Clinical cytogenetics Flashcards
3 common reasons for chomosomal studies
- neonatal and peds - testsing
- infert. and prenatal - 50% of aborts have abnormality
- leukemia and lymphoma - diagnostic and prognostic
def. chromatin
uncondensed DNA
how is karyotype organized
by size and shape
what type of cells must be used for karyotype
dividing
what is G banding and result
technique where treat with 2 dyes and then get band pattern - most genes in light band
what is nomenclature for Downs’ susndrom
47, XY, +21
what are replication phases of meiosis
S phase - chomosomes replicate
prophase 1 - maternal and paternal chromos recombine
telophase 1 - chormosomes separate
M2 - sister chromatids separate - 4 gametes
what is major cause of aneuploidy
nondisjunction
what is result of non-disjunction at M1
2 x n+1
2 x n-1
what is result of non-disjunction at M2
2x n
1 x n +1
1x n-1
what is klinefelters
47, XXY
2 causes of kline
- non-dis in M1 of dad
2. non-dis in M2 of mom
phenotype of klinefelter
- tall
- narrow shoulders
- small testes
- gynecomastia
- T def.
- azoospermia
what is turner
45,X
what is turner rare
very high rate of spont. abortions
features of tri 18
mental ret, failure to thrive, sever heart defects, hypertonic, low set ears, short sternum
features of tri 13
severe mental, poor gorwth, CNS malform,
what is triploidy
3 sets of chromo
- dispermy common
- non-viable
3 types of specimens for chromo analysis and how they must be treated and time periods
all at 37C
- peripheral bloods - 72hrs
- monolayer cell cultures - skin, abortus, amniotic fluid - 1 to 2 weeks
- bone marrow or lymph nodes 1-24hr
2 types of invasive prenatal testing
- amnicenticis - 16-18wk - fine needle through abdo wall and into uterus
- chorionic villus sampling - 10-12 weeks - cells from the developing placenta are tested instead of fluid through vagina or abdo wall
5 indications for invasive testing
- high risk preg
- late maternal age
- abnormal US
- previous trisomy 21
- carrier of a rearrangement
6, fam Hx
adv. and dis adv. of amnio over CVS
adv. - less miscarirgae, better chromo length, less mosaicism,
dis - done later
when to suspect mosasicm
highly variable phenotype, can be hard to detect unless there are pigment variations
what does 46,xx,del(18)(q23)dn mean
deletion of long arm of chromosome 18 new (denovo)
why does a chromo deletion cause a defect
haplotype insufficiency - need enough - generally dose dependent
what is cri du chat
5p deletion - as more is cut it become more severe
types of rearrangments (5)
- deletion
- duplication
- translocation
- ring chromo
- inversion
can chromo rearrangment be inherited
yes
what is reciprocal tranlocation and effect
switch of both ends of two different chromo - carrier is usally fine, but can them pass down and they are at risk for imbalance
example of writing cytogenic translocation
46,XX, t(9;10)(p22;p15)
what does breakpoint position determine
the amount of abnormality, the more that is switched, the less likely they are to be viable
2 reproductive options for carriers of translocations
- genetics - prenatal testing and can terminate preg
2. fertility - donor egg or sperm
how common are chromo abnormalityes at birth
rare - less than 1%
what is CML translocation
somatic - in adulthood
- transfer ABL onto BCL gene - tyrosine kinase activity
what is the cytogenic alternative to G-banding
FISH - used to detect abscence or presence of a particular sequence of chromos
what are adv. of fish
- can detect low level mosaisicm
- fast
- specific
- can do 100s at once
what is a genomic disorder
small recurrent deletions or duplications
- happen frequently and distinct enough to call a syndrome
what is size of genomic disorders
very small - too small to see with G banding
- need FISH or microarray
what are segemental duplications
normal structure in chromo that are repeated mobile elements
sig. of segmental duplications
- was evolotionary
- cause of possible genomic disorders
def. non-homologous allelic recomb.
unequal crossing over that causes both deletions and duplications
how to detect genomic disorders
microarray - 1000s of FISH at once
what is degeorge
micro deletion 22q11.2
- truncus arteriosus
- facial features
- infection prone
- variety of phenotype
what is comparison syndrome of deletion duplication
dup. - william - cocktail party
del - speech delay, schizoid
what is generally better
duplication
how much of genome coded proteins
2%
what are Canadian guidelines for child with dev. delay
genomic micro array - trio with child and parents
what is Gbanding still first test for (4)
- aneuploidy syndromes
- sex chromos
- suspected mosaicism
- infet., multiple miscarriage
see methodology chart
see
what is impact of micro array on clinical genetics
- improve diagnosis, treatment, prevention
- discover new syndromes
- insght into the genes and dev. pathways that lead to harm
what is seen in normal people
high degree of copy number variants
4 possible outcomes of microarray analysis and interpretation
- normal or benign - harmless
- patho or likely patho - trioanalysis reccomneded - known to cause problems
- variant of unknown sig. - trioanalysis reccomend
- unexpected finding -
