CYTOGENETICS 2 Flashcards
WHAT ARE THE 2 POSSIBLE CAUSES OF STRUCTURAL CHROMOSOMAL ABNORMALITIES?
-clastogenes (mutagens)
-robertsonian translocations
WHEN CAN STRUCTURAL CHROMOSOMAL ABNORMALITIES OCCUR?
can occur anytime between G1, S, G2 and M phase as a result of bad (or no) correction of DNA breaks
NAME THE 4 TYPES OF STRUCTURAL CHROMOSOMAL ABNORMALITIES
balanced – abnormal rearrangement without the loss of genetic material
unbalanced – genetic material is missing or gained
congenital – in all types or cells or a large majority
acquired – only in a few cells
-> obtained chromosomal aberration are detected after cultivation of human peripheral lymphocytes
WHAT ARE THE UNBALANCED CHROMOSOMAL ABNORMALITIES?
-deletions
-duplications
-isochromosomes
-ring chromosomes
-dicentric chromosomes
-additional marker chromosomes
-> all are connected with congenital disorders, mental retardations and abnormal development
EXPLAIN DELETIONS
partial monosomy (loss of part of chromosome)
- terminal deletion – cleavage of end part of chromosome
- interstitial deletion when there are two breaks on one arm and a loss of genetic
material between them
- > to place a segment from the fist chromatid into the sister chromatic through “loops” (G2)
- break mostly occurs in G1
- unequal crossing-over, segregation of balanced aberration in meiosis → unbalanced product in meiosis
- e.g. deletion Xp = small stature, patient is still fertile
EXPLAIN DUPLICATION
partial trisomy (2 copies of affected chromosome and a 3rd partial copy)
-duplication or insertion of a segment from a sister chromatid from unequal crossing over
-segregation of balanced aberration in meiosis
DEFINE RING CHROMOSOME
two breaks in G1 at the terminal ends of a chromosome
-breaks join up together to form a circular shape
- Turner syndrome → X-ring → gets lost → 45,X
(missing gene for height on p arm)
(q arm contains genes responsible for fertility)
(both genes active on inactive X)
DEFINE DICENTRIC CHROMOSOME
chromosome with 2 centromeres
-occurs due to 2 breaks of 2 chromosomes during G1 which connect during G2
-two types:
A = translocation dicentric (breaks of two chromosomes → fusion of centric fragments + acentric fragment / both chromosomes non functioning)
B = iso-dicentric (breakage of both chromatids and their connection -> loss of function of 1 centromere = pseudodicentric)
EXPLAIN ISOCHROMOSOME
arms of the chromosome are mirror images of each other
-transverse division in the centromere in M2/mitosis, there is a duplication of one arm and the loss of the other
-Xp loss in women → Xq isochromosome (46,X,i(Xq)) = fertile, small stature
EXPLAIN ADDITIONAL MARKER CHROMOSOME
-small additional chromosome
-found via FISH method
-can have clinical consequences
DO BALANCED STRUCTURAL CHROMOSOMAL ABERRATIONS EFFECT THE PHENOTYPE?
no
-they change the arrangement of the chromosomes not the genetic material
NAME THE BALANCED CHROMOSOMAL ABERRATIONS
-robertsonian translocation
-reciprocal translocation
-inversions
-insertion
WHAT DOES BALANCED CHROMOSOMAL REARRANGEMENT CAUSE IN MEN?
sterility
WHEN DO BALANCED CHROMOSOMAL ABERRATIONS OCCUR?
after reproduction, carriers create unbalanced gametes (parent is fine but child is affected)
- men can be sterile (oligospermia – lower concentration of sperm in ejaculate) due to a disorder in pairing homologous chromosomes in meiosis
- women can cause the transfer of an extra chromosome 21 onto their child
- translocation causes the formation of derivative chromosome
EXPLAIN ROBERTSONIAN TRANSLOCATIONS
exchange of chromosomal segments of two non-homologous acrocentric chromosomes during meiosis
-long arms (q) fuse and short arms (p) fuse → one chromosome of both long arms and one chromosome of both short arms
-chromosome with short arms will get lost (no loss of genetic info, because p arms only contain repetitive genes → no clinical consequences)
-resulted chromosome = two chromosomes, but inherited as one → cause Robertsonian translocation syndrome
-Carrier of the balanced Robertsonian translocation 21/14 faces theoretical risk of 1/3 to have a child with the translocation form of Down syndrome
NAME THE 5 ACROCENTRIC CHROMOSOMES
13, 14, 15, 21, 22
HOW MANY TYPES OF GAMETES AND ZYGOTES DOES A CARRIER OF BALANCED ROBERTSONIAN PRODUCE?
-6 gametes
-6 zygotes
EXPLAIN RECIPROCAL TRANSLOCATION
1 break in each of 2 non-homologous chromosomes
-broken segments exchanged
-occurs in G1/G2
-quadrivalent formation
-10% risk in women
-2 - 5% risk in men
EXPLAIN QUADRIVALENT FORMATION
-prophase M1
-4 chromosomes can pair in a quadrivalent – problems after separation
o T1, T2 - N1, N2 = alternate -> balanced + normal gamete
o T1, N2 - T2, N1 = adjacent 1 = unbalanced gamete with duplication and deletion
o T1, N1 - T2, N2 = adjacent 2 = unbalanced gamete with duplication and deletion
EXPLAIN INVERSIONS
transfer of genetic material within 1 chromosome (rotating mechanism) -> depending on if the rotating part contains centromere or not
-2 types = A: pericentric
B: paracentric
-risk of recombination increases with the size of inverted segment
EXPLAIN PERICENTRIC INVERSION
breakage on small or long arm, centromere also rotates
EXPLAIN PARACENTRIC INVERSIONS
two breaks on one arm, no centromere involved
PARACENTRIC INVERSION
crossing over inside the loop → formation of dicentric chromosome and acentric chromosome
Result of crossing-over in meiosis of a carrier of paracentric inversion can be dicentric chromosome and acentric fragment
Formation of interstitial deletion and duplication
→ unequal crossing over inside the meiotic loop in both inversions
EXPLAIN INSERTION
- segment removed from one chromosome → inserted into another chromosome (in original or inverted orientation)
- 3 breaks rearrangement
WHAT ARE THE CONSEQUENCES OF BALANCED STRUCTURAL ABERRATIONS?
- segregation of unbalanced genome (= disabled child / abortion)
- sterility (mainly in men)
- in women with aberrant chromosomes they prefer to put these chromosomes into polar bodies, that is why they are
more resistant to sterility - phenotypic effect – small deletion, inversion or wrong arrangement of genes can lead to dysregulation of gene
expression, aberration will be expressed
WHAT ARE THE PRENATAL INDICATIONS FOR A CHROMOSOMAL EXAMINATION?
increased age of mother (35+ at time of birth), pathological values of markers, abnormal ultrasound, aberration in at least one parent
WHAT ARE THE POSTNATAL INDICATIONS FOR A CHROMOSOMAL EXAMINATION?
specific phenotype, psycho-motoric retardation, growth disorder, malformation, limb swelling, sterility, delayed puberty, no menstruation in women, malformation of genitals, is family relatives have aberrations
