Chromosome Abnormalities Flashcards
Why would someone be referred for cytogenetic analysis?
Constitutional: prenatal diagnosis (amniocentesis, chorionic villus sampling), birth defects, abnormal sexual devel, infertility. acquired: leukaemias, solid tumours
Why carry out cytogenetic analysis?
Prenatal diagnosis, birth defects, chromosome analysis chromosome reporting
Describe chromosome analysis and reporting
Chromosome analysis = karyotyping, Metaphase chromosomes stained, paired up, grouped. Abnormalities described with standard nomenclature ISCN. Chromosome report = chromosome no., sex complement, structural changes, separated by commas
Give example of some birth defects that can be analysed
Congenital malformations, mental retardation, devel delay, Specific syndromes: Down syndrome (trisomy 21), Williams syndrome (deletion 7q11.23), DiGeorge syndrome (deletion 22q11.2)
What is aneuploidy?
loss or gain of whole chromosomes
What are the 2 causes of aneuploidy?
NON-DISJUNCTION: failure of chromosomes or sister chromatids to separate properly during meiotic divisions. Can occur during mitotic cell divisions = mosaicism (2 cell pop in an individual).
ANAPHASE LAG: defect in spindle function or attachment to chromosome, lagging chromosome may be lost in mitosis/meiosis
What is trisomy?
extra copy of chromosome: down syndrome +21, Edwards syndrome +18, Patau syndrome +13
What is monosomy?
presence of only 1 chromosome from a pair: Turners syndrome 45,X
Describe polyploidy and its cause
Gain of whole haploid set of chromosomes. CAUSE = fertilisation of egg by more than 1 sperm
What is X-chromosome inactivation?
Only 1 will ever inactivate, Males only have a single X chromosome, However, the X and Y chromosomes have short regions in common at the tips of the long and short arms, allows for pairing during cell division: Two pseudo-autosomal regions (PAR1 and PAR2)
Describe mosaicism
presence of 2/more cell lines in an individual. CAUSE = mitotic non-disjunction. Degree of mosaicism depends on when error occurred = First post zygotic division = no mosaicism looks like a meiotic event, Subsequent divisions = 3 cell lines, monosomy cell line usually lost
Name the cytogenetic structural abnormalities
Translocations, Inversions, Deletions – incl. microdeletions, Duplications, Insertions, Rings, Marker chromosomes, Isochromosomes
What is a reciprocal translocation?
2 break rearrangement, exchange of material between non-homologous chromosomes.
Balanced = same amount of genetic material spread across chromosomes
Unbalanced = deletion/addition of genetic material –> abnormal phenotype
What is a Robertsonian translocation?
rare form of chromosomal rearrangement that in humans occurs in the five acrocentric chromosome pairs, namely 13, 14, 15, 21, and 22. Other translocations occur but do not lead to a viable foetus
What is the result of segregation at meiosis?
Alternate, adjescent 1, adjescent 2, 3:1
