Genetic mechanisms in disease Flashcards
Trisomy 21
Downs syndrome
Trisomy
Extra chromosome. Possible in the smaller chromosomes with no critical genes but not seen in larger ones.
Monosomy
Only 2 known examples: 1. Monosomy 21 and Monosomy 22
Klinefelter syndrome
XXY or XXYY
Turner syndrome
Missing a sex chromosome. XO genotype (not possible to be YO)
Barr body
Inactive X chromosome
Mosaicism in women
Some cells in the body have one X activated and some have the other
Microdeletion
Small deletion spanning several genes which can’t be seen in a chromosome test
Microduplication
Small duplication which can’t be seen in a chromosome test. Less problematic than deletions.
Balanced translocation
No missing, extra genetic material, often doesn’t cause disease unless right through important gene
Unbalanced translocation
Can see missing/extra piece. Like having a deletion or duplication. Can happen in children of parent with balanced translocation.
Contiguous gene syndrome
Microdeletion that spans 2 or more genes adjacent to each other
Routine chromosome tests
Karyotyping or cytogenic analysis. Can detect 1. Monosomy 2. Trisomy 3. Big deletions 4. Duplications 5. Rearrangements
Fluorescent in situ hybridization (FISH)
Will detect microdeletions and duplications, but need to know what you are looking for.
Subtelomeric FISH
Detects microdeletions and subtle rearrangements that disrupt genes near ends of chromosomes which can cause mental retardation.
Microarray (CMA, CGH)
Also called genomic array. First line test used-multiple probes and don’t need to know what you’re looking for. Results can be known disease (diagnosis), “variant of unknown significance,” parents have/don’t have (diagnosis) it, benign normal CNVs (copy normal variants). Used for detecting intellectual deficiencies with unknown cause, multiple congenital anomalies, seizures, microcephaly. Costs $2600
Pathogenic CNVs
Usually bigger, deletions/amplifications, genes in CNS
Benign CNVs
Usually smaller, gene-poor, present in healthy relative, duplications better than deletions
Risk CNVs
Inherited, variable penetrance but occur in disease state more often than normal, deletions/duplications, genes in CNS. Genetic counseling difficult.
Williams syndrome
Neurodevelopmental disorder form deletion in 26 genes on chromosome 7
Dominant negative effect
When defective protein inhibits function of normal one in dimer/multimer
Neurophakomatoses
Loss of functionn in tumor suppressor genes-second hit gives cancer
X-linked lethal
Only females get this X-linked disease because males die before birth
Exome sequencing (NextGen)
Looks for homozygous rare variants in affected individuals/families with patterns of dominant or recessive disease. Successful, but sometimes find other risk variants.
Families with recurring recessive disease (inbred)
Homozygosity mapping followed by focused Sanger or focused/whole exome sequencing
Families with recurring dominant disease
Linkage followed by Sanger sequence of candidate genes or focused/whole exome sequencing
