UW FMR Genetics Week 5

karyotype

suspect chromosomal disorder: down syndrome

FISH

confirmation of chromosomal abnormality: 22q11.2 deletion

microarray

suspect copy-number variance

causes of aneuploidy

meiotic nondisjunction (13, 18, 21: Edwards, Patau, Down)

Robertsonian Translocation

long arms of two acrocentric chromosomes fuse together

Philadelphia Chromosome

t(9,22) not heritable, drives myeloid leukemia

most common type of genetic variant

SNP

main mechanism of SNPs arising

CpG demethylation → T:A

identified by GWAS

haplotypes (blocks of inherited unbroken genome)

mutations of protooncogenes

increased activity; point mutation, CNV, or overexpression

mutations in oncogenes

rarely inherited

indication for Sanger sequencing

limited genetic differential diagnosis

indication for gene panels

clustered by category (e.g. suspect genetic retina disease)

indication for exome/whole genome sequencing

useful for evaluating VUS or de novo mutations

indications for karyotyping

suspected chromosomal abnormality and tumor analysis

indication for FISH

confirm ambiguous karyotype findings

indication for microarray

copy number variance, cannot detect balanced rearrangements

best way to find constitutional DNA

skin biopsy