelman syndrome?
It is a microdeletion syndrome of chromosome 15,
causes severe mental retardation
skinny, hyperactive, inappropriate laughter
(happy puppet syndrome)
Results from a maternal deletion or
paternal upd
What is uniparental disomy?
Inheritance of a chromosome or chromosomes from 1 parent to the exclusion of the other parent
What is uniparental heterodisomy?
When one parents contributes both of their homologous chromosomes and none from the other parent are given to the offspring.
What is uniparental isodisomy?
When one parent contributes a single chromosome duplicate to their offspring.
This can be the result of a zygote rescue in the event of a nondisjunction which would have resulted in a monosomy
What is genetic imprinting?
The differential modification of the maternal and paternal genetic contributions to the zygote resulting in the differential expression of parental alleles during development and in the adult
Typically associated with methylation (deactivated genes)
The normal methylation process involves uniformally methylating all gametes based on the sex of the parent so that offspring receive both a paternal and maternally methylated chromosome regardless of sequence.
Which DNA residue is methylated in the process of DNA methylation?
Cytosine
What’s Rett Syndrome?
A neurodevelopmental disorder, mainly affects females, intellectual disability, motor function dirsupted, MECP2 is involved: a transcription factor that can activate or repress transcription, normal function rquired for maturation of nuerons and normal development
What is chromosomal instability?
It is a gain, loss or rearrangement of chromosomes
What is the main function of the tumor suppressor gene Rb1?
Retinoblastoma 1
Tumor Suppressor
controls progression from G1 to S
deletion results in elimination of important mitotic checkpoint
