Zaragoza Flashcards
Questions to ask before genetic testing?
- Why? Indications to test
- Who? Patient vs. family member
- What? Biological sample
- When? Age and patient health
- How? Method/limitations
- Where? Specific laboratory
Three types of genetic test?
Cytogenic, Molecular, Metabolic
Cytogenic tests measure?
Chromosomes
Molecular tests measure?
DNA or RNA
Metabolic tests measure?
Metabolite or Protein/Enzyme
What happens in Meiosis I?
Homologous chromosomes separate
What happens in Meiosis II?
Sister chromatids separate
Karyotyping is sampled from?
Blood
Bone Marrow
Amniotic fluid
Placental tissue
Indications for Cytogenic testing vs array CGH?
Patient with
- Phenotype suggestive of a chromosome abnormality
- Learning disabilities, speech delay, behavioral problems
- Developmental delay / mental retardation / Autism
- One or more congenital abnormalities
- Short stature
- Ambiguous genitalia
- Infertility
- Recurrent pregnancy losses
Family history of
- A chromosome rearrangement
- Mental retardation
3 major diseases to test for in FISH vs Array-CGH?
Williams - 7q11.23 for elastin gene
Prader-Willi/Angelman -15q11-q13 PW/AS region
DiGeorge/VCF 22q11.2 for DiGeorge/VCF region
Williams FISH?
Williams - 7q11.23 for elastin gene
PW/AM FISH?
Prader-Willi/Angelman -15q11-q13 PW/AS region
DiGeorge/VCF FISH?
DiGeorge/VCF 22q11.2 for DiGeorge/VCF region
Array CGH detects?
Chromosome Imbalances
Array CGH indication vs karyotype?
First line testing:
- Karyotype: suspect a disorder with a whole extra or missing chromosome
- FISH (single-probe): suspect a specific microdeletion or microduplication syndrome
- Microarray: multiple congenital anomalies and/or with unexplained intellectual disabilities
A polymorphism is?
A variant present in greater than 1% of population
Four types of DNA mutation?
- Silent: same AA
- Missense: changed AA
- Nonsense: early stop codon
- Frame shift- indels, changed reading frame
Indications for DNA testing?
Diagnostic Confirm a suspected diagnosis Predictive Predict the possibility of future illness Carrier Detect carrier state (unaffected individual) Prenatal Determine status of fetus
Indications for metabolic testing (lots of them)?
Failure to thrive Mental retardation/Devel Delay Recurrent unexplained illness Seizures Ataxia Loss of psychomotor skills Hypotonia ‘‘Coarse’’ appearance Eye abnormalities Recurrent somnolence/coma Abnormal sexual differentiation Hepatosplenomegaly Metabolic/lactic acidosis Hyperuricemia Hyperammonemia Low cholesterol Structural hair abnormalities Unexplained deafness Bone abnormalities Skin abnormalities
Test for klinefelter?
Karyotype
Test for Williams?
FISH for 7q11.23
Test for Fragile X syndrome?
CGG repeat in FMR1 gene
DNA test for repeats
Test for familial hypertrophic cardiomyopathy?
DNA test for TNNT2 gene
Test for San Felipo Syndrome?
Enzyme Test for NAGLU protein
