Chromosome abnormalities and genomic rearrangements Flashcards
What is cytogenietics and what does it look at
study of chromosomes
number, structure, deletions, duplications, instability
what are the types of chromosome abnormalities
chromosome rearrangements, whole chromosome aneuploidy, copy number imbalance
what are the techniques used to investigate chromosomess
traditional cytogenetics (cell culture required to collect metaphase cells): G banding, some FISH, breakage molecular cytogenetics (tests carried out on DNA): QF-PCR, MLPA, array CGGH
What problems can chromosome rearrangements, copy number imbalance, chromosome breakage syndrome cause
chromosome rearrangement: recurrent miscarriage, infertility
copy number imbalance: dysmorphism, developmental delay, learning difficulties, specific phenotypes e.g. epilepsy, diabetes, cardiac malformations
chromosome breakage ssyndromes: facnconi anaemia, ataxia telangiectasia
what does whole chromosome aneuplodiy arise from and what does it cause
arises following nondisjunction at mitosiss or meiosis
large genomic imbalannce leads to loss of conceptions
What does nondissjunction of homologous chromosomes in meiosis I cause
disomic and nullisomic gamete formation
what do the following become:
disomic+normal
nullisomic+normal
disomic+nullisomic
disomic+normal=trisomic conceptus
nullisomic+normal=monosomic conceptus
disomic+nullisomic=uniparental disomy
what is mosaicism and how does it arise in an initially normal conceptus
presence of 2 diff. genotypes from individual arising from single egg due to nondisjunction or anaphase lag
what are the types of mosaicism
somatic-likely to result in abnormal phenotype
gonadal: arises during formation of germ cells
CPM: mosaicism confined to extraembryonic tissue
what are the types of chromosome rearrangements
robertsonian translocation, reciprocal translocation, inversion, intrachromosomal insertions
what does robertsonian translocation arise from and how are balanced carriers phenotypes and reprouctive rissks
fusion of 2 acrocentric chromosomes.(13, 14, 15, 21, 22).
balanced carriers are phenotypicallly normal but have reproductive risks (recurrent miscarriages, patau syndrome, down syndrome, male infertility)
What are the most common robertsonian translocations
der (13;14) der (14;21)
what does reciprocal translocation arise from and how are balanced carriers phenotypes and reprouctive rissks
can be between any segments of any nonhomologous chromosomes
balanced carriers=phenotypically normal but have reproductive risks (infertility, miscarriage, child with congenital abnormalities)
What types of reciprocal translocations are there, draw it out
alternate segregation, adjacent 1 segregation, 3:1 segregatipn
what is a chromosome inversion and what types of chromosome inversions are there
when segment of chromosome rearranged end to end
Paracentric inversions do not include the centromere and both breaks occur in one arm of the chromosome. Pericentric inversions include the centromere and there is a break point in each arm.
Fluorescence In Situ Hybridisation what does it do
uses fluorescent probes that bind to only those parts of a nucleic acid sequence with a high degree of sequence complementarity
What is G banding
produce a visible karyotype by staining condensed chromosomes.
which tests are used for prenatal cytogenetics
traditionally G banding but results needed more quickly so FISH and WF-PCR
What does QF-PCR
amplify specific regions of DNA and quantify the amount of DNA present in those regions.
In terms of QF-PCR, draw sketches of the results for: disomy 1:1, trisomy 2:1, trisomy 1:1:1, uninformative 1:1 or 1:1:1
ref. notes
disomy 1:1 2 homologues different size
trisomy 2:1 if 3 homologues and 2 of them same length
trisomy 1:1:1 if all have different length marker
uninformative 1:1 or 1:1:1
for segmental copy no. imbalance, what are the numbers for: normal, deletion, duplication, triplication
normal=x2
deletion=x1 or x0
duplication=x3
triplication=x4
give examples of microdeletion syndromes and what it effects
DiGeorge-dell(22q) Williams-del(7q) Angelman-del(15q) Prader-willi-del(15q) Wolf-Hirschhorn-del(4p)
Array CGH what it detects
whole chromosomes aneuploidy, microdeletion/duplication syndromes, subtelomere imbalance, other regions of imbalance (copy number variants)
How to ascertain clinical consequences of previously unreported imbalance
ineritance (de novo and inherited from affected=more likely to be pathogenic, inherited from unaffevcted more likely to be benign), number of genes (burden), specific gene content (correlation with phenotype)
