Chromosome Pathologies Flashcards
what is cytogenetics
study of chromosomes, anything larger than a single gene
what do most cytogenic changes result due to
copy number variations - gain or loss of genetic material - usually pathogenic range varies from 1kb o severe mb
may be familial or de novo
what 4 causes of cryogenic abnormalities produce abnormal phenotype e
dosage effect ( deletion or duplication - lose more disruptive than gain)
disruption of a gene (inappropriate activation or inactivation)
position effect - gene in new chromosomal environment
unmasking of a recessive disorder
what are the types of CNV’s (copy number variations)
aneuploidy - gain (trisomy) or los (monosomy) of one chromosome
polyploidy - gain whole sets ie triploidy or tetraploidy)
mosacisim - diploidy ( normal) and (aneuploidy) - different genetic material in the same individual
what are the there origins of numeric abnormalities
gametogenesis (meiosis) - failure of homologous chromosome (M1 or 2) to separate properly during cell division
fertilisation
early cleavage ( post-zygotic MITOTIC non-disjunction)
what is autosomal aneuploidy and give 3 examples
error at gametogenesis
trisomy 21 - downs
trisomy 18 - edwards
trisomy 13 - patau
80-90% caused by non-disjunction at meiosis 1
how does age affect risk of autosomal aneuploidy
increase in maternal age increases risk but paternal age has no significant risk
what is sex chromosome aneuploidy
phenotype less severe than autosomal, sexual orientation not affected turners syndrome (45,X), kleinfelters (47 XXY)
what is polyploidy, origin and examples
error at fertilisation
mostly triploidy - 69 XXY, 69 XYY, 69 XXX
origin - digyny (double female) , diplospermy (2N in sperm) , dispermy (two sperm)
double paternal = large cystic placenta, some growth delay
double maternal = tiny placenta, significant growth delay, head saving macrocephaly
what is moisacisim
error at early cleavage - mitotic non-disjunction
variable phenotype - produces on-identical twin
may generate uniparental disomy (UPD)
all females are mosaic - 2X chromosomes where one randomly inactivates
how often are structural defects in DNA such as duplication or deletion
what test is used to detect this
1/2000
duplication smaug be direct or inverted
detected using microarray CGH
describe the process of microarray CGH
hybridise sample and control DNA to microarray “chip”
genomic imbalances (CNV’s) are produced at high resolution
red bars show loss and green bars show gain
how are haploinsufficinecy sores determined
for deleted regions, low scores indicate greater likelihood of pathogenicity - only relevant in dominant alleles
who are microarray CGH testing used for, advantages and disadvantages
children of moderate and severe learning disability and pregnancies with abnormal ultrasound
ad - early diagnosis, higher resolution, greater accuracy
dis - gives info on dosage change only, no info on mutation, needs quality DNA
what technique is used for aneuploidy detection
quantitative fluorescent PCR (QF-PCR)
PCR of Short tandem repeats (STR) using fluorescent primers
describe the process of QF-PCR
DNA extraction from prenatal or blood sample
PCR amp - primers forms chromosomes with 13,18,21, X and Y
aneuploidy is expressed as a result when 2 markers with abnormal dosage = 2:1 ratio of peak height indicates trisomy
what is NIPT
non-invasive prenatal testing
maternal blood samples - extract free fetal DNA - if risk of aneuploidy do invasive test then QF-PCR
what is cancer and gives examples of how you test for it
disease specific acquired chromosomal changes - mostly translocations
eg leukeamia - bone marrow
solid tumour - tumour tissue
what are the two types of chromosomal inversions
paracentric - inversion on one arm ( breakpoints on same arm)
pericentric - inversion across both arms (breakpoints on different arms)
what are the two types of translocations
reciprocal - break and exchange
robertsonian - whole arm fusion
describe a reciprocal translocation
break and exchange of parts - 1/500, 5-10% phenotype risk
reproductive risk ie balanced translocation so carrier but not in phenotype
describe a robertson ian translocation
whole arm fusion 1/1000 occurs across acrocentric chromosomes no phenotype risk reproductive risk - carriers
how do we name translocations
eg between 4 and 8
if balanced - don’t need to show anything else
der(4) = one chromosome 4 is a derivative chromosome - it has a change in its structure (in this example piece missing and replaced with something from 8
ie der(4)t(4;8) = unbalanced translocation of chromosomes 4 and 8 where one chromosome 4 is derivative and contains some missing of 4 replaced with some of 8
